Characteristics and significance of programmed cell death-related gene expression signature in skin cutaneous melanoma.

BACKGROUND: Programmed cell death (PCD) pathways play crucial roles in the pathogenesis of skin cutaneous melanoma (SKCM). Understanding their prognostic significance and clinical implications is imperative for the development of personalized treatment strategies. METHODS: A total of 1466 PCD-related genes were analyzed using data from The Cancer Genome Atlas (TCGA)-SKCM cohort (n = 353). Prognostic cell death index (CDI) was established and validated through survival analysis and predictive modeling. Functional enrichment, protein-protein interaction (PPI), consensus clustering, and tumor microenvironment assessment and drug sensitivity analysis were performed to elucidate the biological and clinical relevance of CDI. RESULTS: CDI effectively stratified SKCM patients into high and low-risk groups, demonstrating significant differences in survival outcomes. It exhibited predictive value for survival at 1, 3, and 5 years. The concordance index (C-index) was 0.794 in the training set, and 0.792 and 0.821 in the internal and external validation sets, respectively. The corresponding area under curve (AUC) was all above 0.75 in these data sets. Functional enrichment analysis revealed significant associations with immune response and inflammatory processes. PPI analysis identified key molecular modules associated with apoptosis and chemokine signaling. Consensus clustering unveiled three discernible subtypes demonstrating notable disparities in survival outcomes based on CDI expression profiles. Assessment of the tumor microenvironment highlighted correlations with immune cell infiltration such as M1 macrophages and T cells. Drug sensitivity analysis indicated tight correlations between CDI levels and response to immunotherapy. CONCLUSION: Our comprehensive analysis establishes the prognostic significance of PCD-related genes in SKCM. CDI emerges as a promising prognostic biomarker, offering insights into tumor biology and potential implications for personalized treatment strategies. Further validation and clinical integration of CDI are warranted to improve SKCM management and patient outcomes.

Effect of dexmedetomidine infusion on postoperative sleep disturbances in women with breast cancer: A monocentric randomized-controlled double-blind trial.

BACKGROUND: Most women with breast cancer are prone to postoperative sleep disturbances (POSD). Little is known about the differences between sevoflurane and propofol combined with dexmedetomidine on POSD in the same context. We investigated the effect of intra-operative sevoflurane or propofol combined with intravenous dexmedetomidine on the incidence of POSD and postoperative sleep structures. METHODS: A monocentric, randomized-controlled, double-blind trial. Female patients undergoing radical surgery for breast cancer were randomly assigned to receive sevoflurane and placebo, sevoflurane and dexmedetomidine, propofol and placebo, or propofol and dexmedetomidine. Dexmedetomidine was administered at 1.0 µg kg-1 infusion 15 min before induction, then infused at 0.4 µg kg-1 h-1 until the surgical drain started to be placed. The primary outcome was the incidence of POSD within the postoperative first three days (defined as an Athens Insomnia Scale score ≥ 6 points on at least one day of postoperative first three days). The secondary outcome was the duration of sleep structures, collected from the Fitbit Charge 2® smart bracelet (Fitbit, Inc., San Francisco, CA, USA). RESULTS: There were 188 women analyzed with the modified intention-to-treat method. The incidences of POSD in the dexmedetomidine and placebo groups were similar (p = 0.649). In the sevoflurane sedation strategy, dexmedetomidine decreased nocturnal wakefulness on postoperative first day (p = 0.001). In the propofol sedation strategy, dexmedetomidine increased nocturnal deep sleep on postoperative first (p < 0.001) and third (p < 0.001) days. CONCLUSION: Intra-operative infusion of dexmedetomidine had no significant effect on POSD but decreased nocturnal wakefulness in the sevoflurane group and increased nocturnal deep sleep in the propofol group. TRIAL REGISTRATION: Registered at www.chictr.org.cn (ChiCTR2300070136).

