Integrative analyses of bulk and single-cell transcriptomics reveals the infiltration and crosstalk of cancer-associated fibroblasts as a novel predictor for prognosis and microenvironment remodeling in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) is a highly malignant neoplasm and characterized by desmoplastic matrix. The heterogeneity and crosstalk of tumor microenvironment remain incompletely understood. METHODS: To address this gap, we performed Weighted Gene Co-expression Network Analysis (WGCNA) to identify and construct a cancer associated fibroblasts (CAFs) infiltration biomarker. We also depicted the intercellular communication network and important receptor-ligand complexes using the single-cell transcriptomics analysis of tumor and Adjacent normal tissue. RESULTS: Through the intersection of TCGA DEGs and WGCNA module genes, 784 differential genes related to CAFs infiltration were obtained. After a series of regression analyses, the CAFs score was generated by integrating the expressions of EVA1A, APBA2, LRRTM4, GOLGA8M, BPIFB2, and their corresponding coefficients. In the TCGA-CHOL, GSE89748, and 107,943 cohorts, the high CAFs score group showed unfavorable survival prognosis (p < 0.001, p = 0.0074, p = 0.028, respectively). Additionally, a series of drugs have been predicted to be more sensitive to the high-risk group (p < 0.05). Subsequent to dimension reduction and clustering, thirteen clusters were identified to construct the single-cell atlas. Cell-cell interaction analysis unveiled significant enhancement of signal transduction in tumor tissues, particularly from fibroblasts to malignant cells via diverse pathways. Moreover, SCENIC analysis indicated that HOXA5, WT1, and LHX2 are fibroblast specific motifs. CONCLUSIONS: This study reveals the key role of fibroblasts - oncocytes interaction in the remodeling of the immunosuppressive microenvironment in intrahepatic cholangiocarcinoma. Subsequently, it may trigger cascade activation of downstream signaling pathways such as PI3K-AKT and Notch in tumor, thus initiating tumorigenesis. Targeted drugs aimed at disrupting fibroblasts-tumor cell interaction, along with associated enrichment pathways, show potential in mitigating the immunosuppressive microenvironment that facilitates tumor progression.

A meta-analysis between robotic hepatectomy and conventional open hepatectomy.

Current meta-analysis was performed to compare robotic hepatectomy (RH) with conventional open hepatectomy (OH) in terms of peri-operative and postoperative outcomes. PubMed, EMBASE, and the Cochrane Library were all searched up for comparative studies between RH and OH. RevMan5.3 software and Stata 13.0 software were used for statistical analysis. Nineteen studies with 1747 patients who received RH and 23,633 patients who received OH were included. Pooled results indicated that patients who received RH were generally younger than those received OH (P < 0.00001). Moreover, RH was associated with longer operative time (P = 0.0002), less intraoperative hemorrhage (P < 0.0001), lower incidence of intraoperative transfusion (P = 0.003), lower incidence of postoperative any morbidity (P < 0.00001), postoperative major morbidity (P = 0.0001), mortalities with 90 days after surgery (P < 0.0001), and shorter length of postoperative hospital stay (P < 0.00001). Comparable total hospital costs were acquired between RH and OH groups (P = 0.46). However, even at the premise of comparable R0 rate (P = 0.86), RH was associated with smaller resected tumor size (P < 0.00001). Major hepatectomy (P = 0.02) and right posterior hepatectomy (P = 0.0003) were less frequently performed in RH group. Finally, we concluded that RH was superior to OH in terms of peri-operative and postoperative outcomes. RH could lead to less intraoperative hemorrhage, less postoperative complications and an enhanced postoperative recovery. However, major hepatectomy and right posterior hepatectomy were still less frequently performed via robotic approach. Future more powerful well-designed studies are required for further exploration.

Multi-omics data-based analysis characterizes molecular alterations of the vesicle genes in human colorectal cancer.

