ObjectiveTo investigate the inhibitory effect of Biejiajian Pills （BJJW） on the growth of liver cancer， as well as its potential mechanism in mediating the AMP-activated protein kinase （AMPK）/mammalian target of rapamycin （mTOR） pathway through mitochondrial energy metabolism. MethodsHuman hepatoma Huh7 cells were used to establish a nude mouse model of subcutaneous xenograft tumor. A total of 18 tumor-bearing nude mice were randomly divided into model group， BJJW group （2.2 g/kg）， and metformin group （250 mg/kg）， and the corresponding drug was given by gavage for 14 consecutive days. Tumor volume and weight were monitored during the experiment； HE staining was used to observe histopathological changes； the levels of reactive oxygen species （ROS） and adenosine triphosphate （ATP） in tumor tissue were measured； immunohistochemistry and Western blotting were used to measure the expression levels of proteins associated with the AMPK/mTOR pathway. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Tukey’s test was used for further comparison between two groups； the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups， and the Dunn’s test was used for further comparison between two groups. ResultsCompared with the model group， the BJJW group had a tumor inhibition rate of 45.73%， with significant reductions in both tumor volume and weight （P<0.01）. Pathological examination showed that compared with the model group， the BJJW group had a significant reduction in the number of tumor cells and the presence of extensive necrosis. Mechanistic studies showed that compared with the model group， the BJJW group had a significant increase in ROS level （P<0.001） and a significant reduction in ATP level （P<0.001）， as well as significant increases in p-AMPK/AMPK ratio （0.81±0.20 vs 0.13±0.04， P<0.01） and p-ULK1/ULK1 ratio （0.69±0.17 vs 0.18±0.13， P<0.01） and a significant reduction in p-mTOR/mTOR ratio （1.34±0.16 vs 3.20±0.62， P<0.01）. ConclusionBJJW may inhibit the growth of liver cancer by inducing mitochondrial energy metabolism dysfunction， increasing the level of ROS， reducing the level of ATP， and activating the AMPK/mTOR signaling pathway.

Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection. Septic shock is the primary cause of mortality in sepsis, with its core pathophysiological mechanism being severe ischemia and hypoxia in critical units—composed of microcirculation and the mitochondria of functional cells—resulting from disruptions in blood flow and oxygen flow following a dysregulated host response. Due to the systemically convergent yet clinically heterogeneous nature of the host response, current understanding and management strategies for hemodynamics remain inconsistent, often leading to inadequate resuscitation or overtreatment. To improve the quality of care, based on a systematic review of the "blood flow-oxygen flow" theory, an expert panel emphasizes reevaluating septic shock from an integrated perspective of blood flow and oxygen flow, and has formulated the Expert Consensus on Blood Flow and Oxygen Delivery Phenotyping and Clinical Management of Septic Shock (2025). The consensus proposes that clinical typing of blood flow-oxygen flow should comprehensively consider cardiac function, vascular tone, oxygen flow utilization status in critical units, and disease trajectory, while optimizing subtype identification by integrating host response phenotypes and artificial intelligence technologies. It advocates establishing a continuous assessment system through multi-site oxygen flow monitoring for organ perfusion, peripheral perfusion monitoring, and critical care ultrasound. Under the framework of the "critical care triangle", the consensus promotes the implementation of individualized, bundled management strategies, providing guidance for multiple management points to restore blood flow-oxygen flow matching, reduce the risk of organ failure, and decrease patient mortality.

