Hepatitis B: Model Systems and Therapeutic Approaches.

Hepatitis B virus (HBV) infection is a major global health issue and ranks among the top causes of liver cirrhosis and hepatocellular carcinoma. Although current antiviral medications, including nucleot(s)ide analogs and interferons, could inhibit the replication of HBV and alleviate the disease, HBV cannot be fully eradicated. The development of cellular and animal models for HBV infection plays an important role in exploring effective anti-HBV medicine. During the past decades, advancements in several cell culture systems, such as HepG2.2.15, HepAD38, HepaRG, hepatocyte-like cells, and primary human hepatocytes, have propelled the research in inhibiting HBV replication and expression and thus enriched our comprehension of the viral life cycle and enhancing antiviral drug evaluation efficacy. Mouse models, in particular, have emerged as the most extensively studied HBV animal models. Additionally, the present landscape of HBV therapeutics research now encompasses a comprehensive assessment of the virus's life cycle, targeting numerous facets and employing a variety of immunomodulatory approaches, including entry inhibitors, strategies aimed at cccDNA, RNA interference technologies, toll-like receptor agonists, and, notably, traditional Chinese medicine (TCM). This review describes the attributes and limitations of existing HBV model systems and surveys novel advancements in HBV treatment modalities, which will offer deeper insights toward discovering potentially efficacious pharmaceutical interventions.

Specific deletion of Mettl3 in IECs triggers the development of spontaneous colitis and dysbiosis of T lymphocytes in mice.

The enzymatic core component of m6A writer complex, Mettl3, plays a crucial role in facilitating the development and progress in gastric and colorectal cancer (CRC). However, its underlying mechanism in regulating intestinal inflammation remains unclear and poorly investigated. Firstly, the characteristics of Mettl3 expression in IBD patients were examined. Afterwards we generated the mice line with IECs-specific deletion of Mettl3 verified by various experiments. We continuously recorded and compared the physiological status including survival rate etc. between the two groups. Subsequently, we took advantage of staining assays to analyze mucosal damage and immune infiltration of Mettl3WT and Mettl3KO primary IECs. Bulk RNA sequencing was used to pursuit the differential expression of genes (DEGs) and associated signaling pathways after losing Mettl3. Pyroptosis-related proteins were to determine whether cell death was caused by pyroptosis. Eventually, CyTOF was performed to probe the difference of CD45+ cells, especially CD3e+ T cells clusters after losing Mettl3. In IBD patients, Mettl3 was highly expressed in the inner-nucleus of IECs while significantly decreased upon acute intestinal inflammation. IECs-specific deletion of Mettl3 KO mice triggered a wasting phenotype and developed spontaneous colitis. The survival rate, body weight and intestinal length observed from 2 to 8-week of Mettl3KO mice was significantly lower than Mettl3WT mice. The degree of mucosal damage and immune infiltration in Mettl3KO were even more serious than their WT littermate. Bulk RNA sequencing demonstrated that DEGs were dramatically enriched in NOD-signaling pathways due to the loss of Mettl3. The colonic epithelium were more prone to pyroptosis after losing Mettl3. Subsequently, CyTOF revealed that T cells have altered significantly in Mettl3KO. Furthermore, there were abnormal proliferation of CD4+ T and markedly exhaustion of CD8+ T in Mettl3KO mice. In severe IBD patients, Mettl3 located in the inner-nucleus of IECs and declined when intestinal inflammation occurred. Subsequently, Mettl3 prevented mice from developing colitis.

