Safety and efficacy of a programmed cell death 1 inhibitor combined with oxaliplatin plus S-1 in patients with Borrmann large type III and IV gastric cancers.

BACKGROUND: Gastric cancer (GC) is the fifth most common and the fourth most lethal malignant tumour in the world. Most patients are already in the advanced stage when they are diagnosed, which also leads to poor overall survival. The effect of postoperative adjuvant chemotherapy for advanced GC is unsatisfactory with a high rate of distant metastasis and local recurrence. AIM: To investigate the safety and efficacy of a programmed cell death 1 (PD-1) inhibitor combined with oxaliplatin and S-1 (SOX) in the treatment of Borrmann large type III and IV GCs. METHODS: A retrospective analysis (IRB-2022-371) was performed on 89 patients with Borrmann large type III and IV GCs who received neoadjuvant therapy (NAT) from January 2020 to December 2021. According to the different neoadjuvant treatment regimens, the patients were divided into the SOX group (61 patients) and the PD-1 + SOX (P-SOX) group (28 patients). RESULTS: The pathological response (tumor regression grade 0/1) in the P-SOX group was significantly higher than that in the SOX group (42.86% vs 18.03%, P = 0.013). The incidence of ypN0 in the P-SOX group was higher than that in the SOX group (39.29% vs 19.67%, P = 0.05). The use of PD-1 inhibitors was an independent factor affecting tumor regression grade. Meanwhile, the use of PD-1 did not increase postoperative complications or the adverse effects of NAT. CONCLUSION: A PD-1 inhibitor combined with SOX could significantly improve the rate of tumour regression during NAT for patients with Borrmann large type III and IV GCs.

Corrigendum: NanoSIMS analysis of water content in bridgmanite at the micron scale: an experimental approach to probe water in Earth's deep mantle.

[This corrects the article DOI: 10.3389/fchem.2023.1166593.].

NanoSIMS analysis of water content in bridgmanite at the micron scale: An experimental approach to probe water in Earth's deep mantle.

Water, in trace amounts, can greatly alter chemical and physical properties of mantle minerals and exert primary control on Earth's dynamics. Quantifying how water is retained and distributed in Earth's deep interior is essential to our understanding of Earth's origin and evolution. While directly sampling Earth's deep interior remains challenging, the experimental technique using laser-heated diamond anvil cell (LH-DAC) is likely the only method available to synthesize and recover analog specimens throughout Earth's lower mantle conditions. The recovered samples, however, are typically of micron sizes and require high spatial resolution to analyze their water abundance. Here we use nano-scale secondary ion mass spectrometry (NanoSIMS) to characterize water content in bridgmanite, the most abundant mineral in Earth's lower mantle. We have established two working standards of natural orthopyroxene that are likely suitable for calibrating water concentration in bridgmanite, i.e., A119(H2O) = 99 ± 13 µg/g (1SD) and A158(H2O) = 293 ± 23 µg/g (1SD). We find that matrix effect among orthopyroxene, olivine, and glass is less than 10%, while that between orthopyroxene and clinopyroxene can be up to 20%. Using our calibration, a bridgmanite synthesized by LH-DAC at 33 ± 1 GPa and 3,690 ± 120 K is measured to contain 1,099 ± 14 µg/g water, with partition coefficient of water between bridgmanite and silicate melt ∼0.025, providing the first measurement at such condition. Applying the unique analytical capability of NanoSIMS to minute samples recovered from LH-DAC opens a new window to probe water and other volatiles in Earth's deep mantle.

Ruthenium-catalyzed reductive amination of ketones with nitroarenes and nitriles.

The Ru(dppbsa)-catalyzed reductive amination of ketones with nitroarenes and nitriles using H2 as the environmentally benign hydrogen surrogate is developed in this study. Cross-experiments demonstrated that both reactions are initiated by the reduction of nitroarenes or nitriles to the corresponding amines, followed by condensation with ketones to give imines and thereafter hydrogenation. However, the route to the formation of an amino-ligated Ru complex during the reduction of nitroarenes or nitriles, followed by in situ nucleophilic C-N coupling, cannot be completely excluded. This newly developed versatile method features good functional group tolerance, which provides a novel design platform for homogeneous catalysts in constructing motifs of secondary amines.

