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Abstract Background In view of the limited knowledge of plasma biomarkers relating to cancer resistance to radiotherapy, we have set up screening, training and testing stages to investigate the microRNAs (miRNAs) expression profile in plasma to predict between the poor responsive and responsive groups after 6 months of radiotherapy. Methods Plasma was collected prior to and after radiotherapy, and the microRNA profiles were analyzed by quantitative reverse transcription polymerase chain reaction (qRT-PCR) arrays. Candidate miRNAs were validated by single qRT-PCR assays from the training and testing set. The classifier for ancillary prognosis was developed by multiple logistic regression analysis to correlate the ratios of miRNAs expression levels with clinical data. Results We revealed that eight miRNAs expressions had significant changes after radiotherapy and the expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p showed significant differences between the responsive and poor responsive groups in the pre-radiotherapy samples. The Kaplan–Meier curve analysis also showed that low miR-342-5p and miR-519d-3p expressions were associated with worse prognosis. Our results revealed two miRNA classifiers from the pre- and post-radiotherapy samples to predict radiotherapy response with area under curve values of 0.8923 and 0.9405. Conclusions The expression levels of miR-374a-5p, miR-342-5p and miR-519d-3p in plasma are associated with radiotherapy responses. Two miRNA classifiers could be developed as a potential non-invasive ancillary tool for predicting patient response to radiotherapy.

Abstract Background Cannabis use has been increasing among older adults in Canada, particularly during the COVID-19 pandemic. This study aims to examine the association between loneliness and cannabis use among older Canadians during the pandemic. Methods Quantitative data analyses were performed based on 2,020 participants aged 55 years and older from the Canadian Perspectives Survey Series 6, 2021: Substance Use and Stigma During the Pandemic. Results This study found that participants who used cannabis in the 30 days before the survey reported significantly higher loneliness scores than those who never used cannabis after adjusting social-demographic, social interaction, and pandemic-related factors. Participants who kept using cannabis during the pandemic also reported significantly higher loneliness scores than those who never used cannabis. Conclusion The findings about the correlation between cannabis use and greater loneliness contribute to the discourse on potential health and wellbeing harms of cannabis use among older adults.

Abstract Background Individuals who have experienced severe traumatic events are estimated to have a post-traumatic stress disorder (PTSD) prevalence rate ranging from 10 to 50%, while those not affected by trauma exposure are often considered to possess psychological resilience. However, the neural mechanisms underlying the development of PTSD, especially resilience after trauma, remain unclear. This study aims to investigate changes of cortical morphometric similarity network (MSN) in PTSD and trauma-exposed healthy individuals (TEHI), as well as the associated molecular alterations in gene expression, providing potential targets for the prevention and intervention of PTSD. Methods We recruited PTSD patients and TEHI who had experienced severe earthquakes, and healthy controls who had not experienced earthquakes. We identified alterations in the whole-brain MSN changes in PTSD and TEHI, and established associations between these changes and brain-wide gene expression patterns from the Allen Human Brain Atlas microarray dataset using partial least squares regression. Results At the neuroimaging level, we found not only trauma-susceptible changes in TEHI same as those in PTSD, but also unique neurobiological alterations to counteract the deleterious impact of severe trauma. We identified 1444 and 2214 genes transcriptionally related to MSN changes in PTSD and TEHI, respectively. Functional enrichment analysis of weighted gene expression for PTSD and TEHI revealed distinct enrichments in Gene Ontology biological processes and Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, gene expression profiles of astrocytes, excitatory neurons, and microglial cells are highly related to MSN abnormalities in PTSD. Conclusions The formation of resilience may be by an active compensatory process of the brain. The combination of macroscopic neuroimaging changes and microscopic human brain transcriptomics could offer a more direct and in-depth understanding of the pathogenesis of PTSD and psychological resilience, shedding light on new targets for the prevention and treatment of PTSD.

Abstract Background Informal caregivers of older adults play a vital role in improving the degree to which older adults access community and healthcare services in a seamless and timely manner. They are fulfilling important navigation and support roles for their older care recipients. However, there is still little knowledge of the most significant facilitators and barriers to effective and efficient system navigation among caregivers. This paper aims to fill these knowledge gaps through investigation of the key factors (i.e., social capital/cohesion, caregiving supports, and utilization factors) affecting navigation difficulties faced by informal caregivers of older adults. Methods The Behavioural-Ecological Framework of Healthcare Access and Navigation (BEAN) model is used to frame the study. Using the General Social Survey on Caregiving and Care Receiving 2018, we analyzed 2,733 informal caregivers whose primary care recipients were aged 65 or older. Hierarchical logistic regression was conducted to identify the relationship between system navigation difficulties among informal caregivers and four sequentially ordered blocks of predictors: (1) sociodemographic (2), social capital/cohesion (3), caregiving supports, and (4) healthcare demand. Results The fully adjusted model showed that the probability of reporting navigation difficulties was lower for caregivers with social capital/cohesion compared to those without social capital/cohesion. In comparison, the probability of reporting navigation difficulties was higher among caregivers with caregiving support and among caregivers whose care receivers use a higher amount of health service use. Several sociodemographic covariates were also identified. Conclusion Our findings support certain aspects of the BEAN model. This study extends our understanding of potential facilitators and barriers that informal caregivers of older adults face while navigating complex community and health systems. There is a need to implement coordinated schemes and health policies especially for older adults with mental/neurological issues to address the challenges of their caregivers given the specific vulnerability identified in this study. The need for further research using different approaches to examine the disproportionate impact of COVID-19 on caregivers’ system navigation experience is crucial.