The role of vesicular genes in the development of colorectal cancer (CRC) is crucial. Analyzing alterations in these genes at multi-omics can aid in understanding the molecular pathways behind colorectal carcinogenesis and identifying potential treatment targets. However, studies on the overall alteration of vesicular genes in CRC are still lacking. In this study, we aimed to investigate the relationship between vesicle genetic alterations and CRC progression. To achieve this, we analyzed molecular alterations in CRC vesicle genes at eight levels, including mRNA, protein, and epigenetic levels. Additionally, we examined CRC overall survival-related genes that were obtained from a public database. Our analysis of chromatin structural variants, DNA methylation, chromatin accessibility, and proteins (including phosphorylation, ubiquitination, and malonylation), along with RNA-seq data from the TCGA database, revealed multiple levels of alterations in CRC vesicle genes in the collected tissue samples. We progressively examined the alterations of vesicle genes in mRNA and protein levels in CRC and discovered the hub genes. Further investigation identified the probable essential transcription factors. This study contributes to a thorough knowledge of the connection between vesicle gene alterations at multiple levels and the development of CRC and offers a theoretical framework for the identification of novel treatment targets.

Relationship between myopia control and amount of corneal refractive change after orthokeratology lens treatment.

BACKGROUND: To evaluate the relationship between amount of corneal refractive change (CRC) after wearing orthokeratology (Ortho-K) lenses and axial length (AL) growth. METHODS: We retrospectively enrolled 77 patients (77 eyes) aged 8-14 years who wore Ortho-K lenses more than 12 months. We divided the patients into 2 subgroups: spherical equivalent (SE) ≤ -3.0 D and SE > -3.0 D subgroup. The sagittal and tangential curvature maps and corneal topographic data within the 8-mm diameter ring at the baseline and during follow-up visits after wearing Ortho-K lens were recorded in addition to the area, height, and volume of the CRC region. The AL data were recorded at the baseline and during follow-up visits. Multivariate linear regression was conducted to analyze associations between the area, height, and volume of the CRC region, AL elongation, and SE. RESULTS: The average change in the CRC region was 9.77 ± 0.60 D in height, 16.66 ± 3.61 mm2 in area, and 87.47 ± 8.96 D*mm2 in volume on the tangential diagram after wearing Ortho-K lenses for 3 months. The AL showed a change of 0.19 ± 0.14 mm after 1 year of Ortho-K lens wear (P < 0.05). At 1 year, AL elongation was negatively correlated with the area (P = 0.019) and volume (P < 0.001) of the CRC region. At 1 year, for every 1-mm2 increase in the area and every 1-D*mm2 increase in the volume of the CRC region, the average AL elongation decreased by 0.01 mm and 0.002 mm, respectively, in the multivariate analysis. In patients with SE ≤ -3.0 D, AL elongation was negatively correlated with the CRC-region volume (ß = -0.002, P = 0.018), and in patients with SE > -3.0 D, AL elongation was negatively correlated with the CRC-region area (ß = -0.017, P = 0.016). CONCLUSIONS: The AL elongation-control efficacy of Ortho-K lenses may be related to the area and volume of the CRC region.

Artificial mixed microbial system for polycyclic aromatic hydrocarbons degradation.

Polycyclic aromatic hydrocarbons (PAHs) are environmental pollutants with major risks to human health. Biological degradation is environmentally friendly and the most appealing remediation method for a wide range of persistent pollutants. Meanwhile, due to the large microbial strain collection and multiple metabolic pathways, PAH degradation via an artificial mixed microbial system (MMS) has emerged and is regarded as a promising bioremediation approach. The artificial MMS construction by simplifying the community structure, clarifying the labor division, and streamlining the metabolic flux has shown tremendous efficiency. This review describes the construction principles, influencing factors, and enhancement strategies of artificial MMS for PAH degradation. In addition, we identify the challenges and future opportunities for the development of MMS toward new or upgraded high-performance applications.

Should more aggressive surgical resection be considered in the treatment for Bismuth types I and II hilar cholangiocarcinoma? A meta-analysis.

