Mini-dose esketamine-dexmedetomidine combination to supplement analgesia for patients after scoliosis correction surgery: a double-blind randomised trial.

BACKGROUND: Patients often experience severe pain after scoliosis correction surgery. Esketamine and dexmedetomidine each improves analgesia but can produce side-effects. We therefore tested the hypothesis that a mini-dose esketamine-dexmedetomidine combination safely improves analgesia. METHODS: Two hundred male and female adults having scoliosis correction surgery were randomised to patient-controlled sufentanil analgesia (4 µg kg-1 in normal saline) with either a combined supplement (esketamine 0.25 mg ml-1 and dexmedetomidine 1 µg ml-1) or placebo. The primary outcome was the incidence of moderate-to-severe pain within 72 h, defined as a numeric rating scale (NRS: 0=no pain and 10=worst pain) score ≥4 at any of seven time points. Amongst secondary outcomes, subjective sleep quality was assessed with an NRS score (0=best sleep and 10=worst sleep) for the first five postoperative nights. RESULTS: There were 199 subjects included in the intention-to-treat analysis. Mean infusion rates were 5.5 µg kg-1 h-1 for esketamine and 0.02 µg kg-1 h-1 for dexmedetomidine. The primary outcome incidence was lower with the combined supplement (65.7% [65/99]) than with placebo (86.0% [86/100]; relative risk 0.76; 95% confidence interval: 0.65-0.90; P=0.001). Subjects given the combined supplement had lower pain intensity at rest at five time points (median difference -1 point; P≤0.005), lower pain intensity with movement at six time points (median difference -1 point; P≤0.001), and better subjective sleep quality for the first 5 postoperative nights (median difference -2 to -1 points; P<0.001). Adverse events did not differ between groups. CONCLUSIONS: The mini-dose esketamine-dexmedetomidine combination safely improved analgesia and subjective sleep quality after scoliosis correction surgery. CLINICAL TRIAL REGISTRATION: NCT04791059.

Effect of acute pain on the association between preoperative cognitive impairment and postoperative delirium: a secondary analysis of three trials.

BACKGROUND: The association between preoperative cognitive impairment, postoperative pain, and postoperative delirium in older patients after noncardiac surgery is not known. METHODS: This was a secondary analysis of datasets from three previous studies. Patients aged ≥55 yr who underwent elective noncardiac surgery were enrolled. Preoperative cognitive impairment was defined as Mini-Mental State Examination <27. Pain intensity with movement was assessed using an 11-point numeric rating scale at 12-h intervals during the first 72 h after surgery; time-weighted average (TWA) pain score was calculated. Primary outcome was the occurrence of delirium within the first 5 postoperative days. Mediation analysis was used to investigate the relationships between cognitive impairment, pain score, and delirium. RESULTS: A total of 1497 patients were included. Prevalence of preoperative cognitive impairment was 40.3% (603/1497). Patients with cognitive impairment suffered higher TWA pain score within 72 h (4 [3-5] vs 3 [2-5], P=0.004) and more delirium within 5 days (12.9% [78/603] vs 4.9% [44/894], P<0.001) when compared with those without. Total and direct associations between cognitive impairment and delirium were (adjusted ß) 8.3% (95% confidence interval [CI], 4.8-12.0%; P<0.001) and 7.8% (95% CI, 4.4-12.0%; P<0.001), respectively. A significant indirect association with acute pain was observed between cognitive impairment and delirium (adjusted ß=0.4%; 95% CI, 0.1-1.0%; P=0.006), accounting for 4.9% of the total effect. CONCLUSIONS: The association between preoperative cognitive impairment and delirium is significantly mediated by acute pain in patients after noncardiac surgery. Considering the small effect size, clinical significance of this mediation effect requires further investigation.

Delirium in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: a multicentre randomised trial.

