OBJECTIVE To evaluate the anticoagulant efficacy and safety of nafamostat mesylate （NM） in the treatment of uremic patients at high risk of bleeding undergoing continuous veno-venous hemofiltration （CVVH） with different methods （pre- dilution and post-dilution）. METHODS A total of 130 uremic patients at high risk of bleeding who underwent CVVH treatment in the nephrology department of Chongqing University Three Gorges Hospital from July 2023 to September 2024 were selected. They were divided into pre-dilution group and post-dilution group according to the random number table method， with 65 cases in each group. Both groups of patients received CVVH treatment under NM anticoagulation. The pre-dilution group adopted the pre-dilution replacement method， while the post-dilution group adopted the post-dilution replacement method. The coagulation， pressure， and usage duration of the filter and dialysis circuit venous reservoirs were compared between the two groups. The changes in prothrombin time （PT）， prothrombin time-international normalized ratio （PT-INR）， activated partial thromboplastin time （APTT）， and fibrinogen （FIB） in the peripheral venous blood before the heparin pump and after the filter at 1， 4 and 7 h of CVVH treatment， as well as 20 min after the end of treatment， were compared between the two groups. The single-compartment urea clearance rate （spKt/V）， β2-microglobulin （β2-MG） clearance rate and the incidence of adverse reactions were duni2007@foxmail.com compared between the two groups. RESULTS Both the pre-dilution and post-dilution groups had 60 patients who completed the study. The incidence of grade Ⅱ-Ⅲ coagulation of the filter and venous reservoirs， as well as the number of patients with transmembrane and venous pressure alarm intervention in the post- dilution group were significantly higher or more than those in the pre-dilution group （P＜0.05）， while usage time of the filter and the pipeline in the post-dilution group was significantly shorter than that in the pre-dilution group （P＜0.05）. The APTT values before the heparin pump as well as PT and APTT values after the filter at 1 h， 4 h， and 7 h of CVVH treatment in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There were no significant differences in PT， PT- INR， APTT and FIB between the two groups of patients 20 min after the end of treatment （P＞0.05）. The spKt/v and β2-MG clearance rates in the post-dilution group were significantly higher than those in the pre-dilution group （P＜0.001）. There was no significant difference in the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS When NM is used as an anticoagulant in the CVVH treatment of uremic patients at high risk of bleeding， compared with the pre-dilution treatment method， the post-dilution treatment method has a higher incidence of filter and dialysis tubing venous reservoir， a shorter usage time of the filter and pipeline， and a greater impact on extracorporeal coagulation， but has a higher solute clearance rate. Clinically， different dilution methods can be selected according to the different treatment needs of patients.

AIM: To explore the effect of adiponectin(ADPN)on angiogenesis of human retinal microvascular endothelial cells(hRMECs)in high glucose(HG)environment and role of NOD-like receptor family pyrin domain containing 3(NLRP3)inflammasome.METHODS: The hRMECs were divided into six groups, including control group(without treatment), HG group: incubated with D-glucose, ADPN group: pretreatment with ADPN and then incubated with D-glucose, CY-09 group: pretreatment with CY-09(an NLRP3 inhibitor)and then incubated with D-glucose, Nigericin group: pretreatment with nigericin(an NLRP3 activator)and then incubated with D-glucose, Nigericin+ADPN group: pretreatment with nigericin and ADPN and then incubated with D-glucose. NLRP3 level was detected using Western blot analysis. hRMECs migration was measured using scratch wound healing assay. The tube formation of hRMECs was detected using Matrigel.RESULTS: The NLRP3 expression in hRMECs cultured in an HG environment was significantly increased(P<0.01), while ADPN and CY-09 reduced the elevated NLRP3(both P<0.05 vs HG group). Nigericin significantly increased NLRP3 levels(P<0.01 vs control group)which was reversed by ADPN(P=0.032 vs Nigericin group). hRMECs migration ability(P<0.001), and total master segments length and number of meshes increased in HG group(P<0.001)while decreased in ADPN and CY-09 groups(all P<0.01 vs HG group). The hRMECs migration ability and tube formation(total master segments length and number of meshes)in HG environment were significantly increased by nigericin(P=0.003), while ADPN inversed the change. CONCLUSION: ADPN alleviates the migration and angiogenesis of hRMECs under HG conditions.

