Outcomes and prognostic factors in initially unresectable hepatocellular carcinoma treated using conversion therapy with lenvatinib and TACE plus PD-1 inhibitors.

Purpose: To evaluate the outcomes and prognostic factors for patients using conversion therapy with lenvatinib combined with transcatheter arterial chemoembolization (TACE) plus programmed cell death protein-1 (PD-1) inhibitors (LTP) for initially unresectable hepatocellular carcinoma (iuHCC). Methods: Data on 94 consecutive patients with iuHCC who received LTP conversion therapy from November 2019 to September 2022 were retrospectively analyzed. Early tumor response was reported when patients showed complete or partial response at the time of their first follow-up (4-6 weeks) after initial treatment, in accordance with mRECIST. The endpoints consisted of conversion surgery rate, overall survival (OS), and progression-free survival (PFS). Results: Early tumor response was found in 68 patients (72.3%) and not in the remaining 26 patients (27.7%) in the entire cohort. Early responders had a significantly higher conversion surgery rate than non-early responders (44.1% vs. 7.7%, p=0.001). Early tumor response was the only factor independently associated with successful conversion resection, as indicated by multivariate analysis (OR=10.296; 95% CI: 2.076-51.063; p=0.004). Survival analysis showed that early responders had longer PFS (15.4 vs. 7.8 months, p=0.005) and OS (23.1 vs. 12.5 months, p=0.004) than non-early responders. Early responders who underwent conversion surgery also had significantly longer median PFS and OS (not reached, not reached) than those who did not (11.2 months, p=0.004; 19.4 months, p<0.001). In multivariate analyses, early tumor response was identified as an independent prognostic factor for longer OS (HR=0.404, 95% CI: 0.171-0.954; p=0.039). Successful conversion surgery was also an independent predictive factor for longer PFS (HR=0.248, 95% CI: 0.099-0.622; p=0.003) and OS (HR=0.147, 95% CI: 0.039-0.554; p=0.005). Conclusions: Early tumor response is an important predictive marker for successful conversion surgery and prolonged survival in patients with iuHCC treated using LTP conversion therapy. Conversion surgery is necessary to improve survival during conversion therapy, particularly for early responders.

Prognostic role of serum carcinoembryonic antigen in patients receiving liver resection for colorectal cancer liver metastasis: A meta-analysis.

BACKGROUND: Carcinoembryonic antigen (CEA) is a broad-spectrum tumor marker for differential diagnosis, monitoring, and response assessment of a variety of malignancies. AIM: To evaluate whether serum CEA could predict the prognosis in patients with colorectal cancer liver metastasis (CRCLM) before and after liver resection (LR). METHODS: PubMed, Embase, Cochrane, and Web of Science were systematically searched to retrieve literature, with a search cut-off date of February 27, 2023. Articles were strictly screened for inclusion according to pre-specified inclusion and exclusion criteria. Data were pooled and analyzed using Stata 16.0. RESULTS: This meta-analysis included 36 studies involving a total of 11143 CRCLM patients. The results showed that a high pre-LR serum CEA level was correlated with poor overall survival (OS) [hazard ratio (HR) = 1.61, 95% confidence interval (CI): 1.49-1.75, P < 0.001] and recurrence-free survival (HR = 1.27, 95%CI: 1.11-1.45, P < 0.001) in CRCLM patients. A high post-LR serum CEA level predicted poor OS (HR = 2.66, 95%CI: 2.10-3.38, P < 0.001). A comparison by treatment modality, analysis modality, patient source, and cutoff-value showed that overall, high preoperative and postoperative serum CEA levels remained correlated with a poor prognosis. CONCLUSION: This study concluded that high pre-LR and post-LR serum CEA levels were significantly correlated with a poor prognosis in CRCLM patients.

A novel risk factor of contrast associated acute kidney injury in patients after enhanced computed tomography: a retrospective study.

