Objective Orosomucoid1 （ORM1） is a novel target in the quest for anti-fatigue pharmacotherapy. Preliminary investigations have illuminated oleuropein （OLE） as a promising candidate molecule, poised to enhance ORM1 expression. To elucidate the influence of OLE on ORM1 protein expression and assess its ramifications on muscle endurance. Methods The impact of OLE on ORM1 protein expressions within hepatocytes and liver tissue was meticulously quantified through Western blotting; the effects of OLE on muscle endurance were evaluated via the rotarod and forced swimming tests; glycogen content within liver and muscle tissues was determined utilizing a specialized kit; and PAS staining was employed to visualize glycogen deposition in the gastrocnemius muscle. Results OLE demonstrated a capacity to elevate ORM1 protein expression in hepatocytes in a time- and dose-dependent manner, concurrently prolonging the duration of swimming and rotarod performance in mice, also in a time- and dose-dependent manner. Furthermore, OLE augmented ORM1 expression in liver tissue, elevated serum ORM1 levels, and enhanced glycogen reserves within the liver and muscle. Conclusion OLE may serve to amplify muscle endurance by elevating ORM1 levels in vivo and augmenting glycogen stores within skeletal muscle.

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.

By consulting ancient and modern literature， this article systematically reviews and verifies the historical evolution of the herbal medicine known as Baijiang across various dimensions， including name， origin， scientific name verification， medicinal parts， production area， quality， harvesting and processing， as well as its nature， taste， and therapeutic effects， in order to provide a reference for the development and utilization of famous classical formulas containing Patriniae Herba. Patriniae Herba has a long history of use. It derives its name from the distinctive musty odor of its roots， which resembles spoiled soy sauce. However， due to its alias Kucai， there has been much confusion with other plants. Since the Ming dynasty， various plants have been used interchangeably as Baijiang. Herbal textual research showed that Patriniae Herba was first recorded in Shennong Bencaojing， and throughout history， Baijiang has been recognized as its standard name， though it has also been known by alternative names such as Luchang， Lujiang， and Suanyi. The main sources used throughout the ages were Patrinia scabiosaefolia or P. villosa， which is consistent with the 1977 edition of the Pharmacopoeia of the People's Republic of China. However， while the roots were traditionally used medicinally， the whole plant is now more commonly used in modern practice. In addition， the whole plants of Thlaspi arvense from the Cruciferae family and Sonchus brachyotus from the Compositae family are commonly used as regional substitutes for Baijiang. According to ancient records， Patriniae Herba was primarily found in Jiangxia（present-day eastern Hubei province） and Jiangdong（the region south of the lower reaches of the Yangtze River）， but modern literature shows that it is distributed throughout the country without a distinct geographical origin. In ancient times， the roots were harvested in August and sun-dried， today， the whole plant is typically dug up in summer or autumn and sun-dried. In recent times， the quality has been summarized as being best when the roots are long， the leaves are abundant and green， and the aroma is strong. Regarding the processing， ancient methods often involved baking（drying over fire）， while modern methods typically involve removing impurities， washing， and then cutting and drying the segments. The effects of Patriniae Herba are to clear heat and detoxify， eliminate blood stasis and drain pus. During the Han and Northern and Southern dynasties， it was used to treat skin diseases caused by heat， abscesses， postpartum diseases， and rheumatism， during the Five dynasties period， its therapeutic applications expanded to include diseases of the five senses， and by the modern era， conditions such as neurasthenia and insomnia were added. Regarding its properties and taste， it was recorded as bitter and neutral during the Han dynasty. By the Tang dynasty， it was slightly cold， with a taste of acrid and bitter. During the Yuan and Ming dynasties， it was mostly slightly cold and neutral， with a bitter and salty taste. In the Qing dynasty and modern times， it was mostly bitter and neutral， and in contemporary times， it has evolved to a taste of acrid， bitter， and cool. Based on the results of this study， it is recommended that when developing and utilizing famous classical formulas containing Patriniae Herba， one should select the entire herb of the historically mainstream sources， P. scabiosaefolia or P. villosa from the Valerianaceae family， and choose the processing method according to the prescription requirements. It is recommended to use raw products without specific requirements.

