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.

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.

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.

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.

Neoadjuvant chemoradiotherapy for resectable gastric cancer: A meta-analysis.

Objectives: To evaluate the clinical curative effects and toxicity of neoadjuvant chemoradiotherapy for resectable gastric cancer compared to those of neoadjuvant chemotherapy. Methods: A systematic review and meta-analysis of the randomized controlled trials (RCTs) of neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy were performed in patients with resectable gastric cancer. Results: Seven RCTs were included (601 patients; 302 in the neoadjuvant chemoradiotherapy group and 299 in the neoadjuvant chemotherapy group). The neoadjuvant chemoradiotherapy group had an increased number of patients with a complete response [odds ratio (OR) = 3.79, 95% confidence interval (CI): 1.68-8.54, p = 0.001] and improved objective response rate (OR = 2.78, 95% CI: 1.69-4.57, p < 0.0001), 1-year (OR = 3.51, 95% CI: 1.40-8.81, p = 0.007) and 3-year (OR = 2.14, 95% CI: 1.30-3.50, p = 0.003) survival rates, R0 resection rate (OR = 2.21, 95% CI: 1.39-3.50, p = 0.0008), and complete pathologic response (OR = 4.39, 95% CI: 1.59-12.14, p = 0.004). Regarding the incidence of adverse effects after neoadjuvant therapy, only the occurrence rate of gastrointestinal reaction in the neoadjuvant chemoradiotherapy group was higher than that in the neoadjuvant chemotherapy group (OR = 1.76, 95% CI: 1.09-2.85, p = 0.02), and there was no significant difference in other adverse effects. There was no difference in the incidence of postoperative complications between the two groups. Conclusion: Neoadjuvant chemoradiotherapy for resectable gastric cancer has several advantages in terms of efficacy and safety compared to neoadjuvant chemotherapy. Therefore, neoadjuvant chemoradiotherapy has great potential as an effective therapy for resectable gastric cancers. Systematic Review Registration: https://inplasy.com/inplasy-2022-3-0164, registration number INPLASY202230164.

HDAC1 regulates inflammation and osteogenic differentiation of ankylosing spondylitis fibroblasts through the Wnt-Smad signaling pathway.

Ankylosing spondylitis (AS) is a refractory autoimmune disease, whose typical pathology is the development of inflammation to ossification and ankylosis. Histone deacetylase 1 (HDAC1) is considered to be a key factor involved in inflammatory gene transduction, but its role in AS remains unclear. The purpose of this study was to explore the role and possible mechanism of HDAC1 in AS based on the Wnt-Smad pathway. Fibroblasts were isolated from hip synovial tissues of AS patients, adeno-associated virus (AAV) was used to regulate the expression of HDAC1, DKK-1 and SIS3 was used to inhibit Wnt and Smad, respectively. The expressions of Wnt-Smad pathway-related proteins were analyzed by WB, and the TRP ion channel proteins were analyzed by immunofluorescence and WB. The proliferation of AS fibroblasts was detected by CCK-8, the expression of inflammatory cytokines was detected by ELISA, and the effects of HDAC1 on osteogenic differentiation of AS fibroblasts were investigated by alkaline phosphatase (ALP) activity, intracellular calcium concentration, mineralization and osteogenic proteins expressions. Results showed that HDAC1 significantly affected the protein expressions of the Wnt-Smad pathway in AS fibroblasts, and Wnt inhibitor DKK-1 and Smad3 inhibitor SIS3 could significantly reverse the effect of HDAC1 on the Wnt-Smad pathway. In addition, HDAC1 significantly activated the TRP ion channel and promoted the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts. DKK-1 or SIS3 treatment significantly inhibit the effect of HDAC-1 on AS fibroblasts, suggesting that the Wnt-Smad pathway is involved in the regulation of AS by HDAC1. In conclusion, HDAC1 promotes the proliferation, inflammatory response and osteogenic differentiation of AS fibroblasts through the Wnt-Smad pathway.

Ultra-Sensitive Determination of Particulate, Gaseous Inorganic and Organic Iodine-129 and Iodine-127 in Ambient Air.