Background: Contrast associated acute kidney injury (CA-AKI) is a major cause of acute renal failure and the incidence of CA-AKI is still high in recent years. Risk stratification is traditionally based on glomerular filtration rate(GFR). Hence, the aim of this study was to explore the novel risk factors for CA-AKI after enhanced computed tomography (CT). Methods: A retrospective cohort study was conducted in 632 in-hospital patients undergoing enhanced CT. The patients were divided into CA-AKI and no-CA-AKI groups. For comparative analyses, we applied one-to-four cohorts of those two groups using propensity score-matching methods addressing the imbalances of age, gender, weight, and smoking. The baseline clinical and biochemical data were compared. Logistic regression analysis was employed to investigate the CA-AKI risk factors. The receiver operating characteristic (ROC) curve was adopted to test the value of RDW in predicting CA-AKI after enhanced CT. Results: 25 (3.96%) patients suffered from CA-AKI. Those subjects who developed CA-AKI had advanced age, severer renal functional injury, lower albumin, higher baseline RDW, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) than those without CA-AKI. It also exhibited more severe anemia including decreased hemoglobin and red blood cell count (all p < 0.05). The baseline RDW, albumin and PLR between the two groups were statistically significant different after PSM. Binary logistic regression analysis showed that baseline RDW, albumin and eGFR were correlated with CA-AKI after contrast-enhanced CT examination. The RDW exhibited moderated discrimination ability for predicting CA-AKI beyond eGFR, with an AUC of 0.803 (95% CI [0.702-0.90]) vs 0.765 (95% CI [0.70-0.83]). Conclusion: Increased baseline RDW and decreased eGFR are risk factors for CA-AKI after enhanced CT. RDW exhibited good predictive value and can be used as an early warning marker for patients suffering from CA-AKI after enhanced CT.

Novosphingobium arvoryzae sp. nov., isolated from a flooded rice field.

A bacterial strain, designated Jyi-02T, was isolated from a flooded rice field in Taiwan and characterized using the polyphasic taxonomy approach. Cells of strain Jyi-02T were aerobic, Gram-stain-negative, rod-shaped, non-motile and formed yellowish orange coloured colonies. Growth occurred at 10-40 °C (optimum, 20 °C) and pH 5.0-9.0 (optimum, pH 7.0) and in the presence of 0-1.0 % NaCl (optimum, 0 %, w/v). The major fatty acids (>10 %) of strain Jyi-02T were C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C14 : 0 2-OH. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, phosphatidyldimethylethanolamine, sphingoglycolipid, an uncharacterized phospholipid and an uncharacterized lipid. The major polyamine was spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content was 64.8 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Jyi-02T belonged to the genus Novosphingobium and had closest phylogenetic similarity to Novosphingobium soli CC-TPE-1T (97.8 %). The DNA-DNA relatedness of strain Jyi-02T with respect to valid published species of the genus Novosphingobium was less than 35 %. Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Novosphingobium. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain Jyi-02T represents a novel species in the genus Novosphingobium, for which the name Novosphingobium arvoryzae sp. nov. is proposed. The type strain is Jyi-02T (=BCRC 80537T=KCTC 32422T).

Novosphingobium ipomoeae sp. nov., isolated from a water convolvulus field.

A bacterial strain designated Tese-5T was isolated from a water convolvulus field in Taiwan and characterized using the polyphasic taxonomic approach. Strain Tese-5T was an aerobic, Gram-stain-negative, non-motile, rod-shaped bacterium and formed bright yellow coloured colonies. Strain Tese-5T grew at 15-35 °C (optimum, 30 °C), with 0-1.0 % NaCl (optimum, 0-0.5 %) and at pH 5.5-7 (optimum, pH 6). The major fatty acids (>10 %) of strain Tese-5T were C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The polar lipid profile comprised phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine and sphingoglycolipid. The major polyamine was spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content was 65.7 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Tese-5T belonged to the genus Novosphingobium and showed the highest levels of sequence similarity to Novosphingobium chloroacetimidivorans BUT-14T and Novosphingobium mathurense SM117T (96.3 %). Phenotypic characteristics of the novel strain also differed from those of the closest-related species of the genus Novosphingobium. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain Tese-5T represents a novel species in the genus Novosphingobium, for which the name Novosphingobium ipomoeaesp. nov. is proposed. The type strain is Tese-5T (=BCRC 80904T=LMG 28838T=KCTC 42656T).

Cellvibrio zantedeschiae sp. nov., isolated from the roots of Zantedeschia aethiopica.

A bacterial strain, designated TPY-10T, was isolated from calla lily roots in Taiwan and characterized by using a polyphasic taxonomy approach. Cells of strain TPY-10T were Gram-stain-negative, strictly aerobic, motile and creamy white rods. Growth occurred at 15-35 °C (optimum, 25-30 °C), at pH 6-7 (optimum, pH 6) and with 0-1 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TPY-10T belonged to the genus Cellvibrio and was most closely related to Cellvibriomixtus ACM 2601T with sequence similarity of 97.8 %. Strain TPY-10T contained C16 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C18 : 1ω7c as the predominant fatty acids. The only isoprenoid quinone was Q-9. The major polar lipids were phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content of the genomic DNA was 49.8 mol%. The DNA-DNA hybridization value for strain TPY-10T with Cellvibriomixtus ACM 2601T was less than 21 %. On the basis of the phylogenetic inference and phenotypic data, strain TPY-10T should be classified as a novel species, for which the name Cellvibrio zantedeschiae sp. nov. is proposed. The type strain is TPY-10T (=BCRC 80525T=LMG 27291T=KCTC 32239T).