ObjectiveTo investigate the novel post-translational modifications (PTMs) of SnRK2.6, a central component in the abscisic acid (ABA) signaling pathway, such as SUMOylation, and to establish a foundation for revealing the physiological functions and molecular mechanisms of SnRK2.6 regulated by these new modifications. MethodsThe interaction between SnRK2.6 and the SUMO E3 ligase SIZ1, as well as members of the SUMO protease family, was examined using yeast two-hybrid and in vitro pull-down assays. An in vitro SUMOylation system in Escherichia coli was utilized to determine whether SnRK2.6 undergoes SUMOylation. Mass spectrometry, combined with site-directed mutagenesis of candidate lysine residues, was employed to identify potential SUMOylation sites on SnRK2.6. In vitro de-SUMOylation assays were performed to assess whether SUMO proteases interacting with SnRK2.6 could catalyze the removal of SUMO moieties from modified SnRK2.6. The protein stability of SnRK2.6 was assessed in a cell-free degradation assay using bacterial-purified SnRK2.6 incubated with total protein extracts from Col and siz1 mutant seedlings. To dissect the genetic relationship between SnRK2.6 and SIZ1, stomatal aperture assays were performed under ABA treatment using snrk2.6, siz1, and snrk2.6 siz1 double mutant plants. ResultsSnRK2.6 physically interacts with SIZ1 and the SUMO protease ESD4, with the binding domains localized to the C-terminal region of SIZ1 and the N-terminal region of ESD4, respectively. SnRK2.6 was found to be SUMOylated, exhibiting two distinct high-molecular-mass bands ranging from 70 to 100 ku, indicative of modified forms. Bioinformatics analysis predicted four putative SUMOylation sites on lysine residues K57, K63, K142, and K190. Mass spectrometry identified three SUMOylation sites on K63, K142, and K174. However, individual or combinatorial point mutations on these sites had minimal impact on the pattern or intensity of SUMOylation signals, suggesting that these residues may not be responsible for the SUMOylation on SnRK2.6. Instead, such mutations only weaken the protein stability or accelerate the protein mobility of SnRK2.6. Therefore, the exact SUMOylation sites on SnRK2.6 remain unidentified. In de-SUMOylation experiments, incubation of GST-ESD4 with SUMOylated SnRK2.6 for 1-2 h led to the near-complete disappearance of both SUMOylated bands. In contrast, neither the GST control nor the catalytically inactive mutant GST-ESD4^C448S exhibited any de-SUMOylation activity. In protein turnover experiments, SnRK2.6 exhibited markedly enhanced half-life in siz1 compared with Col, indicating that SIZ1-dependent SUMOylation promotes SnRK2.6 turnover. Phenotypically, snrk2.6 mutants were completely insensitive to ABA-induced stomatal closure; siz1 mutants displayed pronounced hypersensitivity; and the snrk2.6 siz1 double mutant phenocopied snrk2.6—showing no significant response to ABA beyond that of the snrk2.6 mutant. These data indicate that SIZ1 acts as a negative regulator of ABA-triggered stomatal closure and SnRK2.6 functions as a positive regulator, and the inhibitory activity of SIZ1 is strictly dependent on SnRK2.6, placing SnRK2.6 genetically upstream of SIZ1 in the ABA signaling pathway. ConclusionSnRK2.6 undergoes SUMOylation, although the specific SUMOylation sites have not been defined. SnRK2.6 is dynamically regulated by reversible SUMOylation—catalyzed by SIZ1 and reversed by ESD4—which controls its protein stability. SUMOylation acts as a destabilizing signal for SnRK2.6, and SIZ1 exerts its negative effect on ABA-triggered stomatal closure probably through promoting SnRK2.6 degradation via SUMOylation. These findings uncover SUMOylation as a critical regulatory layer fine-tuning SnRK2.6 abundance in ABA signaling.

OBJECTIVE To study the quality standard of the ethnic medicine Diplazium lanceum， and to provide reference for its quality control.METHODS The medicinal material of D. lanceum was identified by properties， microscopy， and thin-layer chromatography（TLC）， and its moisture， ash， and extract contents were determined. The contents of chlorogenic acid and rutin in 10 batches of D. lanceum were determined by high-performance liquid chromatography . RESULTS The rhizome of D. lanceum is slender and creeping， the leaf is leathery and shriveled， and yellow sporangia are borne on the abaxial surface of the leaf. The transverse section of the leaf shows inclusions， sclerenchyma， phloem cells， etc.； the transverse section of the petiole shows ground tissue， sclerenchyma， endodermis， etc.； the transverse section of the rhizome shows ground tissue， tracheids， vascular bundles， etc.； and the powder shows spiral vessels and brown inclusions. The TLC identification results showed that the chromatogram of the test sample exhibited spots of the same color at the corresponding positions as the chromatogram of the chlorogenic acid reference substance. The content ranges of moisture， total ash， acid-insoluble ash， extract， chlorogenic acid， and rutin in the 10 batches of samples were 10.18%-12.43%， 7.08%-19.12%， 0.95%-10.62%， 14.13%-26.05%， 0.113 1-1.015 9 mg/g， and 0.009 9-0.208 9 mg/g， respectively. CONCLUSIONS In the quality standard of D. lanceum， the moisture content should be ≤12.5%， total ash content should be ≤20.0%， acid-insoluble ash content should be ≤11.0%， extract content should be ≥14.0%， and chlorogenic acid content should be ≥0.11 mg/g. The established method is simple， specific， and reproducible， and can provide a scientific basis for the quality control of D. lanceum.

