ObjectiveTo optimize and validate the optimal sequential alcohol-water extraction process of modified Banxia Xiexintang（MBXT） based on pharmacodynamic evaluation， combined with the G1-entropy weight method and Box-Behnken response surface methodology， and to systematically and comprehensively analyze the material basis of this formula， providing a scientific basis for its quality control and industrial production. MethodsRats were randomly divided into the normal group， model group， metformin group， and MBXT water extraction， water extraction and ethanol precipitation， sequential ethanol-water extraction groups. Except for the normal group， a polycystic ovary syndrome with insulin resistance（PCOS-IR） model was established in all rats via a high-fat diet combined with letrozole induction. Enzyme-linked immunosorbent assay（ELISA） biochemical assay kits and hematoxylin-eosin（HE） staining were used to compare sex hormone levels in serum and ovarian histopathology， thereby screening extraction process routes. Based on this， a comprehensive score was constructed using the G1-entropy weight method based on the transfer rates of index components（berberine hydrochloride and baicalin） and the dry extract rate. Box-Behnken response surface methodology was then utilized to optimize the extraction process parameters. Finally， the chemical constituents of the sample from the optimal process were qualitatively analyzed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS）. ResultsPharmacodynamic findings revealed that compared with the normal group， serum testosterone（T） and luteinizing hormone（LH） levels were significantly elevated in the model group， while estradiol（E₂） and follicle-stimulating hormone（FSH） levels were significantly decreased（P<0.01）， with polycystic changes observed in ovarian tissues. Compared with the model group， all treatment groups significantly reversed the changes in sex hormone levels， with the sequential ethanol-water extraction group showing the optimal effect in improving the aforementioned indicators and pathological morphology， followed by subsequent process optimization. The optimized process involved adding 12 times the amount of 70% ethanol for extracting twice， each lasting 120 min， and adding 12 times the amount of water for extracting thrice， each lasting 90 min. Validation test results showed that under optimal process conditions， the average transfer rates of berberine hydrochloride and baicalin were 76.05% and 93.38%， respectively. MS analysis identified a total of 377 compounds， including 112 flavonoids， 41 terpenoids， 28 organic acids， 22 coumarins， and 8 alkaloids， while elucidating the cleavage patterns of key components. ConclusionThe optimized sequential ethanol-water extraction process is stable and feasible， effectively preserving the material basis of MBXT for treating PCOS-IR. It further clarifies the main chemical composition of this formula， providing a scientific basis for the development and quality control of its preparations.

ObjectiveTo evaluate the therapeutic effects of modified Banxia Xiexintang（MBXT） on polycystic ovary syndrome with insulin resistance（PCOS-IR） rats and reveal its potential mechanisms based on the integrated analysis of transcriptomics and metabolomics. MethodsFemale SD rats were selected， and a PCOS-IR model was established by intragastric administration of letrozole combined with a high-fat diet for 21 days. The modeled rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， and metformin group（0.158 g·kg^-1）， with a normal group set up separately. After 14 days of administration， the estrous cycle was observed， ovarian morphology was examined by hematoxylin-eosin（HE） staining， and the levels of testosterone（T）， estradiol（E₂）， follicle-stimulating hormone（FSH）， and luteinizing hormone（LH） in serum were detected by enzyme-linked immunosorbent assay（ELISA）. Serum metabolites and ovarian tissue gene expression were detected using ultra-performance liquid chromatography-quadrupole-electrostatic orbitrap mass spectrometry（UPLC-Q-Orbitrap-MS） and RNA-Seq technology， respectively， followed by multi-omics integrated analysis. ResultsPharmacodynamic findings revealed that all MBXT dose groups could reversed abnormal estrous cycles in PCOS-IR rats， improve polycystic ovarian lesions， and normalize dysregulated serum hormone levels（T， LH， E₂， FS， P<0.05， P<0.01）. Metabolomic analysis revealed that compared with the model group， MBXT reversed 278 differential metabolites such as estrone and S-formylglutathione， mainly involving pathways such as steroid hormone biosynthesis， glutathione metabolism， and lipid peroxidation regulation. Transcriptomic analysis identified 434 differentially expressed genes， and enrichment analysis revealed that MBXT significantly regulated lipid peroxidation defense systems， including glutathione metabolism， peroxisome function， and fatty acid metabolism， thereby intervening in ferroptosis processes. It also engaged in inflammation-related pathways such as the chemokine signaling pathway. Integrated analysis revealed that both metabolomics and transcriptomics co-enriched metabolic pathways associated with ferroptosis and fatty acid metabolism. And key Hub genes［such as Ras-related C3 botulinum toxin substrate 2 gene（Rac2） and Fas ligand gene（Faslg）］ showed significant correlations with differential metabolites. ConclusionMBXT can effectively ameliorate reproductive dysfunction and metabolic disorders in PCOS-IR rats. Its mechanism may be related to remodeling the immune-metabolism network， particularly by regulating MHC-mediated immune responses， inhibiting local ovarian ferroptosis， and enhancing steroid hormone synthesis pathways.

