Effect of laparoscopic sleeve gastrectomy on related variables of obesity complicated with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is closely related to obesity, and weight loss can significantly improve the metabolic, endocrine and reproductive functions of obese individuals with PCOS. However, the efficacy of laparoscopic sleeve gastrectomy (LSG) for obesity with PCOS are unclear. AIM: The purpose of the study was to investigate the effect of LSG on related variables in obese patients with PCOS. METHODS: A retrospective analysis was performed on 32 obese patients with PCOS who received LSG treatment at the Third Hospital of Shanxi Medical University from 2013 to 2020. The changes in anthropometric indices, insulin, testosterone, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH), menstrual cycle and LH/FSH ratio before and 1 mo, 3 mo, 6 mo and 12 mo after the operation were statistically analyzed. RESULTS: At 1 mo, 3 mo, 6 mo and 12 mo after surgery, the anthropometric indices, such as body weight and body mass index, of all patients were lower than those before the operation. The percentage excess weight loss (EWL%) at 1 mo, 3 mo, 6 mo and 1 year of follow-up were 25, 40, 46 and 65, respectively. The PCOS-related indices, such as insulin, testosterone, estradiol, follicle stimulating hormone (FSH), luteinizing hormone (LH) and menstrual cycle, were improved to varying degrees. During the 1-year follow-up, the average serum testosterone decreased from preoperative 0.72 ng/mL to 0.43 ng/mL (P < 0.05), average fasting insulin level (9.0 mIU/mL, preoperative 34.2 mil, LH level, 4.4 mIU/mL, preoperative 6.1 mIU/mL). The level of FSH (3.8 U/L, 4.8 U/p0.05) and the ratio of LH/FSH (0.7, 1.3/p0.05) were more relieved than those before surgery. During the postoperative follow-up, it was found that the menstrual cycle of 27 patients (nasty 27) returned to normal, and 6 patients (18%) who intended to become pregnant became pregnant within 1 year after surgery. CONCLUSION: The weight loss effect of LSG is obvious and affirmative, and the endocrine index of obese patients with PCOS is also improved to some extent, although the mechanism is not clear. Laparoscopic sleeve gastrectomy is expected to become a backup choice for patients with polycystic ovaries in the future.

CD168+ macrophages promote hepatocellular carcinoma tumor stemness and progression through TOP2A/ß-catenin/YAP1 axis.

Liver cancer stem-like cells (LCSCs) are the main cause of heterogeneity and poor prognosis in hepatocellular carcinoma (HCC). In this study, we aimed to explore the origin of LCSCs and the role of the TOP2A/ß-catenin/YAP1 axis in tumor stemness and progression. Using single-cell RNA-seq analysis, we identified TOP2A+CENPF+ LCSCs, which were mainly regulated by CD168+ M2-like macrophages. Furthermore, spatial location analysis and fluorescent staining confirmed that LCSCs were enriched at tumor margins, constituting the spatial heterogeneity of HCC. Mechanistically, TOP2A competitively binds to ß-catenin, leading to disassociation of ß-catenin from YAP1, promoting HCC stemness and overgrowth. Our study provides valuable insights into the spatial transcriptome heterogeneity of the HCC microenvironment and the critical role of TOP2A/ß-catenin/YAP1 axis in HCC stemness and progression.

Single-cell RNA Sequencing Analysis Reveals New Immune Disorder Complexities in Hypersplenism.

Hypersplenism (HS) is a concomitant symptom of liver or blood disease. Not only does the treatment of HS face challenges, but the transcriptome of individual cells is also unknown. Here, the transcriptional profiles of 43,037 cells from four HS tissues and one control tissue were generated by the single-cell RNA sequencing and nine major cell types, including T-cells, B-cells, NK cells, hematopoietic stem cells, neutrophil cells, mast cells, endothelial cells, erythrocytes, and dendritic cells were identified. Strikingly, the main features were the lack of CCL5+ B-cells in HS and the presence of SESN1+ B cells in HS with hepatocellular carcinoma (HS-HCC). In cell-cell interaction analysis, CD74-COPA and CD94-HLA-E in HS were found to be up-regulated. We further explored HS-specifically enriched genes (such as FKBP5, ADAR, and RPS4Y1) and found that FKBP5 was highly expressed in HCC-HS, leading to immunosuppression. Taken together, this research provides new insights into the genetic characteristics of HS via comprehensive single-cell transcriptome analysis.

MicroRNA-203-3p inhibits the proliferation, invasion and migration of pancreatic cancer cells by downregulating fibroblast growth factor 2.

