This guideline establishes a comprehensive framework for the application of patient-derived pancreatic cancer organoids. It outlines the stringent technical requirements and testing methods necessary to ensure high fidelity to the original tumor tissue, including morphological assessment, pathological biomarker expression (e.g., CK19, CK7), and genetic concordance (e.g., NRG1, KRAS). By standardizing protocols for in vitro culture, microbiological safety, and STR authentication, this consensus aims to ensure the reproducibility, safety, and stability of organoid models, thereby accelerating their integration into basic research, drug discovery, and precision medicine.

The journal retracts the article, titled “Schisandrin B induces apoptosis and cell cycle arrest of gallbladder cancer cells” [...]

Gallbladder cancer (GBC) is a type of rare but highly aggressive cancer with a dismal prognosis. Runt-related transcription factor 3 (RUNX3), a member of the runt-domain family, and its promoter methylation have been widely observed in a variety of human malignancies. However, the biological function and underlying mechanism of RUNX3 in GBC remain elusive. In this study, bisulfate sequencing PCR (BSP), Western blot, and qPCR were applied to identify the expression level and DNA methylation level of RUNX3 in GBC tissues and cells. The transcriptional relationship between RUNX3 and Inhibitor of growth 1 (ING1) was validated by dual-luciferase reporter assay and ChIP assay. A series of gain-of-function and loss-of-function assays were performed to detect the function and the regulatory relationship of RUNX3 in vitro and in vivo. RUNX3 was aberrantly downregulated in GBC cells and tissues caused by DNA Methyltransferase 1 (DNMT1)-mediated methylation, and downregulation of RUNX3 is associated with poor prognosis of GBC patients. Functional experiments reveal that RUNX3 can induce ferroptosis of GBC cells in vitro and in vivo. Mechanistically, RUNX3 induces ferroptosis by activating ING1 transcription, thereby repressing SLC7A11 in a p53-dependent manner. In conclusion, the downregulation of RUNX3 is mediated by DNA methylation, which promotes the pathogenesis of gallbladder cancer through attenuating SLC7A11-mediated ferroptosis. This study gives novel insights into the role of RUNX3 in the ferroptosis of GBC cells, which may contribute to developing potential treatment targets for GBC.

Background: Surgical resection combined with radiotherapy and chemotherapy remains a common clinical treatment for glioblastoma multiforme (GBM). However, the therapeutic outcomes have not been satisfying due to drug resistance and other factors. Quercetin, a phytoingredient capable of crossing the blood-brain barrier, has shown effectiveness in the treatment of various solid tumors. Nevertheless, the potential of quercetin in GBM treatment has not been adequately explored. Purpose: This study aims to investigate the effects and mechanisms of quercetin on MGMT(+)GBM cells. Methods: The potential targets and mechanisms of quercetin in glioma treatment were predicted based on network pharmacology and molecular docking. The effects of quercetin on cell inhibition rate, cell migration ability, cell cycle arrest, mitochondrial membrane potential (MMP), reactive oxygen species (ROS), Mitochondrial superoxide formation and apoptosis were measured by the CCK8 assay, wound healing assay, PI/RNase staining, JC-1 assay, DCFH-DA assay, MitoSOX staining and Annexin V-FITC/PI double staining, respectively. The methylation status of the MGMT promoter was assessed through methylation-specific polymerase chain reaction (MS-PCR). DNA damage was quantified by alkaline/neutral comet assay and TUNEL assay. The intracellular localization and expression of NF-kappa B and MGMT were revealed by immunofluorescence. The expression of migration-related proteins, matrix metalloproteinases, apoptosis-related proteins, cyclins, DNA damage/repair enzymes and related pathway proteins was detected by Western blot. Results: Network pharmacology identified 96 targets and potential molecular mechanisms of quercetin in glioma treatment. Subsequent experiments confirmed the synergistic effect of quercetin in combination with temozolomide (TMZ) on T98G cells. Quercetin significantly suppressed the growth and migration of human GBM T98G cells, induced apoptosis, and arrested cells in the S-phase cell cycle. The collapse of mitochondrial membrane potential, ROS generation, enhanced Bax/Bcl-2 ratio, and strengthened cleaved-Caspase 9 and cleaved-Caspase 3 suggested the involvement of ROS-mediated mitochondria-dependent apoptosis in the process of quercetin-induced apoptosis. In addition, quercetin-induced apoptosis was accompanied by intense DNA double-strand breaks (DSBs), gamma H2AX foci formation, methylation of MGMT promoter, increased cleaved-PARP, and reduced MGMT expression. Quercetin may influence the expression of the key DNA repair enzyme, MGMT, by dual suppression of the Wnt3a/beta-Catenin and the Akt/NF-kappa B signaling pathways, thereby promoting apoptosis. Inhibition of Wnt3a and Akt using specific inhibitors hindered MGMT expression. Conclusion: Our study provides the first evidence that quercetin may induce apoptosis in MGMT(+)GBM cells via dual inhibition of the Wnt3a/beta-Catenin pathway and the Akt/NF-kappa B signaling pathway. These findings suggest that quercetin could be a novel agent for improving GBM treatment, especially in TMZ-resistant GBM with high MGMT expression.