Objective To investigate the effects of combined exposure to benzene series, dust and noise on occupational high-frequency hearing loss (HFHL) in the electronics manufacturing industry. Methods A total of 740 employees from an electronic manufacturing enterprise were selected as the study subjects. According to the detection of occupational hazard factors, they were divided into noise group, noise benzene group, and noise dust group, with 325, 167, and 248 people, respectively. Occupational health examinations were conducted on the study participants to analyze their HFHL detection status and influencing factors. Results Among all participants (n=740), 456 (61.62%) were male, 284 (38.38%) were female, and 123 (15.62%) were detected with HFHL. The detection rate of HFHL increased with age and length of service (P<0.01). According to the exposure factor grouping, the detection rates of HFHL in the noise group, noise benzene group, and noise dust group were 12.00%, 19.16%, and 20.97%, respectively (P<0.05). Multivariate logistic regression analysis showed that workers aged ≥ 40 years, with 10-20 years of work experience, ≥ 20 years of work experience, exposure to noise and benzene series, and exposure to noise and dust had an increased risk of developing HFHL to 1.734, 1.923, 3.071, 1.706, and 1.527, respectively (P<0.05). Conclusion Combined exposure to noise and benzene series, combined exposure to noise and dust, as well as age and extended length of service may increase the risk of HFHL among workers.

Objective:To explore the effects of workload factors and social psychological factors on work-related musculoskeletal disorders (WMSDs) , construct a preventive decision-assisted ensemble learning model, and propose screening methods with clinical significance.Methods:In October 2022, 1071 workers from optoelectronic enterprises were selected as the research subjects by cluster sampling method. The general situation of workers, workload factors, social psychological factors and the occurrence of WMSDs were collected by using questionnaires. logistic regression, Extreme Gradient Boosting (XGBoost) , ensemble learning and classification chain model were adopted to explore the key factors influencing WMSDs, and the area under curve (AUC) was used to evaluate the model performance.Results:The incidence of WMSDs among workers in optoelectronic enterprises in the past year was 47.7% (511/1071) , among which the incidence of multi-site WMSDs was 54.4% (278/511) . logistic regression analysis showed that prolonged sitting, personnel shortage and forward neck tilt were risk factors for the occurrence of WMSDs in workers ( P<0.05) . XGBoost identified the key social psychological factors influencing WMSDs as low mood, mental tension, perceived happiness level, psychological calmness and tranquility. The integrated classification chain model based on the ordered label order had certain efficacy (AUC>0.7) when analyzing WMSDs at the neck, waist, shoulder, back, elbow and hip positions. Conclusion:Workload factors are the main risk factors for the occurrence of WMSDs among workers in optoelectronic enterprises, and social psychological factors also have potential influences. The construction of a classification chain model can accurately identify the occurrence of WMSDs in multiple parts. The alternating prevention strategy of workload factors and social psychological factors has important public health significance.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

To investigate the impact of high salt stress on the metabolic pathways and regulatory mecha-nisms involved in synthesizing hydroxyectoine(5-HE)in Virgibacillus salexigens,cultures were supple-mented with 1.5 and 2.5 mol/L NaCl as control and experimental groups,respectively.High-perform-ance liquid chromatography(HPLC)was used to detect the difference in the amount of 5-HE synthesis.Transcriptomic and metabolomic analyses identified differential genes and metabolites under varying salt concentrations.Key differential gene expressions related to 5-HE synthesis were validated using qRT-PCR.Results showed that 5-HE synthesis reached 121.9 mg/L at 2.5 mol/L NaCl.Transcriptomic anal-ysis identified 652 differentially expressed genes across 348 KEGG pathways,with 210 upregulated and 442 downregulated,primarily enriched in pathways such as purine metabolism,amino acid biosynthesis,sulfur metabolism,and biotin metabolism.Validation of 13 genes,including lysC,asd,ectA,ectB,ectC,ectD,thrB,thrC,ilvA,ilvE,AGXT,YckA and GlnQ,showed expression trends consistent with transcriptome data.Metabolomic analysis identified 1153 metabolites predominantly enriched in histidine metabolism,lysine degradation,and arginine and proline metabolism.This study preliminarily elucidated the effect of high salt on the 5-HE synthesis pathway,and provided a basis for the subsequent construc-tion of 5-HE high-yielding strains.

