ObjectiveTo investigate the association between immunoglobulin G （IgG）/immunoglobulin M （IgM） ratio and prognosis in patients with initially unresectable hepatocellular carcinoma （iuHCC） receiving TTP triple therapy with transcatheter arterial chemoembolization （TACE）， tyrosine kinase inhibitor （TKI）， and programmed cell death protein-1 （PD-1） inhibitors. MethodsA retrospective analysis was performed for the clinical data of 151 iuHCC patients who received TTP triple therapy in Department of Hepatobiliary Surgery， Guangxi Medical University Cancer Hospital， from November 2019 to December 2022， and according to IgG/IgM ratio， they were divided into high IgG/IgM group （IgG/IgM ratio >13.23） and low IgG/IgM group （IgG/IgM ratio ≤13.23）. The t-test was used for comparison of continuous data between groups， and the chi-square test was used for comparison of categorical data between groups. The Kaplan-Meier method and the log-rank test were used for survival analysis， and the Cox proportional hazards model was used to investigate the potential influencing factors for overall survival （OS）. ResultsThe 151 patients had a median OS of 26.7 months （95% confidence interval ［CI］： 19.8-not reached） and a median progression-free survival of 12.5 months （95%CI： 10.4 — 15.8）. The objective response rate was 83.4% and the disease control rate was 94.0%. There were no significant differences in baseline data between the high IgG/IgM group and the low IgG/IgM group （all P>0.05）. There was a significant difference in median OS between the high IgG/IgM group and the low IgG/IgM group （20.6 months vs not reached， P=0.016）. In both the high IgG/IgM group and the low IgG/IgM group， salvage hepatectomy was significantly associated with the improvement in OS （χ²=8.297 and 10.307， both P<0.05）. The multivariate analysis showed that high IgG/IgM ratio （hazard ratio ［HR］=1.799， 95%CI： 1.077 — 3.006， P=0.025）， baseline alpha-fetoprotein >400 ng/mL （HR=1.762， 95%CI： 1.017 — 3.050， P=0.043）， and BCLC stage （HR=2.265， 95%CI： 1.212 — 4.232， P=0.010） were independent influencing factors for OS. ConclusionHigh IgG/IgM ratio is associated with a poorer prognosis in iuHCC patients receiving TTP triple therapy， and salvage hepatectomy has a potential value in improving the prognosis of patients with a high IgG/IGM ratio.

As the core vehicle for preserving and transmitting traditional Chinese medicine（TCM） academic thought and clinical experience， the establishment of a robust quality evaluation system for TCM clinical case reports is a crucial component in the current standardization and modernization of TCM. Based on the practical experience of constructing the China Clinical Cases Library of Traditional Chinese Medicine by the China Association of Chinese Medicine， this study conducted a comprehensive analysis of critical challenges， including insufficient authenticity and unfocused evaluation criteria. It proposed a three-dimensional evaluation framework grounded in the structure-process-outcome logic， encompassing three dimensions of authenticity and standardization， characteristics and advantages， application and translational impact. This framework integrated 12 key evaluation indicators in a systematic manner. The model preserved the academic characteristics of TCM syndrome differentiation and treatment， while aligning with modern scientific research standards， achieving a balance between individualized TCM experience and standardized evaluation. Concurrently， this study provided theoretical foundations and methodological guidance for evaluating the quality of TCM clinical cases， contributing significantly to the inheritance of TCM knowledge， evidence-based practice， and the reform of talent evaluation mechanisms.