Current treatments and outlook in adenocarcinoma of the esophagogastric junction: a narrative review.

Background and Objective: Adenocarcinoma of the esophagogastric junction (AEG) is a tumor of the esophagogastric junction (EGJ). Research has suggested that AEG may be an independent tumor because of its peculiar site and biological behavior. During the past several decades, the incidence of AEG has increased globally. Therefore, it is necessary to explore appropriate treatments for AEG. The aim of this review is to summarize the current treatments for AEG and forecast their future developments. Methods: We critically conducted a literature search in PubMed (from the inception of the database to October 31, 2021). The keywords used in the search were "adenocarcinoma of the esophagogastric junction", "gastroesophageal adenocarcinoma and surgical treatment", "gastroesophageal adenocarcinoma and target therapy", "gastroesophageal adenocarcinoma and neoadjuvant therapy" and "gastroesophageal adenocarcinoma and immunotherapy". Key Content and Findings: This study introduced the existing treatments for AEG from the aspects of surgical therapy, neoadjuvant therapy and targeted therapy, and prospected the future research direction. Conclusions: Treatments for AEG often have different plans (such as surgical treatment, neoadjuvant therapy, targeted therapy and immunotherapy) according to the pathological type of patients, the status of metastasis, and the conditions of patients. Surgical treatment is the most commonly used treatment in clinical practice. Minimally invasive surgery promising potential for further development. Targeted therapy and immunotherapy can improve the quality of life and survival of patients. Currently, some drugs, such as trastuzumab, ramucirumab, pembrolizumab, and nivolumab have been approved by the Food and Drug Administration (FDA) for clinical treatment of AEG. However, targeted therapy and immunotherapy still have a long way to go and need to be further explored.

Exosomal miR-590-5p in Serum as a Biomarker for the Diagnosis and Prognosis of Gastric Cancer.

The purpose of this study is to explore the expression of miRNA-590-5p, an exosome of gastric cancer (GC), and to evaluate the suitability of miR-590-5p, an exosome with its own clinical characteristics. Serum samples from 168 gastric cancer patients and 50 matched controls were collected and exosomal RNAs were extracted. After that, miR-590-5p is analyzed by quantitative polymerase chain reaction (qRT-PCR), which is more related to clinical and pathological parameters and patient monitoring data. MGC-803 and HGC-27 cells were treated by miR-590-5p mimics, and then the changes of cell fluidity and invasiveness were monitored. The results showed that the expression level of miR-590-5p in exosomes of healthy observation group, early (I and II) stage group, and late stage (III) group was 30.34 ± 6.35, 6.19 ± 0.81, and 2.9 ± 0.19, respectively (all p < 0.05). ROC (receiver-operating characteristic curve) showed that the AUC (area under the curve) of exosomal miR-590-5p was 0.810 with 63.7% sensitivity and 86% specificity. The expression of exosomal miR-590-5p in serum was related to clinical stage (p = 0.008), infiltration depth, and the expression level of ki-67 (p < 0.001). In addition, Kaplan-Meier analysis showed that the decrease of explicit level of exosomal miR-590-5p was related to the decrease of overall survival rate (p < 0.001). Cox regression analysis showed that miR-590-5p can be used as an independent predictor. Furthermore, upregulation of miR-590-5p inhibited cell migration and invasion in MGC-803 cells and HGC-27 cells. The serum expression level of exosomal miR-590-5p may be a biomarker, which is potentially useful and noninvasive for early detection and prediction of GC. In addition, miR-590-5p can play a role in eliminating carcinogens by actively regulating the malignant potential of gastric cancer.

Influence of polymorphisms in the Wnt/ß-catenin pathway genes on hepatocellular carcinoma risk in a Chinese Han population.