Evidence regarding the optical surgical extent for Bismuth type I/II HCCA is lacking. we aims to evaluate the optimal surgical methods for Bismuth type I/II HCCA. Studies comparing bile duct resection (BDR) and BDR combined with liver resection (BDR + LR) for all types of HCCA patients were searched for analyses, and 14 studies were finally included. The main outcomes were the R0 resection rate and overall survival (OS). For all types of HCCA patents, BDR + LR resulted with higher R0 resection rates when comparing with BDR only (RR = 0.70, 95%CI, 0.63-0.78), and patients with R0 resections had eight times longer median survival and more long-time survival outcomes (3 and 5 year OS) comparing to those with non-R0 resections. Bismuth I/II HCCA patients also showed longer median survival and 3-year OS after R0 resections (P = 0.04). Moreover, there was no significant difference in 3-year OS between BDR and BDR + LR (P = 0.89) and we additionally found BDR resulted in less mortality or morbidity rates. In Europe and US, they resulted the R0 resection rates could be comparable between BDR and BDR + LR (P = 0.18), and Bismuth type I HCCA accounted for 75.8%, while in Asia, BDR + LR still resulted with higher R0 resection rates (P < 0.0001) and the Bismuth type I HCCA accounted for only 40.3%. The surgical approaches may not directly impact patient prognosis, patients with R0 resections are usually associated with improved survival outcomes; for selected Bismuth type I/II HCCA, BDR may be an acceptable option with regard to lower morbidity and comparable R0 resection rate comparing with BDR + LR.

The Multifaceted Gene 275 Embedded in the PKS-PTS Gene Cluster Was Involved in the Regulation of Arthrobotrisin Biosynthesis, TCA Cycle, and Septa Formation in Nematode-Trapping Fungus Arthrobotrys oligospora.

The predominant nematode-trapping fungus Arthrobotrys oligospora harbors a unique polyketide synthase-prenyltransferase (PKS-PTS) gene cluster AOL_s00215g responsible for the biosynthesis of sesquiterpenyl epoxy-cyclohexenoids (SECs) that are involved in the regulation of fungal growth, adhesive trap formation, antibacterial activity, and soil colonization. However, the function of one rare gene (AOL_s00215g275 (275)) embedded in the cluster has remained cryptic. Here, we constructed two mutants with the disruption of 275 and the overexpression of 275, respectively, and compared their fungal growth, morphology, resistance to chemical stress, nematicidal activity, transcriptomic and metabolic profiles, and infrastructures, together with binding affinity analysis. Both mutants displayed distinct differences in their TCA cycles, SEC biosynthesis, and endocytosis, combined with abnormal mitochondria, vacuoles, septa formation, and decreased nematicidal activity. Our results suggest that gene 275 might function as a separator and as an integrated gene with multiple potential functions related to three distinct genes encoding the retinoic acid induced-1, cortactin, and vacuolar iron transporter 1 proteins in this nematode-trapping fungus. Our unexpected findings provide insight into the intriguing organization and functions of a rare non-biosynthetic gene in a biosynthetic gene cluster.

N7-Methylguanosine Genes Related Prognostic Biomarker in Hepatocellular Carcinoma.

Background: About 90% of liver cancer-related deaths are caused by hepatocellular carcinoma (HCC). N7-methylguanosine (m7G) modification is associated with the biological process and regulation of various diseases. To the best of our knowledge, its role in the pathogenesis and prognosis of HCC has not been thoroughly investigated. Aim: To identify N7-methylguanosine (m7G) related prognostic biomarkers in HCC. Furthermore, we also studied the association of m7G-related prognostic gene signature with immune infiltration in HCC. Methods: The TCGA datasets were used as a training and GEO dataset "GSE76427" for validation of the results. Statistical analyses were performed using the R statistical software version 4.1.2. Results: Functional enrichment analysis identified some pathogenesis related to HCC. We identified 3 m7G-related genes (CDK1, ANO1, and PDGFRA) as prognostic biomarkers for HCC. A risk score was calculated from these 3 prognostic m7G-related genes which showed the high-risk group had a significantly poorer prognosis than the low-risk group in both training and validation datasets. The 3- and 5-years overall survival was predicted better with the risk score than the ideal model in the entire cohort in the predictive nomogram. Furthermore, immune checkpoint genes like CTLA4, HAVCR2, LAG3, and TIGT were expressed significantly higher in the high-risk group and the chemotherapy sensitivity analysis showed that the high-risk groups were responsive to sorafenib treatment. Conclusion: These 3 m7G genes related signature model can be used as prognostic biomarkers in HCC and a guide for immunotherapy and chemotherapy response. Future clinical study on this biomarker model is required to verify its clinical implications.