Background The quality of occupational health technical services is directly linked to the protection of workers' health rights and the efficacy of occupational disease prevention and control. However, the industry still faces critical challenges: sporadic instances of institutional non-compliance and persistent irregularities in professional practice continue to undermine overall service performance. Objective To assess the current quality status of occupational health technical services in Zhejiang Province and propose countermeasures for quality improvement, providing a scientific basis for policy optimization and service delivery quality enhancement. Methods A total of 69 occupational health technical service institutions in Zhejiang Province that obtained formal accreditation as of April 30, 2024, were sampled, including 3 public institutions and 66 private institutions (comprising 3 formerly Class-A, 28 formerly Class-B, 11 formerly Class-C, and 24 newly certified institutions). Following the Technical Protocol for Quality Monitoring of Occupational Health Technical Service in Zhejiang Province and the Technical Protocol for Proficiency Testing of Occupational Health Detection in Zhejiang Province, a quality assessment task force comprising national and provincial experts was established. Evaluation was conducted across four dimensions: qualification maintenance and compliance, standardization of technical services, authenticity of technical services, and proficiency testing, utilizing a combination of document review, on-site inspections, and technical skill assessments. Results The occupational health technical service institutions in Zhejiang Province were predominantly private entities (82.5%), with significant disparities in overall service quality. The pass rates for qualification maintenance and compliance, technical service standardization, technical service authenticity, and the excellence rate for laboratory proficiency testing were 81.5%, 80.7%, 97.3%, and 90.4%, respectively. Regarding qualification maintenance, the pass rates for "environmental conditions" (49.8%, 56.7%) and "instrumentation and equipment" (58.2%、65.6%) were significantly lower for formerly Class-C and newly certified institutions compared to other categories. In terms of technical standardization, "standardized on-site inspections" recorded the lowest pass rate (67.4%), with newly certified institutions at only 48.0%. Regarding technical service authenticity, formerly Class-C institutions exhibited issues such as missing raw chromatograms for blank samples (85.7% pass rate). In laboratory proficiency testing, public and formerly Class-A institutions achieved 100% excellence rates, but the performance of formerly Class-C and newly certified institutions was comparatively weak; specifically, the failure rate for organic analysis in formerly Class-C institutions reached 20%; the failure rate for dust testing items in newly certified institutions was 10.3%. Conclusion The overall quality of occupational health technical services in Zhejiang Province still requires significant improvement, particularly in basic institutional conditions, the standardization of on-site inspections, and laboratory proficiency in organic and dust analysis. Formerly Class-C and newly certified institutions should be the primary focus of quality management efforts. Differentiated regulatory strategies are recommended, alongside strengthening interim and ex-post supervision to gradually enhance the quality of occupational health technical services across all institutions.

Distinct from the complementary inhibition mechanism through binding to the target with three-dimensional conformation of small molecule inhibitors, targeted protein degradation technology takes tremendous advantage of endogenous protein degradation pathway inside cells to degrade plenty of “undruggable” target proteins, which provides a novel route for the treatment of many serious diseases, mainly including proteolysis-targeting chimeras, lysosome-targeting chimeras, autophagy-targeting chimeras, antibody-based proteolysis-targeting chimeras, etc. Unlike proteolysis-targeting chimeras first found in 2001, which rely on ubiquitin-proteasome system to mainly degrade intracellular proteins of interest, lysosome-targeting chimeras identified in 2020, which was act as the fastly developing technology, utilize cellular lysosomal pathway through endocytosis mediated by lysosome-targeting receptor to degrade both extracellular and membrane proteins. As an emerging biomedical technology, nucleic acid-driven lysosome-targeting chimeras utilize nucleic acids as certain components of chimera molecule to replace with ligand to lysosome-targeting receptor or protein of interest, exhibiting broad application prospects and potential clinical value in disease treatment and drug development. This review mainly introduced present progress of nucleic acid-driven lysosome-targeting chimeras technology, including its basic composition, its advantages compared with antibody or glycopeptide-based lysosome-targeting chimeras, and focused on its chief application, in terms of the type of lysosome-targeting receptors. Most research about the development of nucleic acid-driven lysosome-targeting chimeras focused on those which utilized cation-independent mannose-6-phosphonate receptor as the lysosome-targeting receptor. Both mannose-6-phosphonate-modified glycopeptide and nucleic aptamer targeting cation-independent mannose-6-phosphonate receptor, even double-stranded DNA molecule moiety can be taken advantage as the ligand to lysosome-targeting receptor. The same as classical lysosome-targeting chimeras, asialoglycoprotein receptor can also be used for advance of nucleic acid-driven lysosome-targeting chimeras. Another new-found lysosome-targeting receptor, scavenger receptor, can bind dendritic DNA molecules to mediate cellular internalization of complex and lysosomal degradation of target protein, suggesting the successful application of scavenger receptor-mediated nucleic acid-driven lysosome-targeting chimeras. In addition, this review briefly overviewed the history of lysosome-targeting chimeras, including first-generation and second-generation lysosome-targeting chimeras through cation-independent mannose-6-phosphonate receptor-mediated and asialoglycoprotein receptor-mediated endocytosis respectively, so that a clear timeline can be presented for the advance of chimera technique. Meantime, current deficiency and challenge of lysosome-targeting chimeras was also mentioned to give some direction for deep progress of lysosome-targeting chimeras. Finally, according to faulty lysosomal degradation efficiency, more cellular mechanism where lysosome-targeting chimeras perform degradation of protein of interest need to be deeply explored. In view of current progress and direction of nucleic acid-driven lysosome-targeting chimeras, we discussed its current challenges and development direction in the future. Stability of natural nucleic acid molecule and optimized chimera construction have a great influence on the biological function of lysosome-targeting chimeras. Discovery of novel lysosome-targeting receptors and nucleic aptamer with higher affinity to the target will greatly facilitate profound advance of chimera technique. In summary, nucleic acid-driven lysosome-targeting chimeras have many superiorities, such as lower immunogenicity, expedient synthesis of chimera molecules and so on, in contrast to classical lysosome-targeting chimeras, making it more valuable. Also, the chimera technology provides new ideas and methods for biomedical research, drug development and clinical treatment, and can be used more widely through further research and optimization.