针对我国单病种质量管理中存在的数据上报不规范、对过程质控干预不足、人工统计数据滞后等问题,基于人工智能辅助技术,提出了构建单病种队列数据库与生物样本全息库及多模态真实世界认知体系,通过人工智能提升单病种质量管理水平的思路.

The current performance of nature compounds in antitumor field is gradually attracted more and more attention, we discovered a nature active ingredient alizarin possess potent natural reductive NF-κB activity to against pancreatic cancer.However, the preclinical pharmacology and therapeutic effect, and the underlying mechanisms of alizarin in inhibiting pancreatic cancer are still unclear.After high-throughput screening, this is the first report that alizarin can induce a potent inhibitory effect against pancreatic cancer cells.Alizarin induced cell cycle arrest and promoted cell apoptosis by inhibiting TNF-α-stimulated NF-κB activity and nuclear translocation, and inactivated its related TNF-α-TAK1-NF-κB signaling cascade followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP) and in the cell cycle and growth (cyclin D, c-myc).Due to the abrogation of NF-κB activity, combination of alizarin and gemcitabine exerted a better inhibitory effect on pancreatic cancer.In summary, natural component alizarin, inhibited cell proliferation and induced apoptosis in vitro and in vivo through targeting of the NF-κB signaling cascade with minimal toxicity, which combine with gemcitabine, can significantly enhance the antitumor capability, playing a synergistic effect.Therefore, alizarin may play a role in reversing gemcitabine resistance caused by overactivated NF-κB in clinical application in the future.

Objective: To compare the efficacy of off-pump coronary artery bypass grafting (CABG) or CABG plus mitral valve plasty (MVP) in patients with coronary heart disease complicated with moderate ischemic mitral insufficiency. Methods: The clinical data of 1 050 patients with coronary heart disease complicated with moderate ischemic mitral insufficiency who underwent surgical procedures from January 2009 to December 2020 were analyzed retrospectively. There were 733 males and 317 females, aging (63.3±9.0) years (range: 31 to 83 years). Patients were divided into CABG+MVP group and CABG group according to surgical methods, and the two groups of patients were matched for 1∶4 by the propensity score matching method. There were 107 patients in the CABG+MVP group and 406 patients in the CABG group after matching. The t test, Mann-Whitney U test, χ2 test, Fisher's exact probability method and repeated measures anova were used to compare the surgical outcomes and overall survival in the two groups. Results: There were no significant differences in perioperative death and postoperative complications between the two groups (all P>0.05). Compared with CABG group, CABG+MVP group had longer operation time ((5.6±1.2) hours vs. (4.2±1.0) hours, t=11.528, P<0.01), ICU stay(M(IQR))(43.0(47.3) hours vs. 25.0(33.6) hours, Z=2.483, P=0.013), and postoperative hospital stay (8(4) days vs. 7(5) days, Z=2.143, P=0.032). The amount of erythrocyte and platelet used in CABG+MVP group was significantly increased (2.0(6.5) U vs. 0(2.0) U, Z=7.084, P<0.01; 0(0.5) U vs. 0(0) U, Z=5.210, P<0.01). A total of 463 cases (93.9%) were followed up. Median follow-up was 32(31) months (range: 3 to 105 months). There was no significant difference in overall survival and no major adverse cardic and cerebrovascular events survival between CABG group and CABG+MVP group (P=0.196,P=0.305). Echocardiography showed that there was no significant difference in ejection fraction left ventricular end-diastolic diameter between the two groups (F=0.322, P=0.571; F=0.681, P=0.410). However, CABG+MVP improved mitral regurgitation better than CABG (F=160.222, P<0.01). Conclusions: For patients with coronary heart disease with moderate ischemic mitral insufficiency, the rates of all-cause mortality and major adverse cardiac and cerebrovascular events are similar between the two surgeries. Although CABG+MVP improves mitral regurgitation better than CABG, it increases the duration of surgery, ICU stay, postoperative hospital stay, and blood transfusion requirement.

