BACKGROUND:Multiple studies have confirmed that mitogen-activated protein kinase(MAPK)signaling pathway is involved in cell proliferation,and microRNA(miR)is involved in the occurrence and development of hypertrophic scars.Therefore,the role of miR-27a-3p and MAPK signaling pathways in pathological scar formation has been further explored. OBJECTIVE:To explore the effect of miR-27a-3p on the proliferation of human hypertrophic scar fibroblasts through the MAPK signaling pathway. METHODS:The primary fibroblasts were isolated and collected from the skin samples.The primary fibroblasts were observed by inverted microscope and verified by immunofluorescence.The relative expression level of miR-27a-3p in tissues was detected by qRT-PCR.The target genes of hsa-miR-27a-3p were predicted using the database,and then the predicted target genes were enriched by gene ontology function analysis and biological pathway enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes.There were seven groups:blank control,negative control,miR-27a-3p mimic,miR-27a-3p inhibitor,miR-27a-3p mimic+p38 MAPK inhibitor,miR-27a-3p mimic+extracellular regulated protein kinase inhibitor,miR-27a-3p mimic+c-Jun N-terminal kinase inhibitor.Western blot was used to detect the levels of extracellular regulated protein kinase,c-Jun N-terminal kinase inhibitor.and p38 kinase and their phosphorylation levels.Cell counting kit-8 and EdU were used to detect cell proliferation. RESULTS AND CONCLUSION:Compared with normal skin fibroblasts,hypertrophic scar fibroblasts had stronger proliferative activity(P<0.05)and faster proliferation level(P<0.001).Compared with normal skin,miR-27a-3p was highly expressed in hypertrophic scars(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p could promote cell proliferation activity(P<0.001)and proliferation levels(P<0.001).Compared with the negative control group,knockdown of miR-27a-3p could inhibit the proliferation activity(P<0.05)and proliferation levels(P<0.001).Compared with the negative control group,overexpression of miR-27a-3p promoted the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 mitogen-activated protein kinase(P<0.05).Compared with the negative control group,knockdown of miR-27a-3p inhibited the phosphorylated levels of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK(P<0.05).Compared with the miR-27a-3p mimic group,specific inhibitors of extracellular regulated protein kinase,c-Jun N-terminal kinase,and p38 MAPK reversed the effects of miR-27a-3p on the proliferative activity(P<0.01)and proliferation level(P<0.001)of fibroblasts.To conclude,these results suggest that miR-27a-3p promotes the proliferation of human hypertrophic scar fibroblasts by activating the MAPK signaling pathway.

OBJECTIVE To investigate the effects and mechanism of total alkaloids of Corydalis Rhizoma （TAC） on the regulation of cuproptosis in rats with diabetic cardiomyopathy （DCM） based on silence information regulator 1（Sirt1）/tumor protein 53（P53）signaling pathway. METHODS DCM rat model was induced by high-fat and high-sugar diet and intraperitoneal injection of streptozotocin. Thirty-two model rats were randomly divided into model group， TAC low-dose， medium-dose and high-dose groups （7， 10.5， 14 mg/kg）， with 8 rats in each group. An additional 8 rats were assigned to normal control group. Related drugs or normal saline were administered intragastrically in each group， once a day， for 4 weeks. After the last medication， the fasting blood glucose （FBG） levels of the rats were measured. The levels of myocardial creatine kinase （CK）， creatine kinase isoenzyme （CK-MB）， and lactate dehydrogenase （LDH） in serum and myocardial tissue of rats were all detected. The pathological morphology， fibrosis degree， and Cu2+ deposition of myocardial tissue in rats were observed. The levels of Cu2+ and glutathione （GSH） in myocardial tissue， the expressions of Sirt1/P53 signaling pathway-related proteins [Sirt1， P53， solute carrier family 7 membrane 11 （SLC7A11）]， and iron-sulfur cluster-related proteins [ferredoxin 1 （FDX1）， lipoic acid synthetase （LIAS）， aconitase 2 （ACO2）， NADH-ubiquinone oxidoreductase core subunit S8 （NDUFS8）， dihydrolipoamide acetyltransferase （DLAT）， dihydrolipoamide succinyltransferase （DLST）]， and heat shock protein 70 （HSP70） were all determined. RESULTS Compared with normal control group， the model group exhibited significantly elevated levels of FBG， CK， CK-MB and LDH in both serum and myocardial tissue， as well as increased 2+ levels of Cu in myocardial tissue and the expression of P53 and HSP70 proteins （P＜0.05）； the level of GSH and the expression levels of Sirt1， SLC7A11， FDX1， LIAS， ACO2， NDUFS8， DLAT， and DLST proteins in myocardial tissue were all significantly decreased （P＜0.05）； the myocardial tissue exhibited severe pathological damage， with numerous inflammatory cell infiltrations and significant fibrosis， as well as increased deposition of Cu2+. Compared with model group， most of the above quantitative indicators in rats were significantly reversed in TAC groups （P＜0.05）； the pathological damage to the myocardial tissue was alleviated， with reduced fibrosis and Cu2+ deposition. CONCLUSIONS TAC can ameliorate DCM in rats， and its mechanism of action may be related to activating the activity of the Sirt1/P53 signaling pathway， promoting the chelation of GSH with Cu2+， and inhibiting cuproptosis of cardiomyocyte.

