STARD12/14 are diagnostic and prognostic biomarkers of lung adenocarcinoma associated with epigenetic regulation, immune infiltration and ferroptosis.

Background: Metabolic reprogramming plays an important role in tumor progression and antitumor immunity. START domain-containing proteins (STARDs) are responsible for lipid metabolism. However, the underlying functions of STARDs in lung adenocarcinoma (LUAD) have not been clarified yet. Methods: Oncomine, UALCAN, TCGA and CPTAC were used to explore the expression landscape and clinicopathological characteristics of STARDs in LUAD. Diagnostic and prognostic values were assessed by Kaplan-Meier Plotter, Cox regression analysis, and ROC curve. GeneMANIA, GO, KEGG and GSEA were applied for exploring the potential biological functions. Epigenetic process, including mutation and m6A modification were analyzed by cBioPortal and TCGA. TIMER, TISIDB and TCGA cohort provided an immune signature. The correlation between STARDs expression and ferroptosis was analyzed by TCGA. Finally, the STARDs expression were confirmed by RT-qPCR and western blot. Results: STARD5/10/14 were overexpressed in LUAD compared with normal, while STARD4/7/8/11/12/13 were relatively low. STARD5/12/14 levels were positively related to clinical and lymph node stage. Survival analysis showed high STARD12 expression was associated with favorable overall survival, disease special survival as well as disease free survival, while STARD14 showed the opposite. GSEA analysis found STARD12 and STARD14 were associated with glycolysis, oxidative phosphorylation and tumor related signaling pathways. STARD12 co-expressed genes participated in cell cycle and DNA replication, and STARD14 were enriched in ECM-receptor interaction. Both STARD12 and STARD14 were corelated with epigenetic regulation, especially TP53 mutation and m6A modification. STARD12 expression was positively correlated with TMB level. The level of STARD12 was significantly associated with the abundance of infiltrating immune cells, including B cells, CD8+T cells, macrophages, dendritic cells, and chemokine, receptor, MHC, immunostimulatory related genes. STARD14 was negatively associated with the infiltration of CD8+T cells, while positively with CCL28 and immune checkpoints, including CTLA4 as well as PD-L2. In addition, STARD12/14 could regulate the ferroptosis related genes. Conclusion: STARD12 and STARD14 were expected to be potential biomarkers for LUAD, which were associated with epigenetic regulation, immune infiltration and ferroptosis.

The PI3Kα inhibitor DFX24 suppresses tumor growth and metastasis in non-small cell lung cancer via ERK inhibition and EPHB6 reactivation.

EPHB6 is a metastasis inhibitory gene that is frequently decreased or deficiency in non-small cell lung cancer (NSCLC), which contributed to the subsequent development of distant metastasis. These suggested the possibility that reactivation of EPHB6 might prevent the metastasis of NSCLC. Nevertheless, EPHB6 expression might also promote cancer cell growth and inhibit cell apoptosis by activating Akt and ERK pathway, apart from inhibition of migration and invasion. In the present study, we developed a novel quinazolin-4(3H)-one analog (DFX24) as a potential PI3Kα inhibitor, which inhibited both cell proliferation and metastasis of NSCLC cell lines. Investigation to the molecular mechanisms revealed DFX24 inhibited the cell growth and metastasis via inhibition of PI3Kα and ERK activity, as well as the increase in EPHB6 expression. In addition, DFX24 also induced cell cycle arrest and tumor cell apoptosis by inhibiting PI3K/Akt pathway and activating mitochondria-dependent pathway, respectively. These findings suggested that DFX24 might be considered as a novel drug candidate and may provide a potential therapy for NSCLC.

Investigating the mechanism of ShuFeng JieDu capsule for the treatment of novel Coronavirus pneumonia (COVID-19) based on network pharmacology.

