Chemotherapy is currently the mainstay of systemic management for triple-negative breast cancer (TNBC), but chemoresistance significantly impacts patient outcomes. Our research indicates that Doxorubicin (Dox)-resistant TNBC cells exhibit increased glycolysis and ATP generation compared to their parental cells, with this metabolic shift contributing to chemoresistance. We discovered that ALKBH3, an m¹A demethylase enzyme, is crucial in regulating the enhanced glycolysis in Dox-resistant TNBC cells. Knocking down ALKBH3 reduced ATP generation, glucose consumption, and lactate production, implicating its involvement in mediating glycolysis. Further investigation revealed that aldolase A (ALDOA), a key enzyme in glycolysis, is a downstream target of ALKBH3. ALKBH3 regulates ALDOA mRNA stability through m¹A demethylation at the 3'-untranslated region (3'UTR). This methylation negatively affects ALDOA mRNA stability by recruiting the YTHDF2/PAN2-PAN3 complex, leading to mRNA degradation. The ALKBH3/ALDOA axis promotes Dox resistance both in vitro and in vivo. Clinical analysis demonstrated that ALKBH3 and ALDOA are upregulated in breast cancer tissues, and higher expression of these proteins is associated with reduced overall survival in TNBC patients. Our study highlights the role of the ALKBH3/ALDOA axis in contributing to Dox resistance in TNBC cells through regulation of ALDOA mRNA stability and glycolysis.

Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.

Organoids can well simulate the heterogeneity of tumors,including tumor microenvironment and immune response,which helps to more accurately predict patient responses to drug and treatment effects.Organoids can be used for drug screening before drugs enter body,thus reducing the time and cost of clinical trials.However,research on tissue-organoids still faces some challenges,such as technical limitation and ethical issue.This review mainly introduces the progress in the research of breast cancer organoids,including the definition of organoids,development history,advantages and application in breast cancer research.

Objective:To analyze the changing trend of incidence and prevalence of pneumoconiosis globally, and provide scientific basis for the formulation of health policy.Methods:In June 2022, through the Global Health Data exchange (GHDx) query tool (http: //ghdx.healthdata.org/gbd-results-tool) , the pneumoconiosis incidence and prevalence data was downloaded and organized. Estimated annual percentage change (EAPC) and age-standardized rate (ASR) were used to estimate the trends of pneumoconiosis from 1990 to 2019. EAPC was estimated by linear regression model based on ASR.Results:The overall ASR of the incidence and prevalence of pneumoconiosis decreased from 1990 to 2019, and their EAPCs were-0.85% (95% CI: -1.11%--0.60%) and -0.78% (95% CI: -1.08%--0.49%) . Over the past 30 years, the incidence and prevalence of pneumoconiosis in all SDI areas showed decreasing trends, especially in high SDI areas, their EAPCs were -1.46% (95% CI: -1.76%--1.15%) and -1.99% (95% CI: -2.44%--1.53%) . 110 countries/areas showed increasing trends in age standardized incidence rate (ASIR) , with Iran and Georgia showing the most pronounced upward trend, their EAPCs were 5.32% (95% CI: 4.43%-6.22%) and 4.39% (95% CI: 3.81%-4.97%) . 125 countries/areas showed anincreasing trends in prevalence ASR, with Iran had the fastest rise in prevalence (EAPC=6.40%, 95% CI: 5.33%-7.49%) . Conclusion:Although decreasing trends in the burden of pneumoconiosis are observed globally from 1990 to 2019, but the burden of pneumoconiosis in low-and middle-income countries or regions are still heavy. We need more effective strategies to prevent and reduce the burden of pneumoconiosis.