Bushen Formula promotes the decrease of HBsAg levels in patients with CHB by regulating Tfh cells and B-cell subsets.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Formula (BSF) is the effective traditional Chinese medicine (TCM) for chronic hepatitis B (CHB) according to our previous researches. However, the special effectiveness of BSF treating CHB patients in different stages and the immunoregulatory mechanisms remain to be explored. AIM OF THE STUDY: To compare the therapeutic effects of BSF in both treatment-naive patients and Peg-IFN-α-treated patients, and explore the potential mechanism of immunomodulation. MATERIALS AND METHODS: Ultra-high performance liquid chromatography-quadrupole electrostatic field-orbital trap high resolution mass spectrometry and the TCMSP database were used to determine the main components of BSF. Two hundred and sixty-six patients were enrolled in the retrospective study, and they were divided into the treatment group (T-Group, BSF plus Peg-IFN-α) and the control group (C-Group, Peg-IFN-α monotherapy). Within each group, patients were further grouped into subgroups, namely T1/C1 groups (treatment-naive patients, T1 = 34, C1 = 94) and T2/C2 groups (Peg-IFN-α-treated patients, T2 = 56, C2 = 82). Serum HBV markers, serum HBV DNA levels, serum ALT/AST and TCM symptoms were obtained from the record. Bioinformatics analysis was employed to obtain the potential immunoregulatory mechanisms of BSF treating CHB patients. Among patients in T2 and C2 group, peripheral mononuclear cells from 36 patients were used to analyze the characteristics of peripheral follicular helper T (Tfh) cells and B-cell subtypes by flow cytometry. Preparation of BSF-containing serum in rats. In vitro, the co-culture system of CXCR5+ cells and HepG2.2.15 cells was built to investigate the immunoregulatory effects of BSF. RESULTS: A total of 14 main active compounds were detected in BSF, which were deemed critical for the treatment of CHB. Our findings indicated that the T2-Group exhibited the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the C2-Group (35.7% vs. 15.9%, P = 0.033; 33.9% vs. 11.0%, P = 0.002). Additionally, the T2-Group demonstrated the higher percentage of HBsAg decline ≥ 1-log10 IU/ml and rate of HBeAg seroclearance compared to the T1-Group (35.7% vs. 14.7%, P = 0.031; 33.9% vs. 2.9%, P = 0.000). The total effective rate based on TCM clinical syndrome in T1-Group and T2-Group were significantly greater than those in C1-Group and C2-Group (85.3% vs. 61.7%, P = 0.012; 89.1% vs. 63.4%, P = 0.000). Bioinformatics analysis indicated that the immunoregulatory mechanisms of BSF treating CHB patients were mainly linked to the growth and stimulation of B-cell, T-cell differentiation, and the signaling pathway of the B-cell receptor. Furthermore, the frequencies of Tfh cells and its IL-21 level, and the IL-21R expressed by B-cell were all increased after BSF treatment. Additionally, in the co-culture system of CXCR5+ cells and HepG2.2.15 cells, HBsAg and HBeAg levels were decreased after BSF-containing serum treatment，as well as the up-regulating of Tfh cell frequencies and down-regulating of B-cell frequencies. CONCLUSIONS: BSF have the higher percentage of HBsAg decline and HBeAg seroclearance in Peg-IFN-α-treated patients compared with treatment-naive patients. The potential immunoregulatory mechanism may correlate with promoting the interaction between Tfh cells and B-cell through IL-21/IL-21R signaling pathway.

Intestinal Epithelial Cell-specific Knockout of METTL3 Aggravates Intestinal Inflammation in CLP Mice by Weakening the Intestinal Barrier.

BACKGROUND: Many studies have demonstrated that the expression of methyltransferase- like 3 (METTL3) is altered in various inflammatory diseases. Its specific mechanistic role in the intestinal inflammatory response during sepsis remains limited and requires further investigation. OBJECTIVES: Explore the potential mechanism of METTL3 in the intestinal inflammatory response during sepsis. MATERIALS AND METHODS: Immunohistochemical analysis was utilized to detect the expression of METTL3 in the necrotic intestine of patients with intestinal necrosis and the small intestine of cecal ligation and puncture (CLP) mice. Mice were subjected to the CLP and Sham surgeries, intestine tissue was harvested and performed HE staining, and ELISA to examine intestinal inflammatory responses, while TUNEL staining was applied to detect intestinal cell apoptosis. Additionally, ELISA was used to detect diamine oxidase (DAO) and intestinal fatty acid binding protein (I-FABP) levels in intestinal tissue. Immunohistochemistry and RT-qPCR were also employed to examine the mRNA and protein expression levels of Zona Occludens 1 (ZO-1) and Claudin-1. Finally, transcriptomic sequencing was performed on the small intestine tissues of METTL3 Knock-out (KO) and Wild-type (WT) mice in response to sepsis. RESULTS: METTL3 exhibited lower expression level in the necrotic intestine of patients and the small intestine of CLP mice. Loss of METTL3 in CLP mice triggered significantly higher expression of TNF-α and IL-18, down-regulated expression of ZO-1 and claudin-1, and decreased expression of DAO and I-FABP in the intestinal tissue. KEGG enrichment analysis showed that the differential genes were significantly enriched in immune-related pathways. CONCLUSION: This study reveals a novel mechanism responsible for exacerbated intestinal inflammation orchestrated by METTL3. Particularly, METTL3 null mice displayed decreased ZO- 1 and Claudin-1 expression, which largely hampered intestinal epithelial barrier function, resulting in bacterial and toxin translocation and intestinal immune activation and inflammation against sepsis.

