Objective To explore the functional impact of A-to-I editing in the seed region of miR-411 during post-myocardial infarction (MI) fibrosis and elucidate its therapeutic potential. Methods Integrating GEO database with myocardial RNA-seq data from MI mouse models, we identified dynamic A-to-I RNA editing in small noncoding RNAs across MI progression (1 day to 8 weeks post-MI). Four miRNAs exhibited differential editing rates between MI and controls, with miR-411 showing progressive editing enhancement at seed region position 4 (P＜0.01). This editing event was validated in both murine MI models and human heart failure specimens. Results The A-to-I editing ratio change of the 4th nucleotide in the seed region of miR-411 mainly occurs in cardiac fibroblasts rather than cardiomyocytes, and the editing at this site depends on ADAR2 rather than ADAR1. Edited miR-411 (ED-miR-411) diverged from wild-type miR-411 (WT-miR-411) in suppressing collagen-related pathways (extracellular matrix [ECM]-receptor interaction, collagen-containing ECM, ECM organization; P＜0.01) in cardiac fibroblasts. Mechanistically, dual-luciferase assays confirmed ED-miR-411 directly targeted the 3′UTR and suppressed expression of type Ⅱ transforming growth factor (TGF)-beta receptor (TGFBR2) and CD44, which were key drivers of TGF-β-mediated fibroblast activation. ED-miR-411 overexpression blunted TGF-β-induced collagen synthesis and myofibroblast proliferation (P＜0.05). In vivo, intramyocardial delivery of ED-miR-411 mimics at 1 week post-MI reduced fibrosis by 40% and improved ejection fraction by 15% (P＜0.01 vs controls), whereas WT-miR-411 showed no therapeutic effect. Conclusions A-to-I editing of miR-411 emerges as an endogenous anti-fibrotic mechanism by repressing TGFBR2 and CD44, thereby disrupting TGF-β signaling and ECM dysregulation. Our findings highlight ED-miR-411 as a novel RNA-based therapeutic candidate to mitigate post-infarction cardiac remodeling.

Objective:To investigate the association between the metabolic score for visceral fat(METS-VF)and sarcopenia in older adults in China.Methods:A retrospective cohort study was conducted.A total of 1 262 participants aged ≥60 years old who did not diagnose with sarcopenia in 2011 and had complete follow-up data in 2015 were selected from the China health and retirement longitudinal survey(CHARLS). Participants were divided into the low METS-VF group (n=621)and the high METS-VF group (n=641), and then the corrleation between METS-VF and sarcopenia was analyzed.Results:The inverse probability of treatment weighting(IPTW)was used to balance all covariates between the low METS-VF group and high METS-VF group.The results showed that 30 participants in the low METS-VF group and 47 participants in the high METS-VF group were diagnosed with sarcopenia, with prevalence rates of 4.83%(30/621)and 7.33%(47/641), respectively.The difference in the prevalence of sarcopenia between the two groups was statistically significant after IPTW ( χ2=3.934, P=0.048, SMD=0.150). Logistic regression analysis showed that, after adjusting for various confounders, high METS-VF was significantly associated with an increased risk of sarcopenia in older adults( OR=2.130, 95% CI: 1.294~3.572, P=0.003). Subgroup analyses further indicated that individuals without cardiovascular disease had a relatively higher risk of sarcopenia( P for interaction=0.032). Conclusions:METS-VF is associated with an increased risk of sarcopenia in older adults in China, and its predictive and diagnostic value warrants further investigation.

