Effect of serum lactate dehydrogenase-to-albumin ratio (LAR) on the short-term outcomes and long-term prognosis of colorectal cancer after radical surgery.

BACKGROUND: Whether serum lactate dehydrogenase-to-albumin ratio (LAR) influenced the outcomes of colorectal cancer (CRC) patients after radical surgery remained unclear. Therefore, this study sought to examine how LAR influences the short-term and long-term outcomes of CRC patients who have undergone radical surgery. METHODS: This study retrospectively included CRC patients who underwent radical resection between January 2011 and January 2020. We compared short-term outcomes, as well as overall survival (OS) and disease-free survival (DFS), among various groups. Both univariate and multivariate logistic regression analyses were utilized to pinpoint independent risk factors associated with overall complications and major complications. Moreover, Cox regression analysis were conducted for OS and DFS. Odds ratio (OR) and Hazard ratio (HR) were adjusted. RESULTS: This study encompassed a cohort of 3868 patients. 3440 patients were in the low LAR group and 428 patients constituted the high LAR group. In the high LAR group, patients experienced significantly longer operative times (p < 0.01), larger intraoperative blood loss (p < 0.01), and extended postoperative hospital stays (p < 0.01). Additionally, the incidence of both overall complications (p < 0.01) and major complications (p < 0.01) was higher in the high LAR group compared to the low LAR group. Furthermore, LAR was emerged as an independent prognostic factor for overall complications [OR/95% CI: (1.555/1.237 to 1.954), p < 0.01] and major complications [OR/95% CI: (2.178/1.279 to 3.707), p < 0.01]. As for long-term survival, the high LAR group had worse OS in stage II (p < 0.01) and stage III (p < 0.01). In both stage II (p < 0.01) and stage III (p < 0.01), the high LAR group exhibited poorer DFS. Additionally, according to Cox regression analysis, LAR was identified as an independent predictor for both OS [HR/95% CI: (1.930/1.554 to 2.398), p < 0.01] and DFS [HR/95% CI: (1.750/1.427 to 2.146), p < 0.01]. CONCLUSION: LAR emerged as an independent predictor not only for overall complications and major complications but also for both OS and DFS, highlighting its significance and deserving the attention of surgeons.

Endometrial polyps effect on pregnancy outcomes in infertile women with minimal/mild endometriosis: A retrospective study.

OBJECTIVE: To assess the pregnancy outcomes and associated influencing factors of pregnancy after hysteroscopy combined with laparoscopy treatment in infertile patients with minimal/mild endometriosis. DESIGN: A retrospective study. SETTING: West China Second University Hospital of Sichuan University. PATIENTS: We enrolled 898 infertile women who had their minimal/mild endometriosis lesions removed by laparoscopy, including 271 patients additionally diagnosed with endometrial polyps who also underwent hysteroscopic polypectomy. METHODS: Based on the existence of endometrial polyps, patients with minimal/mild endometriosis were enrolled and divided into polyps group and non-polyps group. MAIN OUTCOME MEASURES: Pregnancy outcomes. RESULTS: A total of 271 women with minimal/mild endometriosis were included in polyps group while 491 women with minimal/mild endometriosis were included in non-polyps group. The pregnancy rate of polyps group was not statistically significant compared with non-polyp group (60.15% vs. 58.25%). The pregnancy rate was higher among patients with polyps ≥1 cm (76.06%, 54/71) than patients with polyps <1 cm (54.50%, 109/200) or patients without polyps (58.25%, 286/491) (p = 0.006). The pregnancy rate was higher for patients with multiple polyps (67.86%, 95/140) than for patients with single polyp (51.91%, 68/131) or without polyps (p = 0.025). CONCLUSIONS: Among women with minimal/mild endometriosis, hysteroscopic polypectomy did significantly increase fertility in infertile patients with multiple polyps or size of polyp ≥1 cm compared with those without endometrial polyps, single polyp, and size of polyp <1 cm. The size and number of polyps were independently associated with the reproductive ability of women with minimal/mild endometriosis.

Progress on mitochondrial silence information regulator family in epilepsy.