Respiratory exposure to graphene oxide induces pulmonary fibrosis and organ damages in rats involving caspase-1/p38MAPK/TGF-ß1 signaling pathways.

Numerous studies have shown that graphene oxide (GO) respiratory exposure led to severe lung injury, but whether pulmonary fibrosis caused by GO respiratory exposure is related to the activation of the caspase-1/p38MAPK/TGF-ß1 remains unclear. In this study, rats were administrated GO by intratracheal instillation and fed for three months, and the molecular mechanisms of GO on the pulmonary fibrosis and other organ damage caused by GO respiratory exposure were examined. The results showed that the expression of caspase-1/p38MAPK/TGF-ß1 pathway-related factors were significantly elevated with the increase of exposure concentrations of GO. Those data proved that the caspase-1/p38MAPK/TGF-ß1 signaling pathway was involved in the pulmonary fibrosis caused by GO respiratory exposure. The trends of related factors also proved that the caspase-1/p38MAPK/TGF-ß1 pathway was likely to play a dominant role in the sub-acute and sub-chronic stages. The other organ damage examination found that the liver and spleen were damaged initially by the GO respiratory exposure. Meanwhile for the testicle, although the acute injury was severe, signs of recovery were found during the three-month trial period.

The effect of orthokeratology treatment zone decentration on myopia progression.

BACKGROUND: This study aimed to compare the changes in the axial length (AL) in myopic children that wear centered and decentered orthokeratology (Ortho-K). METHODS: This retrospective study included 217 subjects who were treated with an Ortho-K lens for >12 months. The subjects were divided into three groups based on the magnitude of the Ortho-K lens treatment zone decentration: mildly, moderately, and severely decentered groups. Distance and direction of treatment zone decentration were calculated using software that was developed in-house. The AL changes in different groups were compared. RESULTS: Based on the distance of the treatment zone decentration, 65 children (65 eyes) were included in the mildly decentered group, 114 children (114 eyes) in the moderately decentered group, and 38 children (38 eyes) in the severely decentered group. The mean decentration distance in the three groups was 0.35 ± 0.11 mm, 0.71 ± 0.13 mm, and 1.21 ± 0.22 mm, respectively. The mean AL increase in the three groups after 12 months of Ortho-K lens wear was 0.24 ± 0.21 mm, 0.23 ± 0.18 mm, and 0.19 ± 0.20 mm, respectively. There were no significant differences in AL changes among the three groups. CONCLUSIONS: Ortho-K lens decentration is common in clinical practice. The AL change after Ortho-K lens wear was not significantly different in subjects with different magnitudes of Ortho-K lens decentration. Fitting the Ortho-K lens in the properly centered zone is recommended to ensure the safety of Ortho-K lens wear and to maintain visual quality.

Temporal-spatial variation, source forensics of PAHs and their derivatives in sediment from Songhua River, Northeastern China.