Molecular mechanism of resveratrol promoting differentiation of preosteoblastic MC3T3-E1 cells based on network pharmacology and experimental validation.

The purpose of this study was to investigate the mechanism by which resveratrol (Res) inhibits apoptosis and promotes proliferation and differentiation of pre-osteoblastic MC3T3-E1 cells, laying the groundwork for the treatment of osteoporosis (OP). The TCMSP database was used to find the gene targets for Res. The GeneCards database acquire the gene targets for OP. After discovering the potential target genes, GO, KEGG, and Reactome enrichment analysis were conducted. Verifying the major proteins involved in apoptosis can bind to Res using molecular docking. CCK8 measured the proliferative activity of mouse pre-osteoblasts in every group following Res intervention. Alkaline phosphatase staining (ALP) and alizarin red staining to measure the ability of osteogenic differentiation. RT-qPCR to determine the expression levels of Runx2 and OPG genes for osteogenic differentiation ability of cells. Western blot to measure the degree of apoptosis-related protein activity in each group following Res intervention. The biological processes investigated for GO of Res therapeutic OP involved in cytokine-mediated signaling pathway, negative regulation of apoptotic process, Aging, extrinsic apoptotic signaling pathway in absence of ligand, according to potential therapeutic target enrichment study. Apoptosis, FoxO signaling pathway, and TNF signaling pathway are the primary KEGG signaling pathways. Recactome pathways are primarily engaged in Programmed Cell Death, Apoptosis, Intrinsic Apoptotic Pathway, and Caspase activation via extrinsic apoptotic signaling pathways. This research established a new approach for Res treatment of OP by demonstrating how Res controls the apoptosis-related proteins TNF, IL6, and CASP3 to suppress osteoblast death and increase osteoclastogenesis.

Global freshwater fish invasion linked to the presence of closely related species.

In the Anthropocene, non-native freshwater fish introductions and translocations have occurred extensively worldwide. However, their global distribution patterns and the factors influencing their establishment remain poorly understood. We analyze a comprehensive database of 14953 freshwater fish species across 3119 river basins and identify global hotspots for exotic and translocated non-native fishes. We show that both types of non-native fishes are more likely to occur when closely related to native fishes. This finding is consistent across measures of phylogenetic relatedness, biogeographical realms, and highly invaded countries, even after accounting for the influence of native diversity. This contradicts Darwin's naturalization hypothesis, suggesting that the presence of close relatives more often signifies suitable habitats than intensified competition, predicting the establishment of non-native fish species. Our study provides a comprehensive assessment of global non-native freshwater fish patterns and their phylogenetic correlates, laying the groundwork for understanding and predicting future fish invasions in freshwater ecosystems.

Shenge Formula attenuates high-fat diet-induced obesity and fatty liver via inhibiting ACOX1.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease worldwide. Shenge Formula (SGF) is a traditional Chinese medicine that has been used in the clinical treatment of NAFLD, and its therapeutic potential in patients and NAFLD animal models has been demonstrated in numerous studies. However, its underlying mechanism for treating NAFLD remains unclear. PURPOSE: The aim of this study was to investigate the mechanism of SGF in the treatment of NAFLD using the proteomics strategy. METHODS: Ultra-high performance liquid chromatography-mass spectrometry (UPLC-MS) was used to determine the main components of SGF. A mouse model of nonalcoholic fatty liver disease was constructed by feeding mice with a high-fat diet for 16 weeks. SGF was administered for an additional 8 weeks, and metformin was used as a positive control. Liver sections were subjected to histopathological assessments. LC-MS/MS was used for the label-free quantitative proteomic analysis of liver tissues. Candidate proteins and pathways were validated both in vivo and in vitro through qRT-PCR, western blot, and immunohistochemistry. The functions of the validated pathways were further investigated using the inhibition strategy. RESULTS: Thirty-nine ingredients were identified in SGF extracts, which were considered to be key compounds in the treatment of NAFLD. SGF administration attenuated obesity and fatty liver by reducing the body weight and liver weight in HFD-fed mice. It also relieved HFD-induced insulin resistance. More importantly, hepatic steatosis was significantly attenuated by SGF administration both in vivo and in vitro. Proteomic profiling of mouse liver tissues identified 184 differential expressed proteins (DEPs) associated with SGF treatment. Bioinformatic analysis of DEPs revealed that regulating the lipid metabolism and energy consumption process of hepatocytes was the main role of SGF in NAFLD treatment. This also indicated that ACOX1 might be the potential target of SGF, which was subsequently verified both in vitro and in vivo. The results demonstrated that SGF inhibited ACOX1 activity, thereby activating PPARα and upregulating CPT1A expression. Increased CPT1A expression promoted mitochondrial ß-oxidation, leading to reduced lipid accumulation in hepatocytes. CONCLUSIONS: Overall, our findings confirmed the protective effect of SGF against NAFLD and revealed the underlying molecular mechanism of regulating lipid metabolism.