Atmospheric iodine cycling is of significance in climate change and environmental and health impacts. To better explore speciation transformation of atmospheric stable and radioactive iodine, an ultra-sensitive analytical method was established for determination of 129I and 127I in particulate, gaseous inorganic, and gaseous organic species, which was conducted with a self-designed cascade sampling apparatus, followed by their separation with a pyrolysis system and accelerator mass spectrometry and ICP-MS measurements. Combustion protocols for three sampling matrices and NaOH concentration for iodine trapping were optimized to achieve a safe analytical procedure with a high chemical yield of iodine. Based on the lowest concentrations of 129I and 127I, a suitable activated carbon product for adsorption of gaseous organic iodine was carefully selected. The detection limits of the three species were 0.30-2.21 ng m-3 for 127I and 0.05-0.22 × 105 atoms m-3 for 129I. This newly established method was successfully applied to analyze the levels and species of 129I and 127I in ambinet air from Xi'an, China, from May to August, 2020. Gaseous organic iodine was found to be the dominant species of 127I and 129I, accounting for about half of total iodine, and gaseous inorganic iodine and particulate iodine accounted for one-quarter each during the whole sampling period. Speciation variation of 129I and 127I indicates that speciation transformation apparently occurred at the turn of spring and summer, mainly between particulate and gaseous organic iodine. This study has implications on delicate tracing of the atmospheric behavior of iodine with long-lived anthropogenic 129I.

Procalcitonin, Interleukin-6 and C-reactive Protein Levels Predict Renal Adverse Outcomes and Mortality in Patients with Acute Type A Aortic Dissection.

Background: Acute type A aortic coarctation (AAAD) is a highly deadly and serious life-threatening disease. The purpose of this study was to estimate the predictive value of peak procalcitonin, interleukin-6, and C-reactive protein levels on adverse renal outcomes and mortality in patients undergoing surgery for AAAD. Methods: Perioperative peak PCT, CRP, and IL-6 levels were retrospectively collected in 331 patients hospitalized with AAAD from 2009 to 2021. The primary endpoints were AKI stage 2-3 and mortality. The receiver operating characteristic (ROC) curves were used to compare the predictive values of peak PCT, CRP, and IL-6 for different clinical outcomes. Multivariable logistic regression analysis was used to find risk factors for AKI and 30-day mortality. Results: The incidence of AKI stage 2-3 following AAAD was 50.8% (168/331). The 30-day and overall mortality were significantly greater in the AKI 2-3 group than in the AKI 0-1 group (P = 0.000). ROC curve analysis showed that peak PCT, with an area under the ROC curve (AUC) of 0.712, was a more accurate predictor of adverse renal outcomes than peak IL-6 and CRP. Multivariable logistic regression analysis revealed that PCT > 0.39 ng/mL was an independent risk factor for AKI stage 2-3. Peak IL-6 > 259 pg/mL was found to be an independent risk factor for 30-day mortality. Conclusion: In patients with surgery for AAAD, peak PCT provides a well-predictive indicator of AKI stage 2-3 and peak IL-6 indicates a favorable predictor of 30-day mortality.

Conversion Paralysis After Cervical Surgery: A Case Report and Literature Review.

We report a case of conversion paralysis triggered by cervical surgery that was caused by cervical spondylotic myelopathy (CSM). A 67-year-old man underwent anterior cervical corpectomy decompression and fusion for CSM. Upon awakening from the anesthesia, he had incomplete paraplegia. Emergency surgery for hematoma evacuation was performed, but no obvious hematoma was found. After the second surgical procedure, he showed paraplegic. When the patient was informed that a third operation was needed, he recovered almost completely without any treatment. This case reminds us that spine surgeons should be aware of possible conversion paralysis, especially in patients who develop a new neurological deficit after spinal surgery.

Atractylenolide III ameliorates Non-Alcoholic Fatty Liver Disease by activating Hepatic Adiponectin Receptor 1-Mediated AMPK Pathway.

Background: Nonalcoholic fatty liver disease (NAFLD) is the most frequent cause of chronic liver diseases worldwide. At present, there are no effective pharmacological therapies for NAFLD except lifestyle intervention-mediated weight loss. Atractylenolide III (ATL III), the major bioactive component found in Atractylode smacrocephala Koidz, has been shown to exert anti-oxidant, anti-tumor, anti-allergic response, anti-bacterial effects and cognitive protection. Here we investigate the therapeutic potential and underlying mechanisms of ATL III for the treatment of NAFLD. Methods: Male C57BL/6J mice were fed a high-fat diet (HFD) and treated with ATL III. Lipid accumulation was analyzed by Oil Red O staining in liver tissues and free fatty acids (FFAs)-treated hepatocytes. AMP-activated protein (AMPK) and sirtuin 1(SIRT1) signaling pathways were inhibited by Compound C and EX527 in vitro, respectively. Small-interfering RNA (siRNA) was used to knockdown adiponectin receptor 1 (AdipoR1) expression in HepG2 cells. Results: ATL III treatment ameliorated liver injury and hepatic lipid accumulation in the HFD-induced NAFLD mouse model as demonstrated by that ATL III administration significantly reduced serum levels of alanine aminotransferase, glutamic oxaloacetic transaminase, triglycerides, total cholesterol and low-density lipoprotein. Furthermore, treatment with ATL III alleviated hepatic oxidative stress, inflammation and fibrosis in the HFD feeding model. To study the underlying mechanisms, we performed Computer Aided Design assay and found that open-formed AdipoR1 and adiponectin receptor 2 were the potential receptors targeted by ATL III. Interestingly, HFD feeding or FFAs treatment only reduced hepatic AdipoR1 expression, while such reduction was abolished by ATL III administration. In addition, in vitro treatment with ATL III activated the AdipoR1 downstream AMPK /SIRT1 signaling pathway and reduced lipid deposition in HepG2 cells, which was diminished by silencing AdipoR1. Finally, inhibition of AMPK or SIRT1, the AdipoR1 downstream signaling, abolished the protective effects of ATL III on lipid deposition and oxidative stress in FFAs-treated HepG2 cells. Conclusion: Our findings suggest that ATL III is a therapeutic drug for the treatment of NAFLD and such protective effect is mediated by activating hepatic AdipoR1-mediated AMPK/SIRT1 signaling pathway.

