Does previous gastrectomy history affect the surgical outcomes of laparoscopic cholecystectomy?

PURPOSE: This current study aimed to explore whether gastrectomy history influenced surgical outcomes while undergoing laparoscopic cholecystectomy (LC). METHODS: The PubMed, Embase, and Cochrane Library databases were searched for eligible studies from inception to April 29, 2023. The Newcastle-Ottawa Scale (NOS) was adopted to assess the quality of included studies. The mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous variables, and the odds ratios (ORs) and 95% CIs were calculated for dichotomous variables. RevMan 5.4 was used for data analysis. RESULTS: Seven studies enrolling 8193 patients were eligible for the final pooling up analysis (380 patients in the previous gastrectomy group and 7813 patients in the non-gastrectomy group). The patients in the gastrectomy group were older (MD = 11.11, 95%CI = 7.80-14.41, P < 0.01) and had a higher portion of males (OR = 3.74, 95%CI = 2.92-4.79, P < 0.01) than patients in the non-gastrectomy group patients. Moreover, the gastrectomy group had longer LC operation time (MD = 34.17, 95%CI = 25.20-43.14, P < 0.01), a higher conversion rate (OR = 6.74, 95%CI = 2.17-20.26, P = 0.01), more intraoperative blood loss (OR = 1.96, 95%CI = 0.59-3.32, P < 0.01) and longer postoperative hospital stays (MD = 1.07, 95%CI = 0.38-1.76, P < 0.01) than the non-gastrectomy group. CONCLUSION: Patients with a previous gastrectomy history had longer operation time, a higher conversion rate, more intraoperative blood loss, and longer postoperative hospital stays than patients without while undergoing LC. Surgeons should pay more attention to these patients and make prudent decisions to avoid worse surgical outcomes as much as possible.

Does PD-1 blockade play a decisive role in the pathological complete remission of unresectable MSS, BRAF V600E-mutated metastatic colorectal cancer: A case report.

Background: Colorectal cancer (CRC) ranks third in highest incidence among human cancers. With the continuous development of anti-cancer drugs, CRC patients are treated more and more effectively. However, the treatment of patients with unresectable metastatic CRC (mCRC) remains a core point for surgeons worldwide, especially for those with microsatellite stability (MSS) and BRAF V600E mutation, who have been reported to have the worst prognosis. Case description: We report a case of pathological complete remission in a patient with unresectable MSS, BRAF V600E-mutated metastatic rectal cancer after using Vemurafenib and Cetuximab in combination with Camrelizumab. Conclusions: This case suggested that Vemurafenib and Cetuximab combined with Camrelizumab is effective in the treatment of MSS, BRAF V600E-mutated mCRC. To benefit more patients, further studies need to be completed.

Analysis of Mono-ADP-Ribosylation Levels in Human Colorectal Cancer.

BACKGROUND: Colorectal cancer remains a major public health problem with high morbidity and mortality rates. In the search for the mechanisms of colorectal cancer occurrence and development, increasing attention has been focused on epigenetics. The overall level of Mono-ADP-ribosylation, an epigenetic, has not been investigated now. The aim of our study was to analysis of the overall level of mono-ADP-ribosylation in colorectal cancer. METHODS: Immunohistochemistry was used to investigate the level of mono-ADP-ribosylation in colorectal cancer and normal colorectal adjacent tissue from 64 CRC patients. The data of patient demographic, clinical and pathological characteristics were acquired and analyzed. RESULTS: Mono-ADP-ribosylation was present in both colorectal adenocarcinoma and normal colorectal tissue. The overall level of mono-ADP-ribosylation in colorectal cancer was significantly higher than that in normal colorectal adjacent tissue. In the nucleus, the majority of samples in the high-level group were colorectal adenocarcinoma (55/64), but the opposite was true for normal colorectal tissues (7/32). In particular, increases in the level of mono-ADP-ribosylation in the cytoplasm of colorectal cancer cells was associated with a greater invasion depth of the tumor. CONCLUSION: The increased level of mono-ADP-ribosylation in colorectal cancer enhances tumor invasion, which suggests that mono-ADP-ribosylation is involved in the development of colorectal cancer and may become a new direction to solve the problem of colorectal cancer.

