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Chen-Hao Zhang,1,&ast; Xiao-Lan Su,2,&ast; Yi-Ying Liu,1 Long Lin,1 Yin-Chun Wang,1 Xiao-Dong Li,1 Jin-Ze Zhang,1 Wei Wei2 1Department of Emergency, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China; 2Department of Gastroenterology, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chen-Hao ZhangDepartment of Emergency, Wangjing Hospital of China Academy of Chinese Medical Sciences, Beijing, 100102, People’s Republic of ChinaTel +86 136 7139 3316Email zhangch_dr@163.comWei WeiDepartment of Gastroenterology, Wangjing Hospital of China Academy of Chinese Medical Sciences, No. 6 of Wangjing Zhonghuan South Street, Chaoyang District, Beijing, 100102, People’s Republic of ChinaTel +86 13601233816Email weiweigrt@163.comBackground: To investigate the effects of Chinese herbal medicine in tonifying qi and attaining hemostasis caused by the metabolism of the drug clopidogrel and as a result of platelet and gastric mucosa injury in an ischemia-reperfusion rat model.Methods: A pharmacokinetic model was established to record the drug metabolism parameters of clopidogrel metabolites. Then, absorption of the drug was compared with approaches using the traditional Chinese medicine (TCM) approach of tonifying qi and establishing hemostasis, to using the drug pantoprazole and applying these approaches in combination with clopidogrel. Intragastric administration was performed, and all indicators were tested.Results: The area under the curve (AUC; 0–T, 300.342 ± 35.832 mg/L&ast; h; AUC 0–∞, 320.462 ± 40.213 mg/L&ast; h), the plasma peak concentration (30.622 ± 9.917 mg/L&ast;), and the peak time and half-life (7.954 ± 1.121 h) in the clopidogrel and the TCM groups were higher than those in the clopidogrel and pantoprazole groups. In terms of antiplatelet aggregation, compared with model group, the platelet aggregation rate induced by arachidonic acid (AA) and adenosine diphosphate (ADP) was significantly decreased by the TCM approach of tonifying qi and stopping bleeding (p < 0.05). The ADP, thromboxane A2, GPII B/Pa-A, CD62P and platelet factor 4 content in the TCM yiqi decoction and hemostasis approach were significantly decreased (p < 0.01). Compared with the clopidogrel group, the gastrin and motilin in the serum, the cyclooxygenase (COX)-1 and prostaglandin E2 in gastric tissue, and expression of vascular endothelial growth factor messenger ribonucleic acid in the serum were all significantly increased using TCM approach to protect against gastric mucosal injury (p < 0.05).Conclusion: TCM invigorating qi and hemostasis has an inhibitory effect on platelet activation. It can reduce the local inflammatory reaction at the same time as protecting gastric mucosa.Keywords: supplementing qi and hemostasis herbs, proton pump inhibition, antiplatelet effect, gastric mucosal protection, traditional Chinese medicine

Haoyu Ren,1 Yifan Shen,2 Daixing Hu,1 Wei He,1 Jing Zhou,1 Yijia Cao,1 Yu Mao,1 Yi Dou,1 Wei Xiong,1 Qi Xiao,1 Yuhong Zhang,2 Xinliang Su1 1Department of Endocrine and Breast Surgery, 2The Center for Clinical Molecular Medical Detection, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China Background: Mutations of BRAFV600E and TERT promoters are associated with thyroid cancer development. This study further investigated association of these mutations with clinicopathological characteristics from patients with papillary thyroid carcinoma (PTC). Methods: Tumor tissues from 342 PTC patients were obtained for DNA extraction and polymerase chain reaction amplification to detect the BRAFV600E mutation using amplification-refractory mutation system-polymerase chain reaction. TERT promoter mutations were assessed using Sanger DNA sequencing. The association of these gene mutations with clinicopathological characteristics was then statistically analyzed. Results: Two hundred and seventy of 342 (78.9%) PTC patients harbored the BRAFV600E mutation, which was associated with older age male patients. Moreover, TERT promoter mutations occurred in 12 of 342 (3.5 %) PTC patients, all of whom also had the BRAF mutation. One hundred thirty-three patients with papillary thyroid microcarcinoma (PTMC) had no TERT mutations. Statistically, the coexistence of BRAF and TERT promoter mutations were significantly associated with older age, larger tumor size, extrathyroidal extension, and advanced tumor stage, but not with central lymph node metastasis, lateral lymph node metastasis, numbers of lymph node metastasis >5, and numbers of involved/harvested lymph nodes (No. of LNs involved or harvested). The multivariate analyses showed older age (odds ratio [OR], 2.194; 95% CI: 1.117–4.311; p=0.023), larger tumor size (OR, 4.100; 95% CI: 2.257–7.450; p

To explore the association between single nucleotide polymorphisms (SNPs) A/G in pre-miR-30c and gastric cancer risk and to assess various genotypes that affected the survival of patients, we performed a hospital-based, case-control study in Inner Mongolia autonomous region of China. A total of 240 gastric cancer patients and 240 age- and sex-matched cancer-free controls collected from 2006 to 2011 were enrolled in this study. Polymorphism rs928508 in pre-miR-30c was analyzed by TaqMan SNP genotyping assay. The expression of mature miR-30c was detected by real-time quantitative reverse transcription PCR in 48 gastric cancer specimens. Survival analysis was analyzed by the Kaplan-Meier survival curves. The genotype frequencies of pre-miR-30c A/G in gastric cancer patients were obviously different from those in the controls (P = 0.022). AA genotype carriers were associated with an increased risk of gastric cancer compared with GG genotype (adjusted odds ratio (OR) = 1.83, 95% confidence interval (CI): 1.07-3.15, P = 0.029). Moreover, the gastric cancer risk especially elevated in older individuals (aged >60 years), males, nonsmokers, and Helicobacter pylori (H. pylori)-infected individuals (adjusted OR = 2.66, 95% CI: 1.38-5.13, P = 0.004; adjusted OR = 1.90, 95% CI: 1.10-3.27, P = 0.022; adjusted OR = 1.94, 95% CI: 1.12-3.35, P = 0.018; adjusted OR = 1.83, 95% CI: 1.08-3.10, P = 0.024, respectively). Further stratified analysis indicated that AA genotype facilitated developing of gastric cancer with lymph node metastasis (adjusted OR = 2.23, 95% CI: 1.07-4.64, P = 0.032). Expression analysis detected that rs928508 AA showed a significantly increased level of mature miR-30c compared with GG or AG/GG genotype (P = 0.011 or P = 0.013). Patients with AA genotype were associated with unfavorable outcome in overall survival compared with AG/GG genotype (Log rank 5.848, P = 0.016). This study demonstrates that pre-miR-30c A/G polymorphism may be associated with an increased risk of gastric cancer in a Chinese population through altering mature miR-30c expression. However, their role as novel biomarkers for the diagnosis and prognosis of gastric diseases still needs to be systematically evaluated. [ABSTRACT FROM AUTHOR]