Pyroptosis is a recently discovered programmed cell death mediated by cysteinyl aspartate specific proteinase （Caspase）， which may lead to the release of intracellular inflammatory substances to extracellular and induce inflammatory cascades.Autoimmune diseases （ADs） is a kind of disease in which the body's immune tolerance is impaired， and the body overproduces autoantibodies， causing damage to its tissues.The pathogenic factors of ADs are complex and the pathogenesis is still unclear. With the deepening of the research on pyroptosis， more and more results show that pyroptosis is involved in the pathogenesis of various ADs such as rheumatoid arthritis， ulcerative colitis， systemic lupus erythematosus， and psoriasis. Glucocorticoid drugs， anti-rheumatism drugs， and biological agents are mostly used in the clinical treatment of ADs， but the therapeutic effect of some drugs is limited， and there are some long-term adverse reactions. Chinese medicine in the treatment of ADs has been proven to be safe and effective in long-term clinical practice. It has the characteristics of multiple targets and few side effects and has certain advantages in controlling the course of the disease. More and more studies have found that a variety of Chinese medicine formulations， single Chinese medicine， and active ingredients of Chinese medicine treat ADs through the intervention of pyroptosis. Therefore， this paper reviewed the experimental studies on the effect of Chinese medicine on pyroptosis in ADs in recent years， hoping to provide references for clinical treatment and scientific research.

Objective To investigate the role and mechanism of circular RNA SNRK (circSNRK) in ischemia-reperfusion injury (IRI). Methods A hypoxia-reoxygenation (IRI) cell model was established. The expression level of circSNRK after IRI treatment and the effect of overexpression of circSNRK on cell proliferation and apoptosis were detected. The targets of circSNRK were identified. HK2 cells were divided into the blank group (Mock group), IRI group, control plasmid+IRI group (IRI+NC group), human circSNRK overexpression+IRI group (IRI+circSNRK group), human circSNRK overexpression+IRI+protein kinase B (Akt) inhibitor group (IRI+circSNRK+MK2206 group) and control plasmid group (NC group). Cell proliferation and apoptosis were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the target of circSNRK were carried out. The expression levels of CDKN1A, Akt, B-cell lymphoma (Bcl)-2, cysteinyl aspartate specific proteinase (Caspase)-9 messenger RNA (mRNA), and those of p21, Bcl-2, Caspase-9, Akt and p-Akt proteins were detected in the Mock, IRI, IRI+NC and IRI+circSNRK groups, respectively. Cell proliferation and apoptosis were determined in the NC, IRI+NC, IRI+circSNRK and IRI+circSNRK+MK2206 groups. Results Compared with the Mock group, the expression level of circSNRK was lower, and cell proliferation capability of HK2 cells was decreased and cell apoptosis was increased in the IRI group. In the IRI+circSNRK group, cell proliferation capability was higher, whereas cell apoptosis was lower than those in the IRI+NC group. circSNRK could act on 648 targets through 51 microRNAs (miRNAs). GO enrichment analysis revealed that the targets of circSNRK were mainly enriched in biological processes (such as cell process and biological regulation), cell components (such as cell parts, cells and extracellular parts), and molecular functions (such as binding, binding proteins and enzymes). KEGG enrichment analysis showed that the targets of circSNRK were mainly enriched in cancer signaling pathway, phosphatidylinositol 3-kinase (PI3K)-Akt signaling pathway, miRNA in cancer and other related signaling pathways. Compared with the Mock group, the relative expression levels of CDKN1A and Caspase-9 mRNA were higher, the expression level of miR-99a-5p RNA was higher and the relative expression levels of Akt and Bcl-2 mRNA were lower in the IRI group. Compared with the IRI+NC group, the relative expression levels of CDKN1A and Caspase-9 mRNA were lower, those of Akt and Bcl-2 mRNA were higher, and the expression level of miR-99a-5p RNA was lower in the IRI+circSNRK group, and the differences were statistically significant (all P < 0.05). Compared with the Mock group, the expression levels of p21 and Caspase-9 proteins were higher, while those of p-Akt, Akt and Bcl-2 proteins were lower in the IRI group. Compared with the IRI+NC group, the expression levels of p21 and Caspase-9 proteins were lower, whereas those of p-Akt, Akt and Bcl-2 proteins were higher in the IRI+circSNRK group. The miR-99a-5p binding sites were observed in circSNRK and Akt. Compared with the NC group, cell proliferation capability was declined in the IRI+NC group. Compared with the IRI+NC group, cell proliferation capability was elevated in the IRI+circSNRK group. Compared with the IRI+circSNRK group, cell proliferation capability was declined in the IRI+circSNRK+MK2206 group (all P < 0.05). The cell apoptosis level in the IRI+NC group was higher than that in the NC group. The cell apoptosis level in the IRI+circSNRK group was lower compared with that in the IRI+NC group. The cell apoptosis level in the IRI+circSNRK+MK2206 group was higher than that in the IRI+circSNRK group. Conclusions Under IRI conditions, circSNRK may affect the proliferation and apoptosis of HK2 cells probably via the Akt signaling pathway.