Abstract Objective Multimorbidity is recognized as a serious health condition faced by a majority of older adults. Research investigating adaptive responses to multimorbidity, termed multimorbidity resilience, has been growing. This paper examines protective and risk factors, with a focus on health behaviours, socio-economic resources, and social support using an established measure of resilience (Connor-Davidson Resilience Scale) among older adults, focusing on older persons with two or more concurrent chronic conditions. Methods Using Baseline (2011–2015), Follow-up One (2015–2018), and Follow-up Two (2018–2021) data from the Comprehensive Cohort of the Canadian Longitudinal Study on Aging, we tested hypotheses using 13,064 participants aged 65 years and older, who completed all waves and reported two or more of 27 chronic conditions, for the full sample of multimorbid individuals and three multimorbidity clusters: Cardiovascular/Metabolic, Musculoskeletal, and Mental Health. Associations between protective and risk factors and resilience were examined using linear regression to model the Connor-Davidson resilience scale, adjusting for illness context and social determinants of health. Results Among all multimorbid individuals, the strongest associations with resilience were found for higher self-rated health, greater sleep satisfaction, better appetite, higher household income, more relatives and friends, being overweight (compared to normal weight), fewer housing problems, and fewer skipped meals. Weaker associations were found for non-smokers, less alcohol consumption, less pain, sedentary behaviour, being non-married (compared to married), and among Canadian born (compared to foreign). The analyses for the three multimorbidity clusters were largely replicated for the three multimorbidity clusters, but with some nuances depending on the cluster. Discussion This research provides confirmatory evidence for several protective and risk factors affecting the ability to cope and recover from multimorbidity adversity among older adults. There are consistent patterns for the multimorbidity disease clusters, but some distinct relationships arise that are worthy of attention. The implications of the findings for modifiable health behaviours and socio-economic factors are discussed for their public health and clinical relevance.

Abstract A knowledge graph can effectively showcase the essential characteristics of data and is increasingly emerging as a significant means of integrating information in the field of artificial intelligence. Coronary artery plaque represents a significant etiology of cardiovascular events, posing a diagnostic challenge for clinicians who are confronted with a multitude of nonspecific symptoms. To visualize the hierarchical relationship network graph of the molecular mechanisms underlying plaque properties and symptom phenotypes, patient symptomatology was extracted from electronic health record data from real-world clinical settings. Phenotypic networks were constructed utilizing clinical data and protein‒protein interaction networks. Machine learning techniques, including convolutional neural networks, Dijkstra's algorithm, and gene ontology semantic similarity, were employed to quantify clinical and biological features within the network. The resulting features were then utilized to train a K-nearest neighbor model, yielding 23 symptoms, 41 association rules, and 61 hub genes across the three types of plaques studied, achieving an area under the curve of 92.5%. Weighted correlation network analysis and pathway enrichment were subsequently utilized to identify lipid status-related genes and inflammation-associated pathways that could help explain the differences in plaque properties. To confirm the validity of the network graph model, we conducted coexpression analysis of the hub genes to evaluate their potential diagnostic value. Additionally, we investigated immune cell infiltration, examined the correlations between hub genes and immune cells, and validated the reliability of the identified biological pathways. By integrating clinical data and molecular network information, this biomedical knowledge graph model effectively elucidated the potential molecular mechanisms that collude symptoms, diseases, and molecules.

Abstract Purpose To summarize and analyze the safety and efficacy of a Y-shape Sigma stent loaded with I125 in patients with inoperable malignant main airway obstruction. Methods This study was approved by the Institutional Ethics Committee, and a written informed consent was obtained from each participant. A Y-shape Sigma stent loaded with I125 was placed under vision from rigid bronchoscopy. The primary endpoint was alleviation of symptoms and improvement of Karnofsky Performance Status (KPS) score, and the secondary endpoint was complications and technical success. Results From November 2018 through June 2023, total 33 patients with malignant airway obstruction were palliatively treated by installing Y-shape Sigma stents loaded with I125. The airway lumen was immediately restored and the average airway opening significantly increased to 70 ± 9.4% after the procedure from baseline 30.2 ± 10.5% (p

Abstract Background The long-term impact of COVID-19-associated public health interventions on zoonotic and vector-borne infectious diseases (ZVBs) remains uncertain. This study sought to examine the changes in ZVBs in China during the COVID-19 pandemic and predict their future trends. Methods Monthly incidents of seven ZVBs (Hemorrhagic fever with renal syndrome [HFRS], Rabies, Dengue fever [DF], Human brucellosis [HB], Leptospirosis, Malaria, and Schistosomiasis) were gathered from January 2004 to July 2023. An autoregressive fractionally integrated moving average (ARFIMA) by incorporating the COVID-19-associated public health intervention variables was developed to evaluate the long-term effectiveness of interventions and forecast ZVBs epidemics from August 2023 to December 2025. Results Over the study period, there were 1,599,647 ZVBs incidents. HFRS and rabies exhibited declining trends, HB showed an upward trajectory, while the others remained relatively stable. The ARFIMA, incorporating a pulse pattern, estimated the average monthly number of changes of − 83 (95% confidence interval [CI] − 353–189) cases, − 3 (95% CI − 33–29) cases, − 468 (95% CI − 1531–597) cases, 2191 (95% CI 1056–3326) cases, 7 (95% CI − 24–38) cases, − 84 (95% CI – 222–55) cases, and − 214 (95% CI − 1036–608) cases for HFRS, rabies, DF, HB, leptospirosis, malaria, and schistosomiasis, respectively, although these changes were not statistically significant besides HB. ARFIMA predicted a decrease in HB cases between August 2023 and December 2025, while indicating a relative plateau for the others. Conclusions China's dynamic zero COVID-19 strategy may have exerted a lasting influence on HFRS, rabies, DF, malaria, and schistosomiasis, beyond immediate consequences, but not affect HB and leptospirosis. ARFIMA emerges as a potent tool for intervention analysis, providing valuable insights into the sustained effectiveness of interventions. Consequently, the application of ARFIMA contributes to informed decision-making, the design of effective interventions, and advancements across various fields.

Abstract Background Performance evaluation is vital for IRB operations. As the number of IRBs and their responsibilities in reviewing and supervising clinical research grow in China, there is a significant need to evaluate their performances. To date, little research has examined IRB performance within China. The aim of this study was to ascertain the perspectives and experiences of IRB employees and researchers to (1) understand the current status of IRBs; (2) compare collected results with those of other countries; and (3) identify shortcomings to improve IRB performance. Methods This study was conducted in China from October 2020 to September 2021, using an online survey with the IRB-researcher assessment tool-Chinese version. Results 757 respondents were included in the analysis and classified into IRB employees, researchers, or those who are both IRB employees and researchers. Overall, the score for an ideal IRB was significantly higher than that of an actual IRB. Compared to the US National Validation study, Chinese participants and American participants both agree and differ in their perspectives on the most and least important ideal items. Conclusion This investigation provides a benchmark of the perceived performance of actual IRBs in China. IRBs in China can be precisely adjusted by targeting identified areas of weakness to improve their performances.

