Background and Aims:Methylenetetrahydrofolate dehydrogenase 1(MTHFD1)is essential in various tumors.However,the role of MTHFD1 in pancreatic cancer remains unclear.This study was conducted to explore the expression and clinical significance of MTHFD1 in pancreatic cancer through bioinformatics analysis and clinical sample validation,as well as to analyze its potential mechanisms of action in pancreatic cancer. Methods:The GEPIA2 online platform was used to analyze the differential expression of MTHFD1,survival,and pathological stage in TCGA pancreatic cancer data,examining the relationship between MTHFD1 expression and clinicopathologic features of pancreatic cancer patients.Univariate and multivariate analyses were performed using the Cox proportional hazards model on TCGA data.GO,KEGG,and GSEA analyses were conducted to predict the possible mechanisms of MTHFD1 in pancreatic cancer.The expression of MTHFD1 in 80 cases of pancreatic cancer and adjacent tissues was detected using immunohistochemistry,qRT-PCR,and Western blot and its expression with clinicopathologic characteristics was analyzed. Results:In the TCGA database,MTHFD1 expression in pancreatic cancer tissues was significantly higher than in normal tissues(P＜0.05).High expression of MTHFD1 was significantly associated with poor prognosis in pancreatic cancer patients(P=0.007).TCGA data indicated a close correlation between MTHFD1 expression and tumor stage(P＜0.05).MTHFD1 expression was identified as an independent prognostic factor for pancreatic cancer(HR=1.777,P=0.01).GO,KEGG,and GSEA analyses showed that MTHFD1 was related to the cell cycle,and correlation heatmaps indicated a strong association between the MTHFD1 gene and the cell cycle.In the TIMER database,MTHFD1 expression level was significantly correlated with various immune cells,including B cells,CD8+T cells,CD4+T cells,macrophages,neutrophils,and dendritic cells(all P＜0.05).The GDSC database revealed that patients with low MTHFD1 expression were more sensitive to various therapeutic agents than those with high expression.In clinical pancreatic cancer specimens,the positive expression rate of MTHFD1 and its mRNA and protein levels were significantly higher in cancer tissues than in adjacent tissues(all P＜0.05).MTHFD1 expression was associated with tumor differentiation,clinical stage,lymph node metastasis,and neural infiltration(all P＜0.05).Patients with high MTHFD1 expression had significantly shorter overall survival than those with low expression(P＜0.05). Conclusion:MTHFD1 is highly expressed in pancreatic cancer tissues and is associated with poor prognosis.It may participate in the occurrence and development of pancreatic cancer through the cell cycle and is related to the infiltration of tumor immune cells.