OBJECTIVE To evaluate the quality of evidence in the systematic evaluation/meta-analysis of traditional Chinese medicine （TCM） for diabetes retinopathy （DR） based on the GRADE system. METHODS Chinese and English databases were searched to obtain the relevant studies of systematic evaluation/meta-analysis of traditional Chinese medicine in the treatment of DR. The search time was from the establishment of each database to January 13th， 2024. According to the inclusion and exclusion criteria， literature screening was conducted. After extracting relevant information from the included literature， the GRADE system was used to evaluate the quality level of the evidence body in the included studies， and the evidence of the outcome indicators was integrated and summarized. RESULTS A total of 51 studies were ultimately included， encompassing 135 outcome indexes. Among these， 19 indicators （14.1%） were of high quality， 87 （64.4%） were of medium quality， 26 （19.3%） were of low quality， and 3 （2.2%） were of very low quality. Overall， the evidence quality of the outcome indicators in the included studies was medium to low quality. The integrated results of evidence on the efficacy of outcome indexes showed that compared with conventional Western medicine， calcium dobesilate or placebo， TCM had significant advantages in improving overall efficacy， reducing bleeding spot area， reducing macular foveal thickness， and increasing visual improvement rate. In addition，the combination of TCM and conventional Western medicine or calcium dobesilate was significantly more effective than using conventional Western medicine or calcium dobesilate alone. CONCLUSIONS The overall quality of the evidence in the systematic evaluation/meta-analysis study on the treatment of DR with TCM is medium to low quality. Based on existing research findings， TCM demonstrates good clinical efficacy in the treatment of DR.

Ferroptosis, a programmed cell death modality discovered and defined in the last decade, is primarily induced by iron-dependent lipid peroxidation. At present, it has been found that ferroptosis is involved in various physiological functions such as immune regulation, growth and development, aging, and tumor suppression. Especially its role in tumor biology has attracted extensive attention and research. Breast cancer is one of the most common female tumors, characterized by high heterogeneity and complex genetic background. Triple negative breast cancer (TNBC) is a special type of breast cancer, which lacks conventional breast cancer treatment targets and is prone to drug resistance to existing chemotherapy drugs and has a low cure rate after progression and metastasis. There is an urgent need to find new targets or develop new drugs. With the increase of studies on promoting ferroptosis in breast cancer, it has gradually attracted attention as a treatment strategy for breast cancer. Some studies have found that certain compounds and natural products can act on TNBC, promote their ferroptosis, inhibit cancer cells proliferation, enhance sensitivity to radiotherapy, and improve resistance to chemotherapy drugs. To promote the study of ferroptosis in TNBC, this article summarized and reviewed the compounds and natural products that induce ferroptosis in TNBC and their mechanisms of action. We started with the exploration of the pathways of ferroptosis, with particular attention to the System X_c^--cystine-GPX4 pathway and iron metabolism. Then, a series of compounds, including sulfasalazine (SAS), metformin, and statins, were described in terms of how they interact with cells to deplete glutathione (GSH), thereby inhibiting the activity of glutathione peroxidase 4 (GPX4) and preventing the production of lipid peroxidases. The disruption of the cellular defense against oxidative stress ultimately results in the death of TNBC cells. We have also our focus to the realm of natural products, exploring the therapeutic potential of traditional Chinese medicine extracts for TNBC. These herbal extracts exhibit multi-target effects and good safety, and have shown promising capabilities in inducing ferroptosis in TNBC cells. We believe that further exploration and characterization of these natural compounds could lead to the development of a new generation of cancer therapeutics. In addition to traditional chemotherapy, we discussed the role of drug delivery systems in enhancing the efficacy and reducing the toxicity of ferroptosis inducers. Nanoparticles such as exosomes and metal-organic frameworks (MOFs) can improve the solubility and bioavailability of these compounds, thereby expanding their therapeutic potential while minimizing systemic side effects. Although preclinical data on ferroptosis inducers are relatively robust, their translation into clinical practice remains in its early stages. We also emphasize the urgent need for more in-depth and comprehensive research to understand the complex mechanisms of ferroptosis in TNBC. This is crucial for the rational design and development of clinical trials, as well as for leveraging ferroptosis to improve patient outcomes. Hoping the above summarize and review could provide references for the research and development of lead compounds for the treatment for TNBC.