SIRT3, SIRT4 and SIRT5 are located in mitochondria and also known as mitochondrial sirtuins. They play important roles in regulating many cellular functions including cell survival, cell cycle or apoptosis, DNA repair and metabolism. Mitochondrial sirtuins are involved in the protection of mitochondrial integrity and energy metabolism under stress regulating the expression of neurotransmitter receptors, neurotrophins, extracellular matrix proteins and various transcription factors, thus involved in epileptogenesis triggered by both genetic or acquired factors. Here we review research progress on the actions of mitochondrial sirtuin in epilepsy; and discuss the challenges and perspectives of mitochondrial sirtuin as a potential therapeutic target for epilepsy.

[Sirt3 gene knockout protects mice from Alzheimer's disease through activating autophagy].

OBJECTIVE: To investigate the protective effect of Sirt3 gene knockout on Alzheimer's disease (AD) in mice. METHODS: The animal model of AD was established by intraperitoneal injection of D-galactose and brain-localized injection of amyloid ß-protein (Aß)1-40 in wild type C57BL/6 mice and Sirt3 gene knockout mice. Morris water maze, Y maze and tail suspension test were used to assess the cognitive function and anxiety-like behaviors in mice. Aß deposition in the hippocampus was detected by immunofluorescent staining. Western blotting analysis was conducted to detect the expression of related proteins in the brain. Mouse cortical primary neurons were cultured and AD cell model was established. MTT assay was used to detect cell viability after modeling. RESULTS: Behavioral results showed that cognitive deficits were found in wide type mice after induction of AD as its prolonged escape latency (P<0.05) and decreased crossing number of platform and target zone duration (all P<0.05); while the knockout of Sirt3 alleviated cognitive deficit induced by AD (all P<0.05). Aß immunofluorescence staining showed that the deposition of Aß in the hippocampal region and expression of cleaved caspase 3 in the brain in Sirt3 knockout mice was reduced compared with that of wild type mice (all P<0.05). The expression of LC3-Ⅱ and P62 increased after AD was induced in wild type mice, while the autophagy in Sirt3 knockout mice was activated as the increase expression of LC3-Ⅱ and decrease expression of P62 (all P<0.05). In the AD cell model, the results of MTT assay were consistent with the animal experiments, and the protective effect of Sirt3 knockdown was eliminated after the treatment of the autophagy inhibitor chloroquine (all P<0.05). CONCLUSIONS: The knockdown of Sirt3 shows a protective effect on AD induced by D-galactose and Aß1-40 in mice, which may be related to its function of activating autophagy.

Impact of preoperative type 2 diabetes mellitus on the outcomes of patients with gastric cancer following gastrectomy: Analysis of 834 patients using propensity score matching.

The purpose of the current study was to compare the outcomes of patients with gastric cancer (GC) between the type 2 diabetes mellitus (T2DM) group and the non-T2DM group. The PubMed, Embase and Cochrane Library databases were searched from inception to March 8, 2022, to identify propensity score matching (PSM) studies that analyzed the effect of T2DM on the outcomes of patients with GC. Total complications, overall survival (OS), disease-free survival (DFS) and cancer-specific survival (CSS) were compared between the T2DM group and the non-T2DM group. A total of four PSM studies with 834 patients were included in the current study. There were 311 and 523 patients in the T2DM group and the non-T2DM group, respectively. Baseline characteristics of the two groups were adjusted with PSM in all the four studies, however, no significant difference was found in baseline characteristics (P>0.05). DFS was significantly worse in the T2DM group compared with that in the non-T2DM group [hazard ratio (HR), 1.45; 95% confidence interval (CI), 1.10-1.90; P=0.007)]. However, after pooling up the data, there was no significant difference between the T2DM group and the non-T2DM group in terms of OS (HR, 1.41; 95% CI, 0.92-2.16; P=0.11), CSS (HR, 1.29; 95% CI, 0.92-1.81; P=0.14) and total complications (odds ratio, 1.01; 95% CI, 0.64-1.60; P=0.95). Patients with GC and T2DM are associated with poor DFS. However, there were no significant differences between the T2DM group and the non-T2DM group in terms of OS, CSS and total complications.

Effectiveness of laparoscopic tubal anastomosis in tubal occlusion patients after laparoscopic salpingostomy for tubal pregnancy.