Objective To establish a highly efficient and sensitive technical system for the identification and analysis of platycodin-type saponins, systematically compare the differences in platycodin-type saponins among Platycodon grandiflorum from different producing areas, and provide scientific references for the screening of high-quality Platycodon grandiflorum resources, authenticity evaluation, and construction of standardized quality control systems. Methods A total of 45 batches of P. grandiflorum medicinal materials from 3 producing areas （Anhui, Henan, and Jilin, with 15 batches per area） were selected as research objects. Qualitative identification and semi-quantitative analysis of saponin components were performed based on ultra-high performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry （UHPLC-Q-TOF/MS） technology. Meanwhile, two multivariate statistical methods, principal component analysis （PCA） and partial least squares-discriminant analysis （PLS-DA）, were combined to analyze the differences in platycodin-type saponins of Platycodon grandiflorus from different producing areas. Results A total of 28 saponin components were identified from Platycodon grandiflorus of the three producing areas. PCA results showed that there were minor differences in platycodin-type saponins between Henan Platycodon grandiflorus and Jilin Platycodon grandiflorus, while Anhui P. grandiflorum exhibited significant differences from both. PLS-DA further screened 15 major differential compounds. Among them, the contents of 6 components including 3''-O-acetylpolygalacin D2 and platycodin H in Anhui Platycodon grandiflorus were higher than those in Henan and Jilin Platycodon grandiflorus; platycodigenic acid A had the highest content in Jilin Platycodon grandiflorus; the contents of platycodin D3, polygalacin J, and polygalacin D were relatively higher in Henan Platycodon grandiflorus. Conclusion This study clarified the characteristic differences in core components of Platycodon grandiflorus from the three major producing areas, which provided an important theoretical basis for the screening of high-quality Platycodon grandiflorus resources, elucidation of the mechanism underlying its authenticity, and construction of a standardized quality control system.

Objective To explore risk factors of sodium-dependent glucose transporters 2 （SGLT2） inhibitor-associated euglycemic diabetic ketoacidosis （euDKA） and to construct a risk prediction model. Methods A retrospective analysis was performed on the clinical data of type 2 diabetes patients treated with SGLT2 inhibitors in Dongnan Hospital of Xiamen University from January 2020 to December 2023, including age, gender and course of diabetes. The risk factors of SGLT2 inhibitor-associated euDKA were analyzed by univariate analysis and multivariate Logistic regression, and a prediction model was established. According to the receiver's operating characteristic （ROC） curve, the area under the curve （AUC） and the optimal critical value of the prediction model were determined. The prediction model was subjected to both internal and external validation. Results A total of 119 patients with type 2 diabetes treated with SGLT2 inhibitors were included in this study. Among them, there were 98 cases without euDKA （non-euDKA group）and 21 cases with euDKA （euDKA group）. Multivariate Logistic regression analysis showed the DKA history (OR=114.153), appetite or diet decreased three days before admission (OR=21.774), elevated neutrophil count (OR=2.056) and pre-hospital adjustment of hypoglycemic agents (OR=45.745) were independent factors to increase risks of euDKA associated with SGLT2 inhibitors （P<0.05）. Surgical history before admission was an independent factor to reduce this risk （OR=0.007, P<0.05）. By establishing the calculation formula of the prediction model = neutrophil count+6.571 （DKA history）−6.874 （surgical history before admission）+4.273 （appetite or diet decreased three days before admission）+5.302 （pre-hospital adjustment of hypoglycemic drugs）, the ROC curve was drawn. The AUC of the ROC of the prediction model was 0.982 （95%CI: 0.961-1.000, P<0.001）, with accuracy of 94.96%, sensitivity of 0.905, specificity of 0.959 and a critical value of 7.405. The AUC of ROC curve after the model’s ten-fold cross validation was 0.930. And the accuracy of the external validation of the prediction model was 85.29%. Conclusion The DKA history, appetite or diet decreased three days before admission, elevated neutrophil count and pre-hospital adjustment of hypoglycemic agents increased the risk of SGLT2 inhibitor-associated euDKA, while the surgical history before admission reduced this risk. The risk prediction model constructed on this basis could better predict the risk of SGLT2 inhibitor-associated euDKA.

To analyze the in vitro antibacterial effects of colistin (COL) or tigecycline (TGC) in combination with imipenem (IPM), amikacin (AMK), and cefoperazone-sulbactam (CSL) against carbapenem-resistant Acinetobacter baumannii(CRAB), so as to provide evidence for screening effective combination regimens for clinical microbial infections.

ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

As a mercury-containing elixir， Hongshengdan has been known as a sacred medicine for surgery by ancient medical practitioners because of its precise curative effects. It originated from Yizong Shuoyue in the Qing dynasty， Qing dynasty and modern medical practitioners have adapted and modified its formula for clinical application. Employing bibliometric methods， the authors systematically organized relevant ancient literature of the Qing dynasty and modern literature， and analyzed the composition and dosage， preparation method， and clinical application. Among the 25 ancient books concerning Hongshengdan， a total of 12 medicinal formulas， 15 refining methods and 9 clinical applications were obtained. Research confirms that Hongshengdan consisted of mercury， saltpeter， alum， soap alum， cinnabar and realgar. Using measurement conversion standards of Qing dynasty， the modern single-batch formulation comprised 37.30 g of mercury， 149.20 g of saltpeter， 37.30 g of alum， 22.38 g of soap alum， 18.65 g of cinnabar， and 18.65 g of realgar. In modern refining of Hongshengdan， most medical practitioners take the core medicines， with dosages approximately 30 g of mercury， 30 g of saltpeter， and 30 g of alum. Refining method involves pretreatment stewing the materials during preparation， and alum， soap alum， and saltpeter are first ground together， then combined with mercury， cinnabar， and realgar for grinding until mercury and other drugs grind to the degree of no star points. The mixture is then placed in a pot or vessel by cold-forming method. After covering， the opening is sealed using either raw gypsum salt mud or honey-dipped cotton paper strips. Sand is packed around the vessel and then pressurized. During the calcination process， begin with a low flame（30 min）， then increase to a medium flame（30 min）， followed by a high flame（30 min）， after removing fire toxins， collect the final product. Hongshengdan has the efficacy of lifting the poison， removing the corrosion， producing muscle and dispersing， and is often used in the treatment of surgical sore and carbuncle type of diseases. Modern research indicates that Hongshengdan is commonly used to treat skin system diseases such as ulcers and herpes. The aforementioned findings provide a reference basis for the subsequent refining method and clinical application of Hongshengdan.

Objective: To examine the causal association and potential mechanisms between bone mineral density in different age groups and primary malignant bone tumor based on two sample Mendelian randomization (MR), so as to provide a reference for the prevention and treatment of primary malignant bone tumor. Methods: The genome-wide association study (GWAS) of bone mineral density was obtained from the GEFOS database,which included 66 628 subjects divided into five age groups (0-15, 15-30, 30-45, 45-60, and >60 years) based on the phases of human bone development. The GWAS of primary malignant bone tumor was sourced from the FinnGen database, including 648 cases and 378 749 controls. Using bone mineral density of five age groups as the exposure and primary malignant bone tumor as the outcome, an MR analysis was performed with the inverse-variance weighted (IVW) method. Sensitivity analysis were conducted using Cochran's Q test, MR-Egger regression, MR-PRESSO test and MR Steiger test. The potential mechanisms underlying the causal association between bone density and primary malignant bone tumors were explored using Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Results: The MR analysis results showed that there was a negative causal association between bone density and primary malignant bone tumors in the 30-45 age group (OR=0.301, 95%CI: 0.126-0.721). No statistically significant associations between bone density and primary malignant bone tumors were found in the 0-15, 15-30, 45-60, and >60 age groups (all P>0.05). Sensitivity analysis did not detect heterogeneity, pleiotropy (all P>0.05) and reverse causality. KEGG enrichment analysis revealed that genes highly associated with bone density and primary malignant bone tumors were enriched in the mTOR signaling pathway and the Wnt signaling pathway, among which Low Density lipoprotein Receptor Related protein 5 and Wnt Family Member 16 are key regulatory genes. Conclusion The decrease in bone mineral density among individuals aged 30-45 may increase the risk of primary malignant bone tumors through the mTOR signaling pathway and the Wnt signaling pathway.