Aberrant expression of fibroblast growth factor 2 (FGF2) is a major cause of poor prognosis in patients with pancreatic cancer. MicroRNA (miRNA/miR) miR-203-3p is a newly identified miRNA that can affect the biological behavior of tumors. The present study investigated the function of miR-203-3p on the regulation of FGF2 expression, and its role in pancreatic cancer cell proliferation, apoptosis, invasion and migration. Reverse transcription-quantitative PCR was used to determine the mRNA expression levels of miR-203-3p and FGF2 in vitro. Cell Counting Kit-8, Annexin V-APC/7-AAD double-staining Apoptosis Detection kit, wound healing and Transwell assays were used to determine the proliferation, apoptosis, migration and invasion of pancreatic cancer cells. The binding of miR-203-3p to FGF2 was assessed by a luciferase reporter assay. The results demonstrated that miR-203-3p expression was downregulated in pancreatic cancer cells. Gain- and loss-of-function experiments indicated that miR-203-3p inhibited the proliferation, migration and invasion, and promoted the apoptosis of pancreatic cancer cells in vitro. In addition, it was found that alteration of miR-203-3p abolished the promoting effects of FGF2 on pancreatic cancer cells. The present study demonstrated that FGF2 significantly promoted the proliferation, invasion and migration of pancreatic cancer cells. The mechanism involved the binding of miR-203-3p to the 3'-untranslated region of FGF2 mRNA, resulting in the downregulation of FGF2. In conclusion, miR-203-3p inhibited FGF2 expression, regulated the proliferation and inhibited the invasion and migration of pancreatic cancer cells.

The Role of Prefoldin and Its Subunits in Tumors and Their Application Prospects in Nanomedicine.

Prefoldin (PFDN) is a hexameric chaperone complex that is widely found in eukaryotes and archaea and consists of six different subunits (PFDN1-6). Its main function is to transfer actin and tubulin monomers to the eukaryotic cell cytoplasmic chaperone protein (c-CPN) specific binding during the assembly of the cytoskeleton, to stabilize the newly synthesized peptides so that they can be folded correctly. The current study found that each subunit of PFDN has different functions, which are closely related to the occurrence, development and prognosis of tumors. However, the best characteristics of each subunit have not been fully affirmed. The connection between research and tumors can change the understanding of PFDN and further extend its potential prognostic role and structural function to cancer research and clinical practice. This article mainly reviews the role of canonical PFDN and its subunits in tumors and other diseases, and discusses the potential prospects of the unique structure and function of PFDN in nanomedicine.

High expression of transform growth factor beta 1 in gastric cancer confers worse outcome: results of a cohort study on 184 patients.

BACKGROUND/AIMS: Transform growth factors beta (TGFbeta) plays different roles at different stages of tumor development. TGFbeta1 is one isoform of TGFbeta, with complex secretion mechanism and bidirectional functions. This study was to investigate TGFbeta1 expression and its clinical significance in different clinicopathological subgroups of gastric cancer (GC) patients. METHODOLOGY: Tumor and peritumoral tissues from 184 GC patients were constructed into three tumor tissue microarrays. The expression of TGFbeta1 was analyzed by immunohistochemistry methods. RESULTS: TGFbeta1 was mainly expressed in the cytoplasm and membrane of GC cells. Low TGFbeta1 expression was observed in 82 (44.6%) tumor and 28 (68.3%) peritumoral tissues, and high expression was observed in 102 (55.4%) tumor and 13 (31.7%) peritumoral tissues. TGFbeta1 expression was significantly higher in tumor than peritumoral tissues (chi2 = 7.554, P = 0.006). The high expression of TGFbeta1 was related to worse overall survival (OS) (P = 0.040). TGFbeta1 expression was higher in the old and intestinal type GC than in the young (P = 0.017) and in diffuse type GC (P = 0.015), respectively. Patients with high TGFbeta1 expression had a worse survival in young people, female, diffuse type GC, poor differentiation, and lymph nodes metastasis. Multivariate Cox proportional hazards analysis showed that age, pathological grading, serosal invasion and TGFbeta1 expression were independent risk factors. CONCLUSIONS: High TGFbeta1 expression may indicate poor prognosis of GC patients and warrant more active treatment against TGFbeta1.

Long term follow up and retrospective study on 533 gastric cancer cases.