OBJECTIVE To investigate the expression and clinical significance of Periostin in tissues of patients with chronic rhinosinusitis(CRS).METHODS Real-time quantitative PCR and immunohistochemistry were used to detect periostin expression in eosinophilic CRS with nasal polyps(ECRSwNP),non-eosinophilic CRS with nasal polyps(non-ECRSwNP),CRS without nasal polyps(CRSsNP),and control tissues.Correlations between periostin levels and blood eosinophil percentage(Eos%),Lund-Mackay score,modified endoscopic score,and Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis(JESREC)score were analyzed.Additionally,changes in SNOT-22 and VAS scores were compared at different preoperative and postoperative times.The predictive value of periostin for ECRSwNP was evaluated using receiver operating characteristic(ROC)curve analysis.RESULTS Periostin expression was detected in all groups(ECRSwNP,non-ECRSwNP,CRSsNP,and controls),with predominant localization in the basement membrane and mucosal subepithelial lamina propria.Significantly elevated periostin levels were detected in the ECRSwNP group compared to the other three groups(P<0.001).Furthermore,Periostin mRNA expression showed significant positive correlations with blood Eos%,JESREC score,and Lund-Mackay score.SNOT-22 and VAS scores were significantly elevated in the ECRSwNP group at preoperative evaluation and 9 months postoperatively(P<0.001).ROC curve analysis demonstrated that periostin had a substantial predictive value for ECRSwNP(AUC=0.957).CONCLUSION Periostin plays a crucial role in the pathogenesis of chronic rhinosinusitis,contributing to the diagnosis,severity assessment,and prognosis evaluation of ECRSwNP,while offering potential therapeutic targets for CRS management.