The Wnt/ß-catenin pathway plays a vital role in initiating and sustaining hepatocellular carcinoma (HCC). However, few studies have investigated polymorphisms in the Wnt/ß-catenin signaling pathway genes in the Chinese Han population. The aim of the present retrospective study was to investigate the correlations between polymorphisms of the Wnt/ß-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression.Twenty tagging single nucleotide polymorphisms were chosen from HapMap data and genotyped in 320 patients with HCC, 320 chronic hepatitis B virus (HBV)-infected patients without HCC (N-HCC, including 95 liver cirrhosis, 164 chronic hepatitis B, and 61 asymptomatic HBV carriers), and 320 healthy controls. Associations between polymorphisms in the 2 Wnt/ß-catenin signaling pathway genes (CTNNB1 and WNT2) and HCC susceptibility, development, and progression were investigated.Genotype AA (P = 0.002, odds ratio [OR] = 2.524) and allele A (P = 0.0003, OR = 1.613) of the WNT2 rs4730775 polymorphism were associated with HCC susceptibility compared with healthy controls. Genotype GA (P = 0.001, OR = 0.567) and allele A (P = 0.002, OR = 0.652) of rs3864004, and genotype AG (P = 0.0004, OR = 0.495) and allele G (P = 0.001, OR = 0.596) of rs11564475 in the CTNNB1 gene were correlated with HCC compared with N-HCC patients. These findings were consistent in dominant and recessive models. Multidimensionality reduction analysis revealed that interactions among rs3864004, rs11564475, and rs4730775 were significantly associated with HCC compared with N-HCC patients. The polymorphism rs4135385 of CTNNB1 genotype GA was associated with a higher risk for Stage III + IV HCC (modified Union for International Cancer Control) (P = 0.001, OR = 2.238).Genetic polymorphisms in the WNT2 and CTNNB1 genes were closely associated with HCC risk and progression in a Chinese Han population.

Lgr5 regulates the regeneration of lesioned nasal respiratory epithelium.

Nasal respiratory epithelium is a ciliated pseudostratified columnar epithelium. The cellular components of nasal respiratory epithelium include ciliated cells, goblet cells, and basal cells. Until now, our knowledge in the development of nasal respiratory epithelium is still limited and the cellular mechanism of regeneration is still elusive. In this study, we found that adult stem cell marker leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) is expressed in the mice nasal respiratory epithelium. Both immunostaining and lineage tracing analysis indicated Lgr5 positive cells in the nasal respiratory epithelium are proliferative stem/progenitor cells. Using the Rosa-Tdtomato and Rosa26-DTR mice, we elucidated that Lgr5+ cells participate in the regeneration of lesioned nasal respiratory epithelium, and this group of cells is necessary in the process of epithelium recovery. Using the in vitro culture system, we observed the formation of spheres from Lgr5+ cells and these spheres have the capacity to generate other types of cells. Above all, this study reported a group of previously unidentified progenitor/stem cells in nasal respiratory epithelium, unveiling the potential cellular mechanism in nasal respiratory epithelium regeneration.

[Study on the ecological risk of wild veined rapa whelk (Rapana venosa) exposured to organotin compounds in Bohai Bay, China].

The present study evaluated the potential ecological risk of organotin compounds (OTs) to wild veined rapa whelk (Rapana Venosa) population in Bohai Bay. The results showed that the imposex rate was 12.5% and 6.48% in Dashentang and Nanpaihe coastal areas, with relative penis size index of 9.61 and 12.45, respectively. The concentrations of butyltin compounds and phenyltin compounds were 39.04 ng x g(-1) dw and 46.48 ng x g(-1) dw in muscle tissues, and 32.09 ng x g(-1) dw and 109.03 ng x g(-1) dw in digest gland, respectively. Based on TBT levels in the muscles of all samples, a risk quotient of 0.024 was derived, indicating certain risk of OTs at current levels to wild veined rapa whelk populations in Bohai Bay.

[Characteristics of heavy metal pollution in Daninghe River and Modaoxi River of Three Gorges Reservoir areas].

In order to explore the potential ecological risk of heavy metals in Three Gorges Reservoir areas, the present study analyzed the heavy metals in sediments and wild crucain carp from Daning River and Modaoxi River which are two typical tributaries, and then the potential risk was evaluated using potential ecological risk index for sediments and comprehensive pollution index for fish, respectively. The results showed that concentrations of Zn and Cr were higher (Daning River: 78.31 and 83.98 mg x kg(-1); Modaoxi River: 99.03 and 94.20 mg x kg(-1)), while Cd was the lowest (Daning River: 0.62 mg x kg(-1); Modaoxi River: 0.75 mg x kg(-1)). Moreover, an obvious increasing trend of these elements was observed in these tributaries from upstream to downstream. For the wild crucain carp, the lowest concentrations of these elements were detected in muscles, and the highest concentrations were in the intestinal. However, no obvious increasing trend of these elements was observed from upstream to downstream. The potential ecological risk in sediments showed a high risk, while no risk was observed in fish.