OBJECTIVE: To evaluate the effectiveness of laparoscopic tubal anastomosis for tubal occlusions associated with infertility in patients with previous laparoscopic salpingostomy for ectopic pregnancy. METHODS: This study is a retrospective analysis of the pregnancy outcomes of 173 infertile patients who underwent hysteroscopy and laparoscopic tubal anastomosis treatment between January 2013 and August 2018 in the Department of Reproductive Endocrinology in West China Second University Hospital of Sichuan University. All patients had a history of laparoscopic salpingostomy for tubal pregnancy. The primary outcomes were intrauterine pregnancy, ectopic pregnancy, and delivery rates. We further studied the associated factors that could influence the change in pregnancy status. RESULTS: The 24-month cumulative clinical pregnancy rate of all patients was 107/173 (61.8%). The distribution of outcomes for the entire group of pregnancies was as follows: intrauterine pregnancy rate, 76/173 (43.9%); ectopic pregnancy rate, 31/173 (17.9%); delivery rate, 68/173 (39.3%); and miscarriage rate, 8/173 (4.6%). Age, type of anastomosis, hydrosalpinx, and endometrial polyps were significant prognostic factors in the multivariate model. CONCLUSION: Laparoscopic tubal anastomosis is an effective treatment for tubal-associated infertility due to previous laparoscopic salpingostomy for ectopic pregnancy, especially for women under 35 years of age.

Inhibition of RhoA/Rho kinase signaling pathway by fasudil protects against kainic acid-induced neurite injury.

AIM: RhoA/Rho kinase pathway is essential for regulating cytoskeletal structure. Although its effect on normal neurite outgrowth has been demonstrated, the role of this pathway in seizure-induced neurite injury has not been revealed. The research examined the phosphorylation level of RhoA/Rho kinase signaling pathway and to clarify the effect of fasudil on RhoA/Rho kinase signaling pathway and neurite outgrowth in kainic acid (KA)-treated Neuro-2A cells and hippocampal neurons. METHOD: Western blotting analysis was used to investigate the expression of key proteins of RhoA/Rho kinase signaling pathway and the depolymerization of actin. After incubated without serum to induce neurite outgrowth, Neuro-2A cells were fixed, and immunofluorescent assay of rhodamine-phalloidin was applied to detect the cellular morphology and neurite length. The influence of KA on neurons was detected in primary hippocampal neurons. Whole-cell patch clamp was conducted in cultured neurons or hippocampal slices to record action potentials. RESULT: KA at the dose of 100-200 µmol/L induced the increase in phosphorylation of Rho-associated coiled-coil-containing protein kinase and decrease in phosphorylation of Lin11, Isl-1 and Mec-3 kinase and cofilin. The effect of 200 µmol/L KA was peaked at 1-2 hours, and then gradually returned to baseline after 8 hours. Pretreatment with Rho kinase inhibitor fasudil reversed KA-induced activation of RhoA/Rho kinase pathway and increase in phosphorylation of slingshot and 14-3-3, which consequently reduced the ratio of G/F-actin. KA treatment induced inhibition of neurite outgrowth and decrease in spines both in Neuro-2a cells and in cultured hippocampal neurons, and pretreatment with fasudil alleviated KA-induced neurite outgrowth inhibition and spine loss. CONCLUSION: These data indicate that inhibiting RhoA/Rho kinase pathway might be a potential treatment for seizure-induced injury.

Astroglial adrenoreceptors modulate synaptic transmission and contextual fear memory formation in dentate gyrus.

Astrocytes perform various supporting functions, including ion buffering, metabolic supplying and neurotransmitter clearance. They can also sense neuronal activity owing to the presence of specific receptors for neurotransmitters. In turn, astrocytes can regulate synaptic activity through the release of gliotransmitters. Evidence has shown that astrocytes are very sensitive to the locus coeruleus (LC) afferents. However, little is known about how LC neuromodulatory norepinephrine (NE) modulates synaptic transmission through astrocytic activity. In mouse dentate gyrus (DG), we demonstrated an increase in the frequency of miniature excitatory postsynaptic currents (mEPSC) in response to NE, which required the release of glutamate from astrocytes. The rise in glutamate release probability is likely due to the activation of presynaptic GluN2B-containing NMDA receptors. Moreover, we showed that the activation of NE signaling in DG is necessary for the formation of contextual learning memory. Thus, NE signaling activation during fear conditioning training contributed to enduring changes in the frequency of mEPSC in DG. Our results strongly support the physiological neuromodulatory role of NE signaling, which is derived from activation of astrocytes.

Quality enhancement of large yellow croaker treated with edible coatings based on chitosan and lysozyme.