ShuFeng JieDu capsule (SFJDC), a traditional Chinese medicine, has been recommended for the treatment of COVID-19 infections. However, the pharmacological mechanism of SFJDC still remains vague to date. The active ingredients and their target genes of SFJDC were collected from TCMSP. COVID-19 is a type of Novel Coronavirus Pneumonia (NCP). NCP-related target genes were collected from GeneCards database. The ingredients-targets network of SFJDC and PPI networks were constructed. The candidate genes were screened by Venn diagram package for enrichment analysis. The gene-pathway network was structured to obtain key target genes. In total, 124 active ingredients, 120 target genes of SFJDC and 251 NCP-related target genes were collected. The functional annotations cluster 1 of 23 candidate genes (CGs) were related to lung and Virus infection. RELA, MAPK1, MAPK14, CASP3, CASP8 and IL6 were the key target genes. The results suggested that SFJDC cloud be treated COVID-19 by multi-compounds and multi-pathways, and this study showed that the mechanism of traditional Chinese medicine (TCM) in the treatment of disease from the overall perspective.

Analysis of inflammatory parameters and disease severity for 88 hospitalized COVID-19 patients in Wuhan, China.

Background and aim: The outbreak of coronavirus disease 2019 (COVID-19) is quickly turning into a pandemic. We aimed to further clarify the clinical characteristics and the relationship between these features and disease severity. Methods: In this retrospective single-center study, demographic, clinical and laboratory data were collected and analyzed among moderate, severe and critically ill group patients. Results: 88 hospitalization patients confirmed COVID-19 were enrolled in this study. The average age of the patients was 57.11 years (SD, ±15.39). Of these 88 patients, the median body mass index (BMI) was 24.03 (IQR, 21.64-26.61; range 15.05-32.39), the median duration from disease onset to hospital admission were 11 days (IQR, 6.50-14.50). 46.59% patients had one or more comorbidities, with hypertension being the most common (26.14%), followed by diabetes mellitus (12.50%) and coronary atherosclerotic heart disease (CAD) (7.95%). Common symptoms at onset of disease were fever (71.59%), cough (59.09%), dyspnea (38.64%) and fatigue (29.55%). 88 patients were divided into moderate (47 [53.41%]), severe (32 [36.36%]) and critically ill (9 [10.23%]) groups. Compared with severe and moderate patients, lymphocytopenia occurred in 85.71% critically ill patients, and serum IL-2R, IL-6, IL-8, TNF-α, LDH, and cTnI were also increased in 71.42%, 83.33%, 57.14%, 71.43%, 100% and 42.86% in critically ill patients. Through our analysis, the age, comorbidities, lymphocyte count, eosinophil count, ferritin, CRP, LDH, PT and inflammatory cytokines were statistically significant along with the disease severity. Conclusion: We found some clinical characteristic and inflammatory cytokines could reveal the severity of COVID-19 during the outbreak phage. Our research could assist the clinicians recognize severe and critically ill patients timely and focus on the expectant treatment for each patient.

α-Tetralonyl Glucosides from the Green Walnut Husks of Juglans mandshurica and Their Antiproliferative Effects.

Two new α-tetralonyl glucosides, (4S)-4,5,8-trihydroxy-α-tetralone-5-O-ß-D-glucopyranosyl(1 → 6)-ß-D-glucopyranoside (1: ) and (4S)-4,8-dihydroxy-α-tetralone-4-O-ß-D-glucopyranosyl(1 → 6)-ß-D-glucopyranoside (2: ), together with eight known compounds (3:  - 10: ) were isolated from the green walnut husks of Juglans mandshurica. The structural characterization of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR and HR-ESI-MS experiments. The isolated compounds were assayed for their cytotoxicity against two human cancer cell lines, A549 and HeLa. Four compounds (7:  - 10: ) exhibited inhibitory effects against two human cancer cell lines with GI50 values between 1.3 and 5.8 µM.

[Cloning and expression analysis of CtbHLH transcription factor gene from Carthamus tinctorius and construction of plant expression vector].