Abstract Background Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China. Methods We retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes. Results Among the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years (P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%). Conclusion The diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors.

Abstract Background Host genetic backgrounds affect gene functions. The genetic backgrounds of genetically engineered organisms must be identified to confirm their genetic backgrounds identity with those of recipients. Marker-assisted backcrossing (MAB), transgenesis and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) editing are three commonly used genetic engineering techniques. However, methods for genetic background screening between genetically engineered organisms and corresponding recipients suffer from low efficiency, low accuracy or high cost. Results Here, we improved our previously reported AmpSeq-SSR method, an amplicon sequencing-based simple sequence repeat (SSR) genotyping method, by selecting SSR loci with high polymorphism among varieties. Ultimately, a set of 396 SSRs was generated and applied to evaluate the genetic backgrounds identity between rice lines developed through MAB, transgenesis, and CRISPR/Cas9 editing and the respective recipient rice. We discovered that the percentage of different SSRs between the MAB-developed rice line and its recipient was as high as 23.5%. In contrast, only 0.8% of SSRs were different between the CRISPR/Cas9-system-mediated rice line and its recipient, while no SSRs showed different genotypes between the transgenic rice line and its recipient. Furthermore, most differential SSRs induced by MAB technology were located in non-coding regions (62.9%), followed by untranslated regions (21.0%) and coding regions (16.1%). Trinucleotide repeats were the most prevalent type of altered SSR. Most importantly, all altered SSRs located in coding regions were trinucleotide repeats. Conclusions This method is not only useful for the background evaluation of genetic resources but also expands our understanding of the unintended effects of different genetic engineering techniques. While the work we present focused on rice, this method can be readily extended to other organisms.

Abstract Background Aging is accompanied with loss of tissue homeostasis and accumulation of cellular damages. As one of the important metabolic centers, liver shows age-related dysregulation of lipid metabolism, impaired detoxification pathway, increased inflammation and oxidative stress response. However, the mechanisms for these age-related changes still remain unclear. In the fruit fly, Drosophila melanogaster, liver-like functions are controlled by two distinct tissues, fat body and oenocytes. Compared to fat body, little is known about how oenocytes age and what are their roles in aging regulation. To characterize age- and stress-regulated gene expression in oenocytes, we performed cell-type-specific ribosome profiling (RiboTag) to examine the impacts of aging and oxidative stress on oenocyte translatome in Drosophila. Results We show that aging and oxidant paraquat significantly increased the levels of reactive oxygen species (ROS) in adult oenocytes of Drosophila, and aged oenocytes exhibited reduced sensitivity to paraquat treatment. Through RiboTag sequencing, we identified 3324 and 949 differentially expressed genes in oenocytes under aging and paraquat treatment, respectively. Aging and paraquat exhibit both shared and distinct regulations on oenocyte translatome. Among all age-regulated genes, oxidative phosphorylation, ribosome, proteasome, fatty acid metabolism, and cytochrome P450 pathways were down-regulated, whereas DNA replication and immune response pathways were up-regulated. In addition, most of the peroxisomal genes were down-regulated in aged oenocytes, including genes involved in peroxisomal biogenesis factors and fatty acid beta-oxidation. Many age-related mRNA translational changes in oenocytes are similar to aged mammalian liver, such as up-regulation of innate immune response and Ras/MAPK signaling pathway and down-regulation of peroxisome and fatty acid metabolism. Furthermore, oenocytes highly expressed genes involving in liver-like processes (e.g., ketogenesis). Conclusions Our oenocyte-specific translatome analysis identified many genes and pathways that are shared between Drosophila oenocytes and mammalian liver, highlighting the molecular and functional similarities between the two tissues. Many of these genes were altered in both oenocytes and liver during aging. Thus, our translatome analysis provide important genomic resource for future dissection of oenocyte function and its role in lipid metabolism, stress response and aging regulation.

Abstract Aims To assess the value of contrast-enhanced ultrasonography (CEUS) for monitoring disease activity of Takayasu arteritis (TA). Methods TA patients were recruited in a Chinese TA clinical center from January 2016 to September 2017. The physician global assessment was used as the referential standard for disease activity. Clinical data, acute phase reactants, and CEUS scans were simultaneously recorded at baseline and after a 3-month therapy. Results A total of 84 TA patients were enrolled, and 47 (55.95%) cases were active at baseline. Macaroni sign and entire artery involvement were characteristic findings of CEUS in TA. The average vascular full thickness of the carotid artery in active TA patients was significantly higher than that in inactive patients (2.36 ± 0.86 vs. 1.79 ± 0.49 mm; p = 0.001). Severe neovascularization (grade 2) was observed in 29 active cases (61.70%) and in 9 inactive cases (24.32%) (p = 0.001). Receiver operating characteristic analysis showed that the combination of CEUS parameters (cutoff of thickness was 1.75 mm or neovascularization grade 2) and erythrocyte sedimentation rate (ESR) (cutoff of 20 mm/H) could help differentiate between active and inactive TA patients with a sensitivity and specificity of 81.1% and 81.5%, respectively. Youdon’s index was 0.626. Furthermore, our study found that patients with decreased ESR and C-reactive protein (CRP) still had a progression of vascular wall inflammation at 3 months of follow-up. Conclusions The evaluation of vascular inflammation by CEUS is more sensitive than acute phase reactants. Neovascularization can still be observed in the vascular lesion sites of those who have reached clinical remission after treatment. Thus, CEUS can be used as an alternative method to assess disease activity for TA patients.

Abstract Background Melatonin is considered to be a polyfunctional master regulator in animals and higher plants. Exogenous melatonin inhibits plant infection by multiple diseases; however, the role of melatonin in Cucumber green mottle mosaic virus (CGMMV) infection remains unknown. Results In this study, we demonstrated that exogenous melatonin treatment can effectively control CGMMV infection. The greatest control effect was achieved by 3 days of root irrigation at a melatonin concentration of 50 μM. Exogenous melatonin showed preventive and therapeutic effects against CGMMV infection at early stage in tobacco and cucumber. We utilized RNA sequencing technology to compare the expression profiles of mock-inoculated, CGMMV-infected, and melatonin+CGMMV-infected tobacco leaves. Defense-related gene CRISP1 was specifically upregulated in response to melatonin, but not to salicylic acid (SA). Silencing CRISP1 enhanced the preventive effects of melatonin on CGMMV infection, but had no effect on CGMMV infection. We also found exogenous melatonin has preventive effects against another Tobamovirus, Pepper mild mottle virus (PMMoV) infection. Conclusions Together, these results indicate that exogenous melatonin controls two Tobamovirus infections and inhibition of CRISP1 enhanced melatonin control effects against CGMMV infection, which may lead to the development of a novel melatonin treatment for Tobamovirus control.

