ObjectiveTo investigate the mechanism of Xiaozhi Qinggan decoction （XQD） in preventing and treating metabolic dysfunction-associated steatotic liver disease （MASLD） by regulating ferroptosis， network pharmacology， in vitro and in vivo experiments. MethodsIn the in vivo experiment， mouse MASLD models were established by high-fat diet （HFD） induction. The model mice were randomly assigned to a positive control group （silybin， 50 mg·kg^-1）， low-， medium- and high-dose XQD groups （4.725， 9.45， 18.9 g·kg^-1）， with a normal control group. After 4 weeks of modeling， mice except the normal group were administered intragastrically for 8 consecutive weeks. Liver function， serum lipid levels， hepatic histopathology， as well as the levels of malondialdehyde （MDA）， superoxide dismutase （SOD）， reduced glutathione （GSH） and oxidized glutathione （GSSG） and Fe²⁺ were detected. The mRNA and protein expression of p53， SLC7A11 and GPX4 were determined by quantitative Real-time quantitative polymerase chain reaction（Real-time PCR） and Western blot. In the network pharmacology analysis， active components and potential targets of XQD for MASLD were screened， followed by functional and pathway enrichment analyses， and molecular docking was performed to verify the target binding activity. In the in vitro experiment， the optimal concentration of XQD-containing serum was screened by cytotoxicity assay. HepG2 cells were transfected with ov-NC or ov-p53 plasmid， and a lipid accumulation model was induced by free fatty acid （FFA， 1.0 mmol·L^-1）. Cells were divided into a normal group， FFA model group， ov-NC+XQD （15%） group and ov-p53+XQD （15%） group. Intracellular Fe²⁺ level and lipid accumulation were evaluated， and the protein expression of p53， SLC7A11 and GPX4 was measured by Western blot. ResultsCompared with the normal group， the model group exhibited markedly elevated body weight， liver weight， liver index， fasting blood glucose， AUC of glucose tolerance test， serum liver function and blood lipid levels at week 12 （P<0.01）. Hepatic steatosis and inflammatory infiltration were observed by pathological staining. Additionally， hepatic levels of MDA， SOD and Fe²⁺ were increased （P<0.01）， while GSH， GSSG and the GSH/GSSG ratio were decreased （P<0.01）. The mRNA and protein expression of hepatic p53 was upregulated （P<0.01）， whereas the expression of SLC7A11 and GPX4 was downregulated （P<0.01）. Compared with the model group， the low- and medium-dose XQD groups showed significantly decreased body weight at week 12 （P<0.05）. The silybin group， together with the medium- and high-dose XQD groups， presented reduced liver weight and liver index （P<0.05）. Fasting blood glucose and the AUC of glucose tolerance test were lowered in all four treatment groups （P<0.05， P<0.01）. Pathological staining revealed alleviated hepatic steatosis and inflammation， accompanied by decreased serum liver function and blood lipid levels （P<0.05， P<0.01）. Moreover， hepatic MDA and SOD levels were markedly reduced， while GSH， GSSG and the GSH/GSSG ratio were significantly elevated （P<0.05， P<0.01）. Hepatic Fe²⁺ level was decreased （P<0.01）. The mRNA and protein expression of hepatic p53 was downregulated， and the expression of SLC7A11 and GPX4 was upregulated （P<0.05， P<0.01）. Network pharmacology analysis identified quercetin， kaempferol， luteolin， tanshinone IIA and isorhamnetin as the core active components of XQD， with p53 serving as the key target. Stable binding was verified between these active components and the p53 protein. The optimal concentration of XQD-containing serum in vitro was determined to be 15%. Compared with the normal group， the model group showed increased intracellular Fe²⁺ and lipid accumulation， significantly upregulated p53 protein expression （P<0.01）， and markedly downregulated SLC7A11 and GPX4 protein expression （P<0.01）. Compared with the model group， the ov-NC group exhibited reduced Fe²⁺ and lipid accumulation， downregulated p53 expression， and upregulated SLC7A11 and GPX4 expression. In the ov-p53 group， p53 expression was upregulated （P<0.01）， while SLC7A11 and GPX4 expression was downregulated （P<0.01）. ConclusionXQD inhibits ferroptosis by downregulating p53 and upregulating SLC7A11 and GPX4， thereby alleviating oxidative stress and lipid peroxidation in hepatocytes and improving MASLD.