Biomarker responses and genotoxicity in the mud snail (Bullacta exarata) as indicators of coastal contamination.

In the present study different biomarker responses and genotoxicity were determined in wild mud snails (Bullacta exarata) collected from 3 sampling sites in Bohai Bay in northeastern China, which is a region that is under considerable anthropogenic influence. Significant spatial variability of superoxide dismutase (SOD) and metallothionein (MT)-like proteins were recorded, while glutathione transferase (GST), catalase (CAT), and vitellin-like proteins (Vn's) were not observed. Furthermore, genomic DNA that was amplified with 4 fluorescence-labeled primer pairs showed variable genetic distances among the 3 wild mud snail populations found in Bohai Bay, which may be correlated with differences in the types of environmental genotoxicants, such as heavy metals and polycyclic aromatic hydrocarbons. This multi-biomarker approach provided an improved understanding of the potential toxicological impact of contaminated sediments on benthic organisms.

Combined use of D-dimer and P-selectin for the diagnosis of splenic or portal vein thrombosis following splenectomy.

To investigate the predictive value of combined use of D-dimer and P-selectin for splenic or portal vein thrombosis (SPVT) after splenectomy. A prospective study was carried out in 82 patients who had undergone splenectomy for portal hypertension secondary to hepatic cirrhosis. Plasma levels D-dimer and P-selectin were measured before and after the surgery.27 (30.1%) patients developed SPVT following the portal hypertension surgery. The post-operative D-dimer and P-selectin levels in patients with SPVT were significantly higher than in those without PVT (n=55, P<0.01). The receiver-operated characteristics curves (ROC) of D-dimer and P-selectin showed a significant predictive value in SPVT (D-dimer, Az=0.880, P<0.01; P-slectin, Az=0.933, P<0.01). The sensitivity and specificity of D-dimer (>500 microg/mL) in diagnosing SPVT were 88.9% and 78.2% respectively. P-selectin >90ng/mL had an 85.2% sensitivity and 85.5% specificity for SPVT. The combination of the D-dimer and P-selectin criteria yielded an 82.0% sensitivity and 97.6% specificity for SPVT. In Conclusion, there was a significant elevation in plasma D-dimer and P-selectin in patients with post-operative SPVT. A combination of plasma D-dimer and P-selectin may be used as biomarkers to screen or diagnose SPVT following splenectomy.

Reduction of cerebrospinal fluid and plasma serotonin in patients with post-stroke depression: A preliminary report.

OBJECTIVE: To investigate the plasma and cerebrospinal fluid (CSF) concentrations of serotonin in patients with post-stroke depression (PSD). METHODS: Serotonin was measured in 30 PSD patients and 30 controls on day 15 and day 30 following stroke. RESULT: There was a good correlation between the plasma and the CSF serotonin concentrations in both PSD (r = 0.641, P = 0.001) and control patients (0.852, P = 0.001) 30 days following the stroke. The average plasma and CSF serotonin concentrations in the PSD patients were lower than in the control group on day 15 (CSF: 0.24+/-0.27 vs 0.82+/-0.48 micromol/L, P < 0.01; plasma, 0.32+/-0.25 vs 0.83+/-0.45micromol/L, P < 0.01) and day 30 (CSF: 0.29+/-0.23 vs 0.78+/-0.47 micromol/L, P < 0.01; plasma, 0.31+/-0.33 vs 0.89+/-0.67 micromol/L, P < 0.01). Reduction of plasma serotonin was found in 90.0% of the PSD group and 13.3% of the control group patients (P < 0.01). Reduction in CSF serotonin in the PSD and control group was 80.0% and 6.7% respectively (P < 0.01%). CONCLUSION: Plasma serotonin levels may be used to represent the CSF serotonin levels in depressed and non-depressed patients following stroke. There is a reduction in the plasma or CSF serotonin concentrations in patients with PSD. Serotonin deficiency may be one of the factors leading to depression following stroke.