Abstract Background Diabetic ulcer is a common complication of diabetes. It is characterized by a long-term disease course and high recurrence rate. Shengji Huayu Formula (SHF) is an effective formula for treating diabetic ulcers. However, the specific effective parts of SHF remain unclear. Clarifying the active polar site of SHF would be helpful to refine research on the components in SHF that promote wound healing. This research aims to focus on evaluating the activity of polar fractions. Methods A diabetic rat model was established by intraperitoneally injecting streptozotocin (STZ) and was adopted to confirm the therapeutic effect of SHF. Four different polarity parts were extracted from SHF and prepared into a cream to evaluate the activity. High-performance liquid chromatography (HPLC) was used to detect chemical constituents in chloroform extracts. Results It was discovered that dracorhodin, aloe-emodin, rhein, imperatorin, emodin, isoimperatorin, chrysophanol, physcion, and tanshinone IIA were the main components of the chloroform extract from SHF. The results revealed that chloroform extract could effectively accelerate diabetic wound healing by promoting collagen regeneration and epidermal repair. Chloroform extract of SHF could stimulate the generation of vascular endothelial growth factor (VEGF). The results are also indicated that the effective active fraction was the chloroform part, and the method of detecting the main chemical constituents in the active part was successfully established. Conclusion SHF could improve diabetic ulcers by promoting granulation tissue synthesis. In this study, four polar parts (petroleum ether, chloroform, ethylacetate, n-butanol) were extracted from a 95% ethanol extract. In contrast, chloroform polar parts showed a higher wound closure rate, stimulated more collagen regeneration and promoted more production of vascular endothelial cells. In conclusion, the chloroform extract of SHF was the effective polar part in ameliorating diabetic wound healing.

Abstract Background Atherosclerosis is a chronic inflammatory disease of arterial wall, which is closely related to inflammatory reaction. In this study, the anti-inflammatory effect of isorhynchophylline was studied by NF- κB / NLRP3 pathway. Methods (1) ApoE−/− mice were fed with high-fat diet to establish atherosclerotic model, while C57 with the same genetic background was fed with common diet as control group. Body weight was recorded and blood lipids were detected. The expression of NLRP3, NF-κB, IL-18 and Caspase-1 in aorta was detected by Western-Blot and PCR, and plaque formation was detected by HE and oil red O staining. (2) Lipopolysaccharide interfered with Human Umbilical Vein Endothelial Cells (HUVECs) and RAW264.7 to form inflammatory model, and was treated with isorhynchophylline. The expression of NLRP3, NF-κB, IL-18 and Caspase-1 in aorta was detected by Western-Blot and PCR, and the ability of cell migration was detected by Transwell and scratch test. Results (1) the expression of NLRP3, NF- κB, IL-18 and Caspase-1 in aorta of model group was higher than that of control group, and plaque formation was obvious. (2) the expressions of NLRP3, NF- κB, IL-18 and Caspase-1 in HUVECs and RAW264.7 model groups were higher than those in control group, while isorhynchophylline decreased their expression and enhanced cell migration ability. Conclusion Isorhynchophylline can reduce the inflammatory reaction induced by lipopolysaccharide and promote the ability of cell migration.

Abstract Background Recently, the BAOCHE trial and ATTENTION trial registry have demonstrated the efficacy of endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO), however, the proportion of patients with favorable post-EVT outcomes remains low. The present study aimed to investigate the individual and joint prognostic values of the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with acute BAO who have undergone EVT. Methods We enrolled patients who underwent EVT from the BASILAR registry. Patients were divided into the following groups based on their modified Rankin Scale (mRS) scores at 90 days: favorable-outcome (mRS score: 0–3) and poor-outcome (mRS score: 4–6) groups. Multivariable logistic regression was performed to analyze the association of NLR and PLR with favorable post-EVT outcomes. Results In total, 585 patients with EVT were recruited. Of these, 189 and 396 patients were in the favorable-outcome and poor-outcome groups, respectively. According to the multivariable logistic regression analyses, both NLR (adjusted odds ratio [aOR], 0.950; 95% confidence interval [CI], 0.920–0.981; P = 0.002) and PLR (aOR, 0.997; 95% CI, 0.995–0.999; P = 0.002) were related to favorable post-EVT outcomes in patients with acute BAO. The optimal cutoff values for the NLR and PLR were 7.75 and 191, respectively. Furthermore, stratified analysis using the multivariable logistic regression model revealed that both NLR and PLR (NLR values ≥ 7.75 and PLR values ≥ 191) were associated with a low rate of favorable outcomes (aOR, 0.292; 95% CI, 0.173–0.494; P

Abstract Background Metastasis is the predominant cause of mortality in patients with breast cancer. Long noncoding RNAs (lncRNAs) have been shown to drive important phenotypes in tumors, including invasion and metastasis. However, the lncRNAs involved in metastasis and their molecular and cellular mechanisms are still largely unknown. Methods The transcriptional and posttranscriptional processing of LINC00478-associated cytoplasmic RNA (LacRNA) was determined by RT-qPCR, semiquantitative PCR and 5′/3′ RACE. Paired-guide CRISPR/cas9 and CRISPR/dead-Cas9 systems was used to knock out or activate the expression of LacRNA. Cell migration and invasion assay was performed to confirm the phenotype of LacRNA. Tail vein model and mammary fat pad model were used for in vivo study. The LacRNA-PHB2-cMyc axis were screened and validated by RNA pulldown, mass spectrometry, RNA immunoprecipitation and RNA-seq assays. Results Here, we identified a novel cytoplasmic lncRNA, LacRNA (LINC00478-associated cytoplasmic RNA), derived from nucleus-located lncRNA LINC00478. The nascent transcript of LINC00478 full-length (LINC00478_FL) was cleaved and polyadenylated, simultaneously yielding 5′ ends stable expressing LacRNA, which is released into the cytoplasm, and long 3′ ends of nuclear-retained lncRNA. LINC00478_3′RNA was rapidly degraded. LacRNA significantly inhibited breast cancer invasion and metastasis in vitro and in vivo. Mechanistically, LacRNA physically interacted with the PHB domain of PHB2 through its 61–140-nt region. This specific binding affected the formation of the autophagy degradation complex of PHB2 and LC3, delaying the degradation of the PHB2 protein. Unexpectedly, LacRNA specifically interacted with PHB2, recruited c-Myc and promoted c-Myc ubiquitination and degradation. The negatively regulation of Myc signaling ultimately inhibited breast cancer metastasis. Furthermore, LacRNA and LacRNA-mediated c-Myc signaling downregulation are significantly associated with good clinical outcomes, take advantage of these factors we constructed a prognostic predict model. Conclusion Therefore, our findings propose LacRNA as a potential prognostic biomarker and a new therapeutic strategy.