Objective:To investigate the risk factors for short-term mortality and long-term survival after liver transplantation in patients with hepatitis B related acute-on-chronic liver failure.Methods:Forty patients with hepatitis B related acute-on-chronic liver failure performing liver transplantation were prospectively collected from August 2018 to July 2021 in Beijing YouAn Hospital of Capital Medical University. The mean age was (44.5±8.79) years, there were 36 males and 4 females. The basic data, including liver and kidney function, blood routine, coagulation function, lactic acid, infection indexes as well as MELD score, MELD-Na score, CLIF-C ACLFs score, CLIF OFs score, CLIF grade within 48 hours before liver transplantation were counted. The post-LT mortality within 90 days and long-term survival were observed for these patients who were divided into survival group ( n=34) and death group ( n=6) according to the survival in 3 months after liver transplantation. The measurement data conforming to the normal distribution were expressed by mean ± standard deviation ( ± s), and the comparison was performed by t-test between groups; The skewness data were expressed by M ( Q1, Q3), and the rank sum test was used for inter-group comparison. The counting data were tested by Chi square test or Fisher exact probability method. The risk factors of short-term mortality and long-term survival were analyzed through univariate and multivariate analysis as well as survival analysis. The sensitivity, specificity and cut off value were calculated by ROC curve. The patients were divided into ≥ 48.5 scores group ( n=10) and < 48.5 scores group ( n=30) by CLIF-C ACLFs score 48.5 as cut-off value. Kaplan Meier was used for survival analysis and comparison. Results:The total bilirubin (TBIL), creatinine (CR), platelet count, international normalized ratio (INR), lactic acid and neutrophil/lymphocyte ratio (NLR) within 48 hours before liver transplantation were 24.30 (13.45, 33.95) mg/dL, 0.68 (0.53, 1.11) mg/dL and 56 (39, 82)×10 9/L, 3.12(2.33, 4.46), 2.14(1.59, 4.14) mmol/L, 4.06(2.12, 9.13) for all forty patients, respectively. The mean MELD, MELD Na, CLIF OFs, CLIF-C ACLFs and AARC scores within 48 hours before transplantation were (32.1±6.3), (33.2±5.3), (11.2±2.6), (43.8±8.8) and (10.6±2.4) scores, respectively. 65% of patients were complicated with hepatic encephalopathy, 17 patients with controllable systemic infection, 10 patients with renal function injury, 2 patients with variceal bleeding and 6 patients underwent ventilator-assisted ventilation (endotracheal intubation). All 40 patients underwent emergency orthotopic liver transplantation. The incidence of postoperative complications was 47.5%, the most common was post-LT infection (27.5%), followed by renal insufficiency (17.5%). There were significant differences in neutrophil lymphocyte ratio (NLR), lactic acid, MELD score, MELD Na score, CLIF-C ACLFs score, CLIF OFs score, CLIF grades, hepatic encephalopathy, infection and renal injury between survival group and death group ( P<0.05). Univariate logistic regression analysis showed that NLR, MELD Na score, CLIF-C ACLFs score and CLIF OFs score were the risk factors for short-term mortality after liver transplantation ( P<0.05). Multivariate logistic regression analysis showed that CLIF-C ACLFs score was an independent risk factor for 3-month mortality after liver transplantation. ROC curve showed that the area under the curve of CLIF-C ACLFs score was 0.895 (95% CI: 0.779-1.000, P=0.002), and the diagnostic sensitivity and specificity were the highest, 83.3% and 85.3% respectively when cut off value was 48.5. Meanwhile, there was significant difference in long-term survival between the patients with CLIF-C ACLFs score ≥ 48.5 and < 48.5 ( P=0.001). Conclusions:NLR, MELD Na score, CLIF-C ACLFs score and CLIF OFs score within 48 hours before liver transplantation are the risk factors for short-term mortality after liver transplantation, however CLIF-C ACLFs score is an independent risk factor for three-months mortality and long-term survival in patients with hepatitis B related acute-on-chronic liver failure after liver transplantation.

Objective:To investigate the safety and efficacy of combining programmed death-1 (PD-1) with tyrosine kinase inhibitors (TKIs) in patients with advanced hepatocellular carcinoma (HCC) before liver transplantation(LT).Methods:The data of six males with a mean ± s. d. age of (57.5±4.3) years who were treated with PD-1 inhibitors combined with TKIs for advanced HCC before LT at Beijing You'an Hospital, Capital Medical University and the First Medical Center of Chinese PLA General Hospital were retrospectively analysed. The tumor stagings, the use of PD-1 inhibitors and TKIs with their discontinuation in pre-LT/post-LT liver function recovery durations, incidences of complication. The tumor recurrence and disease-free survival rates were determined on follow-up of these patients at outpatients clinics.Results:For the 6 patients included in this study, four patients were classified by the Barcelona Clinic Liver Cancer Staging (BCLC) as C and the China Liver Cancer Staging (CNLC) as Ⅲa, and two patients were classified by the BCLC staging as B and the CNLC asⅡb. The mean cycle of PD-1 inhibitor used was 5.5 (1-20), and the mean duration of PD-1 inhibitor discontinuation was 19.5 (12-45) days pre-LT. All patients who were treated with PD-1 inhibitors combined with TKIs reached the liver transplantation standard, and all successfully underwent orthotopic liver transplantation. The liver function recovered well without any serious complications post-LT. All the patients survived without developing any acute rejection or other complications. The follow-up time ranged from 8.2 to 27.3 months, with a median of 11.9 months. No patients had died, and 2 patients developed tumor recurrence. The median (range) tumor-free survival time was 10.9 (2.9-27.3) months.Conclusion:Patients with advanced HCC could benefit from combined PD-1 inhibitors with TKIs therapy pre-LT. There were no increased incidences of acute rejection and other complications post-LT.