To clone bHLH( basic helix-loop-helix) gene from Carthamus tinctorius,analyze the expression level in different plant tissues and construct the plant expression vector. The bHLH1 gene was cloned by RT-PCR techniques,and the protein characteristics were analyzed by bioinformatics,and phylogenetic tree was constructed. The expression of bHLH1 gene in different tissues and the roots after inoculated by Fusarium oxysporum were analyzed using real time-PCR,and the plant expression vector p BASTA-bHLH1 was constructed. The obtained ORF sequence of bHLH1 gene was 897 bp,encoded a protein of 298 amino acids. Sequence alignment and phylogenetic tree analyses showed that C. tinctorius bHLH1 had a certain homology with other species of amino acids,and was the most similar to the amino acid sequence of tobacco. Real-time PCR results showed significant differences,CtbHLH1 gene in red flower petals in different tissues and different flowering period had remarkable difference in expression level,its high amount expressed in petals,flowers third day after blossom expressed the highest quantity,at the end of the flowering the expression quantity is low. In addition,it is expressed in the root,and the expression in the stem and leaves is extremely low. The bHLH1 gene of C. tinctorius is successfully cloned,and the expression is analyzed. The plant expression vector p BASTA-bHLH is constructed.

Respiratory variation in peripheral arterial blood flow peak velocity to predict fluid responsiveness in mechanically ventilated patients: a systematic review and meta-analysis.

BACKGROUND: Fluid overloading is detrimental to organ function and results in a poor prognosis. It is necessary to evaluate fluid responsiveness before fluid loading. We performed a systematic meta-analysis to evaluate the diagnostic value of the respiratory variation in peripheral arterial blood flow peak velocity (△Vpeak PA) in predicting fluid responsiveness in mechanically ventilated patients. METHODS: PubMed, Embase and The Cochrane Library databases were searched for studies that used △Vpeak PA to predict fluid responsiveness in mechanically ventilated patients. We calculated the pooled values of sensitivity, specificity and the area of the summary receiver operating characteristic curve by Meta-Disc 14.0 software. RESULTS: Nine studies with a total of 402 patients were included. Two low quality studies were deleted in further analysis. Moreover, because of different locations of peripheral artery, the rest included studies were divided into brachial site group and carotid site group for meta-analysis individually. The pooled sensitivity, specificity and area under curve were 0.85 (95% confidence interval (CI) 0.77-0.92), 0.86 (95% CI 0.77-0.92) and 0.9268 in carotid site group. The pooled sensitivity, specificity and area under curve were 0.72 (95% CI 0.60-0.81), 0.85 (95% CI 0.74-0.93) and 0.8587 in brachial site group. CONCLUSIONS: △Vpeak of carotid and brachial artery had a diagnostic value in predicting fluid responsiveness respectively. Moreover, △Vpeak of carotid artery had more value than brachial artery in predicting fluid responsiveness. However, there was some clinical heterogeneity; therefore, further studies are needed to confirm diagnostic accuracy.

Synthesis and biological activity of new phthalimides as potential anti-inflammatory agents.

The overproduction of nitric oxide (NO) plays an important role in a variety of pathophysiological processes, including inflammation. Therefore, the suppression of NO production is a promising target in the design of anti-inflammatory agents. In the present study, a series of phthalimide analogs was synthesized, and their anti-inflammatory activities were evaluated using lipopolysaccharide (LPS)-stimulated NO production in cultured murine macrophage RAW264.7 cells. A structure-activity relationship study showed that the free hydroxyl group at C-4 and C-6 and the bulkiness of the N-substituted alkyl chain are associated with biological activity. Among the series of phthalimide derivatives, compound IIh exhibited potent inhibitory activity, with an IC50 value of 8.7µg/mL. Further study revealed that the inhibitory activity of compound IIh was correlated with the down-regulation of the mRNA and protein expression of LPS-stimulated inducible nitric oxide synthase (iNOS). Compound IIh also suppressed the induction of the pro-inflammatory cytokines tumor necrosis factor-α and interleukin-1ß in LPS-stimulated RAW 264.7 cells. The anti-inflammatory activity of compound IIh was also found to be associated with the suppression of the Toll-like receptor (TLR)4 signaling pathway by down-regulating the activation of interferon regulatory factor 3 (IRF-3) and interferon-ß and signal transducer expression. These findings demonstrate that novel phthalimides might be potential candidates for the development of anti-inflammatory agents.

Changes in trehalose content, enzyme activity and gene expression related to trehalose metabolism in Flammulina velutipes under heat shock.