OBJECTIVE To compare the expression characteristics of transforming growth factor-β1(TGF-β1),Smad2,Smad3,and epithelial-mesenchymal transition(EMT)-related markers(E-cadherin,N-cadherin,vimentin)in patients with different types of chronic sinusitis(CRS),to analyze the correlations of E-cadherin,N-cadherin and vimentin with TGF-β1 and the prognosis of surgical treatment in patients with different types of CRS.METHODS The expressions of E-cadherin,N-cadherin,vimentin,TGF-β1,Smad2 and Smad3 in patients with different types of CRS and the control group were compared by Western blotting(WB)and real-time fluorescence quantitative polymerase chain reaction(qRT-PCR).Analyze its correlation with the improvement degree of each clinical score after the operation.RESULTS Compared with the control group,the expression of E-cadherin decreased in the CRSsNP group,the non-ECRSwNP group and the ECRSwNP group,while the expressions of vimentin and N-cadherin increased.The protein expression of TGF-β1 in the CRSsNP group was higher than that in the non-ECRSwNP group and the control group(P<0.001),and the expressions of Smad2 and Smad3 in the CRSsNP group were higher than those in the ECRSwNP group,the non-ECRSwNP group and the control group(P<0.001).In the CRSsNP group,there was a positive correlation between TGF-β1 and vimentin(r=0.675,P=0.011),and a negative correlation with E-cadherin(r=-0.802,P=0.001).The expression of E-cadherin was negatively correlated with the improvement amplitude of SNOT-22 nasal symptom scores in patients with different types of CRS(P<0.05).CONCLUSION The EMT phenomenon occurs in different types of CRS.In CRS SNPS,EMT may be related to the TGF-β1/Smad signaling pathway.The expressions of EMT markers E-cadherin,N-cadherin and vimentin are correlated with the decrease in the severity of postoperative disease in patients with CRS,suggesting a potential association between the EMT process and the surgical prognosis of patients with CRS.

An effective method for simultaneously detecting four semivolatile earthy-musty odors in freshwater fish by gas chromatography-mass spectrometry(GC-MS)was developed.The concurrent extraction of geosmin(GSM),2-methylisoborneol(MIB),2-isopropyl-3-methoxypyrazine(IPMP),and 2-isobutyl-3-methoxypyrazine(IBMP)in fish tissue was conducted with n-hexane.The optimized QuEChERS material was implemented,and it was found that C18,primary secondary amine(PSA)and MgSO4 could adsorb the target analytes in n-hexane.So only the graphitized carbon black(GCB)could be used to purify the extraction.The adsorption rates of different materials for the four kinds of odors materials were explored in n-hexane and ethyl acetate.The experimental results revealed that the adsorption rates of silica for the four targets were 99.5%-100%in n-hexane and 0.7%-5.0%in ethyl acetate respectively.Then the silica solid phase extraction(SPE)method was utilized to eluent the compounds using 1.0 mL n-hexane/ethyl acetate in different proportions.The results of the comparative analysis demonstrated that n-hexane/ethyl acetate(4∶1,V/V)was the optimized eluent.Based on the obtained results,n-hexane extraction and GCB purification combined with silica SPE were used to isolate GSM,MIB,IPMP and IBMP from fish and the method was validated.It was found that the method showed good linearity in the range of 0.5-200 ng/mL,and with detection limits of 0.6 μg/kg for GSM and MIB,0.2 μg/kg for IPMP and IBMP.The limits of quantitation(LOQ)were 1.0 μg/kg for GSM and MIB,0.6 μg/kg for IPMP and IBMP.Good recoveries(77.5%-112.0%)and relative standard deviations(1.56%-9.42%)were also obtained.The use of silica SPE greatly mitigated the issue that the off-flavor compounds were easily lost in the gas blowing concentration process.There was no cross contamination in this method because the sample pretreatments were conducted separately,which was different with the most commonly used HS-SPME method for detecting semi-volatile substances.The sensitivity of this method was high enough to produce good quantitative results below the odor thresholds of the examined off-flavor compounds.

Bongkrekic acid(BA)is a toxin with stable properties and no distinctive smell.It exists in common foods such as fermented edible grain products,potato products,spoiled tremella fuciformis and auricularia polytricha,as well as auricularia polytricha that has been soaked too long.It can easily cause food poisoning.At present,there is still a lack of complete method to detect BA,and no spe-cific antidote of BA has been found.Therefore,BA poisoning is easy to be misdiagnosed or missed diagnosed,and its mortality rate remains high.In recent years,studies have revealed the toxic mecha-nism of BA and found that BA can inactivate some enzymes containing thiol groups(-SH)and in-hibit the synthesis and transport of adenosine triphosphate(ATP),causing damage to liver,kidney,brain and other parenchymal organs.This article reviews the autopsy cases and literature of deaths caused by BA poisoning at home and abroad,systematically summarizes the epidemiology,clinical manifestations,pathological changes,toxicological mechanisms,detection methods,forensic diagnostic key points and challenges of BA in forensic medicine,with the aim of providing a reference for foren-sic identification of related cases.