Objective:To investigate the application value of Laennec approach in laparoscopic anatomical right hemihepatectomy (LARH).Methods:The retrospective and descriptive study was conducted. The clinicopathological data of 2 female patients who underwent LARH via Laennec approach in the First Affiliated Hospital of Kangda College of Nanjing Medical University from May to July 2020 were collected. The two patients were 51 and 57 years old, respectively. Observation indicators: (1) surgical situations; (2) postoperative situations and follow-up. Follow-up using outpatient examination and telephone interview was conducted to detect post-operative survival and tumor recurrence of patients up to December 2020. Count data were repre-sented as absolute numbers.Results:(1) Surgical situations: 2 patients successfully underwent LARH via Laennec approach, without conversion to open surgery. The operation time was 180 minutes and 185 minutes, and the volume of intraoperative blood loss was 200 mL and 400 mL, respectively. No blood transfusion or gastrointestinal decompression was performed in either patient. (2) Postoperative situations and follow-up: 2 patients began to take liquid diet on the first day and out-of-bed activities on the postoperative second to third day. There was no postoperative bile fistula or bleeding, but different degrees of peritoneal and pleural effusion occurred to the 2 patients after operation. One case was improved after right-sided thoracentesis and chest tube drainage due to dyspnea, and the other case was cured after conservative therapy. There was no perioperative death. The duration of postoperative hospital stay of 2 patients was 13 days and 11 days, respectively. Results of pathological examination showed 1 case of hepatic hemangioma and 1 case of primary liver cancer, respectively. The Laennec capsule was observed on the hepatic vein branches of segment Ⅴ, Ⅵ, Ⅶ, Ⅷ, and the gap existed between the Laennec capsule and the hepatic vein. Two patients were followed up for 7 months and 5 months，respectively. They survived during the follow-up，without tumor recurrence.Conclusion:It is safe and feasible to perform LARH by Laennec approach.

BACKGROUND: It is a great challenge for surgeons to resect pulmonary nodules with small volume, deep position and no solid components under video-assisted thoracoscopic surgery. The purpose of this study is to explore the feasibility and necessity of the localization of pulmonary nodules by injecting indocyanine green (ICG) under the guidance of magnetic navigation bronchoscope and the resection of small pulmonary nodules under the fluoroscope. METHODS: Between December 2018 and August 2019, sixteen consecutive patients with 30 peripheral lung lesions in our hospital received fluorescent thoracoscopic pulmonary nodule resection. Electromagnetic navigation bronchoscope (ENB) was performed before surgery to guide ICG to the target lesion. RESULTS: All patients underwent magnetic navigation-guided pulmonary nodule localization, and surgical resection was performed immediately after localization was completed. The average size of the nodules was (11.12±3.65) mm. The average navigation time was (12.06±2.74) minutes, and the average interval between dye labeling and lung resection was (25.00±5.29) minutes. All lesions were completely resected, the localization success rate was 100.00%, no bleeding and other complications occurred after the localization, the postoperative pathological results confirmed the accuracy of the staining. CONCLUSIONS Indocyanine green injection under the guidance of magnetic navigation bronchoscope is an effective way to locate pulmonary nodules, which can locate small and untouchable lesions in the lung. This method can help surgeons identify lesions more quickly and accurately. It is practical and worthy of promotion.