Objective: To evaluate the diagnostic potential of fluid suppression (FS) techniques combined with amide proton transferweighted imaging (APTw) for assessment of isocitrate dehydrogenase (IDH) mutation status, glioma subtypes, and tumor proliferation. Materials and Methods: This retrospective study included 117 patients with adult-type diffuse gliomas. Conventional APTw, FSAPTw, and spillover-corrected FS-APTw (SCFS-APTw) metrics were calculated from 3T MRI data in tumor parenchyma, necrotic or cystic regions, and contralateral normal-appearing white matter. APTw signals were compared across the three techniques within each region, between IDH-mutant and IDH-wildtype gliomas, and among astrocytoma, oligodendroglioma, and glioblastoma subtypes. Diagnostic performance for distinguishing IDH mutation status and glioma subtypes was assessed using receiver operating characteristic (ROC) analysis. Correlations between APTw metrics and Ki-67 expression were also analyzed. Results: Both FS-APTw and SCFS-APTw significantly reduced signal intensity in tumor parenchyma and necrotic or cystic regions, with SCFS-APTw demonstrating a stronger suppression effect. IDH-wildtype gliomas showed significantly higher APTw metrics than IDH-mutant gliomas (all P < 0.001). Glioblastomas exhibited significantly higher metrics than oligodendrogliomas (all corrected P ≤ 0.015) and astrocytomas (all corrected P < 0.001). SCFS-APTw achieved the highest area under the ROC curve (AUC) of 0.846 for identification of IDH mutation status. For differentiation between astrocytomas and glioblastomas, the 90th percentile of APTw yielded the highest AUC (0.860), followed by SCFS-APTw (0.849). For discrimination between oligodendrogliomas and glioblastomas, the highest AUC (0.832) was obtained using the 90th percentile of SCFS-APTw. None of these metrics successfully differentiated oligodendrogliomas from astrocytomas. SCFS-APTw demonstrated the strongest correlation with Ki-67 expression (r = 0.451). Conclusion FS techniques effectively reduce elevated APTw signals originating from fluid compartments. Their combination with APTw imaging enables evaluation of IDH mutation status, glioma subtypes, and tumor proliferative activity in adulttype diffuse gliomas.

Intestinal fibrosis is a significant clinical challenge in inflammatory bowel diseases, but no effective anti-fibrotic therapy is currently available. Glucagon receptor (GCGR) and glucagon-like peptide 1 receptor (GLP1R) are both peptide hormone receptors involved in energy metabolism of epithelial cells. However, their role in intestinal fibrosis and the underlying mechanisms remain largely unexplored. Herein GCGR and GLP1R were found to be reduced in the stenotic ileum of patients with Crohn's disease as well as in the fibrotic colon of mice with chronic colitis. The downregulation of GCGR and GLP1R led to the accumulation of the metabolic byproduct lactate, resulting in histone H3K9 lactylation and exacerbated intestinal fibrosis through epithelial-to-mesenchymal transition (EMT). Dual activating GCGR and GLP1R by peptide 1907B reduced the H3K9 lactylation in epithelial cells and ameliorated intestinal fibrosis in vivo. We uncovered the role of GCGR/GLP1R in regulating EMT involved in intestinal fibrosis via histone lactylation. Simultaneously activating GCGR/GLP1R with the novel dual agonist peptide 1907B holds promise as a treatment strategy for alleviating intestinal fibrosis.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Poly(ADP-ribosyl)ation (PARylation) is a specific form of post-translational modification (PTM) predominantly triggered by the activation of poly-ADP-ribose polymerase 1 (PARP1). However, the role and mechanism of PARylation in the advancement of acute kidney injury (AKI) remain undetermined. Here, we demonstrated the significant upregulation of PARP1 and its associated PARylation in murine models of AKI, consistent with renal biopsy findings in patients with AKI. This elevation in PARP1 expression might be attributed to trimethylation of histone H3 lysine 4 (H3K4me3). Furthermore, a reduction in PARylation levels mitigated renal dysfunction in the AKI mouse models. Mechanistically, liquid chromatography-mass spectrometry indicated that PARylation mainly occurred in receptor for activated C kinase 1 (RACK1), thereby facilitating its subsequent phosphorylation. Moreover, the phosphorylation of RACK1 enhanced its dimerization and accelerated the ubiquitination-mediated hypoxia inducible factor-1α (HIF-1α) degradation, thereby exacerbating kidney injury. Additionally, we identified a PARP1 proteolysis-targeting chimera (PROTAC), A19, as a PARP1 degrader that demonstrated superior protective effects against renal injury compared with PJ34, a previously identified PARP1 inhibitor. Collectively, both genetic and drug-based inhibition of PARylation mitigated kidney injury, indicating that the PARylated RACK1/HIF-1α axis could be a promising therapeutic target for AKI treatment.