Background: Yezo virus (YEZV) is an emerging tick-borne pathogen, which was initially reported in Japan in 2021. Only one patient had been reported in China so far. We aimed to describe the epidemiological, clinical, and laboratory findings of a series of patients, and to characterise the viral genomes of YEZV., Methods: In this active surveillance and genomic analysis, we conducted active surveillance at Mudanjiang Forestry Central Hospital, Heilongjiang Province of northeast China. Participants were eligible for inclusion if they sought medical care for a recent tick bite between May 1 and July 31, in 2022 and 2023, and between May 1 and July 10, in 2024. We collected sera from participants to detect YEZV infection by meta-transcriptomic sequencing, real-time RT-PCR, and indirect immunofluorescence assay. We isolated YEZV by cell culture and characterised the pathogen by morphological and phylogenetic analyses., Findings: A series of 18 patients with YEZV infection (12 male and six female; median age 53 years, IQR 45-60) were identified among 988 participants. The patients presented with fever (18 patients, 100%), headache (ten patients, 56%), dizziness (nine patients, 50%), malaise (three patients, 17%), lumbago (three patients, 17%), and cough (three patients, 17%). Nine (50%) patients had rash around the tick bite site and four (22%) had lymphadenopathy. Nine (50%) patients had gastrointestinal symptoms, and five (28%) had neurological symptoms. We observed leukopenia in ten (63%) and thrombocytopenia in five (31%) of 16 assessed patients. Elevated hepatic transaminase concentrations were identified in 13 (72%) of all 18 patients, lactate dehydrogenase or α-hydroxybutyric dehydrogenase in nine (50%), serum amyloid protein A in 13 (72%), and hypersensitive C-reactive protein in ten (56%). Eight (7%) of 119 Ixodes persulcatus ticks removed from participants were positive for YEZV. Three YEZV strains were isolated from the sera of patients. Ten viral genomes were obtained from five patients, a blood-sucking I persulcatus removed from a participant, and four host-questing tick samples collected in the areas where patients were identified or in the adjacent region. Phylogenetic analyses revealed that YEZVs in either patients or ticks were divided into two clades, each with distinct mutations., Interpretation: Awareness of YEZV infection is important and clinicians should consider the virus when diagnosing patients with suitable symptoms., Funding: National Key Research and Development Program of China., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Ferroptosis is a novel, iron-dependent cell death characterized by the excessive accumulation of ferroptosis lipid peroxides ultimately leading to oxidative damage to the cell membrane. Iron, lipid, amino acid metabolism, and other signaling pathways all control ferroptosis. Numerous bodily tissues experience hypoxia under normal and pathological circumstances. Tissue cells can adjust to these changes by activating the hypoxia-inducible factor (HIF) signaling pathway and other mechanisms in response to the hypoxic environment. In recent years, there has been increasing evidence that hypoxia and ferroptosis are closely linked, and that hypoxia can regulate ferroptosis in specific cells and conditions through different pathways. In this paper, we review the possible positive and negative regulatory mechanisms of ferroptosis by hypoxia-inducible factors, as well as ferroptosis-associated ischemic diseases, with the intention of delivering novel therapeutic avenues for the defense and management of hypoxic illnesses linked to ferroptosis., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Yuting Bai reports financial support was provided by the Basic Research Program of Science and Technology Department of Qinhai Province-Natural Science Foundation Program(2023-ZJ-979Q). If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Viral diseases of sweet potatoes are causing severe crop losses worldwide. More than 30 viruses have been identified to infect sweet potatoes among which the sweet potato latent virus (SPLV), sweet potato mild speckling virus (SPMSV), sweet potato virus G (SPVG) and sweet potato virus 2 (SPV2) have been recognized as distinct species of the genus Potyvirus in the family Potyviridae. The sweet potato virus 2 (SPV2) is a primary pathogen affecting sweet potato crops., Methods: In this study, we detected an SPV2 isolate (named SPV2-LN) in Ipomoea nil in China. The complete genomic sequence of SPV2-LN was obtained using sequencing of small RNAs, RT-PCR, and RACE amplification. The codon usage, phylogeny, recombination analysis and selective pressure analysis were assessed on the SPV2-LN genome., Results: The complete genome of SPV2-LN consisted of 10,606 nt (GenBank No. OR842902), encoding 3425 amino acids. There were 28 codons in the SPV2-LN genome with a relative synonymous codon usage (RSCU) value greater than 1, of which 21 end in A/U. Among the 12 proteins of SPV2, P3 and P3N-PIPO exhibited the highest variability in their amino acid sequences, while P1 was the most conserved, with an amino acid sequence identity of 87-95.3%. The phylogenetic analysis showed that 21 SPV2 isolates were clustered into four groups, and SPV2-LN was clustered together with isolate yu-17-47 (MK778808) in group IV. Recombination analysis indicated no major recombination sites in SPV2-LN. Selective pressure analysis showed d N /d S of the 12 proteins of SPV2 were less than 1, indicating that all were undergoing negative selection, except for P1N-PISPO., Conclusion: This study identified a sweet potato virus, SPV2-LN, in Ipomoea nil. Sequence identities and genome analysis showed high similarity between our isolate and a Chinese isolate, yu-17-47, isolated from sweet potato. These results will provide a theoretical basis for understanding the genetic evolution and viral spread of SPV2., (© 2024. The Author(s).)

Acute-on-chronic liver failure (ACLF) and decompensated cirrhosis (DC) are life-threatening syndromes that can develop at the end-stage of chronic hepatitis B virus (HBV) infection. Both ACLF and DC are complicated by hepatic and extrahepatic pathogeneses. To better understand the compartment-specific metabolic modulations related to their pathogenesis, HBV-DC, HBV-ACLF patients, and controls (30 each) were analyzed by metabolomics using portal (Port), hepatic vein (Hep), and peripheral (Peri) serum. Compartment ratios of metabolites (Ratio Hep/Port , Ratio Peri/Hep , and Ratio Port/Peri ) were calculated. The liver tissues (10 per group) were analyzed using transcriptomics and metabolomics. An additional 75 patients with ACLF, 20 with DC, and 20 with liver cirrhosis (LC) were used to confirm oxlipid dysregulation. Both multi-omics datasets suggest suppressed energy, amino acid, and pyrimidine metabolism in the ACLF/DC liver. The serum metabolomic variations were contributed primarily by disease rather than sampling compartments, as both HBV-ACLF and HBV-DC patients demonstrated abnormal profiles of amino acids and peptides, indoles, purines, steroids, and benzimidazoles. In ACLF/DC patients, impaired hepatic metabolism resulted in a highly correlated hepatic and portal vein serum metabolome and release of inflammatory lipids and heme metabolites from the liver. HBV-ACLF showed higher Ratio Peri/Hep of extrahepatic inflammatory oxlipids, while HBV-DC patients showed higher Ratio Port/Peri of gut microbial metabolites. An inflammatory oxlipid outburst was confirmed in the early stages of HBV-ACLF. The inflammatory effects of the selected oxlipids were confirmed in monocytes. These findings support a synergy between liver-specific mechanisms and systemic inflammation in ACLF/DC development, and that pro-inflammatory oxlipids are metabolic signatures of early HBV-ACLF.

Background: Type 2 diabetes mellitus (T2DM) may affect the oral microbial community, exacerbating periodontal inflammation; however, its pathogenic mechanisms remain unclear. As nucleotide-binding oligomerization domain 2 (NOD2) plays a crucial role in the activation during periodontitis (PD), it is hypothesized that changes in the oral microbial community due to diabetes enhance periodontal inflammation through the activation of NOD2., Methods: We collected subgingival plaque from 180 subjects who were categorized into two groups based on the presence or absence of T2DM. The composition of oral microbiota was detected by 16S rRNA high-throughput sequencing. In animal models of PD with or without T2DM, we assessed alveolar bone resorption by micro-computerized tomography and used immunohistochemistry to detect NOD2 expression in alveolar bone. Primary osteoblasts were cultured in osteogenic induction medium with high or normal glucose and treated with inactivated bacteria. After 24 h of inactivated bacteria intervention, the osteogenic differentiation ability was detected by alkaline phosphatase (ALP) staining, and the expressions of NOD2 and interleukin-12 (IL-6) were detected by western blot., Results: The relative abundance of Parvimonas and Filifactor in the T2DM group was increased compared to the group without T2DM. In animal models, alveolar bone mass was decreased in PD, particularly in T2DM with PD (DMPD) group, compared to controls. Immunohistochemistry revealed NOD2 in osteoblasts from the alveolar bone in both the PD group and DMPD group, especially in the DMPD group. In vitro, intervention with inactivated Parvimonas significantly reduced ALP secretion of primary osteoblasts in high glucose medium, accompanied by increased expression of NOD2 and IL-6., Conclusions: The results suggest that T2DM leading to PD may be associated with the activation of NOD2 by Parvimonas., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Stem cell therapy for periodontal defects has shown good promise in preclinical studies. The purpose of this study was to evaluate the impact of stem cell support on the regeneration of both soft and hard tissues in periodontal treatment. PubMed, Cochrane Library, Embase, and Web of Science were searched and patients with periodontal defects who received stem cell therapy were included in this study. The quality of the included articles was assessed using Cochrane's tool for evaluating bias, and heterogeneity was analyzed using the I 2 method. An Mendelian randomization investigation was conducted using abstract data from the IEU public databases obtained through GWAS. Nine articles were included for the meta-analysis. Stem cell therapy effectively rebuilds periodontal tissues in patients with periodontal defects, as evidenced by a reduction in probing depth, clinical attachment level  and bone defect depth . And delta-like homolog 1 is a protective factor against periodontal defects alternative indicator of tooth loosening. The findings of this research endorse the utilization of stem cell treatment for repairing periodontal defects in individuals suffering from periodontitis. It is recommended that additional extensive clinical investigations be carried out to validate the efficacy of stem cell therapy and encourage its widespread adoption., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Diapause is a widespread adaptation of insects that enables them to survive during unfavorable seasons and is characterized by suppressed metabolism and increased lifespan. Previous works have demonstrated that high levels of reactive oxygen species (ROS) and hypoxia-inducible factor-1α (HIF-1α) in the pupal brain of the moth Helicoverpa armigera induce diapause and extend lifespan by downregulating mitochondrial transcription factor A (TFAM). However, the molecular mechanisms of ROS-HIF-1α regulating metabolic activity to extend lifespan are still poorly understood. Here, we show that the mitochondrial abundance in diapause-type pupal brains is markedly lower than that in their nondiapause-type pupae, suggesting that ROS-HIF-1α signaling negatively regulates the number of mitochondria. The protease Lon, a major mitochondrial matrix protease, can respond to ROS signals. It is activated by transcription factor HIF-1α, which specifically binds the LON promoter to promote its expression. A high level of LON mediates the degradation of TFAM, which is a crucial factor in regulating mitochondrial abundance and metabolic activity. We believe this is the first report that a previously unrecognized regulatory pathway, ROS-HIF-1α-LON-TFAM, reduces mitochondrial activity to induce diapause, extending insect lifespan., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Systemic lupus erythematosus (SLE) is an inflammatory disease caused by autoantibodies, with high morbidity and mortality. It involves multiple systems, particularly the renal, which can lead to lupus nephritis (LN); its multi-system effects have a significant impact on the physical and mental health of patients. Exosomes are vesicles that are secreted during cell activity and carry a variety of nucleic acids, proteins, and lipids. They are distributed through body fluids for cellular communication. MicroRNAs (miRNAs) are nucleic acids that are packaged within the exosome that are taken up and released in response to changes in plasma membrane structure. MiRNAs are potential participants in immune and inflammatory responses, which are transported to target cells and can inhibit gene expression in receptor cells. It has been suggested that exosomal miRNA can regulate the pathogenesis of SLE and, as such, they are of value in diagnosis and treatment. In this paper, we focus on the research progress into exosomal miRNA in SLE and inspire new directions for SLE related research., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Regarding past epidemiological studies, there has been disagreement over whether type 1 diabetes (T1DM) is one of the risk factors for dental caries. The purpose of this study was to determine the causative links between genetic susceptibility to T1DM, glycemic traits, and the risk of dental caries using Mendelian randomization (MR) approaches. Methods: Summary-level data were collected on genome-wide association studies (GWAS) of T1DM, fasting glucose (FG), glycated hemoglobin (HbA1c), fasting insulin (FI), and dental caries. MR was performed using the inverse-variance weighting (IVW) method, and sensitivity analyses were conducted using the MR-Egger method, weighted median, weighted mode, replication cohort, and multivariable MR conditioning on potential mediators. Results: The risk of dental caries increased as a result of genetic susceptibility to T1DM [odds ratio (OR) = 1.044; 95% confidence interval (CI) = 1.015-1.074; p = 0.003], with consistent findings in the replication cohort. The relationship between T1DM and dental caries was stable when adjusted for BMI, smoking, alcohol intake, and type 2 diabetes (T2DM) in multivariable MR. However, no significant correlations between the risk of dental caries and FG, HbA1c, or FI were found. Conclusion: These results indicate that T1DM has causal involvement in the genesis of dental caries. Therefore, periodic reinforcement of oral hygiene instructions must be added to the management and early multidisciplinary intervention of T1DM patients, especially among adolescents and teenagers, who are more susceptible to T1DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Tan, Zhong, Zhao, Zhao, Dusenge, Feng, Ye, Hu, Ou-Yang, Chen, Su, Zhang, Liu, Yuan, Wang, Feng and Guo.)