BACKGROUND: Delirium is a common and disturbing postoperative complication that might be ameliorated by propofol-based anaesthesia. We therefore tested the primary hypothesis that there is less delirium after propofol-based than after sevoflurane-based anaesthesia within 7 days of major cancer surgery. METHODS: This multicentre randomised trial was conducted in 14 tertiary care hospitals in China. Patients aged 65-90 yr undergoing major cancer surgery were randomised to either propofol-based anaesthesia or to sevoflurane-based anaesthesia. The primary endpoint was the incidence of delirium within 7 postoperative days. RESULTS: A total of 1228 subjects were enrolled and randomised, with 1195 subjects included in the modified intention-to-treat analysis (mean age 71 yr; 422 [35%] women); one subject died before delirium assessment. Delirium occurred in 8.4% (50/597) of subjects given propofol-based anaesthesia vs 12.4% (74/597) of subjects given sevoflurane-based anaesthesia (relative risk 0.68 [95% confidence interval {CI}: 0.48-0.95]; P=0.023; adjusted relative risk 0.59 [95% CI: 0.39-0.90]; P=0.014). Delirium reduction mainly occurred on the first day after surgery, with a prevalence of 5.4% (32/597) with propofol anaesthesia vs 10.7% (64/597) with sevoflurane anaesthesia (relative risk 0.50 [95% CI: 0.33-0.75]; P=0.001). Secondary endpoints, including ICU admission, postoperative duration of hospitalisation, major complications within 30 days, cognitive function at 30 days and 3 yr, and safety outcomes, did not differ significantly between groups. CONCLUSIONS: Delirium was a third less common after propofol than sevoflurane anaesthesia in older patients having major cancer surgery. Clinicians might therefore reasonably select propofol-based anaesthesia in patients at high risk of postoperative delirium. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IPR-15006209) and ClinicalTrials.gov (NCT02662257).

Long-term survival in older patients given propofol or sevoflurane anaesthesia for major cancer surgery: follow-up of a multicentre randomised trial.

BACKGROUND: Experimental evidence indicates that i.v. anaesthesia might reduce cancer recurrence compared with volatile anaesthesia, but clinical information is observational only. We therefore tested the primary hypothesis that propofol-based anaesthesia improves survival over 3 or more years after potentially curative major cancer surgery. METHODS: This was a long-term follow-up of a multicentre randomised trial in 14 tertiary hospitals in China. We enrolled 1228 patients aged 65-90 yr who were scheduled for major cancer surgery. They were randomised to either propofol-based i.v. anaesthesia or to sevoflurane-based inhalational anaesthesia. The primary endpoint was overall survival after surgery. Secondary endpoints included recurrence-free and event-free survival. RESULTS: Amongst subjects randomised, 1195 (mean age 72 yr; 773 [65%] male) were included in the modified intention-to-treat analysis. At the end of follow-up (median 43 months), there were 188 deaths amongst 598 patients (31%) assigned to propofol-based anaesthesia compared with 175 deaths amongst 597 patients (29%) assigned to sevoflurane-based anaesthesia; adjusted hazard ratio 1.02; 95% confidence interval (CI): 0.83-1.26; P=0.834. Recurrence-free survival was 223/598 (37%) in patients given propofol anaesthesia vs 206/597 (35%) given sevoflurane anaesthesia; adjusted hazard ratio 1.07; 95% CI: 0.89-1.30; P=0.465. Event-free survival was 294/598 (49%) in patients given propofol anaesthesia vs 274/597 (46%) given sevoflurane anaesthesia; adjusted hazard ratio 1.09; 95% CI 0.93 to 1.29; P=0.298. CONCLUSIONS: Long-term survival after major cancer surgery was similar with i.v. and volatile anaesthesia. Propofol-based iv. anaesthesia should not be used for cancer surgery with the expectation that it will improve overall or cancer-specific survival. CLINICAL TRIAL REGISTRATIONS: ChiCTR-IPR-15006209; NCT02660411.

Effect of one-lung ventilation on the correlation between left and right cerebral saturation.

