Objective To analyze the epidemiological characteristics and disease burden of liver cancer in Guangdong Province in 2020, and to provide a scientific foundation for the development of regionalized prevention and control strategies for liver cancer. Methods According to the cancer registry data of Guangdong Province, the incidence, mortality and age-standardized rate by Chinese standard population in 2020 were calculated to analyze the epidemiological characteristics of liver cancer. The disability adjusted life years (DALYs), year of life loss (YLL), year of lived with disability (YLD), and cause-eliminated life expectancy were used to assess the disease burden of liver cancer. Results In 2020, the crude incidence rate and the age-standardized incidence rate of liver cancer in Guangdong Province were 27.79/100 000 and 20.84/100 000，respectively, and the crude mortality rate and the age-standardized mortality rate of liver cancer were 25.49/100,000 and 17.64/100 000, respectively. The total DALY and DALY rate of liver cancer in Guangdong Province were 515 311 person-years and 513.83/100 000, respectively. After eliminating the causes of death from liver cancer, the life expectancy in Guangdong Province increased from 84.60 years to 84.99 years. All indicators consistently demonstrated that the burden of liver cancer was higher in males than that in females, and the burden of liver cancer was higher in rural areas than that in urban areas. Conclusion Liver cancer in Guangdong Province exhibits a high incidence, mortality and disease burden level in 2020. There are obvious differences of gender, age and region in cancer burden. It is necessary to strengthen liver cancer screening and diagnosis and treatment in men, the elderly and those in rural areas to reduce the burden of liver cancer gradually in Guangdong Province.

ObjectiveTo investigate the mechanism of Zuogui Wan （ZGW） in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells （OSCs） for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase （cGAS）/stimulator of interferon genes （STING） signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group， a model group， a low-dose ZGW group （2.7 g·kg^-1）， a high-dose ZGW group （5.4 g·kg^-1）， and an estradiol valerate group （0.15 mg·kg^-1）， with 8 mice in each group. Except the blank group， all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg^-1 to establish an ovarian aging mouse model. After successful modeling， each group was continuously administered for 4 weeks， once daily. The physiological status of the mice was observed， and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin （HE） staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay （ELISA） was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and mouse interleukin-6 （IL-6） levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS， STING， p-STING， TANK-binding kinase 1 （TBK1）， p-TBK1， interferon-induced transmembrane protein 3 （Fragilis）， and Vasa homolog protein （MVH）. Quantitative real-time polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues， and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 （Oct4） were calculated. ResultsCompared with the blank group， the model group showed reduced body weight， ovarian wet weight， and ovarian index （P<0.01） and a disordered estrus cycle （P<0.01）. In addition， the levels of serum follicle-stimulating hormone （FSH）， TNF-α， IL-6， and IL-1β were increased （P<0.01）， while anti-Müllerian hormone （AMH） and estradiol （E₂） levels were decreased （P<0.01）. The protein expression of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue was increased （P<0.05， P<0.01）， while that of OSCs stemness factors MVH and Fragilis was reduced （P<0.01）. Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs （P<0.01）. The mRNA expression of inflammatory factors TNF-α， IL-6， and IL-1β in ovarian tissue was increased （P<0.05， P<0.01）. Compared with the model group， the treatment groups exhibited improved body weight， ovarian wet weight， and ovarian index （P<0.05） and a reduced rate of estrus cycle disorder （P<0.05， P<0.01）. The levels of serum FSH， TNF-α， IL-6， and IL-1β were decreased （P<0.05， P<0.01）， while AMH and E₂ levels were increased （P<0.01）. The protein expression levels of cGAS， p-STING/STING， and p-TBK1/TBK1 in ovarian tissue were decreased （P<0.05）， while the protein expression of MVH and Fragilis was increased （P<0.05）， and the fluorescence intensities of MVH and Oct4 were increased （P<0.05， P<0.01）. The mRNA expression of inflammatory factors in ovarian tissue was decreased （P<0.05）. ConclusionZGW alleviate ovarian inflammatory response， regulate ovarian microenvironment homeostasis， and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway， thereby improving ovarian function and delaying ovarian aging.