Antioxidant vitamins supplementation reduce endometriosis related pelvic pain in humans: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to clarify the effect of antioxidant vitamins supplementation on endometriosis-related pain. METHODS: A systematic search of PubMed, Web of Science, Cochrane Library, Scopus, and China National Knowledge Infrastructure (CNK) databases was conducted to identify relevant studies published in English and Chinese up to 16 March 2023. The search terms used were "endometriosis" OR "endometrioma" OR "endometrium" AND "antioxidant" OR "Vitamin C" OR "Vitamin E" OR "Vitamin D" OR "25-OHD" OR "25(OH)D" OR "25-hydroxyvitamin D". Eligible studies were randomized controlled trials (RCTs) that assessed pain scores using the Visual Analogue Scale (VAS). Mean differences or odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to evaluate the effect of antioxidant vitamins supplementation on endometriosis. The quality of the included studies was assessed using the Cochrane Risk of Bias Tool. The study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 13 RCTs involving 589 patients were included in this meta-analysis. We identified 11 studies that evaluated the effect of antioxidant vitamins supplementation on endometriosis-related pain. The results indicated that the supplementation of antioxidant vitamins can effectively alleviate endometriosis-related pain. Subgroup analysis showed that the supplementation of vitamin E (with or without vitamin C) had a positive effect on improving clinical pelvic pain in patients with chronic pelvic pain. Conversely, supplementation of vitamin D was associated with a reduction in pelvic pain in endometriosis patients, but the difference was not statistically significant compared to the placebo. Additionally, we observed changes in oxidative stress markers following vitamin supplementation. Plasma malondialdehyde (MDA) concentration decreased in patients with endometriosis after antioxidant vitamin supplementation, and the plasma MDA level was inversely correlated with the time and dose of vitamin E and C supplementation. Furthermore, the inflammatory markers in peritoneal fluid, including RANTES, interleukin-6, and monocyte chemoattractant protein-1, significantly decreased after antioxidant therapy. These findings suggest that antioxidant vitamins may alleviate pain in endometriosis patients by reducing inflammation. CONCLUSIONS: The included studies support the potential role of antioxidant vitamins in the management of endometriosis. Supplementation with antioxidant vitamins effectively reduced the severity of dysmenorrhea, improved dyspareunia and pelvic pain, and enhanced quality of life in these patients. Therefore, antioxidant vitamin therapy could be considered as an alternative treatment method, either alone or in combination with other approaches, for endometriosis-related pain. TRIAL REGISTRATION: PROSPERO registration number: CRD42023415198.

Alteration of the Gut Microbiota in Missed Abortion.

There is a symbiotic relationship between gut microbiota and human beings. Imbalance of the gut microbiota will cause pathological damages to humans. Although many risk factors are associated with missed abortion (MA), the pathological mechanism of it is still unclear. Here, we analyzed gut flora of the patients with MA by S16 high-throughput sequencing. The possible pathogenic mechanisms of the MA were explored. Fecal samples from 14 healthy controls and 16 MA patients were collected to do 16S rRNA gene high-throughput sequencing analysis. The abundance of the Bacteroidetes, Proteobacteria, Actinobacteria, Escherichia, Streptococcus_ Salivarius, and Lactobacillus was significantly reduced in the MA group, while, the abundance of the Klebsiella was significantly increased in the MA patients. The Ruminococcaceae and [Eubacterium]_coprostanoligenes_group were found only in the specimens of the MA patients. The Fabrotax function prediction analysis showed that four photosynthesis function bacteria (cyanobateria, oxygenic_photoautotrophy, photoautotrophy, and phototrophy) only existed in the MA group. In the analysis of the BugBase microbiome function prediction, the Escherichia of the MA group is significantly reduced compared to that of the healthy controls in the items of that Contains_Mobile_Elements, Facultatively_Anaerobic, Forms_Biofilms, Potentially_Pathogenic.png, Gram_Nagative, and Stress_Tolerant_relabundance. These alterations may affect the stability of the host's immune, neural, metabolic and other systems by interfering with the balance of the gut microbiota or by the metabolites of those bacteria, causing the MA. This study explored the possible pathogenic factors of the gut microbiota of the MA. The results provide evidence to figure out the pathogenesis of the MA.

Effect of Different Doses of Butorphanol on Postoperative Shivering in Elderly Patients: A Randomized, Double-Blind, Placebo-Controlled Trial.