BACKGROUND: To investigate if the correlation between left and right cerebral tissue oxygen saturation (SctO2) was affected by one-lung ventilation (OLV) in patients undergoing lung cancer surgery. METHODS: Patients who underwent surgery for lung cancer were enrolled. Left and right SctO2 were collected during anesthesia. The primary outcome was the correlation between left and right SctO2 at 30 min after OLV which was analysed by Pearson correlation and linear regression model. Secondary outcomes included the trend of left-right SctO2 change over the first 30 min after OLV, correlation of left-right SctO2 during OLV for each patient; maximal difference between left-right SctO2 and its relationship with postoperative delirium. RESULTS: Left-right SctO2 was moderately correlated at baseline (r = 0.690, P < 0.001) and poorly correlated at 30 min after OLV (r = 0.383, P < 0.001) in the Pearson correlation analysis. Linear regression analysis showed a poor correlation between left and right SctO2 at 30 min after OLV (r = 0.323, P < 0.001) after adjusting for confounders. The linear mixed model showed a change in left-right SctO2 over the first 30 min after OLV that was statistically significant (coefficient, -0.042; 95% CI, -0.070--0.014; P = 0.004). For the left-right SctO2 correlation during OLV in each patient, 62.9% (78/124) patients showed a strong correlation, 19.4% (24/124) a medium correlation, and the rest a poor correlation. The maximal difference between the left and right SctO2 was 13.5 (9.0, 20.0). Multivariate analysis showed that it was not associated with delirium (odds ratio [OR], 1.023; 95% CI, 0.963-1.087; P = 0.463). CONCLUSIONS: The correlation between left and right SctO2 was affected by one-lung ventilation in patients undergoing lung cancer surgery. This result indicates the requirement of bilateral SctO2 monitoring to reflect brain oxygenation. TRIAL REGISTRATION: This study was a secondary analysis of a cohort study approved by the Clinical Research Review Board of Peking University First Hospital (#2017-1378) and was registered in the Chinese Clinical Trial Registry on 10/09/2017 ( http://www.chictr.org.cn , ChiCTR-ROC-17012627).

Bilateral ultrasound-guided erector spinae plane block versus wound infiltration for postoperative analgesia in lumbar spinal fusion surgery: a randomized controlled trial.

PURPOSE: Both erector spinae plane block and wound infiltration are used to improve analgesia following spinal fusion surgery. Herein, we compared the analgesic effect of bilateral erector spinae plane block with wound infiltration in this patient population. METHODS: In this randomized trial, 60 patients scheduled for elective open posterior lumbar interbody fusion surgery were randomized to receive either ultrasound-guided bilateral erector spinae plane block before incision (n = 30) or wound infiltration at the end of surgery (n = 30). Both groups received standardized general anesthesia and postoperative analgesia, including patient-controlled analgesia with sufentanil and no background infusion. Opioid consumption and pain intensity were assessed at 2, 6, 12, 24, and 48 h after surgery. The primary outcome was cumulative opioid consumption within 24 h after surgery. RESULTS: All 60 patients were included in the intention-to-treat analysis. The equivalent dose of sufentanil consumption within 24 h was significantly lower in patients given erector spinae plane block (median 11 µg, interquartile range 5-16) than in those given wound infiltration (20 µg, 10 to 43; median difference - 10 µg, 95% CI - 18 to - 3, P = 0.007). The cumulative number of demanded PCA boluses was significantly lower with erector spinae plane block at 6 h (median difference - 2, 95% CI - 3 to 0, P = 0.006), 12 h (- 3, 95% CI - 6 to - 1, P = 0.002), and 24 h (- 5, 95% CI - 8 to - 2, P = 0.005) postoperatively. The proportion given rescue analgesia was also significantly lower in patients given erector spinae plane block group within 48 h (relative risk 0.27, 95% CI 0.07 to 0.96, P = 0.037). There were no statistical differences in pain intensity at any timepoints between groups. No procedure-related adverse events occurred. CONCLUSIONS: Compared with wound infiltration, bilateral ultrasound-guided erector spinae plane block decreases short-term opioid consumption while providing similar analgesia in patients following lumbar spinal fusion surgery. Chinese Clinical Trial Registry: ChiCTR2100053008.

[Factors Associated With Coronary Heart Disease Among Adult Residents in Jinjiang District,Chengdu City].

Objective To analyze the prevalence of coronary heart disease among community residents over 18 years old in Jinjiang district of Chengdu city,Sichuan province,and explore its associated factors,so as to provide a reference for the prevention and control of coronary heart disease in communities.Methods From October 15 to November 10 in 2021,a total of 5220 adult residents from 33 communities in Jinjiang were selected by multi-stage stratified random sampling for face-to-face questionnaire survey,physical examination,and laboratory blood test.Binary Logistic regression was employed to predict the factors associated with coronary heart disease among adult residents in Jinjiang.Results The crude and standard prevalence rates of coronary heart disease among 5220 adult residents were 3.39% and 2.11%,respectively.Logistic regression analysis showed that age (OR=1.068,95%CI=1.051-1.086,P<0.001),depressive symptoms (OR=1.639,95%CI=1.037-2.591,P=0.034),regular exercise (OR=0.584,95%CI=0.378-0.902,P=0.015),elevated blood pressure (OR=3.529,95%CI=2.344-5.312,P<0.001),dyslipidemia (OR=2.152,95%CI=1.291-3.587,P=0.003),and core knowledge score of chronic diseases (OR=1.144,95%CI=1.066-1.228,P<0.001) were associated with coronary heart disease among adult residents in Jinjiang.Conclusions The prevalence of coronary heart disease is high among adult residents in Jinjiang district of Chengdu.The urban residents who are older,have depressive symptoms,lack of exercise,elevated blood pressure,dyslipidemia,and score higher on core knowledge of chronic diseases are prone to coronary heart disease.