Objective:To analyze the disease burden and changing trend of pancreatic cancer in our country from 1990 to 2021, and predict the incidence and mortality trends of pancreatic cancer from 2022 to 2036.Methods:Utilizing the data from the Global Burden of Disease 2021 Study, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life rate (DALY) of pancreatic cancer in our country from 1990 to 2021 were evaluated. DALY is calculated by adding the number of years of life lost due to pancreatic cancer to the years of life lost due to disability. The Joinpoint model was used to calculate the average annual percentage change (AAPC), the age-period-cohort model was applied to control the influence of age, period and birth cohort, and the Bayesian age-period-cohort model was used to predict the incidence and mortality trends of pancreatic cancer in our country from 2022 to 2036.Results:Compared with 1990, the data of ASIR, ASMR and age-standardized disability-adjusted life years (DALY) rates of pancreatic cancer in our country in 2021 all increased, and the increase in men was more significant than that in women. The peaks of morbidity and mortality in 1990 and 2021 were both occurred in the elderly. The incidence rate, mortality rate and changes of men in all age groups were higher than those of women. The changes in the age-standardized DALY rate were mainly reflected in the male population. The first peaks of the age-standardized DALY rate in 1990 and 2021 both occurred at the age of 70-74, and the second peak of the age-standardized DALY rate in 2021 shifted to the age of 85-89. The peak rate of age-standardized DALY in females is earlier than that in males. The AAPC of ASIR and ASMR for all genders of pancreatic cancer in our country from 1990 to 2021 was 0.72 (95% CI: 0.50-0.94, P<0.001) and 0.56 (95% CI: 0.31-0.82, P<0.001), respectively, and the difference was statistically significant. In our country men with pancreatic cancer, ASIR (AAPC=0.89, 95% CI: 0.68-1.10, P<0.001) and ASMR (AAPC=0.71, 95% CI: 0.49-0.93, P<0.001) were compared with ASIR (AAPC=0.48, 95% CI: ) in women. 0.22-0.73, P<0.001) and ASMR (AAPC=0.33, 95% CI: 0.08-0.58, P=0.010) increased rapidly, and the difference was statistically significant. The ASDR of all genders showed an upward trend (AAPC=0.36, 95% CI: 0.18-0.54, P<0.001), and the difference was statistically significant. The incidence rate and mortality rate of all genders are on the rise. When the age of the population is over 60 years old, the incidence and mortality of specific diseases show an upward trend with the delay of the birth cohort. It is expected that from 2022 to 2036, the ASIR and ASMR of both men and women will increase annuallyand eventually double. Conclusion:From 1990 to 2021, the burden of pancreatic cancer in our country has generally shown an increasing trend, and it is expected that the disease burden will further increase in the future.

Objective:To investigate the association between the metabolic score for visceral fat(METS-VF)and sarcopenia in older adults in China.Methods:A retrospective cohort study was conducted.A total of 1 262 participants aged ≥60 years old who did not diagnose with sarcopenia in 2011 and had complete follow-up data in 2015 were selected from the China health and retirement longitudinal survey(CHARLS). Participants were divided into the low METS-VF group (n=621)and the high METS-VF group (n=641), and then the corrleation between METS-VF and sarcopenia was analyzed.Results:The inverse probability of treatment weighting(IPTW)was used to balance all covariates between the low METS-VF group and high METS-VF group.The results showed that 30 participants in the low METS-VF group and 47 participants in the high METS-VF group were diagnosed with sarcopenia, with prevalence rates of 4.83%(30/621)and 7.33%(47/641), respectively.The difference in the prevalence of sarcopenia between the two groups was statistically significant after IPTW ( χ2=3.934, P=0.048, SMD=0.150). Logistic regression analysis showed that, after adjusting for various confounders, high METS-VF was significantly associated with an increased risk of sarcopenia in older adults( OR=2.130, 95% CI: 1.294~3.572, P=0.003). Subgroup analyses further indicated that individuals without cardiovascular disease had a relatively higher risk of sarcopenia( P for interaction=0.032). Conclusions:METS-VF is associated with an increased risk of sarcopenia in older adults in China, and its predictive and diagnostic value warrants further investigation.

Objective:To analyze the disease burden and changing trend of pancreatic cancer in our country from 1990 to 2021, and predict the incidence and mortality trends of pancreatic cancer from 2022 to 2036.Methods:Utilizing the data from the Global Burden of Disease 2021 Study, the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and disability-adjusted life rate (DALY) of pancreatic cancer in our country from 1990 to 2021 were evaluated. DALY is calculated by adding the number of years of life lost due to pancreatic cancer to the years of life lost due to disability. The Joinpoint model was used to calculate the average annual percentage change (AAPC), the age-period-cohort model was applied to control the influence of age, period and birth cohort, and the Bayesian age-period-cohort model was used to predict the incidence and mortality trends of pancreatic cancer in our country from 2022 to 2036.Results:Compared with 1990, the data of ASIR, ASMR and age-standardized disability-adjusted life years (DALY) rates of pancreatic cancer in our country in 2021 all increased, and the increase in men was more significant than that in women. The peaks of morbidity and mortality in 1990 and 2021 were both occurred in the elderly. The incidence rate, mortality rate and changes of men in all age groups were higher than those of women. The changes in the age-standardized DALY rate were mainly reflected in the male population. The first peaks of the age-standardized DALY rate in 1990 and 2021 both occurred at the age of 70-74, and the second peak of the age-standardized DALY rate in 2021 shifted to the age of 85-89. The peak rate of age-standardized DALY in females is earlier than that in males. The AAPC of ASIR and ASMR for all genders of pancreatic cancer in our country from 1990 to 2021 was 0.72 (95% CI: 0.50-0.94, P<0.001) and 0.56 (95% CI: 0.31-0.82, P<0.001), respectively, and the difference was statistically significant. In our country men with pancreatic cancer, ASIR (AAPC=0.89, 95% CI: 0.68-1.10, P<0.001) and ASMR (AAPC=0.71, 95% CI: 0.49-0.93, P<0.001) were compared with ASIR (AAPC=0.48, 95% CI: ) in women. 0.22-0.73, P<0.001) and ASMR (AAPC=0.33, 95% CI: 0.08-0.58, P=0.010) increased rapidly, and the difference was statistically significant. The ASDR of all genders showed an upward trend (AAPC=0.36, 95% CI: 0.18-0.54, P<0.001), and the difference was statistically significant. The incidence rate and mortality rate of all genders are on the rise. When the age of the population is over 60 years old, the incidence and mortality of specific diseases show an upward trend with the delay of the birth cohort. It is expected that from 2022 to 2036, the ASIR and ASMR of both men and women will increase annuallyand eventually double. Conclusion:From 1990 to 2021, the burden of pancreatic cancer in our country has generally shown an increasing trend, and it is expected that the disease burden will further increase in the future.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Humans ; Neoplasms, Second Primary/epidemiology* ; Neoplasms/epidemiology* ; Risk Factors ; Prognosis