Objective:To comprehensively analyze the medical resources and services supply in the cancer field of China.Methods:Data of 2018 were sampled from 41 tertiary public cancer hospitals in China, and the factor analysis method was used to extract common factors in resources or services, scoring respectively. Pearson correlation analysis was used in the collinearity test of the variables of both groups of common factors, while the second-order clustering method was used to analyze characteristic differences between the hospitals, and category difference was compared with t test. Results:Resource evaluation covered the two dimensions of basic resources(medical service and basic assurance resources)and high-end resources(high-end talents and academic resources). Service evaluation covered the two dimensions of medical service assurance(clinical services and basic assurance)and disciplinary sphere of influence(discipline construction and clinical efficiency). The factor of basic manpower and beds was significantly correlated with that of medical service and basic assurance( r=0.811, P<0.001), while the factor of high-end talents and academic resources was significantly correlated with that disciplinary construction and resource efficiency( r=0.906, P<0.001). The second-order cluster analysis found the 41 cancer hospitals as two categories, with the first category of five in Guangdong, Shanghai, Beijing and Tianjin, and the second category of the rest 36 hospitals. Significant differences were found between the two categories in terms of resource scoring, service scoring, high-end resources and disciplinary sphere of influence( P<0.001). Meanwhile, the GDP per capita of the cities in which these hospitals are located also had significant differences( P<0.001). Conclusions:Development of public tertiary cancer hospitals in China was imbalanced, as their differences were mainly found in levels of disciplinary development and efficiency of clinical services, which were closely related to the high-end talents and academic resources of the hospital in question.Furthermore, high quality medical care was mostly located in regions of higher development. The authors recommend to take a balanced consideration of the differences and distribution of cancer care services in China, in terms of performance classification of public hospitals and establishment of regional cancer centers of the country.

Objective To investigate the clinicopathological and immunohistochemical features,diagnosis and prognosis of granular cell tumor of breast (GCT)and to improve the awareness of the disease.Methods Three cases of GCT were collected;Specimens were fully drawn,microscopic pathologic examinations and immunohistochemistry (SP method)were performed.Results Three cases were female patients aged from 39 to 56 years old (average 46 years).In clinical,a single indolent or indolent mass with a hard texture was located in the breast parenchyma.In pathological,the lump was mainly solid or hard tumor with clear boundary or infiltration,with a mean diameter of 2.1 (1.2-3.0)cm,and grey to yellow sections.Histologically,large cells were round or polygonal in shape.The cytoplasm was abundant and eosinophilic.The boundary of the tumor was clear in one case,and in the other two cases,the boundary was unclear.The nucleus was small and located in the center or ectopic.The cytoplasm was coarse-grained with s-100 staining positive microparticles and PAS reaction positive (anti-digestive enzymes).Immunohistochemistrically,the tumor cells were strongly positive for S-100,CD56,NSE and Vimentin,and negative for CK and SMA.None of the patients had present malignant transformation or metastasis.Conclusions GCT can occur in any part of the body,but is not common in breast.GCT is similar to breast cancer in clinical manifestations,imaging and macroscopic observation,etc.The correct diagnosis of this lesion depends on HE morphology,immunohistochemistry and special dyeing.The close postoperative follow-up should be performed.