Objectives: The current research on single-nucleotide polymorphism (SNP) mutation sites at different positions of the FAM83H gene and their phenotypic changes leading to amelogenesis imperfecta (AI) is inconsistent. We identified a previously reported heterozygous nonsense mutation c.1192C>T (p.Q398*) in the FAM83H gene and conducted a comprehensive analysis of the dental ultrastructure and chemical composition changes induced by this mutation. Additionally, we predicted the protein feature affected by this mutation site. The aim was to further deepen our understanding of the diversity of AI caused by different mutation sites in the FAM83H gene., Methods: Whole-exome sequencing (WES) and Sanger sequencing were used to confirm the mutation sites. Physical features of the patient's teeth were investigated using various methods including cone beam computer tomography (CBCT), scanning electron microscopy (SEM), contact profilometry (roughness measurement), and a nanomechanical tester (nanoindentation measurement). The protein features of wild-type and mutant FAM83H were predicted using bioinformatics methods., Results: One previously discovered FAM83H heterozygous nonsense mutation c.1192C>T (p.Q398*) was detected in the patient. SEM revealed inconsistent dentinal tubules, and EDS showed that calcium and phosphorus were lower in the patient's dentin but higher in the enamel compared to the control tooth. Roughness measurements showed that AI patients' teeth had rougher occlusal surfaces than those of the control tooth. Nanoindentation measurements showed that the enamel and dentin hardness values of the AI patients' teeth were both significantly reduced compared to those of the control tooth. Compared to the wild-type FAM83H protein, the mutant FAM83H protein shows alterations in stability, hydrophobicity, secondary structure, and tertiary structure. These changes could underlie functional differences and AI phenotype variations caused by this mutation site., Conclusions: This study expands the understanding of the effects of FAM83H mutations on tooth structure., Clinical Relevance: Our study enhances our understanding of the genetic basis of AI and may contribute to improved diagnostics and personalized treatment strategies for patients with FAM83H-related AI., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To understand the incidence of HIV infection, high risk behaviors and pre-exposure prophylaxis/post-exposure prophylaxis (PrEP/PEP) utilization in men who have sex with men (MSM) in Beijing. Methods: Sample size was estimated to be 1 227 persons and 207 person year respectively in the survey and the cohort by using Epi Info 7.0 software. Using convenient sampling method, MSM were recruited by using Wechat app. Questionnaire was completed online to collect the information about demographic characteristics, high risk behavior, and utilization of PrEP/PEP of the MSM. MSM collected dry blood spot (DBS) samples by themselves, and mailed the DBS samples to laboratory for HIV nucleic acid testing. Open cohort was established and those with HIV negative nucleic acid testing results were followed up. Non-conditional binary logistic regression method was used to identify the associated factors for high risk anal sex in the last month and having multiple homosexual partners in the last month. Results: A total of 1 147 MSM were recruited, and follow up for 236 person years was conducted in 956 MSM with negative HIV nucleic acid testing results. The detection rate of new HIV infection was 1.3 per 100 person-years (3/236). During the last month, the proportions of consistent condom use in anal sex and oral sex were 50.7% (238/469) and 4.9% (23/469). In the MSM, 5.9% (43/723) had sex with HIV positive partners in the last month. 9.8% (103/1 049) used PrEP, and 8.7% (91/1 049) used PEP. The proportion of consistent condom use in PrEP and PEP were 34.3% (24/70) and 72.2% (39/54) respectively. Logistic regression analysis revealed that compared with those who used no PrEP/PEP, those who used PrEP/PEP were more likely to have unprotected anal sex in the last month (a OR =3.16, 95% CI :1.45-7.18), and more likely to have multiple homosexual partners in the last month (a OR =2.64, 95% CI :1.19-6.30), and compared with those who used no Rush Popper or drugs in the last month, those who used Rush Popper or drugs in the last month were more likely to have unprotected anal sex in the last month (a OR =2.34, 95% CI :1.67-3.30), and more likely to have multiple homosexual partners (a OR =2.42,95% CI :1.76-3.33). Conclusions: It is necessary to strengthen the health education to promote condom use and introduce the harm of drug use in MSM. In PrEP and PEP services, it is still necessary to suggest consistent condom use for MSM.

Background: The coronavirus disease 2019 (COVID-19) caused a global pandemic, with potential severity. We aimed to investigate whether genetically predicted gut microbiome is associated with susceptibility and severity of COVID-19 risk., Methods: Mendelian randomization (MR) analysis of two sets with different significance thresholds was carried out to infer the causal relationship between the gut microbiome and COVID-19. SNPs associated with the composition of the gut microbiome (n = 5,717,754) and with COVID-19 susceptibility (n = 14,328,058), COVID-19 severity (n = 11,707,239), and COVID-19 hospitalization (n = 12,018,444) from publicly available genome-wide association studies (GWAS). The random-effect inverse variance weighted (IVW) method was used to determine causality. Three more MR techniques-MR Egger, weighted median, and weighted mode-and a thorough sensitivity analysis were also used to confirm the findings., Results: IVW showed that 18 known microbial taxa were causally associated with COVID-19. Among them, six microbial taxa were causally associated with COVID-19 susceptibility; seven microbial taxa were causally associated with COVID-19 severity ; five microbial taxa were causally associated with COVID-19 hospitalization. Sensitivity analyses showed no evidence of pleiotropy or heterogeneity. Then, the predicted 37 species of the gut microbiome deserve further study., Conclusion: This study found that some microbial taxa were protective factors or risky factors for COVID-19, which may provide helpful biomarkers for asymptomatic diagnosis and potential therapeutic targets for COVID-19., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhong, Xie, Feng, Zhang, Xia, Tan, Chen, Su, Zhang, Feng and Guo.)

In recent years, the sugarcane streak mosaic virus (SCSMV) has been the primary pathogen of sugarcane mosaic disease in southern China. In this study, the complete genome of a sugarcane mosaic sample (named YN-21) from Kaiyuan City, Yunnan Province, was amplified and sequenced. By comparing the amino acid sequences of YN-21 and 15 other SCSMV isolates from the NCBI database, the protease recognition site of SCSMV was determined. YN-21 had the highest nucleotide and amino acid identities of 97.66% and 99.30%, respectively, in comparison with the SCSMV isolate (JF488066). The P1 had the highest variability of 83.38-99.72% in the amino acid sequence, and 6K2 was the most conserved, with 97.92-100% amino acid sequence identity. A phylogenetic analysis of nucleotide and amino acid sequences clustered the 16 SCSMV isolates into two groups. All the Chinese isolates were clustered into the same group, and YN-21 was closely related to the Yunnan and Hainan isolates in China. Recombination analysis showed no major recombination sites in YN-21. Selective pressure analysis showed that the d N /d S values of 11 proteins of SCSMV were less than 1, all of which were undergoing negative selection. These results can provide practical guidance for monitoring SCSMV epidemics and genetics.