OBJECTIVETo compare and evaluate the effectiveness of two kinds of medical drainage bag.

METHODS206 patients were randomly divided into two groups each of which consisted of 103 patients. All the data including four indices, such as the time required to replace the drainage bags, the incidence of the bags detached, draining fluid splashing rates during the replacement of the bags, patient and medical staff satisfaction, were collected and analyzed statistically.

RESULTSThe time required to replace the drainage bags, the incidence of the bags detached and draining fluid splashing rates during the replacement of the bags of the experimental group were significantly lower than those of the control group (P < 0.05), while the patient and medical staff satisfaction were significantly higher than those of the control group (P < 0.05).

CONCLUSIONIt is convenient, quick and time and effort saving to use the neotype medical drainage bags. Hence, the use of neotype medical drainage bags could help to improve the work efficiency, effectively prevent occupational injuries and protect health care workers.

Six recombinant plasmids co-expressing the wild-type GP5 gene or the codon-optimized GP5 gene (containing pan-DR epitope) of porcine reproductive and respiratory syndrome virus (PRRSV) and the E2 gene of classical swine fever virus (CSFV) or the E2 fused with the UL49 of pseudorabies virus (PrV) were constructed based on the suicidal DNA vaccine pSFV1CS-E2 described previously. Expression of GP5 and E2 was confirmed by indirect immunofluorescence assay. The immunogenicity of six plasmids was evaluated in BALB/c mouse model. For the six plasmids, low-level of E2 and GP5 protein specific antibodies could be detected in the sera of the immunized mice. Specific lymphoproliferative responses to the PRRSV or CSFV stimulation were induced in the splenocytes of the immunized mice as demonstrated by CFSE staining assay and WST-8 assay. Antigen specific IFN-gamma and L-4 secretion was detected in the splenocytes of some immunized mice by cytokine ELSIA. Fusion with the PrV UL49 in the suicidal vaccines induced significantly higher lymphoproliferative responses and cytokine secretion. Taken together, the suicidal DNA vaccines co-expressing GP5 and E2 could induce PRRSV and CSFV specific humoral and cell-mediated immune responses.
Animals ; Antibodies, Viral ; blood ; Antibody Formation ; Cytokines ; blood ; Female ; Immunity, Cellular ; Lymphocytes ; immunology ; Mice ; Mice, Inbred BALB C ; Random Allocation ; Vaccines, DNA ; biosynthesis ; immunology ; Viral Envelope Proteins ; genetics ; immunology ; Viral Structural Proteins ; genetics ; immunology ; Viral Vaccines ; biosynthesis ; immunology

Objective To investigated the distribution of epidermal stem cells in rat full-thickness wound tissues during the wound healing process and to elucidate the roles of epidermal stem cells in wound repair in vivo. Methods Eighty circular full-thickness wounds were produced on both sides of the back in 20 male Wistar rats labeled with BrdU 60 days previously (4 wounds in each rat). BrdU, β1 integrin and keratin 19 (K19) were employed to determine the epidermal stem cells with SP immunohistochemical methods, and the epithelialization was determined with routine histological methods of HE staining on the 3rd, 7th, 14th, and 21st days after operation. Results No cells with positive immunostaining for β1 integrin, K19 and BrdU were found in granulation tissue of wound in both groups during the healing process. However, a few scattered β1 integrin and K19 positive cells were found within the stratum spinosum and stratum granulosum of the epidermis on the wound edges on the 3rd day post-injury. And these positive cells gradually became more and more in number, and mostly concentrated on the border of wound edges till the wounds healed. In addition, the number of positive cells for β1 integrin and K19 in the infected wounds was less than that in non-infected wounds. These positive cells for β1 integrin and K19 staining on the wound edge were also positively stained with BrdU in the cellular nuclei. Conclusion The above results indicate that ectopia of epidermal stem cells present a major function during wound epithelialization.