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 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.

Objective To explore the polymorphism of tyrosinase (TYR) and melanocortin 1 receptor (MC1R) genes and their mRNA expression levels in relation to coat-color phenotypes in guinea pigs, providing genetic markers for locating dominant traits in guinea pigs. Methods A total of 57 self-bred ordinary-level guinea pigs were selected and divided into three groups based on coat color: white (n=22), variegated (n=22) and black (n=13). The guinea pigs were euthanized with an overdose of pentobarbital sodium via intraperitoneal injection. DNA was then extracted from the dorsal skin tissue. Polymorphism in the coding sequence (CDS) of the exons of the TYR and MC1R genes in each group was detected by cloning and sequencing. The mRNA expression of the two genes in skin tissues was detected by real-time fluorescent quantitative PCR to investigate the relationship between these genes and guinea pig coat color. Results A single nucleotide polymorphism (SNP) site was found in the CDS region of TYR exon Ⅰ, where the base A was replaced by G. All white guinea pigs had the G/G genotype for TYR, while no deep-colored (variegated and black) guinea pigs exhibited the G/G genotype for TYR. Most deep-colored guinea pigs had the A/A genotype, and a few had A/G genotype. The A/A genotype frequency in black guinea pigs was higher than in variegated guinea pigs. A 2 760 bp sequence deletion was identified in the exon of the MC1R gene, marked as the - gene, with non-deleted samples marked as N gene. Most white guinea pigs had the -/- genotype for MC1R, variegated guinea pigs mainly had the -/N genotype, and black guinea pigs mainly had the N/N genotype, with a few showing the -/N. The TYR gene expression level was higher in white guinea pigs, lower in variegated guinea pigs, and intermediate in black guinea pigs, but there was no significant difference among the three groups (P>0.05). The MC1R gene expression level in white guinea pigs was extremely low, while both variegated and black guinea pigs showed significantly higher levels than white guinea pigs (P<0.01). Black guinea pigs showed significantly higher levels than variegated guinea pigs (P<0.05). ConclusionThe TYR and MC1R genes synergistically regulate coat color of guinea pigs. The G-site mutation in the TYR gene may lead to albinism, and the change of N-site in the MC1R gene affects the depth of the coat color.

Objective:To propose a novel radiotherapy marking method-the"#"-character method,which aimed at improving the accuracy and repeatability of positioning during radiotherapy.Methods:A specially"cross-shaped"stamp was designed by this study,which consisted of a handheld square base with a"cross-shaped"protrusion.Using this stamp,the extreme positions of end-expiration and end-inspiration were marked respectively at the laser-guided regions on the directly above and bilateral sides of the patient's body,and each position was printed a"+"character.Finally,a"#-shaped"signal was formed,which represented the full range of respiratory motion of patients.The study included two parts:surface displacement caused by respiration was simulated through a three-dimensional(3D)motion platform,which was used to conduct a phantom experiment for anthropomorphic dummy,A randomized controlled study involving 40 patients,who were treated between January and June 2024 at the Department of Radiotherapy,Cancer Hospital,Chinese Academy of Medical Sciences,were conducted.The cohort included 20 patients with breast tumor(Positioning the outer contour by exposing the chest)and 20 patients with thoracic tumor(fixed position of using thermoplastic film).These patients were divided into two groups for comparison,which received respectively the"#-shaped"method and the conventional"+-shaped"method.The cone-beam computed tomography(CBCT)images before treatment were used to compare the influences of the two kinds of marking methods on the positioning errors of patients with breast tumor and patients with thoracic tumor.Then,the statistical analysis was used to assess precision and accuracy of positioning.Results:The result of phantom experiment indicated that the positioning error of the"#-shaped"method was significantly better than that of the"+-shaped"method under various parameters of respiratory movement.Under three kinds of different respiratory cycles(3,4,and 5 seconds)and amplitudes(8,12,and 15 mm),the positioning errors of the"#-shaped"method were respectively(0.15±0.04)cm,(0.19±0.05)cm and(0.35±0.14)cm,while the"+-shaped"method were respectively(0.42±0.16)cm,(0.64±0.28)cm and(0.88±0.37)cm,and the differences were statistically significant(t=8.347,3.416,2.901,P<0.05).The results of actual patients indicated the positioning error[(0.97±0.32)cm]of the"#-shaped"method was significantly lower than[(1.62±0.47)cm]of the"+-shaped"method for patients with breast tumor(Positioning the outer contour by exposing the chest),and the difference was significant(t=3.615,P<0.05).On the other hand,the positioning error[(0.69±0.24)cm]of the"#-shaped"method was significantly lower than[(0.97±0.39)cm]of the"+-shaped"method for patients with thoracic tumor(fixed position of using thermoplastic film),and the difference also was significant(t=1.934,P<0.05).Conclusion:Compared to the conventional"+-shaped"method,the"#-shaped"method appears higher accuracy and repeatability during the positioning process of radiotherapy,which especially is suitable to the treatment for breast tumor and thoracic tumor that need accurately control the influences of respiratory motion.

