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.

The medicinal use of Malvae Semen has a long history. In this paper， by consulting the ancient materia medica， prescription， agronomy， literature and other aspects of the classics， the name， origin， evolution of scientific name， quality， harvesting and processing， functions and indications and others of Malvae Semen were systematically sorted out and verified， so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research， Shennong Bencaojing began to use Dongkuizi as the correct name， which was used in the past dynasties， and there were also aliases such as Kuicaizi， Huacai， and Kuizi. Through the original research， it can be seen that Kuicai is the mainstream original plant of Malvae Semen， that is， Malva verticillata var. crispa， the Alcea rosea and M. cathayensis are also used. In modern times， the seeds of Abutilon theophrasti have been passed off as Malvae Semen， while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties， the cultivation of Kuicai has been decreasing， while A. theophrasti is more common and easy to obtain， and Abutili Semen and Malvae Semen are similar in morphology and confused， which should be corrected. In addition， Malvae Fructus is a Mongolian customary medicinal herb， which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai， as an important vegetable in history， was widely cultivated and gradually shrunk after the Song dynasty， it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies， full grain， grayish brown color， no mud， and no impurities. The harvesting is generally in the autumn and winter. After drying， it is seeded， sieved peel and impurities， mashed， or slightly stir-fried to yellow-white color with gentle fire. It is sweet， cold and slippery in nature and taste， with the main effects of laxation， diuresis， lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity， promoting diuresis and removing nebula， the efficacy is quite different from that of Malvae Semen. Based on the results of textual research， it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas， the corresponding processing methods should be selected according to the requirements of drug processing in the formulas， while the raw products are recommended to be used if the processing is not specified.

The medicinal use of Malvae Semen has a long history. In this paper， by consulting the ancient materia medica， prescription， agronomy， literature and other aspects of the classics， the name， origin， evolution of scientific name， quality， harvesting and processing， functions and indications and others of Malvae Semen were systematically sorted out and verified， so as to provide a basis for the development and utilization of famous classical formulas containing this herb. According to the textual research， Shennong Bencaojing began to use Dongkuizi as the correct name， which was used in the past dynasties， and there were also aliases such as Kuicaizi， Huacai， and Kuizi. Through the original research， it can be seen that Kuicai is the mainstream original plant of Malvae Semen， that is， Malva verticillata var. crispa， the Alcea rosea and M. cathayensis are also used. In modern times， the seeds of Abutilon theophrasti have been passed off as Malvae Semen， while the seeds of M. verticillata var. crispa have rarely been used in medicine. And Abutili Semen has been another medicinal material with different efficacy since the collection of Newly Revised Materia Medica in the Tang dynasty. Since the Ming and Qing dynasties， the cultivation of Kuicai has been decreasing， while A. theophrasti is more common and easy to obtain， and Abutili Semen and Malvae Semen are similar in morphology and confused， which should be corrected. In addition， Malvae Fructus is a Mongolian customary medicinal herb， which is different from the traditional use of seeds in traditional Chinese medicine. Kuicai， as an important vegetable in history， was widely cultivated and gradually shrunk after the Song dynasty， it is now mainly produced in southern provinces. The quality evaluation of Malvae Semen is better for those with dry bodies， full grain， grayish brown color， no mud， and no impurities. The harvesting is generally in the autumn and winter. After drying， it is seeded， sieved peel and impurities， mashed， or slightly stir-fried to yellow-white color with gentle fire. It is sweet， cold and slippery in nature and taste， with the main effects of laxation， diuresis， lactation and elimination of swelling. The efficacy of Abutili Semen is clearing heat and removing toxicity， promoting diuresis and removing nebula， the efficacy is quite different from that of Malvae Semen. Based on the results of textual research， it is suggested that M. verticillata var. crispa should be used as the medicinal source of Malvae Semen in the development of famous classical formulas， the corresponding processing methods should be selected according to the requirements of drug processing in the formulas， while the raw products are recommended to be used if the processing is not specified.