Objective:To investigate the clinical effect of early bronchoalveolar lavage on patients with aspiration pneumonia.Methods:A retrospective study was conducted on 55 patients with aspiration pneumonia who met inclusion criteria but not exclusion criteria in the Intensive Care Department of our hospital from January 2020 to April 2021. The patients were divided into the control group (32 cases) and the bronchoscopic lavage group (23 cases) according to whether they received bronchoscopic lavage within 24 h after aspiration. Basic information (sex, age, body mass index, chest X-ray score, oxidation index, temperature, heart rate, respiratory rate, white blood cells, PCT, IL-6, CPR and APACHE Ⅱ score), etiology changes at the early stage (≤ 3 d) and later stage (4-7 d after admission), and changes in prognostic indexes (mechanical ventilation time, length of ICU stay, length of stay and mortality) were compared between the two groups. The clinical efficacy of early endoscopy lavage for aspiration pneumonia was evaluated.Results:The positive rate of early etiological culture was 85.2%, the bacterial positive rate was 72.9% and the fungal positive rate was 14.6%. Pseudomonas aeruginosa accounted for 20.8%, Klebsiella pneumoniae accounted for 14.6%, Staphylococcus aureus and Streptococcus accounted for 12.5%, and there was no significant difference in the distribution between the bronchoscopic lavage group and the control group (all P>0.05). The positive rate of late etiological culture was 88.6%, the bacterial positive rate was 85.7% and the fungal positive rate was 2.9%. The positive rate of late bacterial culture was significantly decreased in the bronchoscopic lavage group ( P < 0.05), and the other results were not significantly different from the control group (all P>0.05). After early bronchoscopic lavage, the duration of mechanical ventilation, length of ICU stay and length of stay were significantly shortened, and the fifth day CPIS score was significantly decreased (all P< 0.05). Conclusions:Early endotracheal lavage can reduce mechanical ventilation time, length of ICU stay and length of stay of aspiration pneumonia, and reduce the positive rate of bacterial culture in the lung at the later stage, which needs to be further verified by a large randomized controlled study.

Objective:To explore the airway pathogen characteristics and examine the correlation between donor-derived pathogens and post-transplant outcomes in patients after lung transplantation (LT).Methods:Between January 1, 2015 and December 31, 2019, retrospective review was conducted for clinical and microbiological data of 88 LT recipients.Airway pathogen percentage of different microorganisms and evolution of drug-resistance were examined.Drug-resistant pathogen positive group (n=71) and negative group (n=17) were assigned according to whether or not drug-resistant pathogens were detected.Survival analysis was conducted by Log-rank with 3-year follow-ups.Between April 11, 2020 and September 5, 2020, prospective study was conducted in 14LT recipients.The potential pathogenic bacteria from donor lungs were detected by metagenomic next generation sequencing and the impact of those bacteria was examined on 1-year post-transplantation outcome in 2020.Microbial diversity and richness were shown with Shannon index.The outcome variables included heart rate, neutrophil count, lymphocyte count, immunoglobulin level and pulmonary spirometry.ANOVA and Pearson's correlation analysis were performed for elucidating the relationship between airway microbiota and post-LT outcomes.Results:From 2015 to 2019, 88 recipients were recruited and 992 strains of airway pathogens were isolated, including bacteria 796 strains and fungi 196 strains.Gram-negative bacteria (704 strains) accounted for 88.4% of all bacteria.The detection rates of Gram-positive bacteria, Klebsiella pneumonia (Kp), Acinetobacter baumannii (Ab), Stenotrophomonas maltophilia and Candida increased in 2019 than that in 2015 (8.2% vs. 5.3%, 13.6% vs. 13.2%, 33.2% vs. 17.5%, 6.5% vs. 5.3%, 26.6% vs. 20.2%). Drug resistance rate of Kp to imipenem was 68.18% in 2019 and drug resistance rate of Ab to imipenem 98.44%.The 3-year survival rate was 46.3% and 35.3% in drug-resistance positive and negative groups and the difference was insignificant ( P=0.410). Fourteen recipients were enrolled in 2020.Potential pathogenic bacteria could be detected in all donor samples.Five recipients carried the same bacteria and two died during 1-year follow-up.Nine recipients did not carry the donor-derived pathogens and two died during 1-year follow-up.The diversity of donor/recipient-derived airway microbiota (Shannon index) showed no correlation with the outcomes of 1-year follow-up by Pearson's correlation test. Conclusions:Gram-negative bacteria predominated in airway pathogens of recipients post-LT.The drug resistance rate to imipenem remained high.The donor/recipient-derived pathogen isolates showed no correlation with immediate outcomes post-LT.