Acute lung injury （ALI） is a life-threatening condition characterized by uncontrolled pulmonary inflammatory responses， presenting high morbidity and mortality rates that pose serious threats to patient health. The pathogenesis of ALI involves complex interactions among pathological mechanisms including immune-inflammatory responses， disruption of the alveolar-capillary barrier， mesenchymal stem cell dysfunction， metabolic disorders， ferroptosis， and alterations in the gut microbiota. The dysregulation of programmed cell death （PCD） has increasingly emerged as a research focus. PCD represents a genetically regulated autonomous process of cell death， crucial for maintaining the internal stability of organisms. Recent studies indicate that multiple PCD modes， including apoptosis， pyroptosis， necroptosis， autophagy， and ferroptosis， participate in the development and progression of ALI by mediating pathological processes such as alveolar epithelial cell injury and vascular endothelial barrier disruption. Current therapeutic approaches for ALI encompass lung-protective ventilation， body fluid management， mesenchymal stem cell therapy， and pharmacological interventions. While these measures may alleviate clinical symptoms， they remain unable to reverse the pathological progression of lung injury. Traditional Chinese medicine （TCM） possesses the unique advantages of a holistic perspective and syndrome differentiation-based treatment， achieving breakthrough progress in targeted PCD intervention for ALI. It can mitigate pulmonary tissue injury by suppressing inflammatory responses， regulating immune function， and improving coagulation disorders， thereby delaying the onset and progression of ALI. This paper delves into the molecular mechanisms of PCD in ALI， systematically reviewing the effects of TCM extracts， active constituents （terpenoids， saponins， flavonoids， and phenols）， and compound formulas （e.g.， Qingjie Huagong prescription， Maxing Kugan Tang， and Yifei Jianpi prescription） in improving pulmonary epithelial cell function and mitigating lung injury by modulating PCD pathways. This review aims to provide theoretical underpinnings and novel directions for drug development in the clinical prevention and treatment of ALI.

Acute lung injury （ALI） is a life-threatening condition characterized by uncontrolled pulmonary inflammatory responses， presenting high morbidity and mortality rates that pose serious threats to patient health. The pathogenesis of ALI involves complex interactions among pathological mechanisms including immune-inflammatory responses， disruption of the alveolar-capillary barrier， mesenchymal stem cell dysfunction， metabolic disorders， ferroptosis， and alterations in the gut microbiota. The dysregulation of programmed cell death （PCD） has increasingly emerged as a research focus. PCD represents a genetically regulated autonomous process of cell death， crucial for maintaining the internal stability of organisms. Recent studies indicate that multiple PCD modes， including apoptosis， pyroptosis， necroptosis， autophagy， and ferroptosis， participate in the development and progression of ALI by mediating pathological processes such as alveolar epithelial cell injury and vascular endothelial barrier disruption. Current therapeutic approaches for ALI encompass lung-protective ventilation， body fluid management， mesenchymal stem cell therapy， and pharmacological interventions. While these measures may alleviate clinical symptoms， they remain unable to reverse the pathological progression of lung injury. Traditional Chinese medicine （TCM） possesses the unique advantages of a holistic perspective and syndrome differentiation-based treatment， achieving breakthrough progress in targeted PCD intervention for ALI. It can mitigate pulmonary tissue injury by suppressing inflammatory responses， regulating immune function， and improving coagulation disorders， thereby delaying the onset and progression of ALI. This paper delves into the molecular mechanisms of PCD in ALI， systematically reviewing the effects of TCM extracts， active constituents （terpenoids， saponins， flavonoids， and phenols）， and compound formulas （e.g.， Qingjie Huagong prescription， Maxing Kugan Tang， and Yifei Jianpi prescription） in improving pulmonary epithelial cell function and mitigating lung injury by modulating PCD pathways. This review aims to provide theoretical underpinnings and novel directions for drug development in the clinical prevention and treatment of ALI.