Objective: Oral health-related quality of life (OHRQoL) is a multidimensional concept that is commonly used to examine the impact of oral health status on quality of life. The purpose of this study was to examine the optimal factor model of the Chinese version of the Oral Health Impact Profile (OHIP-14) questionnaire in clinical populations, measurement invariance across clinical status and gender cohorts. This would ensure equal validity of the Chinese version of OHIP-14 in different populations and further support public oral investigations., Methods: The Chinese version of OHIP-14 was used to investigate 490 dental patients and 919 college students. Confirmatory factor analysis (CFA), item analysis and reliability, measurement invariance, and the t-test were used for data analyses., Results: We found that the 7-factor structure had the best-fit index in the sample (CFI = 0.970, TLI = 0.952; SRMR = 0.029, RMSEA = 0.052(0.040,0.063)). The reliability of the scales was satisfactory (Cronbach's α = 0.942). The error variance invariance fitted the data adequately in measurement invariance, indicating that measurement invariance is acceptable both across the clinical and non-clinical populations (∆CFI=-0.017, ∆RMSEA = 0.010) and across genders in the clinical population (∆CFI = 0.000, ∆RMSEA=-0.003). T-test for scores showed that the clinical populations scored significantly higher than the non-clinical populations, as did the overall score (t = 7.046, p < 0.001, d = 0.396), in terms of functional limitation (t = 2.178, p = 0.030, d = 0.125), physical pain (t = 7.880, p < 0.001,d = 0.436), psychological discomfort (t = 8.993, p < 0.001, d = 0.514), physical disability (t = 6.343, p < 0.001, d = 0.358), psychological disability (t = 5.592, p < 0.001, d = 0.315), social disability (t = 5.301, p < 0.001,d = 0.304), social handicap (t = 4.452, p < 0.001, d = 0.253), and that in the non-clinical populations, females scored significantly higher than males, as did in terms of physical pain (t = 3.055, p = 0.002, d = 0.280), psychological discomfort (t = 2.478, p = 0.014, d = 0.222), and psychological disability (t = 2.067, p = 0.039, d = 0.188)., Conclusion: This study found that the Chinese version of OHIP-14 has measurement invariance between the clinical and non-clinical populations and across genders in the clinical populations, and can be widely used in OHRQoL assessment for public oral investigations., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Orofacial pain (OFP) is a highly prevalent disorder in mainland China that predisposes to an associated physical and psychological disability. There is lack of a good properties mainland Chinese version of instrument to examine OFP. This study aims to cross-cultural adaptation and evaluate psychometrics properties of the Manchester Orofacial Pain Disability Scale (MOPDS) in mainland Chinese Mandarin context., Methods: Translation and cross-cultural adaption of the mainland Chinese version MOPDS were conducted following accepted guidelines of self-report measures. Chinese college students (N = 1039) completed the mainland Chinese version of the MOPDS for item analysis, reliability and validity tests, and measurement invariance analysis, and after a one-month interval, around 10% of the sample (n = 110) were invited to retest. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 26 software were used for all additional studies., Results: We found that the mainland Chinese version of MOPDS contains 25 items, divided into two categories: physical disability and psychological disability. The scale demonstrated excellent internal reliability, test-retest reliability, and validity. The measurement invariance results proved that the scale could be applied to people of different gender, age, and health consultation status., Conclusions: The results demonstrated the mainland Chinese version of MOPDS has good psychometric properties and can be used to measure the level of physical and psychological disability of Chinese OFP peoples., (© 2023. The Author(s).)

Background: There are considerable socioeconomic costs associated with bone defects, making regenerative medicine an increasingly attractive option for treating them. Chitosan is a natural biopolymer; it is used in approaches for sustained slow release and osteogenesis, and metformin has osteoinductivity. Our study aimed to synthesize chitosan and human serum albumin (HSA) with a metformin nanoformulation to evaluate the therapeutic effects of this nanoformulation on bone defects in vitro . Methods: A pluripotent differentiation assay was performed in vitro on mouse bone marrow mesenchymal stem cells (BMSCs). Cell Counting Kit-8 was used to detect whether metformin was toxic to BMSCs. The osteogenesis-related gene expression of osteocalcin (OCN) and osteoprotegerin (OPG) from BMSCs was tested by real-time polymerase chain reaction (PCR). HSA, metformin hydrochloride, and chitosan mixtures were magnetically stirred to finish the assembly of metformin/HSA/chitosan nanoparticles (MHC NPs). The MHC NPs were characterized using transmission electron microscopy (TEM), dynamic light scattering (DLS), and Fourier transform infrared spectroscopy (FT-IR). To test the expression of OCN and OPG, western blot were used. MHC NPs were evaluated in vitro for their osteoinductivity using alkaline phosphatase (ALP). Results: BMSCs successfully differentiated into osteogenic and adipogenic lineages in vitro . According to real-time PCR, a 50 µM concentration of metformin promoted osteogenesis in BMSCs most effectively by upregulating the osteogenic markers OCN and OPG. The microstructure of MHC NPs was spherical with an average nanosize of 20 ± 4.7 nm and zeta potential of -8.3 mV. A blueshift and redshift were observed in MHC NPs following exposure to wavelengths of 1,600-1,900 and 2,000-3,700 nm, respectively. The encapsulation (%) of metformin was more than 90%. The simulation study showed that MHC NPs have good stability and it could release metformin slowly in vitro at room temperature. Upon treatment with the studied MHC NPs for 3 days, ALP was significantly elevated in BMSCs. In addition, the MHC NPs-treated BMSCs upregulated the expression of OPG and OCN, as shown by real-time PCR and western blot. Conclusion: MHC NPs have a stable metformin release effect and osteogenic ability. Therefore, as a derived synthetic biopolymer, it is expected to play a role in bone tissue regeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Chen, Su, Feng, Liu, Tan, Yuan, Chen, Zhao, Zhao, Dusenge, Hu, Ye, Ou-Yang, Zhong, Zhang, Guo, Feng and Peng.)

A new hypoxia-tolerant variety of blunt snout bream was obtained by successive breeding of the wild population, which markedly improved hypoxia tolerance. In this study, the hypoxia-tolerant variety was exposed to hypoxia (2.0 mg O 2 ·L -1 ) for 4, 7 days. The contents of blood biochemical indicators including the number of red blood cells (RBC), total cholesterol (T-CHO), total protein (TP), triglyceride (TG), glucose (GLU), and lactic acid (LD) increased significantly (P < 0.05) under hypoxia. The glycogen content in the liver and muscle decreased significantly (P < 0.05) and the LD content in the brain, muscle and liver increased significantly (P < 0.05) under hypoxia. The levels of oxidative stress-related indicators i.e., superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and total antioxidant capacity (T-AOC) also changed significantly (P < 0.05) in the heart, liver, and intestine of the new variety under hypoxia. Additionally, hypoxia has caused injuries to the heart, liver, and intestine, but it shows amazing repair ability during reoxygenation. The apoptotic cells and apoptosis rate in the heart, liver, and intestine increased under hypoxia. Under hypoxia, the expression of the B-cell lymphomas 2 (Bcl-2) gene in the heart, liver, and intestine was significantly (P < 0.05) down-regulated, while the expression of the BCL2-associated agonist of cell death (Bad) gene was significantly (P < 0.05) up-regulated. These results are of great significance for enriching the basic data of blunt snout bream new variety in response to hypoxia and promoting the healthy development of its culture industry., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2022. Published by Elsevier Inc.)

Blunt snout bream (Megalobrama amblycephala) is sensitive to hypoxia environment. Hypoxia-inducible factor (HIF) is the most critical factor in the HIF pathway, which strictly regulates the hypoxia stress process of fish. In this study, we found six hifα genes in blunt snout bream that demonstrated different expressions under hypoxia conditions. In HEK293T cells, all six hifαs were detected to activate the HRE region by luciferase reporter assay. More importantly, we identified two linkage-disequilibrium SNP sites at exon 203 and 752 of the hif2αb gene in blunt snout bream. Haplotype II (A 203 A 752 ) and its homozygous diplotype II (A 203 A 203 A 752 A 752 ) appeared frequently in a selected strain of blunt snout bream with hypoxia tolerance. Diplotype II has a lower oxygen tension threshold for loss of equilibrium (LOE crit ) over a similar range of temperatures. Moreover, its erythrocyte number increased significantly (p < 0.05) than those in diplotype I and diplotype III strains at 48 h of hypoxia. The enzymes related with hypoxia tolerant traits, i.e., reduced glutathione, superoxide dismutase, and catalase, were also significantly (p < 0.05) induced in diplotype II than in diplotype I or III. In addition, the expression of epo in the liver of diplotype II was significantly (p < 0.01) higher than that in the diplotype I or III strains at 48 h of hypoxia. Taken together, our results found that the hypoxia-tolerant-related diplotype II of hif2αb has the potential to be used as a molecular marker in future genetic breeding of hypoxia-tolerant strain., (© 2023. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The objective of this study was to develop the Chinese version of the biopsychosocial impact scale (BPIm-S) to assess functional limitation and psychosocial distress in orofacial pain (OFP) patients in mainland China, and investigate the factor structure, reliability and validity, measurement invariance, as well as scores differences across genders, age and educational status among OFP patients., Methods: The BPIm-S was developed and evaluated in four stages: (1) concept selection and item generation; (2) a pilot study assessing face and content validity; (3) the factors structure, reliability, convergent validity, and measurement invariance; and (4) concurrent validity and clinical responsiveness. Exploratory (EFA) and confirmatory factor analyses (CFA) were performed on data gathered from 406 OFP patients to assess construct validity. Composite Reliability (CR) and the Average Variance Extracted (AVE) were used to assess internal convergent validity. CR, internal consistency, and split-half reliability were also performed to determine the reliability. Multigroup CFA (MGCFA) was used to assess measurement invariance across genders, age and educational status. Mann-Whitney test compared scores across different genders, age and educational status. Participants completed the BPIm-S, visual analog scale (VAS), brief pain inventory facial (BPI-F), General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9), and spearman's correlation coefficient was used to evaluate the concurrent validity and item-total correlations. A total of 12 patients with OFP completed the BPIm-S twice to test clinical responsiveness. To conduct the CFA and measurement invariance analysis, Mplus 8.4 was used. IBM SPSS Statistics 21 software and SPSSAU, a web-based data science algorithm platform tool, were used for all additional studies., Results: For the preliminary version, 17 items were chosen. A total of four items were removed following the pilot research. The remaining 13 items of the BPIm-S comprised an overall summary scale. Excellent reliability (Item-to-total correlations ranged from 0.763 to 0.912) and strong internal consistency (Cronbach's α = 0.970, functional limitation, 0.962, and psychosocial distress, 0.977) were discovered. CFA also validated the structural validity of the 13-item scale. EFA was performed and a two-factor structure was investigated. In addition, MGCFA corroborated the measurement invariance of the BPIm-S across gender, age, and educational status. Patients over the age of 30, those with a medium level of education, and those with a low level of education showed substantially greater levels of functional limitation and psychological distress (Wilcoxon test, p < 0.001). Both concurrent validity and clinical responsiveness were assessed to be of good quality., Conclusion: The BPIm-S demonstrated good psychometric qualities and is a reliable tool that can now be used by clinicians to evaluate functional limitation and psychosocial distress among OFP patient., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Ou-Yang, Feng, Xie, Yang, Chen, Chen, Su, Kuang, Zhao, Zhao, Feng and Guo.)