Objective:To explore the clinical characteristics of biliary system diseases complicated by severe acute pancreatitis(SAP) and the risk factors.Methods:This is a retrospective cohort study. A retrospective analysis was conducted on the clinical data of 159 SAP patients admitted to the Department of Pancreatic and Biliary Surgery,the First Affiliated Hospital of Harbin Medical University from January 2019 to October 2024. There were 105 male cases, 54 female cases;aged (42.3±10.8)years (range:20 to 71 years). Grouping was performed according to the presence or absence of concurrent acute acalculous cholecystitis (AAC) and biliary stricture. There were 58 cases in the AAC group,including 40 males and 18 females;aged (43.8±10.6) years (range:28 to 71 years);101 cases in the non-AAC group,including 64 males and 37 females;aged (41.5±10.8) years (range:20 to 64 years);there were statistically significant differences between the two groups in terms of admission total bilirubin,Balthazar-CTSI score,fasting time,and the proportions of concurrent shock and sepsis (all P<0.05);the time from onset of SAP to diagnosis of AAC( M (IQR)) was 10.5 (13.3) days (range: 3 to 34 days). There were 15 cases in the biliary stricture group,including 13 males and 2 females;age (46.5±10.0) years (range:33 to 63 years);141 cases in the non-biliary stricture group,including 89 males and 52 females;age (41.9±10.8) years (range: 20 to 71 years); there were statistically significant differences between the two groups in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis (all P<0.05);the time from the onset of SAP to the diagnosis of biliary stenosis in patients with biliary stenosis was 2.0 (3.0) months (range: 1 to 19 months). Univariate analysis was performed using independent sample t-test, Mann-Whitney U test, χ 2 test,or Fisher′s exact probability method,and variables with P<0.05 in univariate analysis were included in multivariate logistic regression analysis. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic and predictive value of the multivariate logistic regression model for AAC and biliary stricture. Results:There were statistically significant differences in fasting time,Balthazar-CTSI score,admission total bilirubin,and the proportions of concurrent shock and sepsis between the AAC group and non-AAC group ( P<0.05). Multivariate logistic analysis showed that admission total bilirubin ( OR=1.033,95% CI: 1.010 to 1.058, P=0.004),Balthazar-CTSI score ( OR=1.276,95% CI: 1.036 to 1.572, P=0.022),fasting time ( OR=1.127,95% CI: 1.044 to 1.216, P=0.002), and sepsis ( OR=4.033, 95% CI: 1.419 to 11.462, P=0.009) were independent risk factors for AAC complicated by SAP. The area under the curve (AUC) of the ROC curve was 0.820 (95% CI: 0.752 to 0.888). There were statistically significant differences in the proportions of infected pancreatic necrosis,pancreatic head necrosis,and lower extremity venous thrombosis between the biliary stricture group and non-biliary stricture group ( P<0.05). Multivariate logistic analysis showed that infected pancreatic necrosis ( OR=7.376,95% CI:1.566 to 37.750, P=0.012) and pancreatic head necrosis ( OR=3.898,95% CI:1.180 to 12.877, P=0.026) were independent risk factors for biliary stricture complicated by SAP. The AUC of the ROC curve was 0.806 (95% CI:0.715 to 0.898). Conclusions:AAC typically occurs in the early stage of SAP,and biliary stricture usually occurs in the late stage of SAP. Admission total bilirubin,Balthazar-CTSI score,fasting duration,and concurrent sepsis are independent risk factors for AAC complicating SAP. Infected pancreatic necrosis and pancreatic head necrosis are independent risk factors for biliary stricture complicating SAP.

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.

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.