ObjectiveTo investigate the mechanism of modified Banxia Xiexintang（MBXT） in improving ovarian dysfunction in polycystic ovary syndrome with insulin resistance（PCOS-IR） rats by inhibiting ferroptosis through the adenosine monophosphate（AMP）-activated protein kinase（AMPK）/fatty acid synthase（FASN）/glutathione peroxidase 4（GPX4） signaling pathway. MethodsSeventy-six female SD rats were randomly divided into a normal group（n=13） and a modeling group（n=63）. The modeling group established a PCOS-IR model by intragastric administration of letrozole combined with a high-fat diet for 21 days. After successful modeling， these rats were randomly divided into the model group， MBXT low-， medium-， and high-dose groups（6.62， 13.23， 26.46 g·kg^-1）， metformin group（0.158 g·kg^-1）， and high-dose of MBXT combined with ferroptosis inducer Erastin group（15 mg·kg^-1）， with 10 rats in each group. After 14 days of intervention， ovarian pathological morphology was observed by hematoxylin-eosin（HE） staining， the mitochondrial ultrastructure of granulosa cells was observed by transmission electron microscopy（TEM）， ovarian reactive oxygen species（ROS） levels were detected by dihydroethidium（DHE） probe， biochemical methods were used to detect Fe²⁺， malondialdehyde（MDA）， glutathione（GSH） and other indicators in ovarian tissues， serum sex hormone and insulin levels were measured by enzyme-linked immunosorbent assay（ELISA）， and the protein expressions of AMPK， FASN， acyl-CoA synthetase long-chain family member 4（ACSL4）， GPX4， and solute carrier family 7 member 11（SLC7A11） in ovarian tissues were detected by Western blot. ResultsCompared with the normal group， the model group showed polycystic changes in the ovaries， with atrophy of mitochondria in granulosa cells and increased membrane density. Serum levels of testosterone（T）， luteinizing hormone（LH）， and insulin were significantly increased（P<0.01）. The levels of ROS， MDA， 4-hydroxynonenal（4-HNE）， and Fe²⁺ in ovarian tissues were significantly elevated（P<0.01）， while adenosine triphosphate（ATP）， GSH， and reduced nicotinamide adenine dinucleotide phosphate （NADPH） levels were significantly decreased（P<0.01）. The phosphorylation levels of AMPK and acetyl-CoA carboxylase （ACC）， as well as the protein expressions of SLC7A11， GPX4， and ferroptosis suppressor protein 1（FSP1） were significantly downregulated（P<0.01）， whereas the expressions of FASN， ACSL4， and nuclear receptor coactivator 4（NCOA4） were significantly upregulated（P<0.01）. Compared with the model group， MBXT intervention at various doses improved the above pathological changes and biochemical indicators in a dose-dependent manner， with the high-dose group showing the most significant effect（P<0.01）. Compared with the MBXT high-dose group， the high-dose of MBXT combined with ferroptosis inducer Erastin group restored ovarian ferroptosis characteristics in rats， with increased ROS and lipid peroxidation products， and altered expressions of key proteins（P<0.05， P<0.01）. ConclusionMBXT can effectively improve ovarian function and metabolic disorders in PCOS-IR rats. Its mechanism may be related to activating the AMPK/ACC signaling pathway， downregulating FASN and ACSL4 to reduce lipid peroxidation substrates， and restoring glucose-6-phosphate dehydrogenase/phosphoglycerate dehydrogenase（G6PD/PHGDH） metabolic flux to enhance the GPX4/FSP1 antioxidant defense system， thereby inhibiting ferroptosis in ovarian granulosa cells.