The combination of Aidi Injection(ADI) and doxorubicin(DOX) is a common strategy in the treatment of cancer, which can achieve synergistic anti-tumor effects while attenuating the cardiotoxicity caused by DOX. This study aims to investigate the mechanism of ADI in attenuating DOX-induced cardiotoxicity by multi-omics. DOX was used to induce cardiotoxicity in mice, and the cardioprotective effects of ADI were evaluated based on biochemical indicators and pathological changes. Based on the results, transcriptomics, proteomics, and metabolomics were employed to analyze the changes of endogenous substances in different physiological states. Furthermore, data from multiple omics were integrated to screen key regulatory pathways by which ADI attenuated DOX-induced cardiotoxicity, and important target proteins were selected for measurement by ELISA kits and immunohistochemical analysis. The results showed that ADI significantly reduced the levels of cardiac troponin T(cTnT) and N-terminal pro-B-type natriuretic peptide(NT-proBNP) and effectively ameliorated myocardial fibrosis and intracellular vacuolization, indicating that ADI showed therapeutic effect on DOX-induced cardiotoxicity. The transcriptomics analysis screened out a total of 400 differentially expressed genes(DEGs), which were mainly enriched in inflammatory response, oxidative stress, and myocardial fibrosis. After proteomics analysis, 70 differentially expressed proteins were selected, which were mainly enriched in the inflammatory response, cardiac function, and energy metabolism. A total of 51 differentially expressed metabolites were screened by the metabolomics analysis, and they were mainly enriched in multiple signaling pathways, including the inflammatory response, lipid metabolism, and energy metabolism. The integrated data of multiple omics showed that linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism pathways played an important role in DOX-induced cardiotoxicity, and ADI may exert therapeutic effects by modulating these pathways. Target validation experiments suggested that ADI significantly regulated abnormal protein levels of cyclooxygenase-1(COX-1), cyclooxygenase-2(COX-2), prostaglandin H2(PGH2), and prostaglandin D2(PGD2) in the model group. In conclusion, ADI may attenuate DOX-induced cardiotoxicity by regulating linoleic acid metabolism, arachidonic acid metabolism, and glycerophosphate metabolism, thus alleviating inflammation of the body.
Doxorubicin/toxicity* ; Animals ; Mice ; Cardiotoxicity/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Proteomics ; Metabolomics ; Injections ; Humans ; Multiomics

This study aimed to characterize and identify the non-volatile components in aqueous and ethanolic extracts of the stems and leaves of Rhododendron tomentosum by using sensitive and efficient ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry(UHPLC-Q-TOF-MS) combined with a self-built information database. By comparing with reference compounds, analyzing fragment ion information, searching relevant literature, and using a self-built information database, 118 compounds were identified from the aqueous and ethanolic extracts of R. tomentosum, including 35 flavonoid glycosides, 15 phenolic glycosides, 12 flavonoids, 7 phenolic acids, 7 phenylethanol glycosides, 6 tannins, 6 phospholipids, 5 coumarins, 5 monoterpene glycosides, 6 triterpenes, 3 fatty acids, and 11 other types of compounds. Among them, 102 compounds were reported in R. tomentosum for the first time, and 36 compounds were identified by comparing them with reference compounds. The chemical components in the ethanolic and aqueous extracts of R. tomentosum leaves and stems showed slight differences, with 84 common chemical components accounting for 71.2% of the total 118 compounds. This study systematically characterized and identified the non-volatile chemical components in the ethanolic and aqueous extracts of R. tomentosum for the first time. The findings provide a reference for active ingredient research, quality control, and product development of R. tomentosum.
Rhododendron/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/chemistry* ; Mass Spectrometry/methods* ; Plant Leaves/chemistry*