Purpose: This study was designed to investigate the effects of different doses of butorphanol on postoperative shivering and quality of recovery in elderly patients. Patients and Methods: A total of 147 elderly patients (aged 60 or older) scheduled for elective transurethral resection of the prostate were enrolled in the current study. Patients were randomly and evenly assigned into four groups: Group C (0.9% normal saline), Group B1 (butorphanol 0.01 mg/kg), Group B2 (butorphanol 0.02 mg/kg) and Group B3 (butorphanol 0.03 mg/kg). All drugs were diluted to 5mL and injected intravenously slowly 5 min before induction of anesthesia. The primary outcome measure was the incidence of postoperative shivering in the post-anesthesia care unit. Quality of Recovery-40 (QoR-40) scores were assessed on postoperative day (POD) 1, 2 and 3. Perioperative core and skin temperature, extubation time and adverse events were also recorded. Results: Patients among the four groups had comparable baseline characteristics. Compared with Group C, the incidence of shivering was significantly lower in Group B2 and B3 (P = 0.006 and P = 0.005, respectively). The QoR-40 scores on POD1 were significantly higher in all butorphanol groups than that in Group C (P < 0.0083). In Group B2 and B3, patients experienced lower pain intensity (P < 0.001). In addition, the incidence of catheter-related bladder discomfort (CRBD) was lower in all butorphanol groups than in Group C (P < 0.0083). Conclusion: Butorphanol 0.02 or 0.03 mg/kg could effectively prevent the occurrence of postoperative shivering in elderly patients scheduled for transurethral resection of the prostate, provided effective postoperative recovery and postoperative analgesia.

Effect of Systemic Lidocaine on Postoperative Early Recovery Quality in Patients Undergoing Supratentorial Tumor Resection.

Purpose: Lidocaine has been gradually used in general anesthesia. This study was designed to investigate the effect of systemic lidocaine on postoperative quality of recovery (QoR) in patients undergoing supratentorial tumor resection, and to explore its brain-injury alleviation effect in neurosurgical anesthesia. Patients and Methods: Sixty adult patients undergoing elective supratentorial tumor resection. Patients were randomly assigned either to receive lidocaine (Group L: 1.5 mg/kg bolus completed 10 min before anesthesia induction followed by an infusion at 2.0 mg/kg/h) or to receive normal saline (Group C: received volume-matched normal saline at the same infusion rate). Primary outcome measures were Quality of Recovery-40 (QoR-40) scores on postoperative day (POD) 1 and 2. Plasma concentrations of S100B protein (S100B), neuron specific enolase (NSE), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) before anesthesia induction and at the end of surgery were assessed. Visual Analogue Scale (VAS) scores were assessed at 1, 2, 6, 12, 24 and 48 h after surgery. Perioperative parameters and adverse events were also recorded. Results: Patients between two groups had comparable baseline characteristics. Global QoR-40 scores on POD 1 and POD 2 were significantly higher (P <0.001) in group L (165.5±3.8 vs 173.7±4.7) than those in group C (155.6±4.0 vs 163.2±4.5); and scores of physical comfort, emotional state, and pain in group L were superior to those in group C (P <0.05). In group L, patients possessed lower plasma concentration of pro-inflammatory factors (IL-6, TNF-α) and brain injury-related factors (S100B, NSE) (P <0.05), consumed less remifentanil and propofol, and experienced lower pain intensity. Multiple linear regression analysis demonstrated age and pain were correlated with postperative recovery quality. Conclusion: Systemic lidocaine improved early recovery quality after supratentorial tumor resection with general anesthesia, and had certain brain-injury alleviation effects. These benefits may be attributed to the inflammation-alleviating and analgesic properties of lidocaine.

Gill Transcriptome Analysis Revealed the Difference in Gene Expression Between Freshwater and Seawater Acclimated Guppy (Poecilia reticulata).