BACKGROUND: Gastric cancer (GC) is the third leading cause of cancer death in China and the outcome of GC patients is poor. The aim of the research is to study the prognostic factors of gastric cancer patients who had curative intent or palliative resection, completed clinical database and follow-up. METHODS: This retrospective study analyzed 533 GC patients from three tertiary referral teaching hospitals from January 2004 to December 2010 who had curative intent or palliative resection, complete clinical database and follow-up information. The GC-specific overall survival (OS) status was determined by the Kaplan-Meier method, and univariate analysis was conducted to identify possible factors for survival. Multivariate analysis using the Cox proportional hazard model and a forward regression procedure was conducted to define independent prognostic factors. RESULTS: By the last follow-up, the median follow-up time of 533 GC patients was 38.6 mo (range 6.9-100.9 mo), and the median GC-specific OS was 25.3 mo (95% CI: 23.1-27.4 mo). The estimated 1-, 2-, 3- and 5-year GC-specific OS rates were 78.4%, 61.4%, 53.3% and 48.4%, respectively. Univariate analysis identified the following prognostic factors: hospital, age, gender, cancer site, surgery type, resection type, other organ resection, HIPEC, LN status, tumor invasion, distant metastases, TNM stage, postoperative SAE, systemic chemotherapy and IP chemotherapy. In multivariate analysis, seven factors were identified as independent prognostic factors for long term survival, including resection type, HIPEC, LN status, tumor invasion, distant metastases, postoperative SAE and systemic chemotherapy. CONCLUSIONS: Resection type, HIPEC, postoperative SAE and systemic chemotherapy are four independent prognostic factors that could be intervened for GC patients for improving survival.

Tumor invasion unit in gastric cancer revealed by QDs-based in situ molecular imaging and multispectral analysis.

In tumor tissues, cancer cells, tumor infiltrating macrophages and tumor neo-vessels in close spatial vicinity with one another form tumor invasion unit, which is a biologically important tumor microenvironment of metastasis to facilitate cancer invasion and metastasis. Establishing an in situ molecular imaging technology to simultaneously reveal these three components is essential for the in-depth investigation of tumor invasion unit. In this report, we have developed a computer-aided algorithm by quantum dots (QDs)-based multiplexed molecular imaging technique for such purpose. A series of studies on gastric cancer tumor tissues demonstrated that the tumor invasion unit was correlated with major unfavorable pathological features and worse clinical outcomes, which illustrated the significantly negative impacts and predictive power of tumor invasion unit on patient overall survival. This study confirmed the technical advantages of QDs-based in situ and simultaneous molecular imaging of key cancer molecules to gain deeper insights into the biology of cancer invasion.

Lymph node ratio is a better prognosticator than lymph node status for gastric cancer: A retrospective study of 138 cases.

To study the clinical significance of lymph node ratio (LNR) in gastric cancer (GC), this study analyzed 613 patients with GC who underwent surgical resection. Of 613 patients with GC, 138 patients who had >15 lymph nodes (LNs) resected and radical resection were enrolled into the final study. All major clinicopathological data were entered into a central database. LNR was defined as the ratio of the number of metastatic LNs to the number of removed LNs. In order to determine the best cut-off points for LNR, the log-rank test and X-tile were used. LNR was then substituted for lymph node status (pN) in the 7th American Joint Committee on Cancer tumor-node-metastases (TNM) staging system and this was defined as the tumor-node ratio-metastases (TRM) staging system. Pearson's correlation coefficient (r) was used to study the correlations among the number of removed LNs, pN and LNR. The Kaplan-Meier survival curve was used to study the survival status, and the log-rank test and Cox proportional hazards model were used to identify the independent factors for survival. Receiver operating characteristic curve analysis was used to determine the predictive value of the parameters. By the time of last follow-up (median follow-up period, 38.3 months; range, 9.9-97.7 months), the median overall survival (OS) was 23.9 months [95% confidence interval (CI), 18.8-29.0 months]. The 1-, 2-, 3- and 5-year survival rates were 76.8, 57.2, 50.0 and 46.4%, respectively. The cut-off points were 0, 0.5 and 0.8 (R0, LNR=0; R1, LNR ≤0.5; R2, 0.5> LNR ≤0.8; and R3, LNR >0.8). Univariate and multivariate analyses revealed that both LNR and pN were independent prognostic factors for GC. LNR could better differentiate OS in patients than LN. In addition, the TRM staging system was better at predicting the clinical outcomes than the TNM staging system, and LNR was better than pN. In conclusion, LNR was a better prognosticator than pN for GC.

Clinicopathological and biological significance of cripto overexpression in human colon cancer.