Abstract Background With the increasing morbidity and mortality of preeclampsia (PE), it has posed a huge challenge to public health. Previous studies have reported endoplasmic reticulum (ER) stress could contribute to trophoblastic dysfunction which was associated with the N6-methyladenosine (m6A) modification by methyltransferase-like 3 (METTL3), resulting in PE. However, little was known about the relationship between METTL3 and ER stress in PE. Thus, in vitro and in vivo studies were performed to clarify the mechanism about how METTL3 affects the trophoblasts under ER stress in PE and to explore a therapeutic approach for PE. Methods An ER stress model in HTR-8/SVneo cells and a preeclamptic rat model were used to study the mechanism and explore a therapeutic approach for PE. Western blot, immunohistochemistry, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and methylated RNA immunoprecipitation (MeRIP)-qPCR were performed to detect the protein, RNA, and methylated transmembrane BAX inhibitor motif containing 6 (TMBIM6) expression levels. The m6A colorimetric and mRNA stability assays were used to measure the m6A levels and TMBIM6 stability, respectively. Short hairpin RNAs (shRNAs) were used to knockdown METTL3 and YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Flow cytometry and Transwell assays were performed to evaluate the apoptosis and invasion abilities of trophoblasts. Results Upregulated METTL3 and m6A levels and downregulated TMBIM6 levels were observed in preeclamptic placentas under ER stress. The ER stress model was successfully constructed, and knockdown of METTL3 had a beneficial effect on HTR-8/SVneo cells under ER stress as it decreased the levels of methylated TMBIM6 mRNA. Moreover, overexpression of TMBIM6 was beneficial to HTR-8/SVneo cells under ER stress as it could neutralize the harmful effects of METTL3 overexpression. Similar to the knockdown of METTL3, downregulation of YTHDF2 expression resulted in the increased expression and mRNA stability of TMBIM6. Finally, improved systemic symptoms as well as protected placentas and fetuses were demonstrated in vivo. Conclusions METTL3/YTHDF2/TMBIM6 axis exerts a significant role in trophoblast dysfunction resulting in PE while inhibiting METTL3 may provide a novel therapeutic approach for PE.

Abstract Background The Coronavirus Disease-2019 (COVID-19) pandemic has created a spectrum of adversities that have affected older adults disproportionately. This paper examines older adults with multimorbidity using longitudinal data to ascertain why some of these vulnerable individuals coped with pandemic-induced risk and stressors better than others – termed multimorbidity resilience. We investigate pre-pandemic levels of functional, social and psychological forms of resilience among this sub-population of at-risk individuals on two outcomes – self-reported comprehensive pandemic impact and personal worry. Methods This study was conducted using Follow-up 1 data from the Canadian Longitudinal Study on Aging (CLSA), and the Baseline and Exit COVID-19 study, conducted between April and December in 2020. A final sub-group of 9211 older adults with two or more chronic health conditions were selected for analyses. Logistic regression and Generalized Linear Mixed Models were employed to test hypotheses between a multimorbidity resilience index and its three sub-indices measured using pre-pandemic Follow-up 1 data and the outcomes, including covariates. Results The multimorbidity resilience index was inversely associated with pandemic comprehensive impact at both COVID-19 Baseline wave (OR = 0.83, p

Abstract Background The high potential for tumor recurrence and chemoresistance is a major challenge of clinical gastric cancer treatment. Increasing evidence suggests that the presence of tumor initiating cells (TICs) is the principal cause of tumor recurrence and chemoresistance. However, the underlying mechanism of TIC development remains controversial. Methods To identify novel molecular pathways in gastric cancer, we screened the genomic expression profile of 155 gastric cancer patients from the TCGA database. We then described an improved 3D collagen I gels and tested the effects of collagen on the TIC phenotype of gastric cells using colony formation assay, transwell assay, and nude mouse models. Additionally, cell apoptosis assay was performed to examine the cytotoxicity of 5-fluorine and paclitaxel on gastric cancer cells cultured in 3D collagen I gels. Results Elevated expression of type I collagen was observed in tumor tissues from high stage patients (stage T3–T4) when compared to the low stage group (n=10, stage T1–T2). Furthermore, tumor cells seeded in a low concentration of collagen gels acquired TIC-like phenotypes and revealed enhanced resistance to chemotherapeutic agents, which was dependent on an integrin β1 (ITGB1)/Y-box Binding Protein 1 (YBX1)/Secreted Phosphoprotein 1 (SPP1)/NF-κB signaling pathway. Importantly, inhibition of ITGB1/NF-κB signaling efficiently reversed the chemoresistance induced by collagen and promoted anticancer effects in vivo. Conclusions Our findings demonstrated that type I collagen promoted TIC-like phenotypes and chemoresistance through ITGB1/YBX1/SPP1/NF-κB pathway, which may provide novel insights into gastric cancer therapy.