Two genes encoded by mulberry crinkle leaf virus (MCLV): The V4 gene enhances viral replication, and the V5 gene is needed for MCLV infection in Nicotiana benthamiana.

Mulberry crinkle leaf virus (MCLV) is a member of the genus Mulcrilevirus, family Geminiviridae. The expression and functions of the V4 and V5 genes encoded by the MCLV genome remain unknown. Here, we confirmed the expression of V4 and V5 by analyzing the V4 and V5 mRNAs and the promoter activity of individual ORFs upstream sequences. The functions of V4 and V5 were investigated by constructing Agrobacterium-mediated infectious clones of wild-type MCLV variant П (MCLV vII), MCLVwt and MCLV vП mutants, such as MCLVmV4 (start codon of V4 ORF mutated), MCLVdV4 (5'-end partial deletion of V4 ORF sequence) and MCLVmV5 (V5 ORF start codon mutated). Although MCLVwt, MCLVmV4, and MCLVdV4 could infect natural host mulberry and experimental tomato plants systematically, the replication of the MCLVmV4 and MCLVdV4 genomes was obviously reduced compared to MCLVwt in both mulberry and tomato plants. MCLV vП expressing V5 could infect Nicotiana benthamiana plants systematically, but MCLVmV5 could not, implying that V5 is needed for MCLV vП to infect N. benthamiana plants. Taken together, V4 is involved in replication of the MCLV genome in host plants, and V5 potentially might extend the host range. Our findings lay a foundation for in-depth insight into the functions of MCLV-encoded proteins and provide a novel perspective for the subsequent study of MCLV-host plant interactions.

Integrating bulk and single-cell RNA sequencing data to establish necroptosis-related lncRNA risk model and analyze the immune microenvironment in hepatocellular carcinoma.

Background: The increasing evidence suggests that necroptosis mediates many behaviors of tumors, as well as the regulation of the tumor microenvironment. Long non-coding RNAs (lncRNAs) are involved in a variety of regulatory processes during tumor development and are significantly associated with patient prognosis. It suggests that necroptosis-related lncRNAs (NRlncRNAs) may serve as biomarkers for the prognosis of hepatocellular carcinoma (HCC). Methods: lncRNA expression profiles of HCC were obtained from TCGA database. LncRNAs associated with necroptosis were extracted using correlation analysis. Prognostic models were constructed based on least absolute shrinkage and selection operator algorithm (LASSO) and multivariate Cox regression analysis. The differences of tumor microenvironment between high-risk and low-risk groups were further analyzed. Single-cell RNA sequencing data of HCC was performed to assess the enrichment of necroptosis-related genes in immune cell subsets. Finally, real-time RT-PCR was used to detect the prognosis-related lncRNAs expression in different HCC cell lines. Results: We constructed a prognostic signature based on 8 NRlncRNAs, which also showed good predictive accuracy. The model showed that the prognosis of patients with high-risk score was significantly worse than that of patients with low-risk score (P < 0.05). Combined with the clinical characteristics and risk score of HCC, Nomogram was drawn for reference in clinical practice. In addition, immune cell infiltration analysis and single cell RNA sequencing analysis showed that a low level of immune infiltration was observed in patients at high risk and that there was a significant correlation between NRlncRNAs and macrophages. The results of RT-qPCR also showed that 8 necroptosis-related lncRNAs were highly expressed in HCC cell lines and human liver cancer tissues. Conclusion: This prognostic signature based on the necroptosis-related lncRNAs may provide meaningful clinical insights for the prognosis and immunotherapy responses in patients with HCC.

circ_0000337 Promotes the Progression of Cervical Cancer by miR-155-5p/RAB3B Axis.