Guppy (Poecilia reticulata) can adapt to a wide range of salinity changes. To investigate the gene expression changes in the guppy exposed to seawater, we characterized its gill transcriptome using RNA sequencing. Experimental fish were exposed to salinity increase from 0 to 30‰ within 4 days, while control fish were cultured in freshwater (0‰ salinity). Seven days after salinity exposure, the gills were sampled and the mortality within 2 weeks was recorded. No significant difference in the cumulative mortality at the second week was found between the two groups. Transcriptomic analysis identified 3477 differentially expressed genes (DEGs), including 1067 upregulated and 2410 downregulated genes. These DEGs were enriched in several biological processes, including ion transport, ion homeostasis, ATP biosynthetic process, metabolic process, and immune system process. Oxidative phosphorylation was the most activated pathway. DEGs involved in the pathway "endoplasmic reticulum (ER)-mediated phagocytosis," "starch and sucrose metabolism," and "steroid biosynthesis" were mainly downregulated; chemokines and interleukins involved in "cytokine-cytokine receptor interaction" were differentially expressed. The present results suggested that oxidative phosphorylation had essential roles in osmoregulation in the gills of seawater acclimated guppy, during which the decline in the expression of genes encoding V-ATPases and calreticulin had a negative effect on the phagocytosis and immune response. Besides, several metabolic processes including "starch and sucrose metabolism" and "steroid biosynthesis" were affected. This study elucidates transcriptomic changes in osmotic regulation, metabolism, and immunity in seawater acclimated guppy.

Diagnostic value of acid phosphatases (ACP) in differentiating reactive mesothelial cells from cancer cells in the body fluid effusions.

BACKGROUND: The cytological diagnosis of a malignant epithelial tumor, i.e., a cancer cell in the body fluid effusions is usually made by cytomorphological examination alone; however, diagnostic challenges can occur when the cancer cells are rare or cytological atypia is minimal. Morphological similarity between the cancer and the reactive mesothelial cell is the most common problem in establishing a clear diagnosis. The aim of this study is to investigate whether the cocktail acid phosphatases (ACP) special staining will be a useful tumor marker in differentiation of the reactive mesothelial cells from the cancer cells in the body fluid effusions. METHODS: The cocktail ACP special staining was performed on 212 body fluid effusion samples, which included 128 pleural effusions, 69 ascites, and 15 pericardial effusions. RESULTS: The mesothelial cells were cocktail ACP positive in 84 out of 84 benign effusion cases, and the sensitivity and the specificity were 100% for the benign effusions which including pleural effusions, ascites, and pericardial effusions. On the other hand, 122 out of 128 cancer cases were cocktail ACP negative, indicating that the sensitivity of using the cocktail ACP staining to rule out the malignant effusions was 95.3%. Thus, the cocktail ACP staining is an excellent marker with high sensitivity and specificity to distinguish the carcinoma from the reactive mesothelial cells in the body fluid effusions. CONCLUSIONS: Our finding provided a new tool for cytopathologists in diagnosing the body fluid effusion that could impact clinical decision making.

In vitro fermentation of alginate and its derivatives by human gut microbiota.

Alginate (Alg) has a long history as a food ingredient in East Asia. However, the human gut microbes responsible for the degradation of alginate and its derivatives have not been fully understood yet. Here, we report that alginate and the low molecular polymer derivatives of mannuronic acid oligosaccharides (MO) and guluronic acid oligosaccharides (GO) can be completely degraded and utilized at various rates by fecal microbiota obtained from six Chinese individuals. However, the derivative of propylene glycol alginate sodium sulfate (PSS) was not hydrolyzed. The bacteria having a pronounced ability to degrade Alg, MO and GO were isolated from human fecal samples and were identified as Bacteroides ovatus, Bacteroides xylanisolvens, and Bacteroides thetaiotaomicron. Alg, MO and GO can increase the production level of short chain fatty acids (SCFA), but GO generates the highest level of SCFA. Our data suggest that alginate and its derivatives could be degraded by specific bacteria in the human gut, providing the basis for the impacts of alginate and its derivates as special food additives on human health.

Association between toll-like receptor 6 expression and auxiliary T cells in the peripheral blood of pediatric patients with allergic purpura.