Abstract Background Current treatment options for glioma are limited, and the prognosis of patients with glioma is poor as the available drugs show low therapeutic efficacy. Furthermore, the molecular mechanisms associated with glioma remain poorly understood. METTL1 mainly catalyzes the formation of N(7)-methylguanine at position 46 of the transfer RNA sequence, thereby regulating the translation process. However, the role of METTL1 in glioma has not been studied to date. The purpose of this study was to analyze the expression and prognosis of METTL1 in glioma, and to explore the potential analysis mechanism. Methods Data from five publicly available databases were used to analyze METTL1 expression across different tumor types and its differential expression between carcinoma and adjacent normal tissues. The expression of METTL1 in glioma was further validated using real-time polymerase chain reaction and immunohistochemistry. Meanwhile, siRNA was used to knockdown METTL1 in U87 glioma cells, and the resultant effect on glioma proliferation was verified using the Cell Counting Kit 8 (CCK8) assay. Furthermore, a nomogram was constructed to predict the association between METTL1 expression and the survival rate of patients with glioma. Results METTL1 expression increased with increasing glioma grades and was significantly higher in glioma than in adjacent noncancerous tissues. In addition, high expression of METTL1 promoted cell proliferation. Moreover, METTL1 expression was associated with common clinical risk factors and was significantly associated with the prognosis and survival of patients with glioma. Univariate and multivariate Cox regression analyses revealed that METTL1 expression may be used as an independent prognostic risk factor for glioma. Furthermore, results of functional enrichment and pathway analyses indicate that the mechanism of METTL1 in glioma is potentially related to the MAPK signaling pathway. Conclusions High METTL1 expression is significantly associated with poor prognosis of patients with glioma and may represent a valuable independent risk factor. In addition, high expression of METTL1 promotes glioma proliferation and may regulate mitogen-activated protein kinase (MAPK) signaling pathway. Thus, METTL1 may be a potential biomarker for glioma. Further investigations are warranted to explore its clinical use.

Abstract Background Network meta-analysis (NMA) has been widely used in the field of medicine and health, but the research topics and development trends are still unclear. This study aimed to identify the cooperation of countries and institutes and explore the hot topics and future prospects in the field of NMA. Methods Data of publications were downloaded from the Web of Science Core Collection. We used CiteSpace V, HistCite 2.1, and Excel 2016 to analyze literature information, including years, journals, countries, institutes, authors, keywords, and co-cited references. Results NMA research developed gradually before 2010 and rapidly in the following years. 2846 NMA studies were published in 771 journals in six languages. The PLoS One (110, 3.9%) was the most productive journal, and N Engl J Med (5904 co-citations) was the most co-cited journal. The most productive country was the United States (889, 31%) and the most productive institute was the University of Bristol (113, 4.0%). The active collaborations were observed between developed countries and between productive institutes. Of the top 10 authors, four were from the UK, and among the top 10 co-cited authors, six were from the UK. Randomized evidence, oral anti-diabetic drugs, coronary artery bypass, certolizumab pegol, non-valvular atrial fibrillation, and second-line antihyperglycemic therapy were the hot topics in this field. Conclusions NMA studies have significantly increased over the past decade, especially from 2015 to 2017. Compared with developing countries, developed countries have contributed more to these publications and have closer cooperation, indicating that cooperation between developed and developing countries should be further strengthened. The treatment of diabetes, cardiovascular diseases, and immune rheumatism are the main hot topics.

Abstract Background There has been an increasing number of children with congenital heart disease that undergo primary or second systemic-pulmonary shunt, while there are few reports on the second systemic-pulmonary shunt. Therefore, this study summarizes the experience of second systemic-pulmonary shunt for congenital heart disease in our hospital. Methods and results Sixty-five children with congenital heart disease who underwent systemic-pulmonary shunt for the second time in our hospital were analyzed. At the early stage after the operation, cyanosis improved and SpO2 significantly increased. One patient died in hospital (1.54%) and the causes of death were aggravated atrioventricular regurgitation, low cardiac output syndrome, and liver failure. Early complications occurred in 18 patients (27.7%). All the children were rechecked in our hospital every 3–6 months and the McGoon index significantly increased. Conclusion Systemic-pulmonary artery shunt can promote pulmonary vascular development, improve cyanosis symptoms, and increase the chance of radical treatment in children with pulmonary vascular dysplasia.

Abstract Background The formal risk assessment is essential in the management of acute coronary syndrome (ACS). In this study, we develop a risk model for the prediction of 3-year mortality for Chinese ACS patients with machine learning algorithms. Methods A total of 2174 consecutive patients who underwent angiography with ACS were enrolled. The missing data among baseline characteristics were imputed using the MissForest algorithm based on random forest method. In model development, a least absolute shrinkage and selection operator (LASSO) derived Cox regression with internal tenfold cross-validation was used to identify the predictors for 3-year mortality. The clinical performance was assessed with decision curve analysis. Results The average follow-up period was 27.82 ± 13.73 months; during the 3 years of follow up, 193 patients died (mortality rate 8.88%). The Kaplan–Meier estimate of 3-year mortality was 0.91 (95% confidence interval (CI): 0.890.92). After feature selection, 6 predictors were identified: Age,” “Creatinine,” “Hemoglobin,” “Platelets,” “aspartate transaminase (AST)” and “left ventricular ejection fraction (LVEF)”. At tenfold internal validation, our risk model performed well in both discrimination (area under curve (AUC) of receiver operating characteristic (ROC) analysis was 0.768) and calibration (calibration slope was approximately 0.711). As a comparison, the AUC and calibration slope were 0.701 and 0.203 in Global Registry of Acute Coronary Events (GRACE) risk score, respectively. Additionally, the highest net benefit of our model within the entire range of threshold probability for clinical intervention by decision curve analysis demonstrated the superiority of it in daily practice. Conclusion Our study developed a prediction model for 3-year morality in Chinese ACS patients. The methods of missing data imputation and model derivation base on machine learning algorithms improved the ability of prediction. . Trial registration ChiCTR, ChiCTR-OOC-17010433. Registered 17 February 2017–Retrospectively registered

Abstract Background S100 calcium binding protein A12 (S100A12) is a member of the S100 protein family and is widely expressed in neutrophil and low expressed in lymphocytes and monocyte. However, the role of S100A12 in glioma has not yet been identified. Methods In the present study, we carried out immunohistochemical investigation of S100A12 in 81 glioma tissues to determine the expression of S100A12 in glioma cells, and evaluate the clinical significance of S100A12 in glioma patients. Futher we knockdown the S100A12 by shRNA, and evaluated cell proliferation, cell migration and cell apoptosis by MTT, colony formation assay, transwell assay,flow cytometry assa and western blot. Results We found that S100A12 was upregulated in tissues of glioma patients and the expression was correlated to WHO stage and tumor size. Further, we found that knockdown S100A12 inhibits the proliferation, migration and invasion of glioma cells through regulating cell apoptosis and EMT. Conclusion S100A12 plays a vital role in glioma progression, and may be an important regulatory molecule for biological behaviors of glioma cell lines.