Severe functional impairment increases the risk of major morbidity and mortality in older patients after digestive tract surgery: a retrospective cohort study.

PURPOSE: The relationship between the severity of impairment in basic activities of daily living (ADLs) function and postoperative outcomes in older surgical patients remains unclear. This study aimed to clarify the association between the severity of preoperative functional impairment and the composite postoperative outcome of major morbidity and mortality in older patients undergoing digestive tract surgery. METHODS: This was a retrospective cohort study. We collected perioperative data of older patients (age ≥ 65 years) who underwent digestive tract surgery in our institution. The severity of functional impairment was assessed using the Barthel Index scale before surgery. The major morbidity and mortality were defined as Clavien-Dindo grade III or greater postoperative complications during hospital stay. The association between the severity of functional impairment and the major morbidity and mortality was assessed using a multivariable logistic regression model. RESULTS: 131 of 1076 patients (12.2%) developed major morbidity and mortality. After controlling for confounding factors, high Barthel Index scores were correlated with decreased risk of major morbidity and mortality (OR 0.986, 95% CI 0.976-0.997, P = 0.011); preoperative severe (OR 2.862, 95% CI 1.172-6.989, P = 0.021), but not mild or moderate (OR 1.019, 95% CI 0.602-1.726, P = 0.943) functional impairment was independently associated with an increased risk of major morbidity and mortality, when compared with independent functional status. CONCLUSIONS: Preoperative severe functional impairment in basic ADLs was independently associated with a higher risk of major postoperative morbidity and mortality in older patients undergoing digestive tract surgery.

The anti-inflammatory effect of ent-kaur-15-en-17-al-18-oic acid on lipopolysaccharide-stimulated RAW264.7 cells associated with NF-κB and P38/MAPK pathways.

Ent-kaur-15-en-17-al-18-oic acid (LL-3) was demonstrated that it can inhibit LPS-induced nitric oxide (NO) production and macrophage migration, maintain homeostasis of oxidative stress, including increased mitochondrial membrane potential (MMP), decreased levels of reactive oxygen species (ROS) and malondialdehyde (MDA), and maintenance of superoxide dismutase (SOD) and glutathione (GSH) activities and inhibit oxidative stress-induced P38 and nuclear factor κB (NF-κB) pathways to decrease inducible nitric oxide synthase (iNOS), cyclooxygense-2 (COX-2), and tumour necrosis factor (TNF)-α mRNA expressions without marked cytotoxicity. These findings revealed that LL-3 could serve as a candidate lead compound for further studying anti-inflammatory therapies.[Formula: see text].

Role of STAT3 signaling pathway in breast cancer.

Breast cancer has grown to be the second leading cause of cancer-related deaths in women. Only a few treatment options are available for breast cancer due to the widespread occurrence of chemoresistance, which emphasizes the need to discover and develop new methods to treat this disease. Signal transducer and activator of transcription 3 (STAT3) is an early tumor diagnostic marker and is known to promote breast cancer malignancy. Recent clinical and preclinical data indicate the involvement of overexpressed and constitutively activated STAT3 in the progression, proliferation, metastasis and chemoresistance of breast cancer. Moreover, new pathways comprised of upstream regulators and downstream targets of STAT3 have been discovered. In addition, small molecule inhibitors targeting STAT3 activation have been found to be efficient for therapeutic treatment of breast cancer. This systematic review discusses the advances in the discovery of the STAT3 pathways and drugs targeting STAT3 in breast cancer. Video abstract.

Involvement of Reactive Oxygen Species in the Hepatorenal Toxicity of Actinomycin V In Vitro and In Vivo.