Transcriptome sequencing analysis of mono­ADP­ribosylation in colorectal cancer cells.

Colorectal cancer (CRC) is a global health concern. The role of epigenetics in tumors has garnered increasing interest. ADP ribosylation is an epigenetic modification that is associated with a variety of biological functions and diseases, and its association with tumor development and progression has been hypothesized. However, due to the limitations of available techniques and methods, ADP ribosylation of specific sites is difficult to determine. In previous studies, it was shown that arginine­117 of histone 3 (H3R117) in Lovo cells can be modified by mono­ADP­ribosylation. This site was mutated and Lovo cells overexpressing this mutant construct were established. In the present study, the expression of differentially expressed genes (DEGs) between untransfected Lovo cells and H3R117A Lovo cells was analyzed. A total of 58,174 DEGs were identified, of which 2,324 were significantly differentially expressed (q­value <0.05; fold change >2). Functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment was used to analyze the functions and possible roles of the DEGs. The DEGs were enriched in pathways associated with metabolic process, catalytic activity, organelle and chromatin structure, and dynamics. Through this comprehensive and systematic analysis, the role of mono­ADP­ribosylation in CRC was examined, providing a foundation for future studies.

Inhibition of BAG-1 induced SH-SY5Y cell apoptosis without affecting Hsp70 expression.

OBJECTIVE: To further explore the role of BCL-2 associated anthanogen-1 (BAG-1) in neuronal apoptosis and whether the effect of BAG-1 depends on heat shock protein 70 (HSP70). METHODS: RNA interference (RNAi) technology was used to inhibit the expression of BAG-1 in SH-SY5Y cells. Hypoxia-reoxygenation injury model in the SH-SY5Y cells was established. Cell Counting Kit-8 (CCK-8) was performed for cell viability. Annexin V-APC/7-AAD double-staining followed by flow cytometry was used to measure cell apoptosis. Quantitative reverse-transcription polymerase chain reaction and Western blot analysis were used to detect the messenger RNA (mRNA) and protein expression of genes, respectively. RESULTS: BAG-1 gene silencing decreased SH-SY5Y cell viability and promoted SH-SY5Y cell apoptosis after hypoxia-reoxygenation. However, the down-regulation of BAG-1 had no effect on the mRNA and protein expression of HSP70. CONCLUSION: BAG-1 could protect SH-SY5Y cells from the hypoxia-reoxygenation injury without affecting HSP70 expression.

PARG regulates the proliferation and differentiation of DCs and T cells via PARP/NF­κB in tumour metastases of colon carcinoma.

The present study investigated the effect of poly(ADP­ribose) glycohydrolase (PARG) on the immune response in tumour metastases of colon carcinoma. CT26 cells were transfected with lentivirus PARG­short hairpin RNA (shRNA). A liver metastasis model of colon carcinoma was successfully established by splenic subcapsular inoculation of the various groups of CT26 cells into BALB/c mice. Next, changes in the liver metastases of colon carcinoma nodules and alterations in the survival times were observed in tumour­bearing mice. The numbers of B220+DEC205+ dendritic cells (B220+DEC205+DC) and CD11c+CD11b+ dendritic cells (CD11c+CD11b+DC) in the spleen and liver were measured by the double­label immunofluorescence assay. The distribution pattern of CD4+T cells and CD8+T cells in the spleen and liver was investigated by immunofluorescence staining. The expression levels of PARG, PARP and nuclear factor­κB (NF­κB) proteins in spleen transplant tumours and liver metastases of colon carcinoma were detected by western blotting. An ELISA was used to detect the levels of IL­10 and TGF­ß in the serum of tumour­bearing mice and from the supernatant of tumour cells. The numbers and grading of metastatic liver nodules in the PARG­silenced group were clearly lower than those in the control group. The survival time of the PARG­silenced group mice was longer than that in the control group. In the PARG­silenced group, the levels of B220+DEC205+DC in the spleen and liver were lower and the numbers of CD11c+CD11b+DC in the spleen and liver were more than those in the control group. The ratio of CD4+/CD8+ in the spleen and liver in the PARG­silenced group was increased compared with that in the control group (P<0.05). The levels of PARG, PARP and NF­κB in spleen transplant tumours and liver metastases of colon carcinoma were lower in the PARG­silenced group than in the control group. In addition, the levels of IL­10 and TGF­ß in the serum of tumour­bearing mice and supernatants of tumour cells were both reduced in the PARG­silenced group compared with those in the control group. The present research suggests that the liver metastases of colon carcinoma could be restrained by silencing PARG. Likely, the silencing of PARG could suppress the expression of PARP and NF­κB and subsequently suppress the secretion of IL­10 and TGF­α, finally affecting the proliferation and differentiation of DC and T cells.