Current study aims to investigate the biological function of circular RNA (circRNA, circ_0000337) in cervical cancer (CC). Bioinformatic analyses were used to predict targets for circ_0000337 and miR-155-5p, and analyze the gene expression differences between cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tissues and normal tissues. Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot were applied to assess mRNA and protein expressions of circ_0000337, microRNA-155-5p (miR-155-5p) and member RAS oncogene family (RAB3B), respectively. Following the establishment of gain/loss-of-function models, CCK-8 was performed to evaluate cell proliferation. Bioinformatics analysis, dual-luciferase reporter assay and RNA immunoprecipitation (RIP) were used to identify the interaction in circ_0000337, miR-155-5p, and RAB3B. Circ_0000337 and RAB3B were upregulated, while miR-155-5p was downregulated in CC tissues and cell lines. circ_0000337 overexpression promoted cell proliferation, circ_0000337 knock down inhibited cell proliferation by sponging miR-155-5p. RAB3B was a target of miR-155-5p which was positively regulated by circ_0000337. In the collected CC tissues, there was a negative correlation between miR-155-5p and circ_0000337 or RAB3B, and a positive correlation between circ_0000337 and RAB3B. miR-155-5p was positively, while RAB3B was negatively correlated with OS in patients with CC, and they were negatively correlated. In conclusion, circ_0000337 upregulates RAB3B by sponging miR-155-5p to promote CC cell proliferation.

Comparison of the two surgery methods combined with accelerated rehabilitation in the treatment of lateral compression type 1 pelvic fractures in the elderly.

BACKGROUND: Treating lateral compression type 1 (LC1) pelvic ring injuries in older patients is controversial. This study evaluated surgical treatments combined with ERAS for treating LC1 pelvic fractures in the elderly. METHODS: In this retrospective study, patients who underwent surgery with INFIX (supra-acetabular spinal pedicle screws, and a subcutaneous connecting rod; the experimental group) or superior pubic ramus cannulated screw (the control group) fixation of LC1 pelvic fracture from January 2019 to January 2022 were reviewed. Injury radiography and computed tomography were performed to determine the Young-Burgess classification. All patients performed standardized early rehabilitation exercises after surgery and were followed up for > 12 months. After surgery, the Matta score and the visual analog scale (VAS) were evaluated, and the postoperative weight-bearing time and the length of stay (LOS) were recorded. The Barthel index and the Majeed score were evaluated at 4 months after surgery and at the last follow-up. RESULTS: Fifty-three patients were included. Thirty-two patients included in the experimental group had a mean age of 75.0 ± 6.2 (range, 66-86) years, and the other 21 patients in the control group had a mean age of 74.6 ± 4.6 (range, 68-83) years. The mean follow-up time was 13.1 ± 1.6 (range, 12-18) months in the experimental group and 13.4 ± 1.3 (range, 12-16) months in the control group. There were no significant differences in follow-up time between the groups (P > 0.05). The mean VAS score, time to weight-bearing, and LOS were 2.0 ± 0.7 (range, 1-3), 1.1 ± 0.3 (range, 1-2) d, and 5.8 ± 0.9 (range, 4-7) d in the experimental group and 2.3 ± 1.2 (range, 1-5), 2.5 ± 1.6 (range, 1-7) d, and 6.1 ± 1.6 (range, 5-11) d in the control group, respectively. Between the two groups, there was a significant difference in the postoperative time to weight-bearing (P < 0.05), while there was no significant difference in the LOS (P > 0.05). No bedrest-related complications occurred in either group. The Matta score was 90.6% in the experimental group and 90.4% in the control group (P > 0.05). At the 4-months follow-up, the experimental group had a better Barthel index and Majeed score compared with the control group, which were 86.1 ± 6.2 (range, 70-95) vs. 81.2 ± 4.1 (range, 75-90) and 86.3 ± 3.3 (range, 78-91) vs. 80.3 ± 3.9 (range, 76-86), respectively. The experimental group had better early rehabilitation effect than the control group. There was no significant difference in Barthel index and Majeed score between the two groups at the last follow-up (P > 0.05). CONCLUSION: Both INFIX and intramedullary superior pubic ramus cannulated screws can successfully treat LC1 pelvic fractures and reduce bed rest complications among older patients.