The high toxicity of actinomycin D (Act D) severely limits its use as a first-line chemotherapeutic agent in the clinic. Actinomycin V (Act V), an analog of Act D, exhibited strong anticancer activity in our previous studies. Here, we provide evidence that Act V has less hepatorenal toxicity than Act D in vitro and in vivo, associated with the reactive oxygen species (ROS) pathway. Compared to Act D, Act V exhibited considerably stronger sensitivity for cancer cells and less toxicity to human normal liver LO-2 and human embryonic kidney 293T cells using the MTT (3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide) assay. Notably, Act V caused less damage to both the liver and kidney than Act D in vivo, indicated by organ to body weight ratios, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), and serum creatinine (Scr) levels. Further experiments showed that the ROS pathway is involved in Act V-induced hepatorenal toxicity. Act V generates ROS and accumulates malondialdehyde (MDA), reducing levels of superoxide dismutase (SOD) and glutathione (GSH) in LO-2 and 293T cells. These findings indicate that Act V induces less hepatorenal toxicity than Act D in vitro and in vivo and merits further development as a potential therapeutic agent for the treatment of cancer.

Identification and Functional Study of Chitin Metabolism and Detoxification-Related Genes in Glyphodes pyloalis Walker (Lepidoptera: Pyralidae) Based on Transcriptome Analysis.

Glyphodes pyloalis Walker (Lepidoptera: Pyralididae) is a serious pest in the sericulture industry, which has caused damage and losses in recent years. With the widespread use of insecticides, the insecticide resistance of G. pyloalis has becomes increasingly apparent. In order to find other effective methods to control G. pyloalis, this study performed a transcriptome analysis of the midgut, integument, and whole larvae. Transcriptome data were annotated with KEGG and GO, and they have been shown to be of high quality by RT-qPCR. The different significant categories of differentially expressed genes between the midgut and the integument suggested that the transcriptome data could be used for next analysis. With the exception of Dda9 (GpCDA5), 19 genes were involved in chitin metabolism, most of which had close protein-protein interactions. Among them, the expression levels of 11 genes, including GpCHSA, GpCDA1, GpCDA2, GpCDA4, GPCHT1, GPCHT2a, GPCHT3a, GPCHT7, GpTre1, GpTre2, and GpRtv were higher in the integument than in the midgut, while the expression levels of the last eight genes, including GpCHSB, GpCDA5, GpCHT2b, GpCHT3b, GpCHT-h, GpPAGM, GpNAGK, and GpUAP, were higher in the midgut than in the integument. Moreover, 282 detoxification-related genes were identified and can be divided into 10 categories, including cytochrome P450, glutathione S-transferase, carboxylesterase, nicotinic acetylcholine receptor, aquaporin, chloride channel, methoprene-tolerant, serine protease inhibitor, sodium channel, and calcium channel. In order to further study the function of chitin metabolism-related genes, dsRNA injection knocked down the expression of GpCDA1 and GpCHT3a, resulting in the significant downregulation of its downstream genes. These results provide an overview of chitin metabolism and detoxification of G. pyloalis and lay the foundation for the effective control of this pest in the sericulture industry.

Strepantibins A-C: Hexokinase II Inhibitors from a Mud Dauber Wasp Associated Streptomyces sp.

Two new p-terphenyls, strepantibins A and B (1 and 2), along with the first representative of a naturally occurring bisphenyltropone, strepantibin C (3), were characterized from a Streptomyces sp. associated with the larvae of the mud dauber wasp Sceliphron madraspatanum. Their structures were determined by high-resolution electrospray ionization mass spectrometry, NMR, and X-ray crystallography data interpretation. Strepantibins A-C inhibited hexokinase II (HK2) activity and displayed antiproliferative activity against hepatoma carcinoma cells HepG-2, SMMC-7721 and plc-prf-5. In SMMC-7721 cells treated with strepantibin A, the morphological characteristics of apoptosis were observed.

The IDO genetic polymorphisms and postpartum depressive symptoms: an association study in Chinese parturients who underwent cesarean section.