OBJECTIVE To provide suggestions for improving the path and system construction of patient engagement in drug regulation in China. METHODS By reviewing initiatives and experiences from the United States （U. S.）， European Union （EU）， and Japan in promoting patient engagement， this study summarizes the roles and contributions of patients in the entire drug regulatory process internationally. Combining China’s current progress and challenges in patient engagement， specific proposals are formulated to refine regulatory pathways and institutional systems. RESULTS & CONCLUSIONS With growing global emphasis on patient engagement as a regulatory strategy， countries or regions such as the U.S.， EU， and Japan have established clear policies， designated oversight agencies， and developed diversified pathways for patient engagement. Patients contribute to regulatory processes through advisory meetings， direct decision-making roles， and leveraging lived experiences and expertise to optimize drug evaluation and monitoring. In contrast， China’s patient engagement remains primarily limited to clinical value- oriented drug development， lacking formal policy guidance. It is recommended that China， based on its existing policy system， further strengthen the construction of a safeguard system for patient engagement， improve the capacity building and pathway models for patient participation in pharmaceutical regulation， and promote the continuous development of patient engagement in pharmaceutical regulation in our country.

OBJECTIVE To analyze the potential adverse drug interactions （pADIs） of clarithromycin， and establish refined prescription pre-review rules. METHODS Outpatient prescriptions of clarithromycin in combination with other drugs were collected from January 1， 2024 to June 30， 2024 through hospital information system of the Third People’s Hospital of Bengbu. pADIs were identified and their risk severities were graded according to Lexicomp and Micromedex databases. Then， refined prescription pre- review rules for clarithromycin pADIs-related drugs were established according to the identification and risk level results. RESULTS Among 3 046 clarithromycin combined drug prescriptions， 946 cases of pADIs occurred in 812 prescriptions. There were 6， 415 and 525 cases classified as “contraindicated”，“ major” and “moderate”， respectively. The combination drugs with “contraindicated” levels were tamsulosin， rupatadine， domperidone and ticagrelor， while those with “major” levels were mainly theophylline， dexamethasone and amlodipine. Accordingly， 26 refined rules were established， including 4 items of “warning information→prescription interception”， 11 items of “warning information→prescription double signature” and 11 items of “attention information→prescription approval”. CONCLUSIONS There are “contraindicated” and “major” risks associated with clarithromycin and its combination drugs in the hospital， and refined prescription pre-review rules for clarithromycin combined drug prescription have been established successfully.

Background Recent advances in understanding the toxic effects of inorganic arsenic have revealed that arsenic exposure impacts multiple endocrine organs, thereby altering their functions. However, the mechanisms underlying arsenic-induced thyroid injury remain unclear. Objective To investigate the mechanisms by which sodium arsenite (NaAsO₂) affects the proliferation and apoptosis of normal thyroid cells (Nthy-ori3-1) through the estrogen receptor (ER)-phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway. Methods Nthy-ori3-1 cells were cultured in vitro and divided into the following groups: a control group (complete medium without drugs, 0 μmol·L⁻¹), and NaAsO₂-treated groups at 1, 2, and 4 μmol·L⁻¹. Additionally, 1 μmol·L⁻¹ of the ER inhibitor ICI182780 was used to intervene in the NaAsO₂ exposure groups, resulting in the following combinations: 1 μmol·L⁻¹ NaAsO₂ + ICI182780, 2 μmol·L⁻¹ NaAsO₂ + ICI182780, and 4 μmol·L⁻¹ NaAsO₂ + ICI182780. The median lethal concentration of NaAsO₂ was determined using cell viability assay. Cell viability was assessed at 24, 36, and 48 h using Cell Counting Kit-8 (CCK-8) assay. Colony formation ability was evaluated via plate cloning assay. Apoptosis was detected using Hoechst 33342 staining. Protein and mRNA expression levels of ERα, ERβ, c-MYC, Bax, Bcl-2, PI3K, p-PI3K, AKT, and p-AKT were measured using Western blot (WB) and real-time quantitative PCR (qRT-PCR), respectively. Results The median lethal concentration of NaAsO₂ was determined to be 4.034 μmol·L⁻¹. CCK-8 assay at 24, 36, and 48 h revealed that, compared with the control group, the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups significantly inhibited Nthy-ori3-1 cell proliferation (P < 0.001). The plate cloning assays demonstrated a concentration-dependent reduction in colony formation ability (P < 0.001). Following the ICI182780 intervention, the cell viability and colony formation ability in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups were significantly restored compared with the corresponding NaAsO₂-only groups (P < 0.001, P < 0.01). The Hoechst 33342 staining indicated that compared with the control group, the nuclear staining intensity and apoptosis levels in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups increased in a concentration-dependent manner (P < 0.001). However, the ICI182780 intervention reduced the apoptosis levels in the NaAsO₂-treated groups compared with their NaAsO₂-only counterparts (P < 0.001). The WB analysis showed that, compared with the control group, the protein expression of ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT in the 1, 2, and 4 μmol·L⁻¹ NaAsO₂ groups decreased manner (P < 0.001, P < 0.01), while the Bax expression increased in a concentration-dependent (P < 0.001); the PI3K and AKT protein levels showed no significant differences (P > 0.05). In the ICI182780-treated NaAsO₂ groups, the ERα, ERβ, c-MYC, Bcl-2, p-PI3K, and p-AKT protein expression increased (P < 0.001, P < 0.01), the Bax expression decreased (P < 0.001), and the PI3K and AKT levels remained unchanged (P > 0.05) compared with the corresponding NaAsO₂-only groups. The mRNA expression patterns of ERα, ERβ, c-MYC, Bcl-2, and Bax were consistent with the WB results. Conclusion NaAsO₂ inhibits proliferation and promotes apoptosis in Nthy-ori3-1 cells in a dose-dependent manner. The underlying mechanism likely involves NaAsO₂-mediated suppression of the ER-PI3K/AKT signaling pathway, which subsequently regulates downstream proliferation- and apoptosis-related genes.