Association between sarcopenia with incident cardio-cerebrovascular disease: A systematic review and meta-analysis.

Sarcopenia is an age-associated skeletal muscle disease characterized by the progressive loss of muscle mass and function. The objective of this systematic review and meta-analysis was to evaluate the associations between sarcopenia and cardio-cerebrovascular disease (CCVD). A comprehensive search of the PubMed/Medline, Embase, Web of Science, Scopus, and Cochrane Library databases was conducted from their inception to April 1st, 2023. A total of eight cross-sectional studies involving 63,738,162 participants met the inclusion criteria. Pooled estimates of odds ratios (ORs) were calculated using random-effects models. The findings demonstrated a significant association between sarcopenia and an increased risk of CCVD (OR: 1.33, 95% CI: 1.18 - 1.50, I2 = 1%; p < 0.001). Subgroup analyses indicated that sarcopenia was associated with a 1.67-fold increase in the risk of stroke and a 1.31-fold increase in the risk of CVD. Four studies included in this review examined the association between sarcopenic obesity and the risk of CCVD, and the results revealed that sarcopenic obesity was associated with a higher risk of CCVD (OR: 1.64, 95% CI: 1.08 - 2.49, I2 = 69%; p < 0.001). Meta-regressions and sensitivity analyses consistently supported the robustness of the overall findings. In conclusion, sarcopenia and sarcopenic obesity are significantly associated with an elevated risk of developing CCVD. However, further prospective cohort studies are warranted to validate this relationship while controlling for confounding factors.

PM2.5 and its respiratory tract depositions on blood pressure, anxiety, depression and health risk assessment: A mechanistic study based on urinary metabolome.

Effects of fine particulate matter (PM2.5) and regional respiratory tract depositions on blood pressure (BP), anxiety, depression, health risk and the underlying mechanisms need further investigations. A repeated-measures panel investigation among 40 healthy young adults in Hefei, China was performed to explore the acute impacts of PM2.5 exposure and its deposition doses in 3 regions of respiratory tract over diverse lag times on BP, anxiety, depression, health risk, and the potential mechanisms. We collected PM2.5 concentrations, its deposition doses, BP, the Self-Rating Anxiety Scale (SAS) score and the Self-Rating Depression Scale (SDS) score. An untargeted metabolomics approach was used to detect significant urine metabolites, and the health risk assessment model was used to evaluate the non-carcinogenic risks associated with PM2.5. We applied linear mixed-effects models to assess the relationships of PM2.5 with the aforementioned health indicators We further evaluate the non-carcinogenic risks associated with PM2.5. We found deposited PM2.5 dose in the head accounted for a large proportion. PM2.5 and its three depositions exposures at a specific lag day was significantly related to increased BP levels and higher SAS and SDS scores. Metabolomics analysis showed significant alterations in urinary metabolites (i.e., glucoses, lipids and amino acids) after PM2.5 exposure, simultaneously accompanied by activation of the cAMP signaling pathway. Health risk assessment presented that the risk values for the residents in Hefei were greater than the lower limits of non-cancer risk guidelines. This real-world investigation suggested that acute PM2.5 and its depositions exposures may increase health risks by elevating BP, inducing anxiety and depression, and altering urinary metabolomic profile via activating the cAMP signaling pathway. And the further health risk assessment indicated that there are potential non-carcinogenic risks of PM2.5 via the inhalation route in this area.

Survival and complications after neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy for locally advanced gastric cancer: a systematic review and meta-analysis.