Abstract Background The recruitment of immune system cells into the central nervous system (CNS) has a profound effect on the outcomes of injury and disease. Glia-derived chemoattractants, including chemokines, play a pivotal role in this process. In addition, cytokines and chemokines influence the phenotype of infiltrating immune cells. Depending on the stimuli present in the local milieu, infiltrating macrophages acquire the classically activated M1 or alternatively activated M2 phenotypes. The polarization of macrophages into detrimental M1 versus beneficial M2 phenotypes significantly influences CNS pathophysiology. Earlier studies indicated that a toll-like receptor 9 (TLR9) antagonist modulates astrocyte-derived cytokine and chemokine release. However, it is not known whether these molecular changes affect astrocyte-induced chemotaxis and polarization of macrophages. The present studies were undertaken to address these issues. Methods The chemotaxis and polarization of mouse peritoneal macrophages by spinal cord astrocytes were evaluated in a Transwell co-culture system. Arrays and ELISA were utilized to quantify chemokines in the conditioned medium (CM) of pure astrocyte cultures. Immunostaining for M1- and M2-specific markers characterized the macrophage phenotype. The percentage of M2 macrophages at the glial scar was determined by stereological approaches in mice sustaining a mid-thoracic spinal cord contusion injury (SCI) and intrathecally treated with oligodeoxynucleotide 2088 (ODN 2088), the TLR9 antagonist. Statistical analyses used two-tailed independent-sample t-test and one-way analysis of variance (ANOVA) followed by Tukey’s post hoc test. A p value

Abstract Background The majority of breast cancer patients die of metastasis rather than primary tumors, whereas the molecular mechanisms orchestrating cancer metastasis remains poorly understood. Long noncoding RNAs (lncRNA) have been shown to regulate cancer occurrence and progression. However, the lncRNAs that drive metastasis in cancer patients and their underlying mechanisms are still largely unknown. Methods lncRNAs highly expressed in metastatic lymph nodes were identified by microarray. Survival analysis were made by Kaplan-Meier method. Cell proliferation, migration, and invasion assay was performed to confirm the phenotype of LINC02273. Tail vein model and mammary fat pad model were used for in vivo study. RNA pull-down and RIP assay were used to confirm the interaction of hnRNPL and LINC02273. Chromatin isolation by RNA purification followed by sequencing (ChIRP-seq), RNA-seq, ChIP-seq, and luciferase reporter assay reveal hnRNPL-LINC02273 regulates AGR2. Antisense oligonucleotides were used for in vivo treatment. Results We identified a novel long noncoding RNA LINC02273, whose expression was significantly elevated in metastatic lesions compared to the primary tumors, by genetic screen of matched tumor samples. Increased LINC02273 promoted breast cancer metastasis in vitro and in vivo. We further showed that LINC02273 was stabilized by hnRNPL, a protein increased in metastatic lesions, in breast cancer cells. Mechanistically, hnRNPL-LINC02273 formed a complex which activated AGR2 transcription and promoted cancer metastasis. The recruitment of hnRNPL-LINC02273 complex to AGR2 promoter region epigenetically upregulated AGR2 by augmenting local H3K4me3 and H3K27ac levels. Combination of AGR2 and LINC02273 was an independent prognostic factor for predicting breast cancer patient survival. Moreover, our data revealed that LINC02273-targeting antisense oligonucleotides (ASO) substantially inhibited breast cancer metastasis in vivo. Conclusions Our findings uncover a key role of LINC02273-hnRNPL-AGR2 axis in breast cancer metastasis and provide potential novel therapeutic targets for metastatic breast cancer intervention.

Abstract Background Neuropathic pain is often observed in individuals with multiple sclerosis (MS) and spinal cord injury (SCI) and is not adequately alleviated by current pharmacotherapies. A better understanding of underlying mechanisms could facilitate the discovery of novel targets for therapeutic interventions. We previously reported that decreased plasma membrane calcium ATPase 2 (PMCA2) expression in the dorsal horn (DH) of healthy PMCA2+/− mice is paralleled by increased sensitivity to evoked nociceptive pain. These studies suggested that PMCA2, a calcium extrusion pump expressed in spinal cord neurons, plays a role in pain mechanisms. However, the contribution of PMCA2 to neuropathic pain processing remains undefined. The present studies investigated the role of PMCA2 in neuropathic pain processing in the DH of wild-type mice affected by experimental autoimmune encephalomyelitis (EAE), an animal model of MS, and following SCI. Methods EAE was induced in female and male C57Bl/6N mice via inoculation with myelin oligodendrocyte glycoprotein fragment 35–55 (MOG35–55) emulsified in Complete Freund’s Adjuvant (CFA). CFA-inoculated mice were used as controls. A severe SC contusion injury was induced at thoracic (T8) level in female C57Bl/6N mice. Pain was evaluated by the Hargreaves and von Frey filament tests. PMCA2 levels in the lumbar DH were analyzed by Western blotting. The effectors that decrease PMCA2 expression were identified in SC neuronal cultures. Results Increased pain in EAE and SCI was paralleled by a significant decrease in PMCA2 levels in the DH. In contrast, PMCA2 levels remained unaltered in the DH of mice with EAE that manifested motor deficits but not increased pain. Interleukin-1β (IL-1β), tumor necrosis factor α (TNFα), and IL-6 expression were robustly increased in the DH of mice with EAE manifesting pain, whereas these cytokines showed a modest increase or no change in mice with EAE in the absence of pain. Only IL-1β decreased PMCA2 levels in pure SC neuronal cultures through direct actions. Conclusions PMCA2 is a contributor to neuropathic pain mechanisms in the DH. A decrease in PMCA2 in DH neurons is paralleled by increased pain sensitivity, most likely through perturbations in calcium signaling. Interleukin-1β is one of the effectors that downregulates PMCA2 by acting directly on neurons.