Objective To evaluate the role of 2B subunit-containing NMDA receptors ( NR2B) in the rostal anterior cingulate cortex ( rACC) in development of pain-related aversion in a rat model of bone cancer pain using siRNA technique. Methods Forty-five healthy male Wistar rats, weighing 220-250 g, were divided into 3 groups ( n=15 each) using a random number table method: normal saline blank control group ( group NS) , NR2B-siRNA lentivirus group ( group LV-NR2B) and pGC-FU-siRNA lentivirus group (group LV-NC). A total volume of MADB-106 cells 3μl (4. 8×109 cells∕ml) was inoculated into the bone marrow cavity of the right tibia of rats. At day 2 after inoculation, NR2B∕siRNA recombinant lentivirus 0. 2μl was injected into rACC in group LV-NR2B, and pGC-FU-siRNA negative recombinant lentivirus 0. 2μl was injected into rACC in group LV-NC. The mechanical paw withdrawal threshold ( MWT) was measured at 1 day before inoculation and 3, 7, 14 and 21 days after inoculation. Conditioned place avoidance test was performed at 1 day before inoculation and 14 days after inoculation, and the percentage of residence time in room A was calculated. The rats were sacrificed at 21 days after inoculation and the rACC was re-moved for detecting NR2B protein and mRNA expression by Western blot or real-time polymerase chain re-action. Results Compared with the baseline at 1 day before inoculation, the MWT was significantly de-creased at 7, 14 and 21 days after inoculation, and the percentage of residence time in room A was de-creased at 14 days after inoculation in NS and LV-NC groups (P<0. 05), and no significant change was found in the parameters mentioned above in LV-NR2B group (P>0. 05). Compared with group NS, the MWT was significantly increased at 14 and 21 days after inoculation, the percentage of residence time in room A was increased at 14 days after inoculation, and the expression of NR2B protein and mRNA was down-regulated in group LV-NR2B ( P<0. 05) , and no significant change was found in the parameters men-tioned above in group LV-NC (P>0. 05). Conclusion Up-regulated expression of NR2B in rACC is in-volved in development of pain-related aversion in a rat model of bone cancer pain.

Dexmedetomidine is an α2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 μg/kg load dose, followed by 0.05 μg/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1β, interleukin-6 and tumor nevrosis factor-α as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κBp65, inhibitor of κBα and phosphorylated of κBα in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-κB pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.
Animals ; Brain Edema ; CA1 Region, Hippocampal ; Cyclooxygenase 2 ; Cytokines ; Dexmedetomidine* ; Heart ; Hippocampus ; Infarction, Middle Cerebral Artery ; Inflammation* ; Interleukin-6 ; Kidney ; Neuroprotection* ; Nitric Oxide Synthase Type II ; Rats* ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; RNA, Messenger

Dexmedetomidine is an α2-adrenergic receptor agonist that exhibits a protective effect on ischemia-reperfusion injury of the heart, kidney, and other organs. In the present study, we examined the neuroprotective action and potential mechanisms of dexmedetomidine against ischemia-reperfusion induced cerebral injury. Transient focal cerebral ischemia-reperfusion injury was induced in Sprague-Dawley rats by middle cerebral artery occlusion. After the ischemic insult, animals then received intravenous dexmedetomidine of 1 μg/kg load dose, followed by 0.05 μg/kg/min infusion for 2 h. After 24 h of reperfusion, neurological function, brain edema, and the morphology of the hippocampal CA1 region were evaluated. The levels and mRNA expressions of interleukin-1β, interleukin-6 and tumor nevrosis factor-α as well as the protein expression of inducible nitric oxide synthase, cyclooxygenase-2, nuclear factor-κBp65, inhibitor of κBα and phosphorylated of κBα in hippocampus were assessed. We found that dexmedetomidine reduced focal cerebral ischemia-reperfusion injury in rats by inhibiting the expression and release of inflammatory cytokines and mediators. Inhibition of the nuclear factor-κB pathway may be a mechanism underlying the neuroprotective action of dexmedetomidine against focal cerebral I/R injury.
Animals ; Brain Edema ; CA1 Region, Hippocampal ; Cyclooxygenase 2 ; Cytokines ; Dexmedetomidine* ; Heart ; Hippocampus ; Infarction, Middle Cerebral Artery ; Inflammation* ; Interleukin-6 ; Kidney ; Neuroprotection* ; Nitric Oxide Synthase Type II ; Rats* ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; RNA, Messenger