AIM: To assess the clinicopathological and biological significance of cripto in human colorectal cancer. METHODS: Real-time reverse-transcription polymerase chain reaction (PCR) was used to examine cripto mRNA levels in primary colon cancer and normal colon tissues as well as normal and metastatic lymph nodes from colon cancers. Human colon cancer LS-174T cells were transfected with cripto small interfering RNA (siRNA), and mRNA and protein levels were evaluated using real-time PCR and western blot analysis, respectively. The growth of cancer cells was evaluated using the MTT assay and colony formation in soft agar. Invasion was examined using a Transwell assay, and the expressions of matrix metalloproteinase (MMP)-7 and MMP-9 were determined using western blot assay. RESULTS: Cripto was significantly overexpressed in primary colon cancer and metastatic lymph nodes. Silencing cripto gene expression with cripto siRNA resulted in a significant decrease in colony formation in soft agar in the colon cancer cell line LS-174T. Cripto siRNA treatment decreased the migration and invasion capabilities of the colon cancer cell line LS-174T in vitro. Furthermore, cripto siRNA treatment inhibited the expression of matrix MMP-7 and MMP-9. CONCLUSION: The results provide evidence that cripto siRNA could be an effective approach for the inhibition of cancer cell invasion and migration and thus has potential for use in devising novel preventive and therapeutic strategies for colon cancer metastasis.

MicroRNA-125b functions as a tumor suppressor in hepatocellular carcinoma cells.

MicroRNAs (miRNAs) are important regulators of multiple cellular processes, and the deregulation of miRNA is a common event in diverse human diseases, particularly cancer. However, the mechanisms underlying the relationship between disordered miRNA expression and tumorigenesis have remained largely unknown. In this study, we demonstrated the down-regulation of miR-125b in hepatocellular carcinoma (HCC) tissues and HCC cell lines by Northern blot and quantitative RT-PCR analyses. The ectopic expression of miR-125b reduced the cellular proliferation and cell cycle progression of HCC cells by targeting Mcl-1 and IL6R. Furthermore, the miR-125b-induced inhibition of cell proliferation was rescued by the expression of Mcl-1 or IL6R variants that lacked 3' UTRs. Thus, this study revealed the differential expression of miR-125b in HCC cells and elucidated its potential as a tumor suppressor in HCC development.

[Inhibitory effect of NSC348884, a small molecular inhibitor of nucleophosmin, on the growth of hepatocellular carcinoma cell line hepG2].

OBJECTIVE: To investigate the effect of NSC348884, a nucleophosmin small molecular inhibitor, on the growth of hepatocellular carcinoma cell line HepG2 and its underlying mechanism. METHODS: After HepG2 cells were treated by NSC348884 for 4 days, the effect of HepG2 cells on proliferation was measured by methyl thiazolyl tetrazolium (MTT) assay, the expression variation of nucleophosmin oligomer and monomer was measured using Western blotting, and cell apoptotic rate was detected by flow cytometry. RESULTS: The proliferation of HepG2 cells was remarkably inhibited by NSC348884 treatment when the drug concentration ranged from 1 micromol/L to 10 micromol/L (P < 0.05), with a 50% inhibiting concentration of 1.4 micromol/L. After treatment for 24 hours, the expression level of nucleophosmin oligomer decreased obviously while that of nucleophosmin monomer increased (both P < 0.05). After treatment by 1 micromol/L and 2 micromol/L NSC348884, the 24-hour apoptotic rates of HepG2 cells were (13.770 +/- 0.335)% and (19.021 +/- 0.237)%, respectively, which were significantly higher than in the control group (6.950 +/- 0.207)% (P < 0. 05). CONCLUSION: NSC348884 can promote the transformation of nucleophosmin oligomer to monomer and thus inhibit the growth of hepatic carcinoma cell line HepG2 in vitro.

[Experience of surgical resection of Bismuth-Corlette type I and II hilar cholangiocarcinoma].

OBJECTIVE: To report the experience of surgical resection of Bismuth-Corlette type I and II hilar cholangiocarcinoma. METHODS: From January 1998 and January 2008, 52 cases of Bismuth-Corlette type I and II hilar cholangiocarcinoma were operated on. The clinical data and long-term outcome of the patients was retrospectively analyzed. RESULTS: Of the 52 cases, 44 cases (84.6%) received operation, 28 patients underwent radical resection (63.6%) and 16 patients (36.4%) underwent palliative resection.Seven patients were resected on caudate lobe and other section and lobe of the liver; among them, 2 patients received combined portal vein resection and 4 underwent combined hepatic artery resection respectively. Eleven cases developed postoperative complications and another one died in hospital. The median survival was 33.2 months in radical resection group, and 1-, 3-, 5-year survival rate was 82.6%, 47.8%, 34.7%, respectively, which was significant greater than those in the palliative resection group (41.6%, 16.6%, 8.3%, respectively) (P < 0.05). The median survival was 16.7 months in the palliative resection group. CONCLUSIONS: The radical resection is still the best treatment for Bismuth-Corlette type I and II hilar cholangiocarcinoma. Intraoperative pathology for resection margin, and combined liver resection, portal vein resection and hepatic artery resection can help improve the radical resection rate.