Down-Regulation of Laminin (LN)- α5 is Associated with Preeclampsia and Impairs Trophoblast Cell Viability and Invasiveness Through PI3K Signaling Pathway.

BACKGROUND/AIMS: Preeclampsia (PE) is a gestational disorder defined as hypertension and proteinuria, which is deemed a major cause of maternal and neonatal mortality and morbidity worldwide. The aim of this study was to investigate the expression patterns of placental laminin (LN)-α5 expression in normal and PE pregnancies, as well as evaluating the effects of LN-α5 on trophoblast proliferation, apoptosis, and invasion. METHODS: LN-α5 expression levels were examined by reverse-transcriptase polymerase chain reaction (RT-PCR), and further confirmed by western blotting and immunofluorescence staining. Cell proliferation and apoptosis were measured by CCK-8 assay and flow cytometry. Cell invasion was assessed by matrigel-based transwell assay. LN-α5 DNA methylation in placentas was determined by bisulfite sequencing PCR (BSP). RESULTS: LN-α5 expression levels in PE placentas were significantly lower than that of normal pregnancies. Deficiency in LN-α5 expression resulted in decreased trophoblast proliferation and invasion but increased cell apoptosis, meanwhile, PI3K/AKT/mTOR signaling pathway was impaired by LN-α5 silencing. LN-α5 promoter methylation didn't show significant difference between PE and normal placentas. CONCLUSION: LN-α5 downregulation is associated with PE placenta and impairs trophoblast viability and invasiveness, which could be a causative factor of PE pathogenesis.

Effects of ß-caryophyllene on arginine ADP-ribosyltransferase 1-mediated regulation of glycolysis in colorectal cancer under high-glucose conditions.

Type 2 diabetes mellitus (T2DM) is associated with an increased risk of the development of colorectal cancer (CRC). A previous study revealed that the levels of arginine-specific mono-ADP-ribosyltransferase 1 (ART1) in CRC tissues from patients with T2DM were higher than in non-diabetic patients. Hyperglycemia, which is a risk factor of cancer, is a common feature of T2DM; however, the effects of ART1 on glycolysis and energy metabolism in CRC cells under high-glucose conditions remains to be elucidated. ß-caryophyllene (BCP) has been reported to exert anticancer and hypoglycemic effects. In the present study, CT26 cells were cultured under a high-glucose conditions and the expression levels of relevant factors were detected by western blotting. Cell Counting Kit-8 assay, flow cytometry, Hoechst 33258 staining, ATP assay and lactic acid assay were used to detect the proliferation, apoptosis and energy metabolism of CT26 cells. To observe the effects of ART1 and BCP on tumor growth in vivo, CT26 cell tumors were successfully transplanted into BALB/c mice with T2DM. The results demonstrated that overexpression of ART1 may increase glycolysis and energy metabolism in CT26 CRC cells under high glucose conditions by regulating the protein kinase B/mammalian target of rapamycin/c­Myc signaling pathway and the expression of glycolytic enzymes. BCP inhibited the effects induced by ART1, which may be due to a BCP-induced reduction in the expression levels of ART1 via nuclear factor-κB. Therefore, ART1 may be considered a therapeutic target for the treatment of diabetic patients with CRC.

Mono-ADP-ribosylation of histone 3 at arginine-117 promotes proliferation through its interaction with P300.