The distribution patterns and health risk assessment of nitrated polycyclic aromatic hydrocarbons (NPAHs), hydroxy polycyclic aromatic hydrocarbons (OH-PAHs), and regular 16 priority polycyclic aromatic hydrocarbons (PAHs) in sediment from the Songhua River in northeastern China were investigated in this research. During dry seasons, concentrations of 16 USEPA priority PAHs, OH-PAHs, and NPAHs were extremely high, with average values of 1220 ± 288, 317 ± 641, 2.54 ± 3.98, and 12.2 ± 22.1 ng/g (dry weight, dw). The dry period level was confirmed to be 4 times greater than the wet period concentration. Modeling with positive matrix factorization (PMF) and estimation of diagnostic isomeric ratios were applied for identifying sources, according to the positive matrix factorization model: vehicle emissions (38.1%), biomass burning (25%), petroleum source (23.4%), and diesel engines source (13.5%) in wet season as well as wood combustion (44.1%), vehicle source (40.2%), coke oven (10.8%), and biomass burning (4.9%) in the dry season. The greatest seasonal variability was attributed to high molecular weight compounds (HMW PAHs). BaP was confirmed to be 81% carcinogenic in this study, which offers convincing proof of the escalating health issues.

Polyketide Synthase-Terpenoid Synthase Hybrid Pathway Regulation of Trap Formation through Ammonia Metabolism Controls Soil Colonization of Predominant Nematode-Trapping Fungus.

Polyketide synthase-terpenoid synthase (PKS-TPS) hybrid pathways for biosynthesis of unique sesquiterpenyl epoxy-cyclohexenoids (SECs) have been found to be widely distributed in plant pathogenic fungi. However, the natural and ecological functions of these pathways and their metabolites still remain cryptic. In this study, the whole PKS-TPS hybrid pathway in the predominant nematode-trapping fungus Arthrobotrys oligospora was first proposed according to all the intermediates and their derivatives from all the A. oligospora mutants with a deficiency in each gene involved in SEC biosynthesis. Most mutants displayed significantly increased trap formation which was correlated with alteration of the ammonia level. Further analysis revealed that the main metabolites involved in ammonia metabolism were largely increased in most mutants. However, significantly retarded colonization in soil were observed in most mutants compared to the wild-type strain due to significantly decreased antibacterial activities. Our results suggested that A. oligospora used the PKS-TPS hybrid pathway for fungal soil colonization via decreasing fungal nematode-capturing ability. This also provided solid evidence that boosting fungal colonization in soil was the secondary metabolite whose biosynthesis depended on a PKS-TPS hybrid pathway.

Engineering prokaryotic regulator IrrE to enhance stress tolerance in budding yeast.

BACKGROUND: Stress tolerance is one of the important desired microbial traits for industrial bioprocesses, and global regulatory protein engineering is an efficient approach to improve strain tolerance. In our study, IrrE, a global regulatory protein from the prokaryotic organism Deinococcus radiodurans, was engineered to confer yeast improved tolerance to the inhibitors in lignocellulose hydrolysates or high temperatures. RESULTS: Three IrrE mutations were developed through directed evolution, and the expression of these mutants could improve the yeast fermentation rate by threefold or more in the presence of multiple inhibitors. Subsequently, the tolerance to multiple inhibitors of single-site mutants based on the mutations from the variants were then evaluated, and 11 mutants, including L65P, I103T, E119V, L160F, P162S, M169V, V204A, R244G, Base 824 Deletion, V299A, and A300V were identified to be critical for the improved representative inhibitors, i.e., furfural, acetic acid and phenol (FAP) tolerance. Further studies indicated that IrrE caused genome-wide transcriptional perturbation in yeast, and the mutant I24 led to the rapid growth of Saccharomyces cerevisiae by primarily regulating the transcription level of transcription activators/factors, protecting the intracellular environment and enhancing the antioxidant capacity under inhibitor environments, which reflected IrrE plasticity. Meanwhile, we observed that the expression of the wild-type or mutant IrrE could also protect Saccharomyces cerevisiae from the damage caused by thermal stress. The recombinant yeast strains were able to grow with glucose at 42 â„ƒ. CONCLUSIONS: IrrE from Deinococcus radiodurans can be engineered as a tolerance-enhancer for Saccharomyces cerevisiae. Systematic research on the regulatory model and mechanism of a prokaryotic global regulatory factor IrrE to increase yeast tolerance provided valuable insights for the improvements in microbial tolerance to complex industrial stress conditions.