The aim of this study was to evaluate the preservation effect of chitosan (CS) and lysozyme (Lys) coating on the quality of large yellow croaker (Larimichthys crocea) via physicochemical analyses, microbiological and sensorial assessments during refrigerated storage. Results showed that CS films incorporated with 0.6 mg·mL-1 of lysozyme exhibited the strongest inhibition effect against S. aureus, whose inhibition zone was 16.10 ±â€¯0.71 mm. The utilization of CS singly, or CS-lysozyme (Lys) coating significantly reduced lipid oxidation (thiobarbituric acid value, TBA) and improved the sensorial scores of fishes. Control and treated groups exceeded the maximum permissible level (30 mg N/100 g) of total volatile basic nitrogen (TVB-N) in fishery products on days 6 (control) and 9 (CS or CS-Lys treated), respectively. Fish samples reached the value of 7.0 Log CFU/g (Total Viable Count, TVC) on days 15 (control), whereas both CS and CS-Lys treated flesh samples never exceed this limit value during the refrigerated storage. Results of our study indicate CS-Lys have high efficiency in inhibiting microorganism growth and lipid oxidation and in maintaining sensorial quality, which is a promising method to maintain the quality and extend the shelf life of refrigerated fishes.

The disturbance of hippocampal CaMKII/PKA/PKC phosphorylation in early experimental diabetes mellitus.

BACKGROUND: Defining the impact of diabetes and related risk factors on brain cognitive function is critically important for patients with diabetes. AIMS: To investigate the alterations in hippocampal serine/threonine kinases signaling in the early phase of type 1 and type 2 diabetic rats. METHODS: Early experimental diabetes mellitus was induced in rats with streptozotocin or streptozotocin/high fat. Changes in the phosphorylation of proteins were determined by immunoblotting and immunohistochemistry. RESULTS: Our data showed a pronounced decrease in the phosphorylation of Ca(2+) /calmodulin-dependent protein kinase II (CaMKII) in the hippocampi of both type 1 and type 2 diabetic rats compared with age-matched control rats. Unexpectedly, we found a significant increase in the phosphorylation of synapsin I (Ser 603) and GluR1 (Ser 831) in the same experiment. In addition, aberrant changes in hippocampal protein kinase C (PKC) and protein kinase A (PKA) signaling in type 1 and type 2 diabetic rats were also found. Moreover, PP1α and PP2A protein levels were decreased in the hippocampus of type 1 diabetic rats, but significantly up-regulated in type 2 diabetic rats. CONCLUSIONS: The disturbance of CaMKII/PKA/PKC phosphorylation in the hippocampus is an early change that may be associated with the development and progression of diabetes-related cognitive dysfunction.

Different roles of TGF-ß in the multi-lineage differentiation of stem cells.

Stem cells are a population of cells that has infinite or long-term self-renewal ability and can produce various kinds of descendent cells. Transforming growth factor ß (TGF-ß) family is a superfamily of growth factors, including TGF-ß1, TGF-ß2 and TGF-ß3, bone morphogenetic proteins, activin/inhibin, and some other cytokines such as nodal, which plays very important roles in regulating a wide variety of biological processes, such as cell growth, differentiation, cell death. TGF-ß, a pleiotropic cytokine, has been proved to be differentially involved in the regulation of multi-lineage differentiation of stem cells, through the Smad pathway, non-Smad pathways including mitogen-activated protein kinase pathways, phosphatidylinositol-3-kinase/AKT pathways and Rho-like GTPase signaling pathways, and their cross-talks. For instance, it is generally known that TGF-ß promotes the differentiation of stem cells into smooth muscle cells, immature cardiomyocytes, chondrocytes, neurocytes, hepatic stellate cells, Th17 cells, and dendritic cells. However, TGF-ß inhibits the differentiation of stem cells into myotubes, adipocytes, endothelial cells, and natural killer cells. Additionally, TGF-ß can provide competence for early stages of osteoblastic differentiation, but at late stages TGF-ß acts as an inhibitor. The three mammalian isoforms (TGF-ß1, 2 and 3) have distinct but overlapping effects on hematopoiesis. Understanding the mechanisms underlying the regulatory effect of TGF-ß in the stem cell multi-lineage differentiation is of importance in stem cell biology, and will facilitate both basic research and clinical applications of stem cells. In this article, we discuss the current status and progress in our understanding of different mechanisms by which TGF-ß controls multi-lineage differentiation of stem cells.