Smoothened (SMO) is a member of sonic hedgehog homology (SHH) signaling pathway. It plays a key role as a bridge between patched-1 (PTCH-1) and Gli. Aberrant SHH expression can be detected in various malignant tissues, and the expression in pancreatic cancer stem cells is higher apparently. SHH signals are closely associated with self-duplication of cancer stem cells, formation of tumor vessels as well as matrixes. SMO antagonists such as cyclopamine, GDC-0449 and so on show potential to inhibit activity of SHH signaling, and arrest the growth as well as metastases of tumors. Recently, a few of SMO antagonists have been studied in phase I clinical trials and some are in phase II, meanwhile, phase I or II trials of SMO antagonists to treat pancreatic cancer are performed currently. As the classical SMO antagonist, cyclopamine is extracted from a medicinal plant. Perhaps researchers may be able to determine more effective SMO-targeting drugs from herbal medicines in the future.

Objective To evaluate the analgesic efficacy and effect of high intensity focused ultrasound (HIFU) in the treatment of advanced pancreatic cancer.Methods128 patients with pancreatic cancer ( Ⅲ stage 41 case,Ⅳ stage 87 case) were treated by HIFU.According to some parameters,such as the clinical symptoms,imaging examinations and survival analysis to assess the efficacy of HIFU treatment.Results22.9％ patients’ serum Ca19-9 decreased.The cancer pain was relieved in 72.5％ patients.Coagulated-necrosis by CT/MRI examination was observed.PR,SD and PD of all were 11.7％,70.3％ and 18.0％ respectively.1-year survival rate was 16.7％ for all patients,and median survival time was 7.0 months.1-year survival rate and median survival time for Ⅲ stage group were 28.5％ and 9.0 months,that of 10.8％ and 6.0 months for Ⅳ stage group respectively.ConclusionHIFU may benefit to advanced pancreatic cancer patient by stabilizing tumors,relieving pain and prolonging life expectancy with less side effects.

Objective:This study aimed to analyze and summarize the clinicopathologic characteristics and treatment protocols of large cell lung carcinoma (LCLC). Methods:Clinicopathologic data of 83 cases with LCLC confirmed by pathology in 2012 were retrospectively reviewed. Results:Exactly 83 cases of LCLC accounted for 5.4%of lung cancer in 2012. Sixty-three cases were male and twenty were female. The average age was 60.4 years old. The average maximum diameter of the tumor was 4.6 cm. The common manifestations in imageology were peripheral type. Only four cases were correctly diagnosed by sputum exfoliocytology, biopsy of bronchofibroscope, and paracentesis before surgery. Sixty-three cases (76%) underwent surgical resection, and pulmonary lobectomy was mainly selected. Postoperative pathology diagnosis indicated that 39 cases were classic large cell carcinoma, 31 were large cell neu-roendocrine carcinoma, 2 were combined large cell neuroendocrine carcinoma, 8 were basaloid carcinoma, 2 were clear cell carcinoma, and 1 was lymphoepithelioma-like carcinoma. Each subtype of LCLC had respective characteristics of pathomorphology and immuno-histochemistry. Lymph node metastasis occurred in 62 cases (75%). Conclusion:The incidence rate of LCLC, which is a highly aggres-sive malignancy, is low. The clinical manifestation and imageology characteristics of LCLC do not have specificity, and its final diagno-sis depends on pathology diagnosis. Operation is the main treatment method. Improving the diagnosis rate of LCLC and further subdi-viding the pathological subtypes are important for a normalized comprehensive treatment of LCLC.

With the development of the fourth industrial revolution, the influence of automated and artificial intelligence on the pre-analytic-, analytic, and post-analytic processes of laboratory medicine continues to increase. The application of artificial intelligence to large-scale clinical data sets generated through the improvement of automation helps discover new knowledge, develop new models, and explore new fields. Point-of-care testing has the advantages of easy operation, portability, intelligence, and widely application. The application of artificial intelligence in predictive models will promote precision laboratory medicine. In the recent outbreak of the new coronavirus, artificial intelligence has sprouted a new direction in laboratory medicine.