Background::The calcineurin inhibitor (CNI)-based immune maintenance regimen that is commonly used after renal transplantation has greatly improved early graft survival after transplantation; however, the long-term prognosis of grafts has not been significantly improved. The nephrotoxicity of CNI drugs is one of the main risk factors for the poor long-term prognosis of grafts. Sirolimus (SRL) has been employed as an immunosuppressant in clinical practice for over 20 years and has been found to have no nephrotoxic effects on grafts. Presently, the regimen and timing of SRL application after renal transplantation vary, and clinical data are scarce. Multicenter prospective randomized controlled studies are particularly rare. This study aims to investigate the effects of early conversion to a low-dose CNI combined with SRL on the long-term prognosis of renal transplantation.Methods::Patients who receive four weeks of a standard regimen with CNI + mycophenolic acid (MPA) + glucocorticoid after renal transplantation in multiple transplant centers across China will be included in this study. At week 5, after the operation, patients in the experimental group will receive an additional administration of SRL, a reduction in the CNI drug doses, withdrawal of MPA medication, and maintenance of glucocorticoids. In addition, patients in the control group will receive the maintained standard of care. The patients’ vital signs, routine blood tests, routine urine tests, blood biochemistry, serum creatinine, BK virus (BKV)/cytomegalovirus (CMV), and trough concentrations of CNI drugs and SRL at the baseline and weeks 12, 24, 36, 48, 72, and 104 after conversion will be recorded. Patient survival, graft survival, and estimated glomerular filtration rate will be calculated, and concomitant medications and adverse events will also be recorded.Conclusion::The study data will be utilized to evaluate the efficacy and safety of early conversion to low-dose CNIs combined with SRL in renal transplant patients.Trial registration::Chinese Clinical Trial Registry, ChiCTR1800017277.

Objective:To study on the effects of gastrointestinal function and portal vein hemodynamics applicated with abdominal hot compressing with evodiae fructus and crude salt after hepatectomy.Methods:A total of 60 patients who underwent hepatectomy were randomly divided into 2 groups by random number table method, with 30 in each group. The control group was treated with conventional basic western medicine, while the treatment group was treated with medicinal evodiae fructus and crude salt hot compress on abdomen on the basis of the control group. The portal vein diameter (PVD), portal venous flow velocity (PVV), recovery time of main clinical indexes, clinical symptom scores and liver function indexes were dynamically monitored at different observation time points.Results:The scores of abdominal distension, nausea and vomiting in the treatment group were significantly lower than those in the control group 3 days after treatment ( t values were -3.489 and -2.740, respectively, all Ps<0.05). The recovery time of bowel sounds, first exhaust time and first defecation time in the treatment group were significantly earlier than those in the control group ( t values were -3.622, -4.297 and -4.151, respectively, all Ps<0.01). With the extension of treatment time, ALT in 2 groups showed a gradual downward trend ( P<0.05 or P<0.01), DBIL in control group was significantly higher at 3 days after treatment than before ( t=-2.157, P=0.039), and TBIL was significantly lower at 7 days after treatment than before ( t=2.175, P=0.038). The PVD ( t values were 3.528, 2.160) and PVV ( t values were 11.096, 4.264) of the treatment group were significantly higher than those of the control group 3 and 5 days after treatment ( P<0.01 or P<0.05). Conclusion:Early application of abdominal hot compressing with evodiae fructus and crude salt hot compress on abdomen after hepatectomy can improve the portal vein blood circulation and promote the rehabilitation of gastrointestinal function in patients with hepatectomy.