Background: Glutathione S-transferase kappa 1 (GSTK1) is critical in sarcoma and breast cancer (BRCA) development. However, the clinical significance of GSTK1 in head and neck squamous cell carcinoma (HNSC) remains unclear. This study is the first investigation into the role of GSTK1 in HNSC. Methods: All original data were downloaded from the Cancer Genome Atlas (TCGA) dataset and verified by R Base Package 4.2.0. The expression of GSTK1 in various cancers was explored with TIMER and TCGA databases. Prognostic value of GSTK1 was analyzed via survival module of Kaplan-Meier plotter and Human Protein Atlas database and Cox regression analysis. The association between GSTK1 and clinical features was evaluated by Wilcoxon signed-rank test and logistic regression analysis. The relationship between GSTK1 and immune infiltration and methylation level was further explored. The expression of GSTK1 and its correlation with immune cell infiltration was verified by Immunohistochemical staining (IHC). Results: GSTK1 was lower in HNSC, BRCA, Lung squamous cell carcinoma, and Thyroid carcinoma than in para-carcinoma. Low GSTK1 expression was associated with worse overall survival in Bladder urothelial carcinoma, Kidney renal papillary cell carcinoma, BRCA, and HNSC. However, only in BRCA and HNSC, GSTK1 expression in tumors was lower than that in normal tissues. Cox regression analyses confirmed that GSKT1 was an independent prognostic factor of overall survival in HNSC patients. The decrease in GSTK1 expression in HNSC was significantly correlated with high T stage and smoker history. IHC showed that the expression level of GSTK1 in HNSC was lower than that in para-carcinoma. In addition, GSEA showed that three pathways related to immune infiltration were positively correlated, while two pathways related to DNA methylation were negatively correlated with expression of GSTK1. Further analysis showed that GSTK1 was moderately positively correlated with the infiltration level of T cells and Cytotoxic cells, which was further confirmed by IHC. The methylation level of GSTK1 was associated with prognosis in patients with HNSC. Conclusion: Low GSTK1 expression may be a potential molecular marker for poor prognosis in HNSC and provide new insight for the development of diagnostic marker or therapeutic target., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Feng, Zhou, Zhao, Su, Chen, Zhao, Ye, Hu, Ou-Yang, Zhong, Yang, Han, Guo and Feng.)

Psychological therapies are important for comprehensive chronic orofacial pain (COFP) treatment. This study is to validate the effects of psychological factors on oral health-related quality of life (OHRQoL) among COFP patients in China. Pain catastrophizing, which is a subjective cognitive emotion used to manage the psychological aspects of pain among COFP patients, was examined in relation to COFP severity and OHRQoL. All 479 participants were recruited in Changsha, Hunan Province, China. Cronbach's alpha coefficients (0.868-0.960), composite reliability scores (0.924-0.969), and average variance extracted from each construct (0.555-0.753) all indicated a good model fit. Pearson's correlation analysis showed that age and education status have a positive correlation with COFP severity, pain catastrophizing, and anxiety. COFP severity was related to anxiety, depression, and COFP-OHRQoL. Pain catastrophizing was related to employment status. Anxiety and depression symptoms indirectly mediated the correlation between COFP severity and COFP-OHRQoL. As a second-stage moderator, pain catastrophizing moderated the mediating effects of anxiety symptoms and depression symptoms. Our findings suggest that anxiety, depression, and pain catastrophizing should be evaluated jointly to improve COFP-OHRQoL among COFP patients. This evidence will help therapists to comprehensively treat patients for the best treatment effect.

Mechanochromic (MC) luminescence of organic molecules has been emerging as a promising smart material for optical recording and memory devices. At the same time, pressure-induced blue-shifted and enhanced luminescence are rarely reported now. Herein, a series of cyanostilbene-based AIEgens with different substituents were synthesized to evaluate the influence of morphology transformation and push-pull electronic effect on the MC luminescence. Among these luminophores, compound 1 with one cyano group and diethylamino group was more susceptible to mechanical stimuli and obtained blue-shifted and enhanced fluorescence in response to anisotropic grinding. Powder X-ray diffraction patterns indicated that the MC behaviors were ascribed to the solid-state morphology transition from crystal-to-crystal. Analysis of crystal structures revealed that loose molecular packing is a key factor for high high-contrast MC luminescence. The smart molecular design, together with the excellent performance, verified that luminophores with twisted structures are ideal candidates for MC luminogens.

Atmospheric black carbon (BC), primary and secondary brown carbon (BrC pri and BrC sec ) are the light-absorbing carbonaceous aerosol components. The vertical changes in the BC and BrC distributions are not generally known. Here, we presented a study of the spectral light absorption properties, direct solar absorption, and potential source areas of BC and BrC at the foothill (375 m a.s.l.) and summit (2060 m a.s.l.) of Mt. Hua, China. More than tripled BC and BrC light absorption coefficient were observed at the foothill compared to the summit. The dominant carbonaceous light-absorbing was attributed to BC with the percentages of 77 % (foothill) and 79 % (summit), respectively. The light absorption coefficient and direct solar absorption of BrC pri were much higher than those of BrC sec at foothill, especially in winter. The enhancing contributions of BrC sec light absorption coefficient and direct solar absorption were observed with high RH and visibility at the summit. The light absorption properties of BC, BrC pri , and BrC sec may be attributed to the emissions, meteorological conditions, and photochemical oxidation. The inferred potential source spatial distributions of BC and BrC pri showed different patterns at the foothill and summit. The results underlined the primary emission effects (including BC and BrC pri ) at the foothill and the importance of BrC sec at the summit, respectively., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Objective: Cluster classification based on m6A methylation regulators and construct prognostic evaluation model. Methods: Utilizing consensus cluster to classify the liver cancer samples form TCGA based on the expression of 13 m6A methylation regulators, and verify the function and prognostic significance of the clustered subtypes. Marker genes were further screened to construct a risk prediction model for evaluating the prognosis of liver cancer patients. Results: The two clustered subtypes based on m6A methylation regulators showed significant differences in the prognosis value of liver cancer patients ( P =0.048), and 38 prognostic markers related to m6A methylation in liver cancer were screened from the subgroup with poor prognosis. Two m6A regulatory genes, YTHDF1 and YTHDF2, are proved with adverse prognosis by univariate cox analysis ( P <0.05, Hazard ratio>1). We used Lasso regression method to build risk assessment model and effectively predicted the prognosis status of liver cancer patients within 4 years (4-year AUC=0.685, 3-year AUC=0.669). Moreover, the assessment model was validated in another dataset of Asia liver cancer patients. Conclusion: The study provided ideas for studying m6A methylation in liver cancer, and the risk prediction model can be used to evaluate the short-term prognosis of liver cancer patients.

Plastic debris in the global biosphere is an increasing concern, and nanoplastic (NPs) toxicity in humans is far from being understood. Studies have indicated that NPs can affect mitochondria, but the underlying mechanisms remain unclear. The liver and lungs have important metabolic functions and are vulnerable to NP exposure. In this study, we investigated the effects of 80 nm NPs on mitochondrial functions and metabolic pathways in normal human hepatic (L02) cells and lung (BEAS-2B) cells. NP exposure did not induce mass cell death; however, transmission electron microscopy analysis showed that the NPs could enter the cells and cause mitochondrial damage, as evidenced by overproduction of mitochondrial reactive oxygen species, alterations in the mitochondrial membrane potential, and suppression of mitochondrial respiration. These alterations were observed at NP concentrations as low as 0.0125 mg/mL, which might be comparable to the environmental levels. Nontarget metabolomics confirmed that the most significantly impacted processes were mitochondrial-related. The metabolic function of L02 cells was more vulnerable to NP exposure than that of BEAS-2B cells, especially at low NP concentrations. This study identifies NP-induced mitochondrial dysfunction and metabolic toxicity pathways in target human cells, providing insight into the possibility of adverse outcomes in human health.