Background: There is increasing evidence that neoadjuvant chemoradiotherapy is superior to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. However, a number of studies have come to the opposite conclusion. Therefore, our meta-analysis is to evaluate the efficacy and safety of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy in the treatment of locally advanced gastric cancer. Methods: We searched Wanfang Database, China National Knowledge Network database, VIP database, China Biomedical Literature Database, PubMed, Embase and Cochrane Library. The searched terms included'Stomach Neoplasms', 'Neoadjuvant Therapy' and 'Chemoradiotherapy'. The retrieval time was from the establishment of the corresponding database to September 2022, and our meta-analysis was performed using RevMan (version 5.3) and Stata (version 17) software. Results: A total of 17 literatures were included, which involved 7 randomized controlled trials and 10 retrospective studies, with a total of 6831 patients. The results of meta-analysis showed that compared with NACT group, the complete response rate(RR=1.95, 95%CI 1.39-2.73, p=0.0001), the partial response rate(RR=1.44, 95%CI 1.22-1.71, p=0.0001), the objective response rate(RR=1.37, 95%CI 1.27-1.54, p=0.00001), the pathologic complete response rate(RR=3.39, 95%CI 2.17-5.30, p=0.00001), the R0 resection rate(RR=1.18, 95%CI 1.09-1.29, p=0.0001) and 3-year overall survival rate(HR=0.89, 95%CI 0.82-0.96, p=0.002) of neoadjuvant chemoradiotherapy group were significantly improved. The results of subgroup analyses of gastric cancer subgroup and gastroesophageal junction cancer subgroup were consistent with the overall results. Meanwhile, the stable disease(RR=0.59, 95%CI:0.44-0.81, P=0.0010) of neoadjuvant chemoradiotherapy group was lower than that of neoadjuvant chemotherapy group, and there were no statistical significance in the progressive disease rate(RR=0.57, 95%CI:0.31-1.03, P=0.06), five-year overall survival rate(HR=1.03, 95%CI:0.99-1.07, P=0.839), postoperative complications and adverse reactions between the neoadjuvant chemoradiotherapy group and neoadjuvant chemotherapy group. Conclusion: Compared with neoadjuvant chemotherapy, neoadjuvant chemoradiotherapy might bring more survival benefits without significantly increasing adverse reactions. neoadjuvant chemoradiotherapy may be a recommended treatment for patients with locally advanced gastric cancer. Systematic Review Registration: https://inplasy.com/inplasy-2022-12-0068/, identifier INPLASY202212068.

Circadian aspects of mortality in hospitalized patients: A retrospective observation from a large cohort.

AIM: This study aimed to describe the circadian characteristics of hospitalized mortality in order to provide nursing guidance for preventing in-hospital mortality. DESIGN: A retrospective analysis on inpatient information was implemented. METHODS: Harmonic Analysis of Time Series was applied to quantify the periodic structure of the frequency of the occurrence of death. RESULTS: A total of 3300 cases were included in the present study (male, 63.4% and median age 73 years), including 1540 (46.7%) ICU patients. Incidence of overall hospitalized death exhibited a circadian pattern, presenting peaks from 07:00 to 12:00 and 15:00 to 20:00 P.M., with 21.5% and 13.1% increase above the average at those peak points, respectively. Similarly, the incidence of sudden cardiac death (SCD) showed peaks between 06:00-12:00 and 15:00-20:00, with a 34.7% and 28.0% increase above the average at peak time, respectively. The distribution of death incidence revealed no statistical difference between SCD and non-SCD (p = 0.525).

Biotic resistance to fish invasions in southern China: Evidence from biomass, habitat, and fertility limitation.

Understanding the mechanisms underlying the invasion success or failure of alien species can help to predict future invasions and cope with the invaders. The biotic resistance hypothesis posits that diverse communities are more resistant to invasion. While many studies have examined this hypothesis, the majority of them have focused on the relationship between alien and native species richness in plant communities, and results have often been inconsistent. In southern China, many rivers have been invaded by alien fish species, providing an opportunity to test the resistance of native fish communities to alien fish invasions. Using survey data for 60,155 freshwater fish collected from five main rivers of southern China for 3 years, we assessed the relationships between native fish richness and the richness and biomass of alien fishes at river and reach spatial scales, respectively. Based on two manipulative experiments, we further examined the impact of native fish richness on habitat selection and the reproductive ability of an exotic model species Coptodon zillii. We found no apparent relationship between alien and native fish richness, whereas the biomass of alien fish significantly decreased with increasing native fish richness. In experiments, C. zillii preferred to invade those habitats that had low native fish richness, given evenly distributed food resources; reproduction of C. zillii was strongly depressed by a native carnivorous fish Channa maculata. Together, our results indicate that native fish diversity can continue to provide biotic resistance to alien fish species in terms of limiting their growth, habitat selection, and reproduction when these aliens have successfully invaded southern China. We thus advocate for fish biodiversity conservation, especially for key species, to mitigate against the population development and ecological impact of alien fish species.

Incidence and outcomes of acute kidney disease in patients after type A aortic dissection surgery.