Objective To evaluate the clinical efficacy of Qingrehuashi herbal formula combined with high intensity focused ul-trasound(HIFU ) in the treatment of advanced pancreatic cancer .Methods 86 patients with pancreatic cancer (22 case of III stage and 64 case of IV stage) were included in this study .18 cases were performed the HIFU therapy for 2-3 times .Other 68 cases re-ceived once HIFU therapy ,among 53 cases of liver metastasis ,8 cases were simultaneously conducted HIFU ablation therapy on liv-er metastasis .The patients were given Chinese medicines dominated by Qingrehuashi before and after HIFU therapy and during fol-low up period .Results The single evaluation on HIFU irradiation cases after 1 month:complete remision(CR) in 0 case ,partial re-mission(PR) in 8 cases(9 .3% ) ,stable disease(SD in 64 cases(74 .4% ) and progress disease(PD) in 14 cases(16 .3% ) .The median survival rate of 1 year and half a year was 52 .0% and 11 .4% .Among 73 cases of increased CA199 before treatment ,CA199 after treatment was decreased in 12 cases .Among 36 cases of increased CA242 before treatment ,CA242 after treatment was decreased in 15 cases .The effective rate of analgesic relief in all the cases was 70 .9% (62/86) .Conclusion The integrated therapy of Qingre-huashi herbal formula and HIFU is an effective method for treating advanced pancreatic cancer .

Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P ＞ 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.

Objective To explore the mechanism of thymoquinone (TQ) on NSCLC cytotoxicity.Methods SK-MES-1 was inoculated into 96-well plates and cultured at 20,40,60,80 and 100 μmol/L TQ for 24 h,and the IC50 of TQ was calculated.SK-MES-1 was cultured in close proximity to IC50 concentration TQ,and time-dependent was observed.The ERK inhibitor U0126 and the p38 inhibitor SB203580 were applied to SK-MES-1 and 95-D,respectively,then TQ-activated MAPK-mediated cytotoxicity were observed.The SK-MES-1 expression of p-p38,p38,p-ERK1/2,ERK1/2,pJNK and JNK protein were detected by U0126 pretreatment for 1 h and TQ-cultured for 30 min.Results ① TQ was used to mediate NSCLC cells in a concentration and time-dependent manner,and the viability of NSCLC cells was decreased.② The cell viability of 30 μmol/L TQ and 10 μmol/L U0126 +30 μmol/L TQ showed significant differences (P =0.000),but no significant difference was found when compared with 10 μmol/L SB203580 + 30 μmol/L TQ (P =1.00).10 μmol/L SB203580 + 30 μmol/L TQ was significantly different from 10 μmol/L U0126 + 30 μmol/L TQ (P =0.000).60μmol/LTQ,10μmol/LU0126 + 60μmol/LTQ,10μmol/LSB203580 + 60 μmol/L TQ showed no significant differences between every two groups (P ＞ 0.0 5).With the increase of TQ concentration,the protective effect of SB203580 on 95-D cells gradually decreased,and 10 μmol/L SB203580 +40 μmol/L TQ group was significantly different from 40 μmol/L TQ group (P =0.033).③ Western blot analysis showed that U0126 could significantly inhibit the phosphorylation of ERK1/2,phosphorylated p38 increased with the increasing of TQ concentration.However,ERK1/2 phosphorylation decreased,and JNK phosphorylation did not change significantly.Conclusion TQ can mediate NSCLC cytotoxicity through phosphorylation of p38 pathway,but not ERK1/2 pathway.