Relatively little attention has been paid to ADP-ribosylated modifications of histones, especially to mono-ADP-ribosylation. As an increasing number of mono-ADP-ribosyltransferases have been identified in recent studies, the functions of mono-ADP-ribosylated proteins have aroused research interest. In particular, histones are substrates of some mono-ADP-ribosyltransferases and mono-ADP-ribosylated histone have been detected in physiological or pathological processes. In this research, arginine-117 (Arg-117; R-117) of hsitone3(H3) is identified as the a site of mono-ADP-ribosylation in colon carcinoma(the first such site to be identified); this posttranslational modification may promote the proliferation of colon carcinoma cells in vitro and in vivo. Using a point-mutant lentivirus transfection and using an activator of P300 allowed us to observe the mono-ADP-ribosylation at H3R117 and enhancement of the activity of P300 to up-regulate the level of acetylated ß-catenin, which could increase the expression of c-myc and cyclin D1.

BAG-1L Protects SH-SY5Y Neuroblastoma Cells Against Hypoxia/Re-oxygenation Through Up-Regulating HSP70 and Activating PI3K/AKT Signaling Pathway.

BCL-2-associated athanogene-1(BAG-1) is a multifunctional and anti-apoptotic protein that was first identified as a binding partner of BCL-2. But the effects and mechanisms for BAG-1 against hypoxic damage is unclear up to now. Whether BAG-1 could protect the human brain against hypoxic damage through up-regulating 70 kDa heat shock proteins (HSP70) and PI3K/AKT pathway activation? In present study, we examined the changes of HSP70 and AKT and p-AKT protein level in SH-SY5Y cells with BAG-1L gene over-expression subjected to hypoxia/re-oxygenation injury. BAG-1L over-expression increased neuronal viability, and it reduced apoptosis of neurons after hypoxia/re-oxygenation for 8 h. BAG-1L over-expression enhanced the HSP70 protein levels and increased p-AKT/total AKT ratio after hypoxia/re-oxygenation for 8 h. These results suggest that BAG-1L over-expression protects against hypoxia/re-oxygenation injury, at least in part, by interacting with HSP70, and by accelerating the activation of PI3K/AKT pathways.

Effect of ART1 on the proliferation and migration of mouse colon carcinoma CT26 cells in vivo.

Arginine-specific mono-ADP-ribosyltransferase 1 (ART1) is an important enzyme that catalyzes arginine-specific mono­ADP­ribosylation. There is evidence that arginine­specific mono­ADP­ribosylation may affect the proliferation of smooth muscle cells via the Rho­dependent signaling pathway. Previous studies have demonstrated that ART1 may have a role in the proliferation, invasion and apoptosis of colon carcinoma in vitro. However, the effect of ART1 on the proliferation and invasion of colon carcinoma in vivo has yet to be elucidated. In the present study, mouse colon carcinoma CT26 cells were infected with a lentivirus to produce ART1 gene silencing or overexpression, and were then subcutaneously transplanted. To observe the effect of ART1 on tumor growth or liver metastasis in vivo, a spleen transplant tumor model of CT26 cells in BALB/c mice was successfully constructed. Expression levels of focal adhesion kinase (FAK), Ras homolog gene family member A (RhoA) and the downstream factors, c­myc, c­fos and cyclooxygenase­2 (COX­2) proteins, were measured in vivo. The results demonstrated that ART1 gene silencing inhibited the growth of the spleen transplanted tumor and its ability to spread to the liver via metastasis. There was also an accompanying increase in expression of FAK, RhoA, c­myc, c­fos and COX­2, whereas CT26 cells with ART1 overexpression demonstrated the opposite effect. These results suggest a potential role for ART1 in the proliferation and invasion of CT26 cells and a possible mechanism in vivo.

Heat shock protein 70 protects PC12 cells against ischemia-hypoxia/reoxygenation by maintaining intracellular Ca(2+) homeostasis.