Objective: To analyze the regulatory effect of Atractylodes macrocephala Koidz. extract on the immune function of mice, so as to provide a reference for the study of the mechanism of Atractylodes macrocephala Koidz. regulating immune function. Methods: Forty-eight SPF healthy male ICR mice were randomly divided into control group and low (0.5 g/kg), medium (2.0 g/kg), and high (4.0 g/kg) dose groups, with 12 mice in each group. The mice in control group were given the pure water by gavage once a day, while the mice in each dose group were given the corresponding dose of Atractylodes macrocephala Koidz. extract by gavage once a day. The delayed allergy test was performed for 28 consecutive days. Sixty SPF healthy male ICR mice were randomly divided into a control group, polyinosinic acid injection group (model group), and low, medium, and high dose groups, with 12 mice in each group. The mice in control group were given the pure water by gavage once a day, while the mice in each dose group were given the corresponding dose of Atractylodes macrocephala Koidz. extract by gavage once a day for 14 consecutive days. On days 13 and 14 of administration, the mice in the model group and each dose group were intraperitoneally injected with sterile polyinosinic acid solution to perform the immunosuppressive experiment induced by polyinosinic acid. The mouse ear pieces were weighed, and the thymus and spleen of the mice were weighed and stained with HE to calculate the pathological scores. Peripheral blood was collected for blood cell detection and T cell classification. Results: Mice in each group had normal feeding, activity, and growth status, and no abnormality was observed. In the delayed allergy test, compared with the control group, the degree and rate of ear swelling in the low, medium and high dose groups were higher, the white blood cell count in the medium dose group was higher, and the absolute values of lymphocytes in the low and medium dose groups were higher (all P<0.05). Compared with the control group, the pathological scores of the thymus and spleen in the model group were higher (both P<0.05). In the immunosuppressive experiments in mice induced by polyinosinic acid, compared with the model group, the pathological score of the thymus in the high dose group was lower (P<0.05), and the boundary between the thymus cortex and medulla was improved. Conclusions Atractylodes macrocephala Koidz. extract can increase the degree of ear swelling and peripheral blood white blood cell count in mice. High dose of Atractylodes macrocephala Koidz. extract can improve the thymus injury induced by polyinosinic acid, and has an immunomodulatory effect.

Objective: To investigate the trend in disease burden of injuries among children and adolescents in China from 1990 to 2021, so as to provide a basis for formulating prevention and control strategies and reducing this disease burden. Methods: Data on mortality, disability-adjusted life years (DALY) rate, incidence, and prevalence of injuries among children and adolescents aged <20 years in China from 1990 to 2021 were collected from the Global Burden of Disease (GBD) 2021 database. All rates were standardized using the GBD 2021 world standard population. The trend in incidence of disease burden of injuries among children and adolescents across differents genders and ages from 1990 to 2021 was evaluated using average annual percent change (AAPC). Results: From 1990 to 2021, the standardized mortality (AAPC=-5.435%), standardized DALY rate (AAPC=-5.311%), standardized incidence (AAPC=-0.466%), and standardized prevalence (AAPC=-0.810%) of injuries among children and adolescents in China showed downward trends (all P<0.05). Among these, the standardized mortality of animal contact (AAPC=-9.138%) and the standardized DALY rate of medical side effects (AAPC=-8.389%) decreased at a relatively fast pace, while the standardized incidence of falls (AAPC=0.083%) and the standardized prevalence of exposure to natural forces (AAPC=2.656%) showed upward trends (all P<0.05). The standardized mortality, standardized DALY rate, standardized incidence and standardized prevalence of injuries were higher in males than in females. The trend in males showed a downward trend (all P<0.05), consistent with the total population. The crude incidence of injuries in the group aged 15-<20 years showed an upward trend (AAPC=0.391%, P<0.05), while the trend in the group aged 10-<15 years was not statistically significant (P>0.05). The crude incidence of injuries in the groups aged 5-<10 years and <5 years showed downward trends (AAPC=-0.488% and -2.275%, both P<0.05). In 2021, the <5 years age group had the highest crude mortality and crude DALY rate of injuries, at 13.94/100 000 and 1 257.26/100 000, respectively. The 15-<20 years age group exhibited the highest crude incidence and crude prevalence, at 4 874.05/100 000and 4 050.35/100 000, respectively. Drowning and falls were major components of the disease burden across all age groups. Conclusions From 1990 to 2021, the disease burden of injuries among children and adolescents in China showed an overall downward trend. The disease burden was consistently higher in males than in females. Children aged <5 years face a high risk of fatality and disability, while adolescents aged 15-<20 years experience a high incidence and frequency of injuries. Drowning and falls were key priorities for prevention and control.