Sesquiterpenyl Epoxy-Cyclohexenoids and their Signaling Functions in Nematode-Trapping Fungus Arthrobotrys oligospora.

In this study, we purified three new sesquiterpenyl epoxy-cyclohexenoid (SEC) analogues, arthrobotrisin D (11) and its two derivatives, from nematode-trapping fungus Arthrobotrys oligospora. Our results revealed that arthrobotrisin type SEC metabolites could be detected in all the test fungal strains from geographically distinct regions grown on different nutrient media, indicative of unique diagnostic character as chemical indicators for A. oligospora. The time course designs over short-term intervals of the fungus under direct contact and indirect contact with living or dead nematodes revealed that arthrobotrisin B and D (6 and 11) displayed significant relationships (positive or negative correlation) with fungal saprophytic and pathogenic stages during a nematode predation event. Interestingly, fungus on nutrient-limiting medium conducive to fungal trap formation could rapidly drop the concentration levels of arthrobotrisins B and D within 6 h when dead nematodes were around, in great contrast to that for living nematodes. Moreover, only in the fungal strain under direct contact with living dominant soil bacteria, arthrobotrisins B and D exhibited significant increase in amounts. Among them, the new SEC, arthrobotrisin D (11) was found to be a key unique metabolic signal for fungal colony growth and fungal interaction with prey and bacteria. Our study suggested that chemical analysis of SEC metabolites in A. oligospora provides a window into the fungal growth status and much valuable information about ecological environments associated with the nematode infections.

[Role of limb-bud and heart development expression in prostate cancer].

OBJECTIVE: To investigate the expression and biological function of limb-bud and heart development (LBH) in prostate cancer. METHODS: Using real-time quantitative polymerase chain reaction (RT-qPCR), Western blot and immunohistochemistry, we detected the expression of LBH in the prostate cancer and adjacent normal tissues of 20 prostate cancer patients. We transfected the PC-3 and LNCaP cells with siRNA-1, siRNA-2 or negative control siRNA to silence the expression of LBH, and then observed the proliferation, immigration and invasiveness of the cells by CCK-8 and Transwell assays. RESULTS: The expression of LBH mRNA was significantly higher in the prostate cancer than in the normal tissue (4.8 ± 2.4 vs 1.8 ± 1.1, P = 0.032), and so was that of the LBH protein (3.5 ± 1.2 vs 1.3 ± 0.6, P = 0.019) and the positive rate of LBH expression was (90% ï¼»18/20ï¼½ vs 15% ï¼»3/20ï¼½, P = 0.006). Interfering with the LBH expression significantly reduced the proliferation of both the PC-3 and LNCaP cells, with a remarkable decrease at 96 hours in the A450 value of the PC-3 cells transfected with siRNA-1 (1.2 ± 0.1) and siRNA-2 (1.1 ± 0.1) as compared with that in the negative control group (1.8 ± 0.2) (P < 0.01) as well as in the A450 value of the LNCaP cells (1.4 ± 0.2 and 1.1 ± 0.2 vs 1.9 ± 0.2, P < 0.01). The count of the PC-3 cells that migrated through the polycarbonate membrane was significantly lower in the siRNA-1 and siRNA-2 transfection groups than in the negative control (55.5 ± 6.4 and 44.9 ± 4.5 vs 175.6 ± 25.8, P < 0.05), and so was that of the LNCaP cells (46.4 ± 5.8 and 40.2 ± 8.2 vs 125.3 ± 13.5, P < 0.05). Cell invasion assay also showed significant lower number of the PC-3 cells penetrating the polycarbonate membrane and matrigel in the siRNA-1 and siRNA-2 transfection groups than in the negative control (82.5 ± 7.5 and 68.4 ± 5.5 vs 138.2 ± 10.7, P < 0.05) as well as in that of the LNCaP cells (46.4 ± 5.8 and 23.1 ± 6.2 vs 92.1 ± 10.5, P < 0.05). CONCLUSIONS: The overexpression of LBH may play an important role in the development and progression of prostate cancer and serve as a therapeutic target in the treatment of the malignance.