Trehalose plays important roles in the protection of organisms against adverse environmental conditions. The growth and development of Flammulina velutipes is regulated and controlled under complex external conditions. This study investigated the effect of heat stress on trehalose metabolism in mycelia and fruiting bodies. The activities of enzymes involved in trehalose metabolism, the transcriptional levels of the corresponding genes and the trehalose content in the mycelia of Flammulina velutipes strain Dan3 under relatively high temperatures were investigated. The mycelia and fruiting bodies of a strain cultivated in a factory were collected at different stages to examine the trehalose content and expression levels of various genes. The results showed that intracellular trehalose significantly accumulated in the mycelia in response to 37 °C heat shock. Heat shock significantly stimulated the activities of trehalose-6-phosphate synthase and trehalose-6-phosphate phosphatase, thereby promoting the accumulation of trehalose for the first 2-6 h. The activity of neutral trehalase also decreased during this period. In addition, changes in the activities of trehalose-6-phosphate synthase, trehalose-6-phosphate phosphatase and neutral trehalase paralleled changes in the expression levels of the regulatory genes. As for the trehalose phosphorylase, the degradation of trehalose was stronger than its synthesis under heat stress. Heat shock can induce a stress response in the mycelia through the regulation of genes related to trehalose metabolism and the subsequent promotion and control of the transcription and translation of enzymes. The analysis of the trehalose and gene expression levels in the cultivated strain suggests that a substantial amount of trehalose had accumulated in the mycelia prior to induction of the primordia, and the fruiting bodies could possibly utilize degraded trehalose that translocated from the mycelia to maintain their growth.

AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway.

To investigate apoptosis mechanisms in lymphocytes induced by aluminum trichloride (AlCl3) through the mitochondria-caspase dependent pathway, the spleen lymphocytes of rats were cultured with RPMI-1640 medium and exposed to AlCl3·6H2O in the final concentrations of 0 (control group, CG), 0.3 (low-dose group, LG), 0.6 (mid-dose group, MG), and 1.2 (high-dose group, HG) mmol·L(-1) for 24 h, respectively. Mitochondrial transmembrane potential (ΔΨm), cytochrome C (Cyt C) protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, DNA ladder and lymphocytes apoptosis index were detected. The results showed that Cyt C protein expression in cytoplasm, Caspase-3 and Caspase-9 activity, Bcl-2, Bax, Caspase-3 and Caspase-9 mRNA expressions, the ratio of Bcl-2 and Bax mRNA expression, lymphocytes apoptosis index increased, while ΔΨm decreased in the AlCl3-treated groups compared with those in CG. The results indicate that AlCl3 induces lymphocyte apoptosis in rats through the mitochondria-caspase dependent pathway.

Nomogram for Predicting Emergent Conversion to General Anaesthesia in Stroke Patients During Thrombectomy.

RATIONALE AND OBJECTIVES: The aim of this study was to develop and validate a nomogram for predicting emergent conversion to general anaesthesia (GA) in stroke patients during thrombectomy. METHODS: In this retrospective study, 458 patients (320 and 138 were randomised into the training and validation cohorts) were enroled. Univariable and multivariable logistic regression analyses were employed to identify risk factors for emergent conversion to GA. Subsequently, a nomogram was constructed based on the identified risk factors. The discriminative ability, calibration, and clinical utility of the nomogram were assessed in both the training and validation cohorts using receiver operating characteristic (ROC) curve analysis, Hosmer-Lemeshow test, and decision curve analysis (DCA). RESULTS: The emergent conversion to GA occurred in 56 cases (12.2%). In the training cohort, four independent predictors of emergent conversion to GA were identified and incorporated into the nomogram: core infarct volume > 70 mL, severe aphasia, severe cerebral vessel tortuosity, and vertebrobasilar occlusion. The ROC curves illustrated area under curve values of 0.931 (95% CI: 0.863-0.998) and 0.893 (95% CI: 0.852-0.935) for the training and validation cohorts, respectively. Hosmer-Lemeshow testing resulted in average absolute errors of 0.028 and 0.031 for the two cohorts. DCA demonstrated the nomogram's exceptional utility and accuracy across a majority of threshold probabilities. CONCLUSION: The constructed nomogram displayed promising predictive accuracy for emergent conversion to GA in stroke patients during thrombectomy, thereby providing potential assistance for clinical decision-making.