Novosphingobium colocasiae sp. nov., isolated from a taro field.

A novel bacterial strain, designated Teta-03T, was isolated from a taro field in Taiwan and characterized using a polyphasic taxonomic approach. Cells of strain Teta-03T were aerobic, Gram-stain-negative, rod-shaped and non-motile and formed bright yellow colonies. Growth occurred at 10-37 °C (optimum, 20 °C), with 0-1.0 % (w/v) NaCl (optimum, 0 %) and at pH 3.0-9.0 (optimum, pH 7.0-8.0). The major fatty acids (>10 %) of strain Teta-03T were C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine, sphingoglycolipid, phosphatidylcholine, an uncharacterized glycolipid and an uncharacterized aminolipid. The major polyamine was spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content was 65.0 mol%. On the basis of 16S rRNA gene sequence analysis, strain Teta-03T was shown to belong to the genus Novosphingobium and showed highest similarity to Novosphingobium barchaimii LL02T (96.8 %). Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Novosphingobium. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain Teta-03T represents a novel species of the genus Novosphingobium, for which the name Novosphingobium colocasiae sp. nov. is proposed. The type strain is Teta-03T ( = LMG 27385T = KCTC 32255T).

Vogesella amnigena sp. nov., isolated from a freshwater river.

A bacterial strain, designated Npb-02T, was isolated from a freshwater river in Taiwan and characterized in a taxonomic study using a polyphasic approach. Cells of strain Npb-02T were Gram-stain-negative, aerobic, poly-ß-hydroxybutyrate-accumulating, rod-shaped and non-motile. Growth occurred at 15­40 °C (optimum 25­30 °C), at pH 7.0­8.0 (optimum pH 7.0) and with 0­1 % NaCl (optimum 0.5 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Npb-02T belonged to the genus Vogesella and was most closely related to Vogesella perlucida DS-28T with sequence similarity of 98.3 %. Strain Npb-02T contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0 as the major fatty acids. The major respiratory quinone was Q-8.The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an uncharacterized aminophospholipid and an uncharacterized phospholipid. The genomic DNA G+C content of strain Npb-02T was 64.1 mol%. The DNA­DNA hybridization values for strain Npb-02T with Vogesella perlucida DS-28T, Vogesella mureinivorans 389T and Vogesella lacus GR13T were less than 25 %. On the basis of phylogenetic inference and phenotypic data, strain Npb-02T represents a novel species of the genus Vogesella, for which the name Vogesella amnigena sp. nov. is proposed. The type strain is Npb-02T ( = BCRC 80887T = LMG 28419T = KCTC 42195T).

Autophagy-related gene 7 is downstream of heat shock protein 27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.

BACKGROUND: Autophagy and molecular chaperones both regulate protein homeostasis and maintain important physiological functions. Atg7 (autophagy-related gene 7) and Hsp27 (heat shock protein 27) are involved in the regulation of neurodegeneration and aging. However, the genetic connection between Atg7 and Hsp27 is not known. METHODS: The appearances of the fly eyes from the different genetic interactions with or without polyglutamine toxicity were examined by light microscopy and scanning electronic microscopy. Immunofluorescence was used to check the effect of Atg7 and Hsp27 knockdown on the formation of autophagosomes. The lifespan of altered expression of Hsp27 or Atg7 and that of the combination of the two different gene expression were measured. RESULTS: We used the Drosophila eye as a model system to examine the epistatic relationship between Hsp27 and Atg7. We found that both genes are involved in normal eye development, and that overexpression of Atg7 could eliminate the need for Hsp27 but Hsp27 could not rescue Atg7 deficient phenotypes. Using a polyglutamine toxicity assay (41Q) to model neurodegeneration, we showed that both Atg7 and Hsp27 can suppress weak, toxic effect by 41Q, and that overexpression of Atg7 improves the worsened mosaic eyes by the knockdown of Hsp27 under 41Q. We also showed that overexpression of Atg7 extends lifespan and the knockdown of Atg7 or Hsp27 by RNAi reduces lifespan. RNAi-knockdown of Atg7 expression can block the extended lifespan phenotype by Hsp27 overexpression, and overexpression of Atg7 can extend lifespan even under Hsp27 knockdown by RNAi. CONCLUSIONS: We propose that Atg7 acts downstream of Hsp27 in the regulation of eye morphology, polyglutamine toxicity, and lifespan in Drosophila.