Postpartum depressive symptoms (PDS) are not an uncommon mood disorder in postpartum women. Our previous research indicated a role for increased tryptophan (TRP) metabolism along the kynurenine pathway (KP) in the pathogenesis of PDS. Accordingly, this study was going to investigate the association of indoleamine-2,3-dioxygenase (IDO, a key enzyme of KP) genetic polymorphisms with PDS. Seven hundred twenty-five women receiving cesarean section were enrolled in this study. PDS was determined by an Edinburgh Postnatal Depression Scale (EPDS) score ≥ 13. Subsequently, 48 parturients with PDS and 48 parturients without PDS were selected for investigation of perinatal serum concentrations of TRP, kynurenine (KYN), and KYN/TRP ratio, the latter is the representative of IDO activity. In addition, seven single nucleotide polymorphisms of the IDO gene were examined. Following this genotyping, 50 parturients carrying the IDO rs10108662 AA genotype and 50 parturients carrying the IDO rs10108662 AC + CC genotype were selected for comparisons of TRP, KYN, and KYN/TRP ratio levels. This study showed the PDS incidence of 6.9% in the Chinese population, with PDS characterized by increased IDO activity (p < 0.05), versus women without PDS. We also found that the variations of IDO1 gene rs10108662 were significantly related to PDS incidence (p < 0.05). Furthermore, there was a significant difference in IDO activity between the IDO rs10108662 CA + AA, versus CC, genotypes. Our findings indicate a role of the kynurenine pathway in the development of PDS, rs10108662 genetic polymorphism resulting in changes of IDO activity might contribute to PDS pathogenesis.

Actinomycin V Suppresses Human Non-Small-Cell Lung Carcinoma A549 Cells by Inducing G2/M Phase Arrest and Apoptosis via the p53-Dependent Pathway.

Actinomycin V, extracted and separated from marine-derived actinomycete Streptomyces sp., as the superior potential replacement of actinomycin D (which showed defect for its hepatotoxicity) has revealed an ideal effect in the suppression of migration and invasion in human breast cancer cells as referred to in our previous study. In this study, the involvement of p53 in the cell cycle arrest and pro-apoptotic action of actinomycin V was investigated in human non-small-cell lung carcinoma A549 cells. Results from the 3-(4,5-dimethylthiazol)-2,5-diphenyltetrazolium bromide assay showed that cytotoxic activity of actinomycin V on A549 cells (with wild-type p53) was stronger than the NCI-H1299 cells (p53-deficient). Actinomycin V upregulated both of the protein and mRNA expression levels of p53, p21Waf1/Cip1 and Bax in A549 cells. For this situation, actinomycin V decreased the M-phase related proteins (Cdc2, Cdc25A and Cyclin B1) expression, arrested cells in G2/M phase and subsequently triggered apoptosis by mediating the Bcl-2 family proteins' expression (Bax and Bcl-2). Furthermore, the effects of cell cycle arrest and apoptosis in A549 cells which were induced by actinomycin V could be reversed by the pifithrin-α, a specific inhibitor of p53 transcriptional activity. Collectively, our results suggest that actinomycin V causes up-regulation of p53 by which the growth of A549 cells is suppressed for cell cycle arrest and apoptosis.

Protective effects of 3ß-angeloyloxy-8ß, 10ß-dihydroxyeremophila-7(11)-en-12, 8α-lactone on paraquat-induced oxidative injury in SH-SY5Y cells.

3ß-Angeloyloxy-8ß,10ß-dihydroxyeremophila-7(11)-en-12,8α-lactone (FJ1) inhibited effectively paraquat (PQ)-induced injury in SH-SY5Y cells. In this way, FJ1 was shown to reverse the PQ-induced activation of caspase-9 and caspase-3, the increase in Bax/Bcl-2 ratio, and the release of cytochrome c. The mechanism was associated with a reduction of oxidative stress, including the decrease in the levels of ROS and MDA and maintaining the activity of SOD and GSH. Taken together, findings revealed that FJ1 had protective effects against PQ-induced injury via attenuating the oxidative stress in SH-SY5Y cells, which suggested that FJ1 might be a candidate for further evaluation against neurodegeneration in Parkinson's disease.

Ivalin Induces Mitochondria-Mediated Apoptosis Associated with the NF-κB Activation in Human Hepatocellular Carcinoma SMMC-7721 Cells.