Heat shock protein 70 (HSP70) maintains Ca(2+) homeostasis in PC12 cells, which may protect against apoptosis; however, the mechanisms of neuroprotection are unclear. Therefore, in this study, we examined Ca(2+) levels in PC12 cells transfected with an exogenous lentiviral HSP70 gene expression construct, and we subsequently subjected the cells to ischemia-hypoxia/reoxygenation injury. HSP70 overexpression increased neuronal viability and ATPase activity, and it decreased cellular reactive oxygen species levels and intracellular Ca(2+) concentration after hypoxia/reoxygenation. HSP70 overexpression enhanced the protein and mRNA expression levels of sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase (SERCA), but it decreased the protein and mRNA levels of inositol 1,4,5-trisphosphate receptor (IP3R), thereby leading to decreased intracellular Ca(2+) concentration after ischemia-hypoxia/reoxygenation. These results suggest that exogenous HSP70 protects against ischemia-hypoxia/reoxygenation injury, at least in part, by maintaining cellular Ca(2+) homeostasis, by upregulating SERCA expression and by downregulating IP3R expression.

Regulation of the RhoA/ROCK/AKT/ß-catenin pathway by arginine-specific ADP-ribosytransferases 1 promotes migration and epithelial-mesenchymal transition in colon carcinoma.

Arginine-specific ADP-ribosytransferases 1 (ART1) is able to modify the arginine of specific proteins by mono-ADP-ribosylation. We previously reported that the expression of ART1 in human colon adenocarcinoma tissues was higher than in adjacent tissues. Herein, we primarily revealed that ART1 could regulate the epithelial-mesenchymal transition (EMT) and, therefore, the development of colon carcinoma. In CT26 cells, which overexpressed ART1 by lentiviral transfection, the following were promoted: alterations of spindle-like non-polarization, expression of EMT inducers and mesenchymal markers, migration, invasion and adhesion. However, epithelial marker expression was decreased. Correspondingly, knockdown of ART1 in CT26 cells had the opposite effects. The effect of ART1 on EMT and carcinoma metastasis was also verified in a liver metastasis model of BALB/c mice. To further explore the molecular mechanism of ART1 in EMT, CT26 cells were treated with several specific inhibitors and gene silencing. Our data suggest that ART1 could regulate EMT by regulating the RhoA/ROCK1/AKT/ß-catenin pathway and its downstream factors (snail1, vimentin, N-cadherin and E-cadherin) and that it therefore plays an important role in the progression of colon carcinoma.

Effects of thoracic epidural analgesia on plasma cAMP and cGMP levels in patients with heart failure.

BACKGROUND AND AIM: The progression of heart failure is affected by several factors, including chronic stimulation of the ß-adrenoceptor. This clinical study was designed to measure the effects of thoracic epidural analgesia (TEA) on the plasma levels of norepinephrine (NE), cAMP, and cGMP in patients with heart failure and assess the clinical implication of TEA. METHODS: Forty patients with heart failure were randomly assigned to TEA (TEA plus standard care) and control groups (standard care). The plasma concentrations of cAMP, cGMP, brain natriuretic peptide (BNP), and NE were measured using ELISA before treatment, the second and fourth weeks of treatment. RESULTS: The plasma concentrations of cAMP, cGMP, BNP, and NE in the TEA group were significantly reduced by the fourth week compared to their initial concentrations (P < 0.01, for all parameters) and the control group (P < 0.05, P < 0.05, P < 0.01, and P < 0.05, respectively). The values for left ventricular end diastolic diameter (LVEDD), ejection fraction (EF), and fractional shortening (FS) in the TEA group improved significantly compared to their initial values and the control group. However, the changes in levels for these indices in the control group were no statistical significant compared to the initial levels. CONCLUSIONS: TEA can effectively decrease the plasma concentrations of cAMP and cGMP and improve cardiac function in patients with heart failure. The decreased levels of NE and cAMP occurred before the improvement in cardiac function, indicating that the abnormal epidural signal transduction can be corrected in patients with heart failure.

The expression of pentraxin 3 and tumor necrosis factor-alpha is increased in preeclamptic placental tissue and maternal serum.