Objective : To investigate the effect of the miR-155-5p/silent information regulator 1(sirt1) signaling pathway on the immune function ofCandida albicansinduced Kawasaki disease model mice. Methods : C56BL/6 mice were separated into control group, Kawasaki disease group, antagonist control group, miR-155-5p antagonist group, miR-155-5p antagonist+si-NC group, and miR-155-5p antagonist+si-sirt1 group, with 12 mice in each group. Except for the control group, mice in all other groups were used to construct a Kawasaki disease model by intraperitoneal injection of water-solubleCandida albicans. After successful modeling, administration was performed once a day for 7 days. QRT-PCR was applied to detect the expression of miR-155-5p in coronary arteries. Western blot was applied to detect sirt1 protein in coronary arteries. HE staining was applied to detect pathological changes in coronary arteries. Mouse thymus index and spleen index were detected. Flow cytometry was applied to detect helper T cells 17(Th17)/regulatory T cells(Treg) in peripheral blood. ELISA was applied to detect the levels of interleukin(IL)-17 and IL-10 in mouse serum. The targeting relationship between sirt1 and miR-155-5p was validated. Results: Compared with the control group, there was a large amount of inflammatory cell infiltration in the coronary arteries of mice in the Kawasaki disease group. The miR-155-5p expression, Th17 ratio, Th17/Treg ratio, and IL-17 level increased. The sirt1 protein expression, thymus index, spleen index, Treg ratio, and IL-10 level decreased(P<0.05). Compared with the Kawasaki disease group, the inflammatory cell infiltration in the coronary arteries of mice in the miR-155-5p antagonist group was alleviated. The miR-155-5p expression, Th17 ratio, Th17/Treg ratio, and IL-17 level decreased. The sirt1 protein expression, thymus index, spleen index, Treg ratio, and IL-10 level increased(P<0.05). Si-sirt1 weakened the promoting effect of miR-155-5p inhibition on Th17/Treg balance and the inhibitory effect on vascular inflammation in Kawasaki disease mice, miR-155-5p targeted and regulated sirt1. Conclusion The mechanism by which inhibiting miR-155-5p promotes Th17/Treg balance and inhibits vascular inflammation in Kawasaki disease mice may be related to the upregulation of sirt1 expression.

Objective:To identify the clinical characteristics and prognosis of patients with hematological disease and neutropenic sepsis in the hematological intensive care unit (HCU).Methods:A retrospective analysis was conducted on patients with hematological disease and sepsis who admitted to HCU, the First Affiliated Hospital of Harbin Medical University from October 2017 to October 2024, to examine the primary therapeutic options, prognosis, cause of death, and infectious features of sepsis.Results:A total of 245 septic patients were included in the study, comprising 88 cases in the neutropenic sepsis group (neutropenic group) and 157 cases in the non-neutropenic sepsis group (non-neutropenic group). Acute leukemia was more prevalent in the neutropenic group [55.68% (49/88) ]. At the time of admission to the HCU, the neutropenic group exhibited unstable vital signs, lower blood cell counts, higher inflammatory markers, elevated Sequential Organ Failure Assessment (SOFA) scores, increased creatinine levels (120.00 μmol/L vs 77.10 μmol/L, P<0.01), higher total bilirubin levels (24.70 μmol/L vs 17.90 μmol/L, P<0.01), and significantly elevated B-type natriuretic peptide levels (567.90 ng/L vs 134.50 ng/L, P<0.01) compared with the non-neutropenic group. Furthermore, septic shock was more common in the neutropenic group [53.40% (47/88) vs 36.94% (58/157), P<0.05]. The mortality rate was also higher in the neutropenic group [46.59% (41/88) ] compared with the non-neutropenic group [32.48% (51/157) ] ( P<0.05), with septic shock accounting for the majority of deaths [70.73% (29/41) ]. Infections caused by gram-negative bacteria [55.68% (49/88) vs 36.30% (57/157), P<0.01] and fungi [14.77% (13/88) vs 6.36% (10/157), P<0.05] were more common in the neutropenic group. However, lung infections were significantly less frequent in the neutropenic group ( P<0.01). Kaplan-Meier survival analysis revealed a substantially worse 28-day overall survival rate for the neutropenic group compared with the non-neutropenic group ( P<0.05) . Conclusion:Patients with hematological diseases and neutropenic sepsis presented with more severe clinical conditions, a higher likelihood of organ failure and septic shock, and significantly increased mortality compared with patients with non-neutropenic sepsis.