Gallbladder cancer (GBC) is one of the most lethal neoplasm and is the fifth most common malignancy of gastrointestinal tract. The prognosis of gallbladder cancer is extremely terrible partially due to metastasis. Thus, understanding the molecular pathways controlling metastasis of this lethal disease may provide new targets for targeted therapeutic approach. In this study, we investigated the function of nemo-like kinase (NLK) in GBC growth and migration. Lentivirus-mediated siRNA was employed to alleviate the expression level of NLK in GBC cell lines (GBC-SD and SGC-996). Real-time PCR and western-blot analysis demonstrated that both mRNA and protein levels of NLK in GBC-SD and SGC-996 cells were decreased after infection with NLK-siRNA-expressing lentivirus (Lv-shNLK). The proliferation and in vitro tumorigenesis (colony formation) ability as well as migration of GBC-SD and SGC-996 cells with low NLK expression decreased significantly. Our results suggested that NLK is a key regulator involved in proliferation and migration of GBC, and it could be used as a potential therapeutic target for GBC.

Neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) is a rare but extremely malignant subtype of gallbladder cancer (GBC). The genetic and molecular signatures of GB-NEC are poorly understood; thus, molecular targeting is currently unavailable. In the present study, we applied whole-exome sequencing (WES) technology to detect gene mutations and predicted somatic single-nucleotide variants (SNVs) in 15 cases of GB-NEC and 22 cases of general GBC. In 15 GB-NECs, the C>T mutation was predominant among the 6 types of SNVs. TP53 showed the highest mutation frequency (73%, 11/15). Compared with neuroendocrine carcinomas of other organs, significantly mutated genes (SMGs) in GB-NECs were more similar to those in pulmonary large-cell neuroendocrine carcinomas (LCNECs), with driver roles for TP53 and RB1. In the COSMIC database of cancer-related genes, 211 genes were mutated. Strikingly, RB1 (4/15, 27%) and NAB2 (3/15, 20%) mutations were found specifically in GB-NECs; in contrast, mutations in 29 genes, including ERBB2 and ERBB3, were identified exclusively in GBC. Mutations in RB1 and NAB2 were significantly related to downregulation of the RB1 and NAB2 proteins, respectively, according to immunohistochemical (IHC) data (p values=0.0453 and 0.0303). Clinically actionable genes indicated 23 mutated genes, including ALK, BRCA1, and BRCA2. In addition, potential somatic SNVs predicted by ISOWN and SomVarIUS constituted 6 primary COSMIC mutation signatures (1, 3, 30, 6, 7, and 13) in GB-NEC. Genes carrying somatic SNVs were enriched mainly in oncogenic signaling pathways involving the Notch, WNT, Hippo, and RTK-RAS pathways. In summary, we have systematically identified the mutation landscape of GB-NEC, and these findings may provide mechanistic insights into the specific pathogenesis of this deadly disease.