Background: Surgery with total gastrectomy and D2 lymph node dissection (LND) has been recommended as the standard treatment for patients with advanced upper and middle gastric carcinoma and/or Siewert type II/III adenocarcinoma of the esophagogastric junction (AEG). However, whether the No. 10 lymph node (No. 10 LN, also known as splenic hilar LN) should be dissected in total gastrectomy remains controversial. We aimed to evaluate whether the No. 10 LND with spleen preservation has survival benefit for patients with gastric cancer and/or AEG who underwent the total gastrectomy., Methods: The PubMed, Embase, the Cochrane Library, ClinicalTrials.gov and American Society of Clinical Oncology.org (ASCO.org) were electronically searched to identify eligible studies. The primary outcome was the survival rate, and secondary outcomes included the disease-free survival (DFS) rate and side effects. The Review Manager 5.3.5 software was used for the meta-analysis. The odds ratio (OR) and mean difference with 95% confidence interval (CI) were calculated. The statistical heterogeneity was assessed using chi-square (χ 2 ) and I 2 tests., Results: Eight studies enrolling a total of 4,131 patients were eligible for our review. The meta-analysis results demonstrated that the No. 10 LND group was significantly better than the non-No. 10 LND group in terms of the 3- (OR =0.71, 95% CI: 0.62-0.81, P<0.00001) and the 5-year (OR =0.66, 95% CI: 0.58-0.75, P<0.00001) survival rates but not in the 1-year survival rate (OR =0.91, 95% CI: 0.75-1.11, P=0.36). The DFS rates in the No. 10 LND group were significantly increased after 1 (OR =0.76, 95% CI: 0.61-0.93, P=0.008), 3 (OR =0.69, 95% CI: 0.60-0.81, P<0.00001), and 5 (OR =0.66, 95% CI: 0.56-0.76, P<0.00001) years compared with those in the non-No. 10 LND group., Discussion: Evidence shows that the No. 10 LND with spleen preservation can improve the survival and the DFS rates for patients with gastric cancer and/or Siewert type II/III AEG who underwent the total gastrectomy. High-quality prospective trials are expected., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tcr.amegroups.com/article/view/10.21037/tcr-22-522/coif). The authors have no conflicts of interest to declare., (2022 Translational Cancer Research. All rights reserved.)

Connexin 43 (Cx43) is the most important protein in the gap junction channel between cardiomyocytes. Abnormalities of Cx43 change the conduction velocity and direction of cardiomyocytes, leading to reentry and conduction block of the myocardium, thereby causing arrhythmia. It has been shown that IL-1β reduces the expression of Cx43 in astrocytes and cardiomyocytes in vitro. However, whether caspase-1 and IL-1β affect connexin 43 after myocardial infarction (MI) is uncertain. In this study we investigated the effects of VX765, a caspase-1 inhibitor, on the expression of Cx43 and cell-to-cell communication after MI. Rats were treated with VX765 (16 mg/kg, i.v.) 1 h before the left anterior descending artery (LAD) ligation, and then once daily for 7 days. The ischemic heart was collected for histochemical analysis and Western blot analysis. We showed that VX765 treatment significantly decreased the infarct area, and alleviated cardiac dysfunction and remodeling by suppressing the NLRP3 inflammasome/caspase-1/IL-1β expression in the heart after MI. In addition, VX765 treatment markedly raised Cx43 levels in the heart after MI. In vitro experiments were conducted in rat cardiac myocytes (RCMs) stimulated with the supernatant from LPS/ATP-treated rat cardiac fibroblasts (RCFs). Pretreatment of the RCFs with VX765 (25 μM) reversed the downregulation of Cx43 expression in RCMs and significantly improved intercellular communication detected using a scrape-loading/dye transfer assay. We revealed that VX765 suppressed the activation of p38 MAPK signaling in the heart tissue after MI as well as in RCMs stimulated with the supernatant from LPS/ATP-treated RCFs. Taken together, these data show that the caspase-1 inhibitor VX765 upregulates Cx43 expression and improves cell-to-cell communication in rat heart after MI via suppressing the IL-1β/p38 MAPK pathway., (© 2021. The Author(s), under exclusive licence to CPS and SIMM.)

Background: Wear particles-induced osteolysis is a major long-term complication after total joint arthroplasty. Up to now, there is no effective treatment for wear particles-induced osteolysis except for the revision surgery, which is a heavy psychological and economic burden to patients. A metabolite of gut microbiota, short chain fatty acids (SCFAs), has been reported to be beneficial for many chronic inflammatory diseases. This study aimed to investigate the therapeutic effect of SCFAs on osteolysis., Methods: A model of inflammatory osteolysis was established by applying CoCrMo alloy particles to mouse calvarium. After two weeks of intervention, the anti-inflammatory effects of SCFAs on wear particle-induced osteolysis were evaluated by Micro-CT analysis and immunohistochemistry staining. In vitro study, lipopolysaccharide (LPS) primed bone marrow-derived macrophages (BMDMs) and Tohoku Hospital Pediatrics-1 (THP-1) macrophages were stimulated with CoCrMo particles to activate inflammasome in the presence of acetate (C2), propionate (C3), and butyrate (C4). Western blotting, Enzyme-linked immunosorbent assay, and immunofluorescence were used to detect the activation of NLRP3 inflammasome. The effects of SCFAs on osteoclasts were evaluate by qRT-PCR, Western blotting, immunofluorescence, and tartrate-resistant acid phosphatase (TRAP) staining. Additionally, histone deacetylase (HDAC) inhibitors, agonists of GPR41, GPR43, and GPR109A were applied to confirm the underlying mechanism of SCFAs on the inflammasome activation of macrophages and osteoclastogenesis., Results: C3 and C4 but not C2 could alleviate wear particles-induced osteolysis with fewer bone erosion pits (P < 0.001), higher level of bone volume to tissue volume (BV/TV, P < 0.001), bone mineral density (BMD, P < 0.001), and a lower total porosity (P < 0.001). C3 and C4 prevented CoCrMo alloy particles-induced ASC speck formation and nucleation-induced oligomerization, suppressing the cleavage of caspase-1 (P < 0.05) and IL-1β (P < 0.05) stimulated by CoCrMo alloy particles. C3 and C4 also inhibited the generation of Gasdermin D-N-terminal fragment (GSDMD-NT) to regulate pyroptosis. Besides, C3 and C4 have a negative impact on osteoclast differentiation (P < 0.05) and its function (P < 0.05), affecting the podosome arrangement and morphologically normal podosome belts formation., Conclusion: Our work showed that C3 and C4 are qualified candidates for the treatment of wear particle-induced osteolysis., (© 2022. The Author(s).)

Background: Hypertension (HTN) and type 2 diabetes mellitus (T2DM) are often coincident, and each condition is considered a risk factor for the other. Both occur frequently in the Inner Mongolia region of China. The reasons for differences in risk between Han and Mongolian ethnic groups are not known. The LEPR gene and its polymorphism, rs1137101 (Gln223Arg), are both considered risk factors for HTN and T2DM, but any role of rs1137101 in the occurrence of HTN + T2DM remains unclear for Mongolian and Han populations in the Inner Mongolia region., Aim: To investigate the relationship between rs1137101 and the occurrence of HTN with T2DM in Mongolian and Han populations in Inner Mongolia., Methods: A total of 2652 subjects of Han and Mongolian ethnic origins were enrolled in the current study, including 908 healthy controls, 1061 HTN patients and 683 HTN patients with T2DM., Results: The association between the rs1137101 polymorphism and HTN with T2DM was analyzed, and differences between Han and Mongolian individuals assessed. There was a significant correlation between rs1137101 and HTN (co-dominant, dominant, over-dominant and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) after adjustment for sex and age in individuals of Mongolian origin. rs1137101 was significantly associated with HTN (co-dominant, recessive and log-additive models) and HTN + T2DM (co-dominant, dominant, over-dominant and log-additive models) in the Han Chinese population., Conclusion: Mongolian and Han subjects from Inner Mongolia with HTN who had rs1137101 were protected against the development of T2DM. Allele A has the opposite impact on the occurrence of HTN in Mongolian and Han Chinese populations., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Hypertension is a major risk factor for cardiovascular disease and Chinese herb monomers could provide new structural skeletons for anti-hypertension new drug development. Paeonol is a Chinese herbal monomer extracted from Cortex moutan, exhibited some anti-hypertensive activity. The study focused on the structural optimization of paeonol to provide promising lead compounds for anti-hypertension new drug development. Herein, twelve new paeonol derivatives (PD) were designed and synthesized and their vasodilation activity was evaluated by in vitro vasodilation drug screening platform based on Myograph. Its anti-hypertension activity, PD-C302 (2-hydroxy-4-methoxyvalerophenone) as a representative with the optimal vasodilation activity, was determined by its response to blood pressure in spontaneously hypertensive rats (SHR) in vivo. Moreover, its molecular mechanism was probed by the vasodilation activity of rat superior mesenteric artery rings with or without endothelium pre-contracted by potassium chloride (KCl) or phenylephrine hydrochloride (PE). It was indicated that PD-C302 significantly reduced the blood pressure in SHR, which would involve in PD-C302-induced vasodilation. Furthermore, endothelium-dependent pathways and endothelium-independent pathways both contributed importantly to PD-C302-induced vasodilation at low concentration of PD-C302. Endothelium-independent pathways (vascular smooth muscle cell-mediated vasodilation), were mainly responsible for the PD-C302-induced vasodilation at high concentration of PD-C302, which involved in opening multiple K + channels to restrain Ca 2+ channels, and then triggered vasodilation to reduce blood pressure. PD-C302 has a simple structure and favorable anti-hypertensive activity in vivo, which could be a promising lead compound for anti-hypertension new drug development., (Copyright © 2022 Elsevier B.V. All rights reserved.)