Occult hepatitis B virus(HBV)infection(OBI)represents a potential reservoir for HBV transmission,capable of spreading through routes such as blood transfusion.Additionally,OBI can con-tribute to the chronic progression of hepatitis B-related diseases,sustaining a state of chronic HBV infec-tion.In individuals with compromised immune function or undergoing immunosuppressive therapy,OBI may lead to HBV re-activation,potentially triggering severe liver conditions such as acute hepatitis or liv-er failure.As a result,OBI poses a significant public health challenge,profoundly impacting the health and well-being of affected populations and complicating HBV infection control efforts in China.Clinically diagnosing OBI remains challenging,but its hallmark is serum hepatitis B surface antigen negative and the presence of HBV covalently closed circular DNA(cccDNA)in the liver.With the increasing focus on achieving functional cure for chronic hepatitis B,both domestic and international guidelines have re-fined functional cure.Notably,these guidelines acknowledge that cccDNA may persist in the liver tissue of individuals who have achieved functional cure,suggesting resemblance of an occult infection state.Here,we provide a comprehensive overview of OBI,including its definition,classification,public health implications,underlying mechanisms,and clinical reactivation.By updating the understanding of OBI,we aim to raise awareness among clinicians and public health professionals regarding the significance of OBI in the current context and encourage greater attention to this population.

Objective To explore the relationship between C-reactive protein/albumin ratio(CAR)and the disease severity in patients with severe pneumonia,and its predictive value for 28-day mortality risk.Methods A retrospective analysis was conducted on 152 patients with severe pneumonia admitted to Fuyang People's Hospital from January 2020 to January 2022.They were divided into non-critical illness group(n=51),critical illness group(n=63),and extremely critical illness group(n=38)based on the disease severity.The clinical data such as age and gender of patients was collected,and Pearson correlation analysis was used to explore the correlation between CAR and the severity of illness[determined by Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score].Multivariate logistic regression was employed to identify independent influencing factors of the severity of illness.According to the survival status of patients after 28 days of treatment,they were divided into survival group(n=107)and death group(n=45).CAR was categorized into quintiles(Q1-Q5),and multivariate logistic regression analysis was conducted to explore the correlation between CAR and 28-day mortality risk in severe pneumonia patients.A restricted cubic spline(RCS)model was used to analyze the dose-response relationship between CAR and mortality risk.The predictive value of CAR and related indicators for patient mortality risk was evaluated using the receiver operating characteristic curve(ROC).Results CAR was significantly positively correlated with the severity of the disease(APACHE Ⅱ score)(r=0.716,P<0.05).Neutrophil/lymphocyte ratio(NLR),blood lactate(Lac),and high CAR were independent risk factors for the disease severity in patients with severe pneumonia(P<0.05).After adjusting for confounding factors,the mortality risk increased with the increase of CAR(P<0.05).Subgroup analysis of the screened confounding factors revealed that the correlation between CAR and 28-day mortality risk in severe pneumonia patients remained stable across different APACHE Ⅱ scores,GCS scores,SOFA scores,white blood cell counts(WBC),neutrophils(NEU),red cell volume distribution width(RDW),procalcitonin(PCT),and Lac,with interactions observed between NLR and Lac subgroups(P<0.05).The RCS model indicated that there was no non-linear dose-response relationship between CAR and 28-day mortality risk in patients with severe pneumonia of different genders.ROC curve analysis showed that CAR,Lac,and NLR had good predictive value for 28-day mortality in severe pneumonia patients,with the combined predictive efficacy being significantly higher than that of individual indicators.Conclusion There is a close relationship between CAR and the progression and prognosis of severe pneumonia,making it a new approach to assessing the severity of illness and predicting mortality risk in patients.

Hospital pharmacy research is significant in enhancing the level of rational drug use,improving the quality of pharmacy services,and promoting the improvement of drug treatment effects.To guarantee the standardization of hospital pharmacy research,the compilation team of"Hospital Pharmacy Research Standards"adheres to the principles of scientificity,universality,guidance,and operability,combs through the key management contents from three aspects,namely,relevant national policy docu-ments,relevant domestic and international standards and norms,and literature analysis,combines with the actual working condition of hospital pharmacy research,and formulates the standards after several rounds of opinion collection and expert argumentation.This paper analyzes the key contents of the standard,including basic requirements,research process management,and research re-sults management,to provide guidance and reference for hospital pharmacy researchers to understand the standard in-depth and further improve the standardization of hospital pharmacy research.