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Long Non-coding RNA Linc-ITGB1 Knockdown Inhibits Cell Migration and Invasion in GBC-SD/M and GBC-SD Gallbladder Cancer Cell Lines' by Lei Wang, Yunjiao Zhang, Wenjie Lv, Jianhua Lu, Jiasheng Mu, Yingbin Liu & Ping Dong.([1]) The above article from Chemical Biology & Drug Design, published online on May 20, 2015 in Wiley Online Library (), and in Volume 86, pp. 1064-1071, has been retracted by agreement between the authors Lei Wang, Yunjiao Zhang, Wenjie Lv, Jianhua Lu, Jiasheng Mu, Yingbin Liu and Ping Dong, the journal Editor in Chief David Selwood, and John Wiley and Sons Ltd. The retraction has been agreed upon following the admission of the authors that there are several serious errors with this paper with incorrect shRNA sequences being used. The paper has therefore been retracted, and the authors apologise for any inconvenience caused. REFERENCE [1] L. Wang, Y. Zhang, W. Lv, J. Lu, J. Mu, Y. Liu, P. Dong, Chem. Biol. Drug Des. 2015, 86, 1064.

Objective: To explore the characteristics and methods of different fixation methods and prevention of open knee joint fracture. Methods: The data of 86 cases of open knee joint fracture admitted from January 2002 to December 2015 in Department of Orthopaedics, Affiliated Hospital of Chengdu University were analyzed retrospectively.There were 65 males and 21 females aged of 38.6 years. There were 38 cases treated with trans articular external fixation alone, 48 cases were in the trans articular external fixation plus auxiliary limited internal fixation group. All the patients were treated according to the same three stages except for different fixation methods. Observation of external fixation and fracture fixation, fracture healing, wound healing and treatment, treatment and related factors of infection control and knee function recovery. χ(2) test was used to analyze data. Results: Eleven patients had primary wound healing, accounting for 12.8%. Seventy-five patients had two wounds healed, accounting for 87.2%. Only 38 cases of trans articular external fixator group had 31 cases of articular surface reduction, accounting for 81.6%; Five cases of trans articular external fixator assisted limited internal fixation group had 5 cases of poor reduction, accounting for 10.4%; There was significant difference between the two groups (χ(2)=44.132, P<0.05). Take a single cross joint external fixation group, a total of 23 cases of patients with infection, accounted for 60.5% of external fixation group; trans articular external fixation assisted limited internal fixation group there were 30 cases of patients with infection, accounting for the assistance of external fixator and limited internal fixation group 62.5%; There was significant difference between the two groups(χ(2)=0.035, P>0.05). Five cases of fracture nonunion cases of serious infection, patients voluntarily underwent amputation. The Lysholm Knee Scale: In the external fixation group, 23 cases were less than 50 points, accounting for 60.5%, 15 cases were more than 50 points, accounting for 39.5%, external fixation and limited internal fixation group 20 cases were less than 50 points, accounting for 41.7%, 28 cases were more than 50 points, accounting for 58.3%; There was significant difference between the two groups(χ(2)=1.279, P>0.05). Conclusions: Prevention and control of infection is a central link in the treatment of open fracture of the knee. Trans articular external fixator plus limited internal fixation is an important measure to treat open fracture of the knee-joint.

200031, China Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China Department of Otorhinolaryngology Head and Neck Surgery, The Sixth Hospital of Sun Yat-sen University, Guangzhou 510655, China Department of Radiation Oncology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, 19104 Cancer stem cells are a subpopulation of cancer cells which have stem cell characteristics and play vital role in tumor formation, metastasis, relapse and resistance to chemodrugs. Exploring drugs or designing novel approaches to target cancer stem cells will contribute greatly to cancer therapy. The first step of exploring effective drugs to cancer stem cells is to acquire cancer stem cells and characterize their properties. Developing the targeting drugs could be based on the characteristics of cancer stem cells, like signal pathways contributing to self-renew, ability to pump small molecules out and quiescence. This review will summarizing the current approaches of designing drugs to target cancer stem cells.