Androgen deprivation therapy and radiotherapy in intermediate-risk prostate cancer: A systematic review and meta-analysis.

Objectives: Androgen deprivation therapy combined with radiotherapy for intermediate-risk prostate cancer is still a matter of debate. We conducted a meta-analysis to evaluate the necessity of androgen deprivation therapy combined with radiotherapy for intermediate-risk prostate cancer patients. Methods: A comprehensive literature search of articles was performed in PubMed, Embase, Cochrane library, Web of Science, Chinese National Knowledge Infrastructure, Chinese Biological Medicine, Wanfang, and VIP Databases published between February 1988 and April 2022. Studies comparing the survival of patients diagnosed with intermediate-risk prostate cancer who were treated with androgen deprivation therapy combined with radiotherapy or radiotherapy alone were included. Data were extracted and analyzed with the RevMan software (version 5.3) and the Stata software (version 17). Results: Six randomized controlled trials and nine retrospective studies, including 6853 patients (2948 in androgen deprivation therapy combined with radiotherapy group and 3905 in radiotherapy alone group) were enrolled. Androgen deprivation therapy combined with radiotherapy did not provide an overall survival (HR 1.12, 95% CI 1.01-1.12, p=0.04) or biochemical recurrence-free survival (HR 1.23, 95% CI 1.09-1.39, P=0.001) advantage to intermediate-risk prostate cancer patients. Conclusion: Androgen deprivation therapy combined with radiotherapy did not show some advantages in terms of overall survival and biochemical recurrence-free survival and radiotherapy alone may be the effective therapy for intermediate-risk prostate cancer patients. Systematic review registration: https://inplasy.com/inplasy-2022-8-0095/, identifier 202280095.

Incidence- and In-hospital Mortality-Related Risk Factors of Acute Kidney Injury Requiring Continuous Renal Replacement Therapy in Patients Undergoing Surgery for Acute Type a Aortic Dissection.

Background: Few studies on the risk factors for postoperative continuous renal replacement therapy (CRRT) in a homogeneous population of patients with acute type A aortic dissection (AAAD). This retrospective analysis aimed to investigate the risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery and to discuss the perioperative comorbidities and short-term outcomes. Methods: The study collected electronic medical records and laboratory data from 432 patients undergoing surgery for AAAD between March 2009 and June 2021. All the patients were divided into CRRT and non-CRRT groups; those in the CRRT group were divided into the survivor and non-survivor groups. The univariable and multivariable analyses were used to identify the independent risk factors for CRRT and in-hospital mortality. Results: The proportion of requiring CRRT and in-hospital mortality in the patients with CRRT was 14.6 and 46.0%, respectively. Baseline serum creatinine (SCr) [odds ratio (OR), 1.006], cystatin C (OR, 1.438), lung infection (OR, 2.292), second thoracotomy (OR, 5.185), diabetes mellitus (OR, 6.868), AKI stage 2-3 (OR, 22.901) were the independent risk factors for receiving CRRT. In-hospital mortality in the CRRT group (46%) was 4.6 times higher than in the non-CRRT group (10%). In the non-survivor (n = 29) and survivor (n = 34) groups, New York Heart Association (NYHA) class III-IV (OR, 10.272, P = 0.019), lactic acidosis (OR, 10.224, P = 0.019) were the independent risk factors for in-hospital mortality in patients receiving CRRT. Conclusion: There was a high rate of CRRT requirement and high in-hospital mortality after AAAD surgery. The risk factors for CRRT and in-hospital mortality in the patients undergoing AAAD surgery were determined to help identify the high-risk patients and make appropriate clinical decisions. Further randomized controlled studies are urgently needed to establish the risk factors for CRRT and in-hospital mortality.