Impact of uterine artery embolization on ovarian function and pregnancy outcome after uterine-fibroids treatment: A prospective study.

BACKGROUND: Uterine fibroids are benign tumors that originate from smooth muscle cells of the uterus. It is the most common gynecological disorder, affecting up to 80% of women of reproductive age. Uterine fibroids can cause various symptoms such as abnormal uterine bleeding, pelvic pain, infertility, and pregnancy complications. The treatment options for uterine fibroids include medical therapy, surgical intervention, and minimally invasive techniques. AIM: To compare ovarian function of women with uterine fibroids who did or did not undergo uterine artery embolization (UAE). METHODS: This prospective cohort study enrolled 87 women with symptomatic uterine fibroids who underwent UAE, and 87 women with the same symptoms who did not undergo UAE but received conservative management or other treatments. The two groups were matched for age, body mass index, parity, and baseline characteristics of uterine fibroids. The primary outcome was ovarian function that was evaluated by serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and anti-Müllerian hormone (AMH), as well as ovarian reserve tests, such as antral follicle count (AFC) and ovarian volume (OV). The secondary outcome was fertility that was evaluated based on the menstrual cycle, ovulation, conception, pregnancy, and delivery. The participants were followed-up for 36 months and assessed at 1, 3, 6, 12, 24, and 36 months after treatment. RESULTS: The study found that the most common minor complication of UAE was postembolization syndrome in 73.6% of women, resolving within a week. No significant differences were observed between the UAE group and the control group in serum levels of reproductive hormones (FSH, LH, E2, AMH) and ovarian reserve indicators (AFC, OV) at any point up to 36 months post-treatment. Additionally, there were no significant differences in conception, pregnancy, or delivery rates, with the average time to conception and gestational age at delivery being similar between the two groups. Birth weights were also comparable. Finally, there was no significant correlation between ovarian function, fertility indicators, and the type or amount of embolic agent used or the change in fibroids post-treatment. CONCLUSION: UAE resulted in significantly positive pregnancy outcomes, no adverse events post-treatment, and is a safe and effective treatment for uterine fibroids that preserves ovarian function and fertility.

Triterpene saponins from Clematis mandshurica and their antiproliferative activity.

Six new triterpene saponins, clematomandshurica saponins F-K (1-6), together with a known compound (7), were isolated from the roots and rhizomes of Clematis mandshurica. Their structures were elucidated on the basis of spectroscopic evidence and hydrolysis. Compounds 5-7 exhibited antiproliferative effects against PC-3 human prostate cancer cells with GI50 values of 1.29, 1.50, and 0.71 µM, respectively.

Expression of terpene synthase-related genes in parents and offspring of Flammulina filiformis based on differences in volatile aroma components.

Flammulina filiformis (F. filiformis) is one of the four major edible types of fungus in the world and has been cultivated in China since 800 CE (Anno Domini). Some of the most essential criteria for evaluating the quality of F. filiformis are the types and contents of volatile components present. A focused study on screened the terpene synthase genes involved in the aroma of offspring and compared key terpenoids between parents and offspring, which is helpful for the development and application of F. filiformis. Firstly, the volatile aroma components of parent and offspring F. filiformis were extracted using two pretreatment procedures, and then were semi-quantified by an internal standard. Forty-eight, fifty-eight, and forty-eight volatile compounds were identified in parents and offspring of three different strains, and 15, 22, and 12 aroma compounds (OAVs ≥ 1) were further screened out via calculating their odor activity values (OAVs). Terpenoids, in particular linalool and eucalyptol, which contribute more to the aroma, result in the unique green and grassy aroma of the offspring. At last, the F. filiformis genome was resequenced and the coordinates of genes related to terpenoid synthase were determined. The results showed that Scaffolds, including scaffold3.t874 and scaffold9.t157 were connected to terpenoid synthesis of offspring (No. 61523). The variant genes g269 and g61 were related to terpenoid synthase sequences. This study provides a theoretical foundation for the cultivation of more diverse and unique varieties of F. filiformis.