Is there comparable morbidity in pylorus-preserving and pylorus-resecting pancreaticoduodenectomy? A meta-analysis.

Pancreaticoduodenectomy (PD) is the most effective treatment for patients with pancreatic head or periampullary lesions. Two major strategies exist: pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD). However, it is yet unclear regarding the morbidity after PPPD and PRPD. This study analyzed the morbidity after PPPD and PRPD to determine the optimal surgical treatment of masses in the pancreatic head or periampullary region. A systematic search of databases identifying randomized controlled trials (RCTs) from the Cochrane Library, PubMed, EMBASE and Web of Science was performed. Outcome was compared by postoperative morbidity including overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and delayed gastric emptying (DGE) rate between PPPD and PRPD. The DGE rate in the PRPD subgroups (conventional PD [CPD] and subtotal stomach-preserving PD [SSPPD], respectively) was also analyzed. The results showed that 9 RCTs including 722 participants were included for meta-analysis. Among these RCTs, 7 manuscripts described PRPD as CPD, and 2 manuscripts described PRPD as SSPPD. There were no significant differences in the overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding, or biliary leakage between PPPD and PRPD. There was a lower rate of DGE with PRPD than that with PPPD (RR=2.15, P=0.03, 95% CI, 1.09-4.23). Further subgroup analysis indicated a comparable DGE rate for the CPD but a lower DGE rate for the SSPPD group than the PPPD group. However, the result did not indicate any difference between CPD and SSPPD regarding the DGE rate (P=0.92). It is suggested that PPPD is comparable to PRPD in overall morbidity, pancreatic fistulas, wound infections, postoperative bleeding and biliary leakage. The current data are not sufficient to draw a conclusion regarding which surgical procedure is associated with a lower postoperative DGE rate. Our conclusions were limited by the available data. Further evaluations of RCTs are needed.

Pylorus-preserving versus pylorus-resecting pancreaticoduodenectomy for periampullary and pancreatic carcinoma: a meta-analysis.

BACKGROUND: The aim of this meta-analysis was to compare the long-term survival, mortality, morbidity and the operation-related events in patients with periampullary and pancreatic carcinoma undergoing pylorus-preserving pancreaticoduodenectomy (PPPD) and pylorus-resecting pancreaticoduodenectomy (PRPD). METHOD: A systematic search of literature databases (Cochrane Library, PubMed, EMBASE and Web of Science) was performed to identify studies. Outcome measures comparing PPPD versus PRPD for periampullary and pancreatic carcinoma were long-term survival, mortality, morbidity (overall morbidity, delayed gastric emptying [DGE], pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage) and operation related events (hospital stays, operating time, intraoperative blood loss and red blood cell transfusions). RESULTS: Eight randomized controlled trials (RCTs) including 622 patients were identified and included in the analysis. Among these patients, it revealed no difference in long-term survival between the PPPD and PRPD groups (HR = 0.23, p = 0.11). There was a lower rate of DGE (RR = 2.35, p = 0.04, 95% CI, 1.06-5.21) with PRPD. Mortality, overall morbidity, pancreatic fistula, wound infection, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage were not significantly different between the groups. PPPDs were performed more quickly than PRPDs (WMD = 53.25 minutes, p = 0.01, 95% CI, 12.53-93.97); and there was less estimated intraoperative blood loss (WMD = 365.21 ml, p = 0.006, 95% CI, 102.71-627.71) and fewer red blood cell transfusions (WMD = 0.29 U, p = 0.003, 95% CI, 0.10-0.48) in patients undergoing PPPD. The hospital stays showed no significant difference. CONCLUSIONS: PPPD had advantages over PRPD in operating time, intraoperative blood loss and red blood cell transfusions, but had a significantly higher rate of DGE for periampullary and pancreatic carcinoma. PPPD and PRPD had comparable mortality and morbidity including pancreatic fistulas, wound infections, postoperative bleeding, biliary leakage, ascites and gastroenterostomy leakage. Our conclusions were limited by the available data. Further evaluations of high-quality RCTs are needed.