OBJECTIVE: To evaluate the expression of pentraxin 3 (PTX3) and tumor necrosis factor-alpha (TNF-α) in preeclampsia. METHODS: Twenty-two preeclamptic patients, six preeclamptic patients with intrauterine growth restriction (IUGR) and 30 women with uncomplicated pregnancies were included in this study. The expression of PTX3 and TNF-α in placental tissue was analyzed by quantitative real-time polymerase chain reaction (qRT-PCR) and Western immunoblotting. Enzyme-linked immunosorbent assay (ELISA) was used to measure the concentration of PTX3 and TNF-α in maternal sera. The localization and immunoreaction of PTX3 and TNF-α in placenta were determined via immunohistochemistry (IHC). RESULTS: Expression of PTX3 and TNF-α in placental tissues and maternal sera was significantly increased in preeclamptic patients, as well as in those with IUGR. PTX3 was mainly expressed in villous stroma, decidual cells and terminal villi, and TNF-α was mostly localized in trophoblast, vascular endothelial cells, decidual cells and in the stroma of the stem villi. Moreover, PTX3 expression was correlated with TNF-α expression in maternal sera of preeclamptic women. CONCLUSIONS: PTX3 and TNF-α are increased in preeclampsia and are likely involved in the pathogenesis of preeclampsia.

Gadd45α as an upstream signaling molecule of p38 MAPK triggers oxidative stress-induced sFlt-1 and sEng upregulation in preeclampsia.

Preeclampsia (PE) is known to be associated with increased circulating levels of anti-angiogenic factors, such as soluble fms-related tyrosine kinase-1 (sFlt-1) and soluble endoglin (sEng). However, the way that placental oxidative stress results in the elevation of these two factors remains enigmatic. We have observed the overexpression of growth arrest and DNA damage-inducible 45 alpha (Gadd45α) and excessive activation of p38 mitogen-activated protein kinase (MAPK) in preeclamptic placentas compared with normotensive controls, together with increased levels of sFlt-1 and sEng in maternal sera in patients with PE. Moreover, Gadd45α knockdown or p38 inhibition provides protective effects in hypoxia/reoxygenation (H/R)-exposed human umbilical vein endothelial cells (HUVECs) by suppressing oxidative stress, inhibiting apoptosis, and promoting their potential for in vitro angiogenesis. A regulatory signaling pathway in which H/R intervention causes the induction of Gadd45α leading to p38 activation and ultimately an increase in sFlt-1 and sEng secretion in HUVECs has concurrently been established. Our study opens up a promising new avenue of investigation for increasing the understanding of the origin of sFlt-1 and sEng in PE and provides novel therapeutic targets for pregnancy complications arising from placental endothelial dysfunction.

[Expression of bone morphogenetic protein-2 in fetal membranes from pregnant women with premature rupture of membranes and its clinic significance].

OBJECTIVE: To study the relationship between bone morphogenetic protein-2 (BMP-2) and premature rupture of membranes (PROM). METHODS: Ninety gravidas giving birth at 4 hospitals in Chongqing from January 2006 to January 2007 were selected and divided into 5 groups (18 in each): term labor group ( with intact membranes), term PROM group, preterm labor group (with intact membranes), preterm PROM (PPROM) group and control group (term pregnancy not in labor). The expression of BMP-2 in the chorioamniotic membranes of each group were detected by streptavidin-peroxidase methods and its relationship with PROM plus histological chorioamnionitis were analyzed. RESULTS: (1) BMP-2 was detected in the cytoplasm of epithelial and interstitial cells of membranes in each group. (2) BMP-2 expression in term labor group, term PROM group, preterm labor group and PPROM group were 0.0137 +/- 0.0094, 0.0269 +/- 0.0127, 0.0273 +/- 0.0145, 0.0456 +/- 0.0114, respectively, which higher than that of the control group 0.0060 +/- 0.0079 (P < 0.01). BMP-2 expression in the term PROM group was higher than that of the term labor group (P < 0.01), that in the PPROM was higher than in the preterm labor group and term PROM group (P < 0.01). (3) Pathological examination found that 17 out of the 90 women with histologic chorioamnionitis, of which 13 (36%) came from the term PROM and PPROM group with a higher level of BMP-2 expression than those without chorioamnionitis (0.0201 +/- 0.0107 vs 0.0105 +/- 0.0092, P < 0.05). CONCLUSION: The expression of BMP-2 in chorioamniotic membranes is closely related to PROM.