Enterprise stents versus low-profile visualized intraluminal support stents for stent-assisted coiling of unruptured paraclinoid aneurysms.

BACKGROUND: The microsurgical treatment of paraclinoid aneurysms can be challenging due to the anatomical structures that surround them. OBJECTIVE: This study compared the clinical and angiographic outcomes of unruptured paraclinoid aneurysms treated with enterprise (EP) stents and low-profile visualized intraluminal support (LVIS) stents. METHODS: A retrospective analysis of the clinical and radiological data from 133 patients with 139 unruptured paraclinoid aneurysms, who received an EP or an LVIS stent between January 2017 and June 2021 at Taizhou People's Hospital, was performed. Immediate postoperative and follow-up angiographic results were analyzed retrospectively using the Raymond-Roy occlusion classification (RROC). Any complications following the procedure and the patients' clinical outcomes were noted. RESULTS: Enterprise stents were used for stent-assisted coiling in 64 patients with 68 aneurysms and LVIS stents were used in 69 patients with 71 aneurysms. Both groups exhibited an increase in the proportion of aneurysms meeting the criteria for RROC class I, but the LVIS group demonstrated a higher rate of aneurysms meeting the class I criteria compared with the EP group, both on immediate postoperative angiography (45.1% vs. 11.8%, p< 0.001) and on follow-up angiography (94.9% vs. 80.6%, p= 0.025). Procedure-related complications were experienced by 9.4% of patients in the EP group (one coil prolapse, two parent artery occlusions, and three thromboembolic events), and 8.7% of patients in the LVIS group (three stent-related thrombosis and three thromboembolic events). There were no statistically significant differences between the two groups in relation to perioperative complications (p= 0.746) or favorable clinical outcomes (p= 0.492). CONCLUSION: A greater proportion of aneurysms in the LVIS group met the criteria for RROC class I compared with the EP group. There is no significant difference in procedural complications or clinical outcomes between EP and LVIS stents. Although no aneurysm recurrence was observed during the short follow-up period, continued monitoring is required.

Discovery of a natural small-molecule AMP-activated kinase activator that alleviates nonalcoholic steatohepatitis.

Non-alcoholic steatohepatitis (NASH) is a primary cause of cirrhosis and hepatocellular carcinoma. Unfortunately, there is no approved drug treatment for NASH. AMP-activated kinase (AMPK) is an important metabolic sensor and whole-body regulator. It has been proposed that AMPK activators could be used for treating metabolic diseases such as obesity, type 2 diabetes and NASH. In this study, we screened a marine natural compound library by monitoring AMPK activity and found a potent AMPK activator, candidusin A (CHNQD-0803). Further studies showed that CHNQD-0803 directly binds recombinant AMPK with a KD value of 4.728 × 10-8 M and activates AMPK at both molecular and intracellular levels. We then investigated the roles and mechanisms of CHNQD-0803 in PA-induced fat deposition, LPS-stimulated inflammation, TGF-ß-induced fibrosis cell models and the MCD-induced mouse model of NASH. The results showed that CHNQD-0803 inhibited the expression of adipogenesis genes and reduced fat deposition, negatively regulated the NF-κB-TNFα inflammatory axis to suppress inflammation, and ameliorated liver injury and fibrosis. These data indicate that CHNQD-0803 as an AMPK activator is a novel potential therapeutic candidate for NASH treatment. Supplementary Information: The online version contains supplementary material available at 10.1007/s42995-023-00168-z.

Saponins with neuroprotective effects from the roots of Pulsatilla cernua.

Four new oleanene-type triterpenoid saponins together with six known saponins were isolated from the roots of Pulsatilla cernua and their structures were elucidated on the basis of spectroscopic data, including 2D NMR spectra and chemical evidence. Among these one of the aglycones (gypsogenin) is reported for the first time from this genus. Some of these compounds showed significant neuroprotective effects against the cytotoxicity induced by ß-amyloid(25-35) (Aß(25-35)) on human neuroblastoma SH-SY5Y cells.

[A clinical study on multi-disciplinary team and surgery for resectable colorectal cancer with liver metastases].