By consulting ancient and modern literature， this article systematically reviews and verifies the historical evolution of the herbal medicine known as Baijiang across various dimensions， including name， origin， scientific name verification， medicinal parts， production area， quality， harvesting and processing， as well as its nature， taste， and therapeutic effects， in order to provide a reference for the development and utilization of famous classical formulas containing Patriniae Herba. Patriniae Herba has a long history of use. It derives its name from the distinctive musty odor of its roots， which resembles spoiled soy sauce. However， due to its alias Kucai， there has been much confusion with other plants. Since the Ming dynasty， various plants have been used interchangeably as Baijiang. Herbal textual research showed that Patriniae Herba was first recorded in Shennong Bencaojing， and throughout history， Baijiang has been recognized as its standard name， though it has also been known by alternative names such as Luchang， Lujiang， and Suanyi. The main sources used throughout the ages were Patrinia scabiosaefolia or P. villosa， which is consistent with the 1977 edition of the Pharmacopoeia of the People's Republic of China. However， while the roots were traditionally used medicinally， the whole plant is now more commonly used in modern practice. In addition， the whole plants of Thlaspi arvense from the Cruciferae family and Sonchus brachyotus from the Compositae family are commonly used as regional substitutes for Baijiang. According to ancient records， Patriniae Herba was primarily found in Jiangxia（present-day eastern Hubei province） and Jiangdong（the region south of the lower reaches of the Yangtze River）， but modern literature shows that it is distributed throughout the country without a distinct geographical origin. In ancient times， the roots were harvested in August and sun-dried， today， the whole plant is typically dug up in summer or autumn and sun-dried. In recent times， the quality has been summarized as being best when the roots are long， the leaves are abundant and green， and the aroma is strong. Regarding the processing， ancient methods often involved baking（drying over fire）， while modern methods typically involve removing impurities， washing， and then cutting and drying the segments. The effects of Patriniae Herba are to clear heat and detoxify， eliminate blood stasis and drain pus. During the Han and Northern and Southern dynasties， it was used to treat skin diseases caused by heat， abscesses， postpartum diseases， and rheumatism， during the Five dynasties period， its therapeutic applications expanded to include diseases of the five senses， and by the modern era， conditions such as neurasthenia and insomnia were added. Regarding its properties and taste， it was recorded as bitter and neutral during the Han dynasty. By the Tang dynasty， it was slightly cold， with a taste of acrid and bitter. During the Yuan and Ming dynasties， it was mostly slightly cold and neutral， with a bitter and salty taste. In the Qing dynasty and modern times， it was mostly bitter and neutral， and in contemporary times， it has evolved to a taste of acrid， bitter， and cool. Based on the results of this study， it is recommended that when developing and utilizing famous classical formulas containing Patriniae Herba， one should select the entire herb of the historically mainstream sources， P. scabiosaefolia or P. villosa from the Valerianaceae family， and choose the processing method according to the prescription requirements. It is recommended to use raw products without specific requirements.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

OBJECTIVE To comprehensively analyze the effectiveness， safety and economic value of carfilzomib in the treatment of multiple myeloma （MM）， and provide evidence-based guidance for clinical rational drug use. METHODS A systematic search was performed in PubMed， Embase， the Cochrane Library， Web of Science， CNKI， Wanfang， VIP， and relevant health technology assessment （HTA） websites， from database inception to December 31， 2024. Two researchers independently screened studies based on predefined inclusion and exclusion criteria， extracted data， and assessed study quality. Descriptive statistical analyses were conducted. RESULTS A total of 21 studies were included， comprising 7 systematic reviews/meta-analyses， 5 clinical trials， 5 pharmacoeconomic studies， and 4 HTA reports. Effectiveness analysis indicated that， compared with control groups， carfilzomib significantly improved overall response rate and clinical benefit rate （ P ＜0.05）， prolonged progression-free survival， and enhanced patient’s quality of life （ P ＜0.05）， while its impact on overall survival remains to be further confirmed. Safety analysis showed there was no significant difference in the risk of peripheral neuropathy between carfilzomib and controls， while the risks of cardiotoxicity and hypertension were significantly increased （ P ＜0.05）. Economic analysis suggested that carfilzomib regimens demonstrated certain cost-effectiveness in second-line treatment in the U.S. and some European countries. However， its economic value was influenced by drug price， dosing regimen， and regional differences， and it may lack a cost advantage in some countries or in third-line treatment. CONCLUSIONS Carfilzomib shows definite efficacy and generally acceptable safety in the treatment of MM， but cardiotoxicity and hypertension risks require careful monitoring. Given its high treatment cost， pharmacoeconomic studies in the Chinese population are urgently needed.