NPM1 plays an important role in the occurrence and development of leukemia and various solid tumors. This study aimed to investigate the expression of NPM1 in gastric cancer (GC) and adjacent normal tissues, study the relationship between NPM1 expression and clinicopathological characteristics in GC patients, and explore the impact of NPM1 expression on the diagnosis and prognosis of GC. We used tissue microarray immunohistochemical analysis to examine the expression level of NPM1 in GC and adjacent tissues and analyzed the relationship between NPM1 expression, clinicopathological factors, and GC prognosis. Prognostic values of NPM1 mRNA were also investigated using an online database. qRT-PCR was used to detect the expression of NPM1 mRNA in cancer and adjacent tissues. According to microarray immunohistochemical analysis and qRT-PCR results, NPM1 had a high expression in all adjacent normal tissues. Microarray immunohistochemical analyses demonstrated that the NPM1 was lowly expressed in 75.5% of GC tissues but highly expressed in 24.5% of GC tissues. qRT-PCR results showed NPM1 mRNA low expression in most GC tissues. NPM1 high expression group was associated with a better overall survival rate and disease-free survival rate than the NPM1 low expression group (p<0.01). This result is consistent with that of the online database. The receiver operating characteristics curve showed that NPM1 was valuable in the diagnosis of GC. The assessment of NPM1 expression in GC samples may represent a useful tool for GC diagnosis and prognosis assessment.

Background: Lymph node metastasis (LNM) of papillary thyroid carcinoma (PTC) has a certain regularity and occurs first to the central lymph node and then to the lateral lymph node. The pathway of PTC LNM can guide surgical prophylactic lymph node dissection (LND) for clinical surgeons., Aim: To investigate the relationship between subgroups of central LNM and lateral LNM in unilateral clinically node-negative PTC (cN0-PTC)., Methods: Data were collected for 1089 PTC patients who underwent surgical treatment at the Department of Endocrine and Breast Surgery of the First Hospital of Chongqing Medical University from January 2016 to December 2017. A total of 388 unilateral cN0-PTC patients met the inclusion criteria and were enrolled in this study. The clinical and pathological data for these 388 patients who underwent total thyroidectomy + central LND + lateral LND were retrospectively analyzed. The relationship between the central LNM and lateral LNM subgroups was investigated., Results: The coincidence rate of cN0-PTC was only 30.0%.Optimal scaling regression analysis showed that sex (57.1% vs 42.9%, P = 0.026), primary tumor size (68.8% vs 31.2%, P = 0.008), tumor location (59.7% vs 40.3%, P = 0.007), extrathyroid extension (ETE) (50.6% vs 49.9%, P = 0.046), and prelaryngeal LNM (57.1% vs 42.9%, P = 0.004) were significantly associated with ipsilateral level-II LNM. Their importance levels were 0.122, 0.213, 0.172, 0.110, and 0.227, respectively. Primary tumor size (74.6% vs 30.2%, P = 0.016), pretracheal LNM (67.5% vs 32.5%, P < 0.001), and paratracheal LNM (71.4% vs 28.6%, P < 0.001) were significantly associated with ipsilateral level-III LNM. Their importance levels were 0.120, 0.408, and 0.351, respectively. Primary tumor size (72.1% vs 27.9%, P = 0.003), ETE (70.4% vs 29.6%, P = 0.016), pretracheal LNM (68.3% vs 31.7%, P =0.001), and paratracheal LNM (80.8% vs 19.2%, P < 0.001) were significantly associated with ipsilateral level-IV LNM. Their importance levels were 0.164, 0.146, 0.216, and 0.472, respectively., Conclusion: The LNM pathway of thyroid cancer has a certain regularity. For unilateral cN0-PTC patients with a tumor diameter > 2 cm and pretracheal or ipsilateral paratracheal LNM, LND at ipsilateral level III and level IV must be considered. When there is a tumor in the upper third of the thyroid with prelaryngeal LNM, LND at level II, level III and level IV must be considered., Competing Interests: Conflict-of-interest statement: All authors have no potential conflicts of interest to disclose., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

We previously demonstrated that GSK-3β mediates NLRP3 inflammasome activation and IL-1β production in cardiac fibroblasts (CFs) after myocardial infarction (MI). In this study, we show how GSK-3β-mediated activation of the NLRP3 inflammasome/caspase-1/IL-1β pathway leads to apoptosis and pyroptosis of cardiomyocytes (CMs) and CFs. Administration of lipopolysaccharide (LPS)/ATP to primary newborn rat cardiac fibroblasts (RCFs) led to increase in proteins of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), caspase-1, IL-1β, and IL-18. Additionally, the expression of caspase-3 and N-terminal fragments of gasdermin D (N-GSDMD) and the Bax/Bcl-2 ratio increased. Administration of the GSK-3β inhibitor SB216763 reduced the levels of apoptosis- and pyroptosis-related proteins regulated by NLRP3 inflammasome activation in RCFs. Next, we transferred the culture supernatant of LPS/ATP-treated RCFs to in vitro primary newborn rat cardiomyocytes (RCMs). The results showed that SB216763 attenuate the upregulation of the ratios of Bax/Bcl-2 and the expression of caspase-3 and N-GSDMD in RCMs. Direct stimulation of RCMs and H9c2 cells with recombinant rat IL-1β increased the p-GSK-3β/GSK-3β and Bax/Bcl-2 ratios and the expression of caspase-3 and N-GSDMD, while both SB216763 and TLR1 (an IL-1β receptor inhibitor) markedly reduced these effects, as assessed using propidium iodide positive staining and the lactate dehydrogenase release assay. The caspase-11 inhibitor wedelolactone decreased the expression level of N-GSDMD but did not alter the p-GSK-3β/GSK-3β ratio. Lastly, we established a Sprague-Dawley rat MI model to confirm that SB216763 diminished the increase in caspase-3 and N-GSDMD expression and the Bax/Bcl-2 ratio in the ischemic area. These data demonstrate that GSK-3β regulates apoptosis and pyroptosis of RCMs and RCFs due to NLRP3 inflammasome activation in RCFs., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Functional and structural adaptation of common carotid artery could be one of the important causes of postflight orthostatic intolerance after microgravity exposure, the mechanisms of which remain unclear. Recent evidence indicates that long-term spaceflight increases carotid artery stiffness, which might present a high risk to astronaut health and postflight working ability. Studies have suggested that vascular calcification is a common pathological change in cardiovascular diseases that is mainly manifested as an increase in vascular stiffness. Therefore, this study investigated whether simulated microgravity induces calcification of common carotid artery and to elucidate the underlying mechanisms. Four-week-old hindlimb-unweighted (HU) rats were used to simulate the deconditioning effects of microgravity on cardiovascular system. We found that simulated microgravity induced vascular smooth muscle cell (VSMC) osteogenic differentiation and medial calcification, increased receptor activator of nuclear factor κB (NF-κB) ligand (RANKL) and RANK expression, and enhanced NF-κB activation in rat common carotid artery. In vitro activation of the RANK pathway with exogenous RANKL, a RANK ligand, increased RANK and osteoprotegerin (OPG) expression in HU rats. Moreover, the expression of osteogenic markers and activation of NF-κB in HU rats were further enhanced by exogenous RANKL but suppressed by the RANK inhibitor osteoprotegerin fusion protein (OPG-Fc). These results indicated that the OPG/RANKL/RANK system modulates VSMC osteogenic differentiation and medial calcification of common carotid artery in simulated microgravity rats by regulating the NF-kB pathway.

Background: We aimed to develop and validate a new nomogram for predicting the risk of intracranial hemorrhage (ICH) in patients with acute ischemic stroke (AIS) after intravenous thrombolysis (IVT)., Methods: A retrospective study enrolled 553 patients with AIS treated with IVT. The patients were randomly divided into two cohorts: the training set (70%, n = 387) and the testing set (30%, n = 166). The factors in the predictive nomogram were filtered using multivariable logistic regression analysis. The performance of the nomogram was assessed based on the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, and decision curve analysis (DCA)., Results: After multivariable logistic regression analysis, certain factors, such as smoking, National Institutes of Health of Stroke Scale (NIHSS) score, blood urea nitrogen-to-creatinine ratio (BUN/Cr), and neutrophil-to-lymphocyte ratio (NLR), were found to be independent predictors of ICH and were used to construct a nomogram. The AUC-ROC values of the nomogram were 0.887 (95% CI: 0.842-0.933) and 0.776 (95% CI: 0.681-0.872) in the training and testing sets, respectively. The AUC-ROC of the nomogram was higher than that of the Multicenter Stroke Survey (MSS), Glucose, Race, Age, Sex, Systolic blood Pressure, and Severity of stroke (GRASPS), and stroke prognostication using age and NIH Stroke Scale-100 positive index (SPAN-100) scores for predicting ICH in both the training and testing sets ( p < 0.05). The calibration plot demonstrated good agreement in both the training and testing sets. DCA indicated that the nomogram was clinically useful., Conclusions: The new nomogram, which included smoking, NIHSS, BUN/Cr, and NLR as variables, had the potential for predicting the risk of ICH in patients with AIS after IVT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Weng, Huang, Deng, Yang, Li, Zang, Li, Liu, Wu, Zhang, Su, Lu and Xu.)