The aim of the present study was to investigate the correlations between toll-like receptor 6 (TLR6) expression in the peripheral blood mononuclear cells (PBMCs) and auxiliary T cells of children with purpura. A total of 42 children with acute Henoch-Schönlein purpura (HSP) were selected for the study, and a further 30 healthy children were selected as a control group. Enzyme-linked immunosorbent assays were performed to detect the levels of plasma interferon (IFN)-γ, interleukin (IL)-4 and IL-17, and flow cytometry was performed to detect the TLR6 protein expression levels in PBMCs. The plasma levels of IL-4, IFN-γ and IL-17 in the HSP group were significantly higher compared with those in the normal control group. TLR6 protein expression was significantly increased in the PBMCs of the HSP patients. The TLR6 protein expression levels in the monocytes of the HSP group significantly positively correlated with the serum IL-4 and IL-17 levels, but not with the serum levels of IFN-γ. Therefore, the results of the present study suggest that the activation of TLR6 may be involved in the immunopathogenesis of HSP, and that the activated TLR6 may mediate this process by upregulating the immune responses of type 2 T helper (Th2) and Th17 cells.

Water hyacinth (Eichhornia crassipes) waste as an adsorbent for phosphorus removal from swine wastewater.

Both live plants and dried straw of water hyacinth were applied to a sequential treatment of swine wastewater for nitrogen and phosphorus reduction. In the facultative tank, the straw behaved as a kind of adsorbent toward phosphorus. Its phosphorus removal rate varied considerably with contact time between the straw and the influent. In the laboratory, the straw displayed a rapid total phosphorus reduction on a KH(2)PO(4) solution. The adsorption efficiency was about 36% upon saturation. At the same time, the water hyacinth straw in the facultative tank enhanced NH(3)-N removal efficiency as well. However, no adsorption was evident. This study demonstrated an economically feasible means to apply water hyacinth phosphorus straw for the swine wastewater treatment. The sequential system employed significantly reduced the land use, as compared to the wastewater stabilization pond treatment, for pollution amelioration of swine waste.

17beta-estradiol combined with testosterone promotes chicken osteoblast proliferation and differentiation by accelerating the cell cycle and inhibiting apoptosis in vitro.

Medullary bone is a unique tissue in the long bones cavities of lay hens, and plays an important role as a calcium reservoir for egg-shell formation. Medullary bone formation requires the synergistic action of estrogen and androgen on osteoblasts during the early stage of sexual maturity. The objective of the current study was to investigate the effects of 17beta-estradiol, testosterone, and the combination on the proliferation, alkaline phosphatase (ALP) activity, apoptosis, the cell cycle of chicken osteoblasts in vitro. The proliferation of osteoblasts was examined with the MTT assay. Apoptosis and the cell cycle were assessed with flow cytometry. Either 17beta-estradiol (200 pg ml(-1)) or testosterone (100 pg ml(-1)) or the combination (100 pg ml(-1) each) significantly enhanced osteoblast proliferation and ALP activity, accelerated the osteoblast cell cycle, and stimulated osteoblast DNA synthesis in a period of 24 h. 17beta-estradiol, used alone or with testosterone, inhibited chicken osteoblast apoptosis; However, testosterone alone induced cell apoptosis. In conclusion, 17beta-estradiol combined with testosterone promoted osteoblast proliferation and ALP activity, accelerated the osteoblast cell cycle, inhibited osteoblast apoptosis.

Use of biogas fluid-soaked water hyacinth for cultivating Pleurotus geesteranus.

Experiments were carried out to test the viability of growing Pleurotus geesteranus on media containing varying amounts of crushed water hyacinth slices, which were soaked in pig farm biogas fluid and dried. The water hyacinth material was utilized to substitute sawdust in the media for mushroom cultivation. Mushroom fruiting bodies harvested were evaluated for yield, amino acid and heavy metal contents. Among the eight treatment groups, the greatest yield and highest amino acid content in the mushrooms were obtained when the proportions of water hyacinth and sawdust in the medium were equal. The concentrations of heavy metals, Hg, Pb and Cd, in most of the present mushroom samples did not exceed the maximum allowed levels according to the limits set forth by the food hygienic and safety regulations for edible mushrooms in China. The proposed waste utilization of water hyacinth could conceivably benefit the environment in various aspects including conservation of forest by reducing the demand on natural woods for mushroom production.

Activity of gallium on prevention of fatal cage-layer osteoporosis.