In this work,a fluorescent probe PIN was synthesized using indole-3-carbohydrazide and pyrenecarboxaldehyde as raw materials.PIN showed weak fluorescence emission in aqueous solution with acetonitrile volume fraction of 70％.However,when Cu2+was added to this aqueous solution of PIN,a new fluorescence emission peak appeared at 495 nm,and the intensity of this peak gradually increased with the increase of concentration of Cu2+,and also caused a significant change in the fluorescence color of the solution.In contrast,the addition of 15 kinds of other common metal ions did not cause such change.The detection limit of PIN for Cu2+was 78.7 nmol/L,which was much lower than the maximum permitting level of Cu2+in drinking water in hygienic standard for drinking water in China.Therefore,PIN was a highly selective and sensitive fluorescence-enhanced probe for Cu2+.Meanwhile,the addition of Cu2+could also cause a new absorption peak at 440 nm in the ultraviolet-visible absorption spectrum of the aqueous solution of PIN,and meanwhile the colorless PIN solution changed into yellow,exhibiting the performance of PIN as a colorimetric probe for Cu2+.By fitting with the Levenberg-Marquardt algorithm equation,the binding ratio of PIN to Cu2+was 2:1,and the binding constant was 3.42×1012 L2/mol2.In addition,the binding mode of PIN with Cu2+was explored by using proton nuclear magnetic resonance(1H NMR)titration experiments and density functional theory simulations.The results showed that the addition of Cu2+could cause the aggregation of PIN molecules to form excimers,thus showing highly selective recognition.Finally,PIN was made into a simple test strip,which could achieve rapid and convenient fluorescence detection of Cu2+in actual water samples.

In the 1950s and 1960s,Japan's implementation of policies prioritizing economic develop-ment caused a lack of effective supervision over the discharge of industrial wastewater and exhaust gases,which led to the occurrence of the"Four Major Pollution Diseases",including Minamata disease,causing serious social and public health problems.To more effectively address public nuisances and pro-vide compensation to victims,the Japanese government gradually established an environmental damage compensation system with administrative relief characteristics since the 1970s.Through long-term prac-tice and system optimization,this system has evolved into a mature institutional framework with a clear division of labor and efficient collaboration.This paper systematically reviews the development process of Japan's environmental damage compensation system and deeply analyzes its legal frame-work and supporting policies,aiming to provide useful references for the construction and improve-ment of China's environmental damage compensation system.Meanwhile,through the case analysis of Minamata disease,the paper explores the specific mechanisms and effects in the compensation practices,further revealing the system's operational characteristics and implications,and providing a reference ba-sis for the construction of China's environmental governance legal system.

Objective To verify the efficacy of a domestic human DNA quantification kit based on real-time fluorescence quantitative PCR in detecting the total human DNA concentration,male DNA concen-tration in mixed male/female DNA samples,the degree of DNA degradation and inhibitor tolerance.Methods Samples with different concentrations,different male/female ratios,different concentrations of inhibitors,and different degradation degrees were tested using the domestic human DNA quantification kit based on real-time fluorescence quantitative PCR.This kit was compared with a similar product on the market and was applied to the detection of DNA from real cases.Results This human DNA quan-tification kit can effectively detect human DNA as low as 0.001 65 ng/μL,and 6.25 pg/μL of male DNA in mixed samples with a male-to-female ratio of 1∶15 000.Even when the sample contains as high as 400 ng/μL of humic acid or 1 000 μmol/L of hemin alone,the DNA concentration can still be accurately detected.The degradation index can effectively characterize the degradation degree of the sample.This kit has been successfully applied in forensic practice.Conclusion This human DNA quan-tification kit is accurate and reliable in detection.It can accurately reflect the degradation of DNA and inhibitor tolerance.It has good performance in quantitative accuracy,determination of the male/female ratio in mixed samples,and inhibitor tolerance.It has application potential in forensic case examination.