BACKGROUND: Acute kidney injury (AKI), acute kidney disease (AKD) and CKD (chronic kidney disease) were a continuous process. There has been little discussion of risk factors for AKD in the population undergoing surgery for acute type A aortic dissection (AAAD). OBJECTIVE: The main objective of this study was to investigate the risk factors for AKD after surgery for acute type A aortic dissection and the impact of AKD on early and late mortality. DESIGN: AKI was to be defined as an increase in serum creatinine to >0.3 mg/dL or 1.5 times above baseline within 7 days. AKD was defined as the kidney damage within 90 days after AKI. Logistic regression models were performed to identify the risk factors of AKD and the association between AKD and early mortality after AAAD surgery. PARTICIPANTS: Patients with AKI after AAAD surgery admitted in ICU from March 2009 to September 2021 were included. KEY RESULTS: Among the 328 patients who developed AKI after AAAD surgery, 98 patients (29.9%) progressed to AKD. Multivariable analysis revealed that AKI stage 2 (OR, 3.032) and AKI stage 3 (OR, 4.001) have been shown to be independent risk factors for the development of AKD. AKD (OR, 3.175) proved to be an independent risk factor for early mortality, while no significant difference in late mortality was observed between patients in the AKD and non-AKD groups. CONCLUSION: The severity of AKI after surgery of AAAD was independently associated with AKD. The occurrence of AKD had a negative impact on early mortality. CLINICAL TRIAL REGISTRATION: ChiCTR, ChiCTR1900021290. Registered 12 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35795.

Identification of viral genes involved in pepper mottle virus replication and symptom development in Nicotiana benthamiana.

Pepper mottle virus (PepMoV) infects primarily Capsicum species, including pepper and bell pepper which are important vegetable and spice crops in Korea. We have previously collected 13 PepMoV isolates from nine regions comprising five provinces, causing different symptoms on inoculated indicator host plants in Korea. To further identify the responsible symptom determinant(s) and explore viral protein functions of PepMoV, two out of 13 isolates, including 134 and 205136, were used in this study. Isolate 134 causes necrosis and yellowing, while 205136 causes severe mottle and yellowing symptoms on Nicotiana benthamiana. All chimeric and site-directed mutants contain the PepMoV 134 genome as a backbone with specific regions switched for those from counterparts of PepMoV 205136. Effects of all mutants compared with 134 after inoculation onto N. benthamiana by agroinfiltration. Results from our study provide direct evidence that the helper component-proteinase (HC-Pro) and the nuclear inclusion protein b (NIb)-coat protein (CP) regions are involved in virus accumulation and symptom determinants. In addition, we mapped to amino acid residues tyrosine, glycine, and leucine at position 360, 385, and 527, respectively, in the HC-Pro region participate in faster viral accumulation or movement in the plant. The residue valine at position 2773 of NIb plays an essential role in isolate 134 symptom development. As part of this study, we seek to gain insight into viral factors involved in the PepMoV infection cycle and a better understanding of plant-virus interactions. These findings complement the insufficiency of the gene function study of the PepMoV virus and provide a novel perspective for the protein function study of the Potyvirus.

Nimotuzumab combined with chemoradiotherapy for the treatment of cervical cancer: A meta-analysis of randomized controlled trials.

Objectives: To assess the clinical efficacy and toxicity of nimotuzumab in combination with chemoradiotherapy or chemoradiotherapy alone in the treatment of cervical cancer. Methods: The PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, China Biomedical Medicine, Wanfang, and VIP databases were systematically searched for relevant literature. Ultimately, six randomised controlled trials (n=393) were included in our meta-analysis. Results: A total of 393 patients were included, of which 197 were in the nimotuzumab combined with chemoradiotherapy group and 196 were in the chemoradiotherapy group. The results of our meta-analysis showed that the complete remission rate (risk ratio [RR] = 1.34, 95% confidence interval [CI]: 1.08-1.65, P = 0.007), objective response rate (RR = 1.30, 95% CI: 1.16-1.44, P < 0.05), and three-year survival rate (RR = 1.27, 95% CI: 1.06-1.51, P = 0.008) in the nimotuzumab combined with chemoradiotherapy group were significantly improved compared with the chemoradiotherapy group. This difference was not statistically significant when comparing the incidence of adverse reactions (such as leukocytopenia, gastrointestinal reaction, radiocystitis, and radioproctitis) between the two groups. Conclusions: Nimotuzumab in combination with chemoradiotherapy has some advantages over chemoradiotherapy alone in the treatment of cervical cancer and does not increase toxicity. Therefore, nimotuzumab has the potential to be an effective treatment for cervical cancer; however, further evidence from large-scale randomised controlled trials is needed.