Ivalin, a natural compound isolated from Carpesium divaricatum, showed excellent microtubule depolymerization activities among human hepatocellular carcinoma in our previous work. Here, we investigated its functions on mitochondria-mediated apoptosis in hepatocellular carcinoma SMMC-7721 cells. DAPI (4',6-diamidino-2-phenylindole) staining, annexin V-fluorexcein isothiocyanate (FITC) apoptosis detection, and western blotting were applied to explore the apoptotic effect of Ivalin. Next, the induction effect of Ivalin on the mitochondrial pathway was also confirmed via a series of phenomena including the damage of mitochondria membrane potential, mitochondria cytochrome c escape, cleaved caspase-3 induction, and the reactive oxygen species generation. In this connection, we understood that Ivalin induced apoptosis through the mitochondrial pathway and the overload of reactive oxygen species. Furthermore, we found that the activation of nuclear factor-κB (NF-κB) and subsequent p53 induction were associated with the apoptotic effect of Ivalin. These data confirmed that Ivalin might be a promising pro-apoptotic compound that can be utilized as a potential drug for clinical treatment.

Ivalin Inhibits Proliferation, Migration and Invasion by Suppressing Epithelial Mesenchymal Transition in Breast Cancer Cells.

Ivalin, an eudesmane-type sesquiterpene compound, was isolated from the Chinese herb Carpesium divaricatum in our chemistry group. In this study, we investigated the anti-migration and anti-invasion activities and underlying mechanisms of Ivalin in breast cancer cells in vitro. Cell viability was evaluated using the MTT assay, Western blotting was used to determine the expression of E-cadherin, N-cadherin, vimentin and ZEB1, and mRNA levels were analyzed by qPCR. The anti-migration and anti-invasion effects of Ivalin were measured by wound-healing and Transwell assays. In this connection, Ivalin treatment reduced the mRNA and protein expressions of ZEB1 as well as N-cadherin and vimentin expression in various breast cancer cells. E-cadherin expression was enhanced by Ivalin in the same cells, which implied that Ivalin depressed the process of epithelial-to-mesenchymal transition (EMT). Our results revealed that Ivalin significantly inhibited cell proliferation, migration and invasion in breast cancer cells in a dose-dependent manner in vitro. This study suggests that Ivalin may merit further investigation as a potential therapeutic leading compound for the treatment of breast cancer migration and invasion.

Association between Helicobacter pylori infection and gallbladder diseases: A retrospective study.

BACKGROUND AND AIM: The association between Helicobacter pylori (H. pylori) and gallbladder diseases is still unclear and is controversial. We conducted a retrospective study to clarify the prevalence of gallbladder diseases and factors related to gallbladder diseases and relationships between H. pylori infection, gallstones, cholecystitis, and cholecystic polypus. METHODS: The retrospective study was performed at the Aerospace Center Hospital in Beijing. The subjects in this study were a healthy population who underwent health examinations at the hospital between 2012 and 2015. The logistic regression models were used to explore the relationships between H. pylori infection and gallbladder diseases. RESULTS: There were 7803 (43.4%) subjects with H. pylori infection, 995 (5.5%) with gallstones, 219 (1.2%) with cholecystitis, and 1003 (5.6%) with cholecystic polypus amongst 17 971 subjects, respectively. In subjects aged 45 years or less, the prevalence of gallstones in the H. pylori (+) group was lower than that in the H. pylori (-) group (odds ratio = 0.653; 95% confidence interval: 0.468-0.911; P = 0.012). The prevalence of cholecystic polypus in the H. pylori (+) group was significantly higher than that in the H. pylori (-) group (odds ratio = 1.160; 95% confidence interval: 1.012-1.328; P = 0.033). CONCLUSIONS: Helicobacter pylori infection was related with cholecystic polypus and gallstones in a Chinese population.

The role of tryptophan metabolism in postpartum depression.

The Postpartum depression (PPD) is the most common postpartum psychiatric disorder, afflicting approximately 10%-20% of new mothers. Clinical symptoms of the PPD include depressive disorder, agitation, insomnia, anxiety and confusion, resulting in an increase in suicidal tendencies, thereby having significant impacts on the puerpera, newborn and their family. A growing body of data indicate a role for alterations in tryptophan metabolism in the PPD. The metabolism of tryptophan produces an array of crucial factors that can differentially regulate key physiological processes linked to the PPD. Importantly, an increase in stress hormones and immune-inflammatory activity drives tryptophan to the production of neuroregulatory kynurenine pathway products and away from the serotonin and melatonin pathways. This links the PPD to other disorders of depressed mood, which are classically associated with decreased serotonin and melatonin, coupled to increases in kynurenine pathway products. Several kynurenine pathway products, such as kynurenic acid and quinolinic acid, can have neuroregulatory effects, with consequences pathological underpinnings of the PPD. The current article reviews the role of alterations in tryptophan metabolism in the PPD.