Objective: To elucidate the expression levels of key immune biomarkers, phosphate and tension homology deleted on chromosome ten (PTEN) and programmed cell death protein1(PD-1),of different immune tolerance pathway in classic Hodgkin’s lymphoma (CHL) to further determine their clinical role and prognostic significance. Methods: The clinical features and prognostic factors of 56 CHL patients, who were admitted to the TianJin Medical University Cancer Institute from February 2003 to August 2013, were retrospectively analyzed. PTEN and PD-1 protein expression levels were analyzed by immunohistochemistry, Epstein-Barr virus encoded RNA (EBER) was performed by in situ hybridization assay. Correlations between the expression of biomarkers and clinicopathologic parameters were examined and survival analyses were performed. Results: This cohort of 56 CHL patients included 34 males and 22 females with a median age of 25 years (ranged from 7 to 71 years). In a univariate analysis, age≥45, IPS score >2, EBER positive, high expression of PTEN protein conferred inferior 5-year OS and 5-year PFS; In a multivariate model, age≥45, IPS score >2, EBER positive, high expression of PTEN protein were identified as the independent adverse prognostic factors for CHL. Conclusions This study suggested for the first time that PTEN was independent prognostic immune biomarkers in CHL, which provided the novel therapeutic strategy of immune therapy for CHL.

ObjectiveTo investigate the feasibility and safety of endoscopic retrograde cholangiopancreatography （ERCP） combined with oral cholangiopancreatography in the treatment of major duodenal papilla gallbladder polyps. MethodsA retrospective analysis was performed for the clinical data of eight patients with choledocholithiasis and gallbladder polyps who underwent ERCP and combined with oral cholangiopancreatography for major duodenal papilla cholecystectomy in Center of Digestive Endoscopy， Jilin People’s Hospital， from May 2022 to June 2024， and related data were collected， including the success rate of surgery， the technical success rate of gallbladder polyp removal， the superselective method of cystic duct， the time of operation， the time of gallbladder polyp removal， and surgical complications. ResultsBoth the success rate of surgery and the technical success rate of gallbladder polyp removal reached 100%， and of all eight patients， three patients used guide wire to enter the gallbladder under direct view， while five patients received oral cholangiopancreatography to directly enter the gallbladder. The time of operation was 51.88±12.34 minutes， and the time of gallbladder polyp removal was 23.13±10.94 minutes. The diameter of gallbladder polyp was 2‍ ‍—‍ ‍8 mm， and pathological examination showed inflammatory polyps in three patients， adenomatous polyps in one patient， and cholesterol polyps in four patients. There were no complications during or after surgery. The patients were followed up for 2‍ ‍—‍ ‍27 months after surgery， and no recurrence of gallbladder polyp was observed. ConclusionOral cholangiopancreatography is technically safe and feasible in endoscopic major duodenal papilla cholecystectomy.

Objective: To evaluate Magnetic Resonance Imaging (MRI) at 3.0T in differential diagnosis of the origin of adenocarcinoma at the junction of the lower uterine segment and endocervix. Methods: 71 patients with adenocarcinoma at the junction of the lower uterine segment and endocervix were retrospectively collected. Pelvic MR examinations, including diffusion-weighted imaging (DWI) and dynamic contrast-enhanced (DCE) sequences, were performed within 2 weeks before surgery. MR images were analyzed and measured by two radiologists, including the location of the tumor center, the enhancement pattern, the anterior and posterior diameters, the left and right diameters, the upper and lower diameters, and the apparent diffusion coefficient (ADC) of the tumor. Immunohistochemical method was used as gold standard in distinguishing cervical adenocarcinoma and uterine adenocarcinoma. Results: The upper and lower diameters of uterine adenocarcinoma were [(5.80±2.31) cm], significantly larger than those of cervical adenocarcinoma [(4.16±2.17) cm, P=0.009]. Using 4.5cm as the best cutoff point value, the sensitivity and specificity in distinguishing uterine adenocarcinoma and cervical adenocarcinoma were 68.4% and 65.4%, respectively. According to the location of tumor center, the sensitivity and specificity were 84.2% and 73.1%, respectively. Using tumor enhancement pattern as the criterion, the sensitivity and specificity of diagnosing uterine adenocarcinoma and cervical adenocarcinoma were 68.4% and 80.8% respectively. Conclusions MRI has certain clinical value in evaluating the origin of adenocarcinoma at the junction of the lower uterine segment and endocervix. The lesions can be diagnosed according to the main location, the characteristics of dynamic enhancement and the growth pattern of the tumor.