It has been reported previously that a dopamine receptor D2 (DRD2) antagonist was able to induce cancer cell apoptosis and that DRD2 was expressed at high levels in pituitary adenomas. However, the expression of DRD2 in gastric cancer and its correlation with the prognosis of patients with gastric cancer remain to be elucidated. In the present study, the expression of DRD2 in 84 paired gastric cancer tissues and respective adjacent non-cancerous tissues were detected using an immunohistochemical assay. The correlation between the expression of DRD2 and the with survival durations of the patients with gastric cancer was analyzed using Kaplan-Meier analysis. In addition, online resources were utilized to further analyze the correlation between the mRNA expression level of DRD2 and prognosis. The effect of the DRD2 antagonist, thioridazine, on the proliferation of the AGS gastric cancer cells was determined. The results of the present study showed that the percentage of gastric cancer cases with a high expression level of DRD2 (51.2%) was higher, compared with that of cases with a low expression level of DRD2 (39.3%). Patients with a higher expression of DRD2 had shorter survival durations. The online database analysis revealed that the expression of DRD2 was also inversely correlated with the prognosis of patients with gastric cancer. Furthermore, the DRD2 antagonist, thioridazine, inhibited the growth of AGS gastric cancer cells. In conclusion, as the expression of DRD2 was negatively correlated with survival durations in patients with gastric cancer, it may be considered as a prognosis marker in the future. Developing DRD2 antagonists may assist in increasing the efficiency of cancer therapy.

The objective of this study was to compare long-term surgical outcomes and complications of laparoscopy-assisted distal gastrectomy (LADG) with open distal gastrectomy (ODG) for the treatment of early gastric cancer (EGC) based on a review of available randomized controlled trials (RCTs) evaluated using the Cochrane methodology. RCTs comparing LADG and ODG were identified by a systematic literature search in PubMed, Cochrane Library, MEDLINE, EMBASE, Scopus, and the China Knowledge Resource Integrated Database, for papers published from January 1, 2003 to July 30, 2015. Meta-analyses were performed to compare the long-term clinical outcomes. Our systematic literature search identified 8 eligible RCTs including 732 patients (374 LADGs and 358 ODGs), with low overall risk of bias. Long-term mortality and relapse rate were comparable for both techniques. The long-term complication rate was 8.47% in LADG groups and 13.62% in the ODG group, indicating that LADG was associated with lower risk for long-term complications (RR = 0.63; 95%CI = 0.39–1.00; P = 0.03). In the treatment of EGC, LADG lowered the rate of long- and short-term complications and promoted earlier recovery, with comparable oncological outcomes to ODG.

Objective To compare the safety and effectiveness between modified Kugel (MK)repair and Lichtenstein repair for recurrent inguinal hernia. Methods A total of 91 patients with recurrent inguinal hernia from Jan 2010 to Dec 2013 in Xinhua Hospital were retrospectively analyzed. Sixty-three cases were divided into MK group and 28 cases in Lichtenstein group. The clinical data including operation time, postoperative hospital stay, recovery time, hospital costs and postoperative complication were analyzed between two groups. Results No significant difference was observed between two groups in terms of operational time, postoperative hospital stay, recovery time and postoperative complication rate. MK repair led to significantly higher hospital costs and significantly lower incidence of postoperative recurrence when compared with those in Lichtenstein group. Conclusions MK repair offers a safe and effective option to treat recurrent inguinal hernia.

Recently, pyruvate kinase M2 (PKM2) has been implicated in the progression of certain cancers and might play pivotal roles in the formation of malignancy. However, the role of PKM2 in gallbladder cancer had not been well investigated. This study analyzed associations between PKM2 expression status with various clinical and pathologic parameters in a large cohort of gallbladder cancer (GBC) patients from a long term follow up results. The expression level of pyruvate kinase isotypes in GBC tissues and their adjacent normal gallbladder tissues were estimated by qRT-PCR and Western blot. PKM2 mRNA level were significantly high in gallbladder cancer tissues than in adjacent noncancerous tissues (P < 0.001). High expression of the PKM2 was detected in 55.71% paraffin-embedded GBC tissue. The high PKM2 expression was independently associated with poorer overall survival in patients with GBC (median survival 11.9 vs 30.1 months; hazard ratio 2.79; 95% CI = 1.18 to 6.55; P = 0.02). These findings indicated elevated expression of PKM2 is a prognostic factor for poor GBC clinical outcomes, implied involving of PKM2 in GBC progression.