The prevention of fatal cage-layer osteoporosis of gallium was studied in this paper. One-day-old hens were fed up to 68 weeks on a control diet and diets containing gallium. Plasma variables were measured during lay. End-of-lay trabecular and medullary bone volumes in the proximal tarsometatarsus and free thoracic vertebra were measured by histomorphometry. Medullary and trabecular bone volumes were increased significantly by supplementation with gallium. The experiment confirmed that dietary gallium supplementation was an effective way to enhance the egg production and reduce mortality percentage. The beneficial effects of gallium supplementation over the lifetime of the hens were attributable mainly to improved cage-layer osteoporosis.

[Study on the interaction of hesperidin or icariin with lysozyme by fluorescence spectroscopy].

The interaction of hesperidin (HES) or icariin (ICA) and lysozyme (LYS) was studied by fluorescence spectroscopy in physiological buffer solution. It was observed that there was a strong fluorescence quenching effect of hesperidin or icariin on lysozyme. The quenching constants of the drugs with lysozyme were measured at different temperatures, and the quenching mechanism was suggested as dynamic quenching for HES-LYS system and both static and dynamic quenching for ICA-LYS system. The thermodynamic parameters of the interaction of hesperidin or icariin and lysozyme were measured according to the Van's Hoff equation: the enthalpy change (DeltaH) and the entropy change (DeltaS) of HES-LYS system and ICA-LYS system were calculated to be 20.29 kJ x mol(-1) and 146.28 J x mol(-1) x K(-1), and -3.47 kJ x mol(-1) and 81.16 J x mol(-1) x K(-1), respectively, which indicated that the interaction of hesperidin and lysozyme was driven mainly by hydrophobic force, whereas the interaction of icariin and lysozyme was driven mainly by electrostatic force. It was showed that the reaCtion processes of the two systems occurred spontaneously since Gibbs free energy change (DeltaG) values were negative. The binding distances of hesperidin and icariin from the lysozyme tryptophan residue were calculated to be 1.34 nm and 1.24 nm, respectively, based on the Förster's theory of non-radiation energy transfer. The results of synchronous fluorescence spectra showed that the binding of hesperidin or icariin to lysozyme induced conformational changes in lysozyme.

[The effects of diazoxide on myocardium function and the expressions of ERK and JNK in isolated spontaneous hypertension rat hearts].

AIM: To investigate the effect of diazoxide preconditioning and the role of ERK and JNK in cellular signaling during diazoxide preconditioning protection in isolated spontaneous hypertension rat (SHR) hearts. METHODS: Hearts were isolated from male SHR rats, and perfused on a Langendorff apparatus. Five groups were considered (n = 6). Con: after 40 min perfusion the hearts were submitted to 25 min ischemia followed by 30 min reperfusion. IP: the hearts were preconditioned with 2 periods of 5 min ischemia and 10 min reperfusion prior to 25 min ischemia. DP: the hearts were preconditioned with 2 periods of 10 min K-H solution with 50 micromol x L(-1) diazoxide and 5 min K-H solution reperfusion prior to 25 min ischemia. 5-HD: perfuse with 100 micromol x L(-1) 5-HD (a special mitochondrial ATP sensitive potassium channel blocker) for 10 min followed by 30 min K-H solution perfusion before 25 min ischemia. 5-HD + DP: 100 micromol x L(-1) 5-HD was given for 10 min before diazoxide preconditioning. RESULTS: During reperfusion, comparing with Con group, the recoveries of left ventricle developed pressure (LVDP), + dP/dt(max), - dP/dt(max) and left ventricle end diastolic pressure (LVEDP) were improved in IP and DP groups (P < 0.01 vs Con). At the end of reperfusion, compared with Con group, the expression of ERK in myocardium were higher in IP and DP groups (P < 0.01 vs Con), there was no significance between 5-HD and Con group, but 5-HD couldn't inhibit the expression of ERK induced by diazoxide preconditioning. The expression of JNK in IP and DP groups were decreased (P < 0.05 vs Con), this effect could been inhibited by 5-HD. CONCLUSION: These results indicated that diazoxide preconditioning could mimic ischemic preconditioning, the activation of ERK expression and the declining of JNK expression involved in diazoxide preconditioning in isolated SHR hearts.