Objective To identify the key influencing factors and role mechanisms of large-scale medical equip-ment allocation decision-making in public hospitals,and to provide a reference basis for optimizing resource alloca-tion strategies.Methods Through searching the literature related to large-scale medical equipment decision-making in public hospitals and combing the policies,the system of decision-making influencing factors was initially screened.The Delphi method and decision-making trial and evaluation laboratory method were used to obtain the key influencing factors of equipment allocation decision-making and to determine the interaction effects among the factors.Results A total of seven cause factors and nine effect factors were screened.Among them,cost-benefit analysis,equipment technical performance,and evaluation of similar equipment were the top three key drivers;leadership emphasis,equipment market price,and equipment supporting facilities were the top three key con-straints.Conclusion Priority be given to strengthening the management of driving factors,mainly by conducting a full-cycle assessment of cost-effectiveness,paying attention to the clinical value output of equipment technical performance,and monitoring regionally similar equipment.A dynamic response mechanism for constraints should be established,mainly to strengthen leadership decision-making,implement a centralized procurement price nego-tiation model and improve the pre-assessment system for ancillary facilities.

The strategy of pelvic lymph node dissection in patients with localized intermediate- and high-risk prostate cancer（PCa）has been one of the research hotspots in recent years. This review synthesizes recent progress in clinical，diagnostic imaging and immunological aspects of pelvic lymph node dissection.It is found that the detection rate of metastatic lymph nodes in patients with localized intermediate-risk PCa is relatively low，and the survival benefit after dissection is not significant. PSMA PET/CT examination can be used instead of lymph node dissection for staging. Extended lymph node dissection in patients with localized high-risk PCa can achieve a higher detection rate of metastatic lymph nodes and possible survival benefits. However，excessive lymph node dissection can weaken the response ability to immunotherapy. The strategy for pelvic lymph node dissection in patients with localized intermediate-high-risk PCa needs further study.

Objective:To analyze the respiratory virus infection status and epidemiological characteristics of influenza-like illness (ILI) cases in Shandong Province during the 2020 -2021 influenza surveillance year. Methods:According to the National Influenza Surveillance Plan (2017 version), throat swab samples of ILI cases were collected from 14 surveillance sentinel hospitals in Shandong Province. Nucleic acid was extracted from all samples. Real-time fluorescence quantitative PCR (RT-PCR) was utilized to detect six common viruses, including human metapneumovirus (HMPV), human parainfluenza virus (HPIV) types 1, 2 and 3, respiratory syncytial virus (RSV), and adenovirus (ADV). Subsequently, the obtained detection results were analyzed.Results:A total of 2 386 specimens were collected, with a detection rate of 24.22% (578). Six viruses were detected, with detection rates of 6.75% (162 cases) for HMPV, 5.87% (140 cases) for RSV, 3.56% (85 cases) for HPIV3, 3.14% (75 cases) for HPIV2, 2.98% (71 cases) for HPIV1, and 2.77% (66 cases) for ADV. There was no significant difference in detection rates between genders, but a notable variation among different age groups ( P<0.001). The highest detection rate was observed in individuals aged 0-4 years (31.94%), followed by those aged≥60 years (26.06%). The prevalence of six viruses showed a monthly variation, with the detection rate of HMPV being higher in December and HPIV1 being higher in February. HPIV2, HPIV3, RSV, and ADV had higher detection rates in November. The co-detection rate of multiple viruses was 0.80%, with RSV being the most common pathogen involved in co-detection, primarily in individuals aged 0-4 years. Conclusion:The detection of six multiple pathogens in ILI cases in Shandong Province is dominated by HMPV, RSV and HPIV3. The prevalence of respiratory viruses varies by age and time.