Abstract Background Food-borne trematodiases are an important group of neglected global diseases. Affected patients in regions with low prevalence usually experience delayed diagnosis, especially when presenting with atypical clinical symptoms. Here, we presented a rare case of a Chinese patient infected with three food-borne trematodiases. Case presentation A 42-year-old man presented with diarrhea, lower extremity edema, and symptoms of cardiac dysfunction. He had a history of intermittent consumption of raw freshwater fishes for 6–7 years. Upon evaluation, he had eosinophilia, anemia, intrahepatic bile duct dilatation and a growing space-occupying lesion in the left atrium. The patient underwent a cardiac surgery which revealed an endocardial hematoma due to mechanical injuries. Imaging investigations also revealed intracranial and pulmonary lesions. A total of three trematodiases were diagnosed based upon microscopic stool examination, from which eggs of Clonorchis sinensis, Heterophyidae and Echinostomatidae were identified. Deposition of Clonorchis sinensis eggs was also observed from ileocecal squash slides. The patient was successfully treated with three cycles of praziquantel. Conclusions Food-borne trematodiases may present with systemic involvement. Patients with dietary history of high risk or atypical ingestions should be evaluated for parasitic infection, even in non-endemic areas.

Abstract Background Chemotherapy is the primary established systemic treatment for patients with breast cancer, especially those with the triple-negative subtype. Simultaneously, the resistance of triple-negative breast cancer (TNBC) to chemotherapy remains a major clinical problem. Our previous study demonstrated that the expression levels of PTN and its receptor PTPRZ1 were upregulated in recurrent TNBC tissue after chemotherapy, and this increase was closely related to poor prognosis in those patients. However, the mechanism and function of chemotherapy-driven increases in PTN/PTPRZ1 expression are still unclear. Methods We compared the expression of PTN and PTPRZ1 between normal breast and cancer tissues as well as before and after chemotherapy in cancer tissue using the microarray analysis data from the GEPIA database and GEO database. The role of chemotherapy-driven increases in PTN/PTPRZ1 expression was examined with a CCK-8 assay, colony formation efficiency assay and apoptosis analysis with TNBC cells. The potential upstream pathways involved in the chemotherapy-driven increases in PTN/PTPRZ1 expression in TNBC cells were explored using microarray analysis, and the downstream mechanism was dissected with siRNA. Results We demonstrated that the expression of PTN and PTPRZ1 was upregulated by chemotherapy, and this change in expression decreased chemosensitivity by promoting tumour proliferation and inhibiting apoptosis. CDKN1A was the critical switch that regulated the expression of PTN/PTPRZ1 in TNBC cells receiving chemotherapy. We further demonstrated that the mechanism of chemoresistance by chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis depended on the NF-κB pathway. Conclusions Our studies indicated that chemotherapy-driven increases in the CDKN1A/PTN/PTPRZ1 axis play a critical role in chemoresistance, which suggests a novel strategy to enhance chemosensitivity in breast cancer cells, especially in those of the triple-negative subtype.

Abstract Background The potential toxicity of Chinese herbal medicine has attracted more attention in recent years. Jueyin granules (JYG), a polyherbal formula, have been proven to be an effective agent for treating psoriasis in both animal models and clinical research. However, little is known about the possible acute and chronic toxicity of JYG. The objective of this study was to investigate the safety of JYG in ICR mice and Wistar rats. Methods To examine the acute toxicity of JYG, ICR mice were randomly divided into an experimental group and a control group, each comprising 20 mice (10 male and 10 female). The experimental group was fed JYG solution at a dose of 21.5 g/kg, equivalent to 143 times the clinical human dosage, for 14 days, whereas control animals were fed distilled water. In the chronic toxicity test, Wistar rats were divided into four groups, each comprising 40 rats (20 male and 20 female). For 6 months, the experimental animals were given JYG at a dose of 7.5, 3.75 and 1.875 g/kg, whereas control animals were given distilled water. The animals’ body weight, food and water consumptions were monitored weekly. In addition, their biochemical and hematological parameters, histopathology, and body and organ weights were all measured at specific observation time points. Results According to the results of the acute toxicity test, no mortality was found and no abnormal pathological changes in major organs were observed in mice treated with JYG. In the chronic toxicity test, JYG did not cause significant abnormalities in the physiological parameters or pathological changes in the major organs of the rats. Conclusion The results indicated that JYG at the given doses did not induce any harmful effects in animals. Thus, it is reasonable to conclude that JYG is safe at the studied dosage levels and causes no acute or chronic toxicity in animal models.

Abstract Background Sheng-ji Hua-yu(SJHY) formula is one of the most useful Traditional Chinese medicine (TCM) in the treatment of the delayed diabetic wound. However, elucidating the related molecular biological mechanism of how the SJHY Formula affects excessive inflammation in the process of re-epithelialization of diabetic wound healing is a task urgently needed to be fulfilled. The objectives of this study is to evaluate the effect of antagonisic expression of pro−/anti-inflammatory factors on transforming growth factor-β(TGF-β) superfamily (activin and follistatin) in the process of re-epithelialization of diabetic wound healing in vivo, and to characterize the involvement of the activin/follistatin protein expression regulation, phospho-Smad (pSmad2), and Nuclear factor kappa B p50 (NF-kB) p50 in the diabetic wound healing effects of SJHY formula. Methods SJHY Formula was prepared by pharmaceutical preparation room of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine. Diabetic wound healing activity was evaluated by circular excision wound models. Wound healing activity was examined by macroscopic evaluation. Activin/follistatin expression regulation, protein expression of pSmad2 and NF-kB p50 in skin tissue of wounds were analyzed by Real Time PCR, Western blot, immunohistochemistry and hematoxylin and eosin (H&E) staining. Results Macroscopic evaluation analysis showed that wound healing of diabetic mice was delayed, and SJHY Formula accelerated wound healing time of diabetic mice. Real Time PCR analysis showed higher mRNA expression of activin/follistatin in diabetic delayed wound versus the wound in normal mice. Western Blot immunoassay analysis showed reduction of activin/follistatin proteins levels by SJHY Formula treatment 15 days after injury. Immunohistochemistry investigated the reduction of pSmad2 and NF-kB p50 nuclear staining in the epidermis of diabetic SJHY versus diabetic control mice on day 15 after wounding. H&E staining revealed that SJHY Formula accelerated re-epithelialization of diabetic wound healing. Conclusion The present study found that diabetic delayed wound healing time is closely related to the high expression level of activin/follistatin, which leads to excessive inflammation in the process of re-epithelization. SJHY Formula accelerates re-epithelialization and healing time of diabetic wounds through decreasing the high expression of activin/follistatin. Graphical abstract