[Functional study of transcription factor Hlx modified dendritic cell line DC2.4].

AIM: To transfect Hlx into mouse dendritic cell line DC2.4 and observe the effect of hlx on function of dendritic cells. METHODS: The eukaryotic expression vector PIRES2-EGFP/Hlx was transfected into DC2.4 by liposomes. The transfection efficiency was identified through FACS. RT-PCR and Real-time PCR were used to test the transcription level of Hlx in DC2.4. Forty-eight hours after transfection, DC2.4 cells were studied for cytokine production, cell phenotype, phagocytosis, unilateral mixed lymphocyte reaction. RESULTS: The pIRES2-EGFP/Hlx vector was transfected into DC2.4 with the transfection efficiency of up to 60%. Highly expressed Hlx in DC2.4 increased the expression of maturation makers including CD80 and CD86, and major histocompatibility complex-II. Functional assay showed that over-expression of Hlx in DC2.4 increased the interleukin-12 transcription and decreased DC endocytosis. The Hlx modified DC2.4 highly expressed IL-10 and TGF-ß at the same time. Furthermore, it was shown that in a unilateral mixed lymphocyte reaction model, Hlx modified DC2.4 inhibited proliferation of lymphocytes. CONCLUSION: Transient over-expression of Hlx in DC2.4 promotes DC2.4 maturation and up-regulates IL-12, IL-10 and TGF-ß expression. However, the Hlx modified DC2.4 cells functionally appear as regulatory dendritic cells.

[Expression of TLR8 in human cervical cancer HeLa cells and the effect of TLR8 agonist on the cell proliferation and apoptosis].

OBJECTIVE: To observe the expression of Toll-like receptor 8 (TLR8) in human cervical cancer cell-line HeLa cells, and the effects of TLR8 agonist CL075 on the survival and proliferation of HeLa cells. METHODS: PCR and RT-PCR were used to detect the expression of TLR8 in 13 cancer cell lines, and the expression of COX-2, Bcl-2, VEGF mRNA in the HeLa cells stimulated by TLR8 agonist CL075 were also measured by RT-PCR. Immunofluorescence technique was used to determine the exact location of TLR8 in the cells. The percentage of viable cells was determined by trypan blue exclusion after the HeLa cells were stimulated with TLR8 agonist CL075 (0.1 µg/ml, 0.5 µg/ml, 1.0 µg/ml, 2.5 µg/ml), and cell cycle and apoptosis were analyzed by flow cytometry, and the proliferation was measured by MTT. RESULTS: Compared with the other cancer cell lines, the expression of TLR8 in HeLa cells was the highest (703.7 ± 20.6). After stimulation by CL075, the cells had a remarkable increase of the percentage of cells in G(2)/M + S phases. In the control group, the percentage of cells in G(2)/M +S phases was (39.02 ± 2.33)%, whereas after stimulated with 1.0 µg/ml CL075, the percentage of cells in G(2)/M + S phases reached the highest ratio (57.67 ± 1.73)%, and the percentage of cells in G(2)/M + S phases had a less decrease after 2.5 µg/ml CL075 stimulation and the percentage was (56.14 ± 3.73)%. After the CL075 treatment, there was no significant changes of apoptosis compared with that of the control cells (P > 0.05), but after DDP treatment the apoptosis had a significant change (P < 0.01). After stimulation by 1.0 µg/ml CL075 for 24 h, no significant difference (P > 0.05) was found by MTT test, but a significant difference was found at 48 h and 72 h (P < 0.01). An increased expression of COX-2, Bcl-2 and VEGF mRNA was observed in HeLa cells after stimulation by TLR8 agonist CL075 for 24 h and 48 h (P < 0.05). CONCLUSIONS: Expression of TLR8 is significantly increased in HeLa cells. The proportion of cells at different phases has a significant change after CL075 stimulation, which may up-regulate the proliferation of HeLa cells. These data suggested that TLR8 agonist may influence the tumor development and TLR8 may become a potential target in the treatment for cervical cancer.