OBJECTIVES: To analyze the survival outcomes of the surgery for colorectal cancer with liver metastases (CRCLM), and study the mode of multi-disciplinary team (MDT) for CRCLM. METHODS: The retrospective analysis was conducted for 38 patients with CRCLM received MDT management and surgical treatment from January 2009 to August 2011. The peri-operative and survival outcomes of MDT and surgery were evaluated. RESULTS: All the cases met the present criteria of resetability for CRCLM, but only 4 cases (10.5%) met the previous one. Coloproctectomy and hepatectomy were performed in all cases, with 39 colorectal neoplasms and 155 liver lesions removed. One case died of postoperative septic shock. Colorectal and hepatic specific complications were absent in the others patients except one case of biliary leak which was treated with conservative management. Neoadjuvant chemotherapy was arranged in 13 cases. Adjuvant chemotherapy was administered for every patient. After a mean follow-up of (22 ± 10) months according to the finding time of liver metastases, recurrence and metastases were observed in 16 cases and 6 cases died of late-stage cachexia. The 1-, 2- and 3-overall survival rate were 94.4%, 85.3% and 75.8% respectively, and the 1-, 2- and 3-disease-free survival rate were 70.1%, 54.2% and 54.2% respectively. CONCLUSIONS: MDT mode for resectable CRCLM is recommendable. Surgical resection of CRCLM is feasible and safe, which seems to achieve favourable short-middle oncologic outcomes. And long-term survival is expected.

Alteration of gut microbiota and metabolomics in critically ill patients by sequential feeding: A pilot study.

BACKGROUND: Sequential feeding (SF) is a new feeding mode for critically ill patients that involves a combination of continuous feeding (CF) in the beginning, rhythmic feeding in the second stage, and oral feeding in the last stage. In this study, we investigated the influence of SF on gut microbiota and metabolomics in critically ill patients. METHODS: Stool specimens from 20 patients (10 patients with the SF group, 10 patients with the CF group) were collected for full-length 16S ribosomal RNA gene sequencing and untargeted metabolomics analysis. RESULTS: The proportion of patients with low bacterial diversity (Shannon index < 4) in the SF group was much lower than that in the CF group, but there was no significant difference in the proportions (20% vs 50%, P = .350). The abundances of Actinobacteria/Actinobacteria (at the phylum and class levels), Pseudomonadaceae/Pseudomonas (at the family and genus levels), and Fusobacteria/Fusobacteriaceae/Fusobacteriales/Fusobacteria/Fusobacterium (at the phylum, class, order, family, and genus levels) were all higher in the SF group than in the CF group. Actinobacteria/Actinobacteria (at the phylum and class levels) were the most influential of these gut flora. Retinoic acid and leucine were upregulated in the SF group and were respectively responsible for the intestinal immune network for immunoglobulin A production and the mammalian target of rapamycin signaling pathway in the enriched pathways according to the Kyoto Encyclopedia of Genes and Genomes database classification. CONCLUSIONS: SF could alter gut microbiota and metabolomics in critically ill patients. Because of the small sample size, further study is required.

The role of autophagy in idiopathic pulmonary fibrosis: from mechanisms to therapies.

Idiopathic pulmonary fibrosis (IPF) is an interstitial pulmonary disease with an extremely poor prognosis. Autophagy is a fundamental intracellular process involved in maintaining cellular homeostasis and regulating cell survival. Autophagy deficiency has been shown to play an important role in the progression of pulmonary fibrosis. This review focused on the six steps of autophagy, as well as the interplay between autophagy and other seven pulmonary fibrosis related mechanisms, which include extracellular matrix deposition, myofibroblast differentiation, epithelial-mesenchymal transition, pulmonary epithelial cell dysfunction, apoptosis, TGF-ß1 pathway, and the renin-angiotensin system. In addition, this review also summarized autophagy-related signaling pathways such as mTOR, MAPK, JAK2/STAT3 signaling, p65, and Keap1/Nrf2 signaling during the development of IPF. Furthermore, this review also illustrated the commonly used autophagy detection methods, the currently approved antifibrotic drugs pirfenidone and nintedanib, and several prospective compounds targeting autophagy for the treatment of IPF.