Objective:To study the growth inhibition of Thunberg Fritillary extract on non-small cell lung cancer.Methods:The Thunberg Fritillary extract was prepared and characterized by UPLC-QE/MS.Replicated Lewis lung carcinoma ectopic tumor-bear-ing mouse model,yeast injection induced acute inflammation,compared the effect of Thunberg Fritillary extract combination with acute inflammation on the growth,tumor volume and tumor suppression rate of Lewis lung carcinoma mice,and determine the content of inflammatory factors by the flow CBA method(IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,IL-23,TNF-α,IFN-γ,IFN-β,GM-CSF,MCP-1).Results:The inhibition of Lewis lung carcinoma mice was similar to that of cisplatin alone,and the tumor suppression rate was 35%;the tumor suppression rate of Thunberg Fritillary extract combined with acute inflammatory stimulation of yeast was 62%,1.8 times that of cisplatin alone.The decrease in the expressions of cytokines IL-23,MCP-1 after acute inflammatory stimulation in yeast was associated with tumor suppression;while the increased expressions of IL-6,IL-1β,IL-1α,IL-10,IL-27,IL-17A,IL-12p70,TNF-α,IFN-γ,IFN-β and GM-CSF cytokines were associated with tumor suppression.Conclusion:The Thun-berg Fritillary extract combination with acute inflammation can play a positive role against non-small cell lung cancer,which will pro-vide new research ideas and methods for the prevention and treatment of non-small cell lung cancer.

Objective:To construct a risk assessment index system for occupational disease hazards in the automotive repair industry using the Delphi method, providing a scientific basis and systematic evaluation framework for occupational hazard management in this sector.Methods:In January 2024, an expert survey method was employed to identify occupational hazard risk indicators through in-depth expert discussions. A multidimensional and hierarchical assessment system was designed based on the two core elements of "comprehensive prevention-on-site hazards."Results:The consultation results from 20 authoritative experts demonstrated that the expert authority coefficient (0.84), coordination coefficient (0.73), and reliability coefficient (0.83) all reached robust levels. The importance scores of the indicators (ranging from 3.47 to 5.59 points) exhibited clear discriminative validity. Ultimately, an assessment system comprising 2 first-level indicators, 5 second-level indicators, and 14 third-level indicators was established.Conclusion:The index system developed in this study demonstrates high scientific rigor and practical applicability. It provides a systematic evaluation tool for the hierarchical management and targeted prevention of occupational disease hazards in the automotive repair industry, offering both theoretical support and practical guidance for occupational hazard risk control in this field.

Binge eating disorder(BED)is a common eating disorder whose pathogenesis involves both neurobiological and psychological mechanisms.At the neurobiological level,the development of BED is associated with abnormal resting-state brain functional connectivity in the reward circuitry,dysregulation of the endocannabinoid system,and elevated leptin levels.This paper reveals that the neurobiological mechanisms of BED may influence psychological processes,including habitual behavioral imbalances and impaired emotion regulation.Conversely,the dysfunction of behavior in the psychological domain may further modulate neurobiological manifestations.This finding provides insights for future research aimed at systematically integrating neural mechanisms into clinical interventions,ultimately facilitating treatment advancement and prognostic improvement.

Trichotillomania, also known as Hair Pulling Disorder, is a unique obsessive-compulsive spectrum disorder characterized by repeated removal of hair from various parts of the body. Patients attempt to control this behavior but often fail, causing impairment to important functional areas such as social interaction, work, and academics. Trichotillomania typically begins in childhood or adolescence, and is often comorbid with anxiety and depression. The resulting physical damage and changes in appearance further exacerbate the social functional impairment of patients, resulting in most patients being diagnosed only in adulthood, and missing the optimal intervention period. Current pharmacological treatments for Trichotillomania are not satisfactory, while various psychological therapies have shown potential value and prospects. Therefore, this article focuses on Trichotillomania in children and adolescents, providing a comprehensive review from multiple aspects including disease diagnosis, clinical characteristics and typing, functional impairment, neuroimaging mechanisms, and the latest developments in psychological therapy, to provide references for the clinical diagnosis, assessment, and effective intervention of Trichotillomania.

Alexithymia refers to a deficiency of emotional structure, but the neurologic and psychological mechanisms of non-suicidal self-injury (NSSI) in adolescents are still unclear. The neural basis of alexithymia may play a role in adolescents′ NSSI by affecting the function of emotion regulation and emotion expression. At the same time, NSSI is also considered to be a non-adaptive emotional regulation mode for alexithymia individuals, which interacts with personality factors and psychosocial factors. This study explored the neuropsychological mechanism of alexithymia in adolescent NSSI from the perspective of emotional function, and provided theoretical basis for early identification and precise intervention of alexithymia and adolescent NSSI.