It is believed that patients with cirrhotic ascites exhibit a pathological mechanism characterized by the decline of healthy qi and the accumulation of pathogenic factors. Clinically， treatment should be based on the theory of tonification and purging， with a staged approach distinguishing between the active phase and the remission phase. The balance between tonification and purging should be adjusted according to the progression of pathogenic and healthy actors. In the acute phase， purging should take precedence over tonification， using purging as a means of tonification to facilitate the flow of water and qi through the triple energizer. The severity of water retention， dampness， blood stasis， and heat should be carefully assessed to ensure thorough elimination of pathogenic factors while avoiding harm to healthy qi. Medication adjustments should be made once the pathogenic factors are significantly weakened. In the remission phase， an integrated approach combining both tonification and purging should be adopted， incorporating purging within tonification to clear residual pathogens and prevent recurrence. Concurrently， proactive treatment of the underlying disease is essential to achieve complete recovery and prevent the recurrence of ascites.

Objective:To analyze the factors influencing postoperative complications and survival in patients undergoing hepatectomy for primary liver cancer (PLC).Methods:Two hundred and eighty-eight patients with PLC who underwent hepatectomy at Tianjin Medical University Cancer Hospital from April 2018 to December 2020 were prospectively enrolled, including 235 males and 53 females, aged (58.5±9.5) years. Nutritional evaluations included the nutritional risk screening 2002 (NRS-2002), patient-generated subjective global assessment (PG-SGA), and physical metrics such as body mass index, handgrip strength, arm circumference, mid-arm muscle circumference (MAMC), and triceps skinfold thickness (TSF). Based on the occurrence of postoperative complications during hospitalization including abdominal infection, bleeding, bile leakage, intra-abdominal fluid accumulation, pulmonary infection, intestinal fistula, and wound dehiscence, patients were divided into two groups: the complication group ( n=205) and the non-complication group ( n=83). Multivariate logistic regression analysis was performed to identify the factors related to postoperative complications, while Cox proportional hazards regression was used to evaluate the impact of various variables on postoperative survival. Survival analysis was conducted using the Kaplan-Meier method, and differences in survival rates were compared using the log-rank test. Results:Compared with the non-complication group, patients in the complication group had a significantly longer postoperative hospital stay [13(8, 16) d vs. 7(5, 9) d], higher proportions of low MAMC [34.1% (24/83) vs. 20.0% (41/205)], lower grip strength [28.9% (24/83) vs. 17.6% (36/205)], higher incidence of intraoperative blood loss ≥200 ml [44.6% (37/83) vs. 22.0% (45/205)], and greater proportion of resection involving ≥3 liver segments [45.8% (38/83) vs. 26.3% (54/205)] (all P<0.05). Multivariate logistic regression analysis identified the low MAMC ( OR=2.01, 95% CI: 1.09-3.71, P=0.025), intraoperative blood loss ≥200 ml ( OR=2.75, 95% CI: 1.55-4.90, P=0.001), and resection involving ≥3 liver segments ( OR=2.02, 95% CI: 1.15-3.55, P=0.015) as independent risk factors for postoperative complications in patients undergoing hepatectomy for PLC. Multivariate Cox regression analysis revealed that low TSF ( HR=1.94, 95% CI: 1.01-3.72, P=0.047), low handgrip strength ( HR=2.23, 95% CI: 1.29-3.88, P=0.004), and resection involving ≥3 liver segments ( HR=1.96, 95% CI: 1.15-3.36, P=0.014) were risk factors associated with poor survival after surgery. Conclusions:Low MAMC, intraoperative blood loss ≥200 ml, and resection involving ≥3 liver segments are risk factors for postoperative complications in patients undergoing hepatectomy for PLC, while low TSF, reduced handgrip strength, and resection involving ≥3 liver segments are predictors of poor postoperative survival.