CRISPR/Cas9-based therapeutics face significant challenges in penetrating the dense microenvironment of solid tumors, resulting in insufficient gene editing and compromised treatment efficacy. Current nanostrategies, which mainly focus on the paracellular pathway attempted to improve gene editing performance, whereas their efficiency remains uneven in the heterogenous extracellular matrix. Here, the nanoCRISPR system is prepared with self-cascading mechanisms for gene editing-mediated robust apoptosis and transcellular penetration. NanoCRISPR unlocks its self-cascade capability within the matrix metallopeptidase 2-enriched tumor microenvironment, initiating the transcellular penetration. By facilitating cellular uptake, nanoCRISPR triggers robust apoptosis in edited malignancies, promoting further transcellular penetration and amplifying gene editing in neighboring tumor cells. Benefiting from self-cascade between robust apoptosis and transcellular penetration, nanoCRISPR demonstrates continuous gene transfection/tumor killing performance (transfection/apoptosis efficiency: 1st round: 85%/84.2%; 2nd round: 48%/27%) and homogeneous penetration. In xenograft tumor-bearing mice, nanoCRISPR treatment achieves remarkable anti-tumor efficacy (∼83%) and significant survival benefits with minimal toxicity. This strategy presents a promising paradigm emphasizing transcellular penetration to enhance the effectiveness of CRISPR-based antitumor therapeutics.

Mesangial cell proliferation is an early pathological indicator of diabetic nephropathy (DN). Growing evidence highlights the pivotal role of paired-related homeobox 1 (Prrx1), a key regulator of cellular proliferation and tissue differentiation, in various disease pathogenesis. Notably, Prrx1 is highly expressed in mesangial cells under DN conditions. Both in vitro and in vivo studies have demonstrated that Prrx1 overexpression promotes mesangial cell proliferation and contributes to renal fibrosis in db/m mice. Conversely, Prrx1 knockdown markedly suppresses hyperglycemia-induced mesangial cell proliferation and mitigates renal fibrosis in db/db mice. Mechanistically, Prrx1 directly interacts with the Yes-associated protein 1 (YAP) promoter, leading to the upregulation of YAP expression. This upregulation promotes mesangial cell proliferation and exacerbates renal fibrosis. These findings emphasize the crucial role of Prrx1 upregulation in high glucose-induced mesangial cell proliferation, ultimately leading to renal fibrosis in DN. Therefore, targeting Prrx1 to downregulate its expression presents a promising therapeutic strategy for treating renal fibrosis associated with DN.

Objective:To investigate the predictive value of refeeding syndrome (RFS) and its influencing factors for 30-day intensive care unit (ICU) readmission in critically ill patients.Methods:A prospective cohort study was conducted. Critically ill patients admitted to the department of critical care medicine, department of respiratory and critical care medicine, and department of neurology at Tianjin Medical University General Hospital from January to April in 2025 were enrolled. Patients were assessed for RFS according to the American Society for Parenteral and Enteral Nutrition (ASPEN) criteria. General information within 24 hours of ICU admission was collected via the electronic medical record system. Treatment details and 30-day ICU readmission status were dynamically recorded. Participants were divided into readmission and non-readmission groups based on whether ICU readmission occurred within 30 days. Intergroup comparisons were performed to identify differences. Multivariate Logistic regression was used to analyze the relationship between RFS and its influencing factors with 30-day ICU readmission. Receiver operator characteristic curve (ROC curve) was plotted to evaluate the predictive performance of risk factors.Results:A total of 196 critically ill patients were enrolled, among whom 25 (12.76%) were readmitted to ICU within 30 days and 171 (87.24%) were not. Significant differences were observed in the readmission group compared with the non-readmission group, including significantly higher rates of nasogastric decompression, higher acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score, a higher incidence of RFS, and a longer duration of nasogastric decompression. Multivariate Logistic regression analysis showed that RFS was an independent risk factor for 30-day ICU readmission [odds ratio ( OR) = 5.756, 95% confidence interval (95% CI) was 1.603-20.670, P = 0.007]. APACHEⅡ score showed a positive correlation trend with 30-day ICU readmission ( OR = 1.057, 95% CI was 0.991-1.127, P = 0.092). ROC curve analysis showed that the combined prediction model incorporating RFS and APACHEⅡ score had an area under the ROC curve (AUC) of 0.766 (95% CI was 0.668-0.864), with a sensitivity of 88.0% and a specificity of 62.0%, which was significantly superior to a single indicator (the AUC of RFS and APACHEⅡ score was 0.639 and 0.624, respectively). Conclusions:RFS significantly increases the risk of 30-day ICU readmission in critically ill patients. A combined model incorporating RFS and APACHEⅡ score demonstrates good predictive efficacy for 30-day ICU readmission in critically ill patients.