Background: Abnormal ion channel currents caused by myocardial electrical remodeling is one of the main causes of malignant arrhythmias. Glycogen synthase kinase 3β (GSK-3β) is the main therapeutic target following ischemia as it regulates nerve cell channels. However, few studies have investigated its role in myocardial electrical remodeling. The present study aimed to investigate the role of GSK-3β in a rat myocardial infarction (MI)-induced electrical remodeling and potential effects on cardiac ionic channels including KCNJ2/Kir2.1/I K1 ., Methods: Ligation of the left anterior descending artery in rats was performed to establish a MI model. The rats were randomly divided into three groups, the sham, MI, and MI + SB group. The animals in the latter group were administered SB216763 (GSK-3β inhibitor) at a dose of 0.6 mg·kg -1 ·day -1 . The ventricular function was assessed by echocardiography, electrocardiography, and histological analysis 7 days post-surgery. Serum was collected to measure lactate dehydrogenase and cardiac troponin I levels, and the mRNA and protein levels of the KCNJ2/Kir2.1/I K1 channel in the heart tissues were assessed. H9c2 cells were cultured to examine the effects of SB216763 on the protein expression of Kir2.1 channel under hypoxic conditions., Results: The results revealed that SB216763 ameliorated acute cardiac injury and improved myocardial dysfunction. Moreover, SB216763 increased the mRNA and protein expression of Kir2.1 during MI. Furthermore, SB216763 treatment abrogated the decreased expression of Kir2.1 in H9c2 cells under hypoxic conditions., Conclusions: GSK-3β inhibition upregulates Kir2.1 expression in a rat model of MI., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Blunt snout bream (Megalobrama amblycephala) is sensitive to hypoxia. A new blunt snout bream strain, "Pujiang No.2", was developed to overcome this shortcoming. As a proteasome inhibitor, bortezomib (PS-341) has been shown to affect the adaptation of cells to a hypoxic environment. In the present study, bortezomib was used to explore the hypoxia adaptation mechanism of "Pujiang No.2". We examined how acute hypoxia alone (hypoxia-treated, HN: 1.0 mg·L - 1 ), and in combination with bortezomib (hypoxia-bortezomib-treated, HB: Use 1 mg bortezomib for 1 kg fish), impacted the hepatic ultrastructure and transcriptome expression compared to control fish (normoxia-treated, NN)., Results: Hypoxia tolerance was significantly decreased in the bortezomib-treated group (LOE crit , loss of equilibrium, 1.11 mg·L - 1 and 1.32 mg·L - 1 ) compared to the control group (LOE crit , 0.73 mg·L - 1 and 0.85 mg·L - 1 ). The HB group had more severe liver injury than the HN group. Specifically, the activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the HB group (52.16 U/gprot, 32 U/gprot) were significantly (p < 0.01) higher than those in the HN group (32.85 U/gprot, 21. 68 U/gprot). In addition, more severe liver damage such as vacuoles, nuclear atrophy, and nuclear lysis were observed in the HB group. RNA-seq was performed on livers from the HN, HB and NN groups. KEGG pathway analysis disclosed that many DEGs (differently expressed genes) were enriched in the HIF-1, FOXO, MAPK, PI3K-Akt and AMPK signaling pathway and their downstream., Conclusion: We explored the adaptation mechanism of "Pujiang No.2" to hypoxia stress by using bortezomib, and combined with transcriptome analysis, accurately captured the genes related to hypoxia tolerance advantage., (© 2022. The Author(s).)

Objective: To observe the therapeutic effect of Wumei Baijiang prescription empirical prescription of Lu Zhizheng, on experimental ulcerative colitis (UC) mice, and to investigate the mechanism of the prescription in UC from the perspective of the immune balance of regulatory T cells (Treg) and helper T cells (Th17)., Methods: Sixty C57BL/6 mice were randomly divided into 6 groups: normal group, model group, Chinese medicine group (high, medium and low dose group of Wumei Baijiang prescription) and control group (mesalazine sustained-release granules). Except for the normal group, the other groups used 2.5% dextran sulfate sodium to induce UC mice model. At the end of the model, the Chinese medicine group was given high, medium and low dose administration of Wumei Baijiang prescription, the control group was given slow-release granules of mesalazine, and the model group was given equal volume saline for 10 d. The changes of food intake, body weight, disease activity index (DAI) score, length of large intestine and histopathology were observed. The number of Treg, Th17, CD4+, CD8+ cells in spleen was detected by flow cytometry. The expression of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10) and C-reactive protein (CRP) in serum was detected by enzyme-linked immunosorbent assay., Results: The middle and high-dose groups of Wumei Baijiang prescription were superior to the model group in terms of increasing food intake and body weight of colitis mice, restoring colon morphology, improving pathological damage, and reducing DAI (P < 0.05). There was no statistical difference with the mesalazine group (P > 0.05). Compared with the model group, the spleen Treg and CD4+ of the mice in the high and middle dose groups of Wumei Baijiang prescription were higher, while Th17 and CD8+ were lower (P < 0.05), and there was no statistical difference compared with the mesalazine group (P > 0.05). In addition, compared with the model group, the serum levels of TNF- and CRP in mice with high and middle doses of Wumei Baijiang prescription and mesalazine group were lower (P < 0.05), and IL-10 content was higher ( P < 0.05)., Conclusions: Wumei Baijiang prescription can improve the general conditions of colitis mice, such as diarrhea, hematochezia, weight loss, and mucosal damage. The mechanism may be related to the regulation of Treg/Th17 immune balance.

Blunt snout bream plays an important role in freshwater aquaculture in China, but the development of its culture industry has been restricted by increasing hypoxia problem. Through the breeding of wild blunt snout bream populations (F0), a hypoxia-tolerant new variety (F6) was obtained. In this study, the new variety was stressed under low oxygen concentration (2.0 mg·L -1 ) for 4 and 7 days, the morphological structure of the gill tissue showed a striking change, the interlamellar cell mass (ILCM) volume reduced significantly (P < 0.05), and the lamellar respiratory surface area enlarged significantly (P < 0.05), compared to normoxic controls. After 7 days of oxygen recovery, gill remodeling was completely reversed. Additionally, the TUNEL-positive apoptotic fluorescence signals increased in the gills exposed to hypoxia up to 4 and 7 days; the apoptosis rate also increased significantly (P < 0.05). Under 4 and 7 days of hypoxia stress, the expression of anti-apoptotic gene Bcl-2 in the gills downregulated significantly (P < 0.05), with the significantly (P < 0.05) upregulated expression of pro-apoptotic gene Bad. Furthermore, under hypoxia stress, the activity or content of oxidative stress-related enzymes (superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and glutathione (GSH)) in gill tissue increased to varying degrees compared to normoxic controls. These results offer a new perspective into the cellular and molecular mechanism of hypoxia-induced gill remodeling in blunt snout bream and a theoretical basis for its hypoxia adaptation mechanism., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Background: The lesions besides lateral ventricle and motor recovery following rehabilitation have hardly been studied., Objective: To explore the relationship between the size, location of infarction beside the lateral ventricle and motor recovery following rehabilitation., Methods: A prospective cohort of 55 patients submitted to a Rehabilitation Medical Center between January 2015 and June 2019 who suffered a single cerebral infarction beside the lateral ventricle were included in the study. The size and distance between the posterior margin and the frontal-middle line (FML) of the lesion were measured. Follow-up was conducted until the recovery was no longer progressing. Barthel index and Brunstrom stages were used to evaluate the outcome (full recovery, partial recovery and poor recovery). Variance analysis and nonparametric test were used for the comparison between groups. Multivariate logistic regression analysis was used to screen the factors affecting the outcomes. The Pearson correlation coefficient was used to compare the volume of infarction, behind the FML and the outcomes., Results: Among the 55 patients, the outcome was full recovery (n = 28), partial recovery (n = 13) and poor recovery (n = 14). Multivariate logistic regression analysis showed that volume and location of the infarction were significantly correlated with the outcome (p = 0.039, 0.050). The lesion volume in the full recovery patients was significantly smaller than that in the poor recovery patients (p < 0.01). The posterior edge of the lesion in the full recovery patients behind the FML was statistically significant compared with that in the poor recovery patients (p < 0.01). Spearman correlation analysis showed that the motor recovery was negative correlation to lesion volume (r = -0.508, P < 0.01) and location (r = -0.450, P < 0.01) of the infarction., Conclusion: The motor recovery of patients with cerebral infarction beside lateral ventricle is related to the volume and location of the lesion. The larger the volume of the lesion, and the farther the posterior margin of the lesion to the FML, the worse the motor recovery.