Objective To investigate the expression level and clinical application value of circular RNA hsa_circ_0001766 in gastric cancer(GC)tissues and serum of patients with GC.Methods The PCR amplification products from GES-1 cells of normal gastric mucosa were analyzed for the cyclic sites of hsa_circ_0001766 by the Sanger sequencing technique.The expression levels of hsa_circ_0001766 in GES-1 cells treated or untreated with RNase R(RNase R)were detected by real-time fluorescence quantitative PCR(qRT-PCR).The expression levels of hsa_circ_0001766 in GC and adjacent tissues of 73 GC patients and serum samples of 34 GC patients were also detected by qRT-PCR.The receiver operating characteristics(ROC)curve was used to evaluate the clinical diag-nostic value of hsa_circ_0001766 in GC.The correlations between hsa_circ_0001766 and clinicopathological parameters in GC patients were also analyzed.Results There was cyclic sites in hsa_circ_0001766 and RNase R had no significant impact on the expression lev-el of hsa_circ_0001766 in GES-1 cells(t=1.678,P=0.169).Compared with adjacent tissues,the expression levels of hsa_circ_0001766 in GC tissues were significantly up-regulated(U=1 360,P<0.001).Compared with healthy controls,the expres-sion levels of hsa_circ_0001766 in serum of GC patients were significantly up-regulated(U=375,P<0.001).The area under the ROC curve(AUCROC),sensitivity,and specificity of hsa_circ_0001766 in GC tissues for diagnosing GC were 0.759(95％CI:0.682-0.837,P<0.000 1),79.45％,and 68.49％,respectively.The AUCROC,sensitivity,and specificity of serum hsa_circ_0001766 in diagnosing GC were 0.773(95％CI:0.662-0.884,P<0.000 1),73.53％,and 72.12％,respectively.The expression levels of hsa_circ_0001766 in GC tissues were correlated with lymph node metastasis(x2=5.509,P=0.019)and TNM staging(x2=5.161,P=0.023).The 3-year survival rate of GC patients with high expression of hsa_circ_0001766 in GC tissues was significantly lower than that with low ex-pression(x2=3.700,P=0.037).Conclusion The hsa_circ_0001766 in GC tissues and serum of GC patients is highly expressed,and its change in the expression level is of great significance for the diagnosis and prognostic evaluation of GC patients.

Objective:To evaluate the feasibility of transjugular transcatheter tricuspid valve replacement (TTVR) using the LuX-Valve Plus system (Ningbo Jenscare Scientific, China) for the treatment of severe tricuspid regurgitation in real-world clinical settings.Methods:This prospective study enrolled 81 patients with severe ricuspid regurgitation (≥3+) who underwent TTVR with the LuX-Valve Plus system at the Department of Cardiology, West China Hospital of Sichuan University between May 2022 and March 2024. Among them, 44 patients were from a compassionate-use study, and 37 were from two premarket clinical trials. Baseline clinical data, preprocedural imaging, procedural outcomes, and postprocedural follow-up data were collected. The primary endpoint events included device success, procedural success, and 30 d composite adverse events.Results:The age of the cohort was (74.5±7.8) years, with 54 females (67%). Device success and procedural success rates were both 90% (73/81). Post-procedural tricuspid regurgitation improved, with a 6% (5/81) incidence of moderate-to-severe paravalvular leakage. The rate of permanent pacemaker implantation was 12% (10/81), of which 5% (4/81) had pre-existing indications for pacemaker implantation. Major bleeding events occurred in 10% (8/81) of patients, and the 30 d composite endpoint rate was 25% (20/81).Conclusion:TTVR using the LuX-Valve Plus system demonstrates promising feasibility for high-risk surgical patients with severe tricuspid regurgitation, effectively reducing or eliminating regurgitation with acceptable safety. However, challenges remain in reducing risks of major adverse events, including permanent pacemaker implantation and severe bleeding.