The traditional Chinese medicine （TCM） myocardial infarction （MI） unit is a standardized， regulated， and continuous integrated care unit guided by TCM theory and built upon existing chest pain centers or emergency care units. This unit emphasizes multidisciplinary collaboration and forms a restructured clinical entity without altering current departmental settings， offering comprehensive diagnostic and therapeutic services with full participation of TCM in the treatment of MI. Its core medical model is patient-centered and disease-focused， providing horizontally integrated TCM-based care across multiple specialties and vertically constructing a full-cycle treatment unit for MI， delivering prevention， treatment， and rehabilitation during the acute， stable， and recovery phases. Additionally， the unit establishes a TCM-featured education and prevention mechanism for MI to guide patients in proactive health management， reduce the incidence of myocardial infarction， and improve quality of life.

Objective To analyze the current situation of the knowledge-attitude-practice among noise-exposed workers at an airport apron. Methods A total of 494 noise-exposed workers from an airport apron were selected as the study subjects using the judgmental sampling method. A self-designed "Occupational Protection Knowledge, Attitudes, and Practices Questionnaire" was used to assess the current situation of knowledge-attitude-practice on occupational protection. Results Regarding the awareness of noise hazards among the study subjects, the awareness rates of noise-induced impairment on digestive function and reproductive system were the lowest (44.9% and 37.7%, respectively). The awareness rate of noise-induced negative emotions increased with length of service (P<0.01). Regarding the occupational protection knowledge for noise, the awareness rate of occupational noise-induced deafness was “incurable” was the lowest (39.1%). The support rate for five kinds of occupational protection attitudes for noise was generally >85.0%, while only 58.3% of the study subjects consistently or frequently wearing earplugs during work. The most common source of noise hazard and protection knowledge was pre-employment training (76.9%), followed by occupational disease prevention and control campaigns (76.1%). Conclusion Noise-exposed workers in this airport apron have incomplete awareness of non-auditory system hazards caused by noise, and the awareness of knowledge of some occupational protection is relatively low. Although their attitudes toward occupational protection are positive, many workers still fail to consistently wear personal protective equipment at work.

Objective To understand the status of quality control in occupational medical examination (OME) institutions in Guizhou Province. Methods A total of 124 registered OME institutions actively conducting OME in Guizhou Province were selected as the study subjects using the judgment sampling method. The evaluation was conducted by on-site document reviews, practical skill assessments, and investigation of OME practices for quality evaluation and analyzing their quality control performance. Results The public institutions accounted for 71.0% with a 41.5% of OME workload, while private institutions accounted for 29.0% with a 58.5% of OME workload among these 124 OME institutions. The overall pass rate for quality evaluation of OME institutions was 16.9% (21/124), with a total of 1 296 items failed to pass the quality evaluation. Among the unqualified items, organizational structure, quality control management systems, OME quality control, and information reporting accounted for 15.2%, 21.7%, 52.8%, and 10.3%, respectively. The unqualified rate of quality assessment items of OME institutions was 24.5% (1 296/5 288), and the unqualified rate was lower in public institutions compared with private institutions (22.4% vs 29.3%, P<0.01). The rates of the three key unqualified items, including chest radiography conclusion evaluation, audiogram calculation and conclusion evaluation, and blood lead comparison were 9.8%, 74.8% and 71.4%, respectively. The rates of unqualified audiometry operation test and chief physician theory test were 74.8% and 9.7%, respectively. Conclusion The quality of OME institutions in Guizhou Province requires continuous improvement, particularly in enhancing the abilities of audiometry operation, calculating audiogram results and conducing right conclusion, and blood lead inter-laboratory comparision.