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

AIM: To investigate the potential inhibitory effect of pterostilbene on the endothelial-to-mesenchymal transition(EndMT)induced by high glucose conditions in human retinal microvascular endothelial cells(HRMECs).METHODS: The optimal concentration of pterostilbene for treating HRMECs was determined using the CCK-8 assay, with 12.5 and 25 μmol/L concentrations selected for subsequent experiments. Four experimental groups were established: control group, high glucose group, high glucose combined with 12.5 μmol/L pterostilbene treatment group, and high glucose combined with 25 μmol/L pterostilbene treatment group. The expression levels of HDAC7 and EndMT-associated markers were detected via Western blot analysis. Cell migration ability was assessed using Transwell migration assays and scratch wound healing tests, while vasculogenic capability was evaluated through tube formation assays.RESULTS: The CCK-8 assay revealed that pterostilbene at a concentration of 22.07 μmol/L inhibited 50% of cell viability in HRMECs. Western blot analysis demonstrated that compared with the control group, the expression levels of HDAC7, ZEB1, Vimentin, and Snail were significantly upregulated in HRMECs cultured in high glucose(all P<0.01), while the expressions of VE-cadherin and CD31 were significantly reduced(all P<0.01). Compared to the high glucose group, the treatment with 12.5 and 25 μmol/L pterostilbene significantly reduced the expression of HDAC7, ZEB1, Vimentin, and Snail under high glucose conditions(all P<0.01). Notably, 25 μmol/L pterostilbene enhanced the expression of VE-cadherin and CD31(all P<0.01). Scratch wound healing tests revealed that HRMECs treated with high glucose exhibited a significantly increased cell migration rate compared to the control group(P<0.05), while the application of 25 μmol/L pterostilbene significantly suppressed HRMECs migration under high glucose conditions(P<0.01). Transwell migration assays demonstrated that the cell migration rate in the high glucose group was significantly higher than that in the control group(P<0.01), with cell migration rate markedly reduced following treatment with both of 12.5 and 25 μmol/L pterostilbene(all P<0.01). The tube formation assay revealed that the ability of HRMECs to form tubular structures was significantly enhanced under high glucose conditions(P<0.01), and both 12.5 and 25 μmol/L of pterostilbene effectively inhibited this effect(all P<0.01).CONCLUSION: Pterostilbene can inhibit HDAC7 expression, suppress EndMT-mediated migration of HRMECs, and impair tube formation under high-glucose conditions.

Objective To investigate the therapeutic mechanism of Wendan Decoction for phlegm syndrome in rats with metabolic syndrome(MS).Methods Forty Wistar rats were randomly divided into normal control group(n=8)and 3 phlegm syndrome model groups(induced by high-fat,high-sugar,and high-salt feeding and a single-dose intraperitoneal STZ injection;n=24)treated with daily gavage of saline,Wendan Decoction(3.6 g/kg),or metformin(0.1 g/kg)for 4 weeks.General conditions and glucose and lipid metabolism parameters of the rats were monitored,and serum LPS,liver histopathology,hepatic expressions of FXR,CYP7A1 and FGFR4 and ileal expressions of FXR and FGF15 were examined.Gut microbiota structure was analyzed using 16S rDNA sequencing,and serum bile acids were quantified with UHPLC-MS/MS.Results The rat models of phlegm syndrome exhibited severe hepatic steatosis and necrosis,increased body weight,abdominal circumference,Lee's index,FBG,FINS,HOMA-IR,TG,TC,LDL and LPS,and decreased HDL level.The abundance of Bacteroidetes,Megamonas,and Bacteroides in gut microbiota increased while Firmicutes,Lachnospiraceae_NK4A136_group,isohyodeoxycholic acid,and glycohyodeoxycholic acid decreased significantly;hepatic FXR and FGFR4 expressions and ileal FXR and FGF15 expressions decreased while hepatic CYP7A1 expression increased significantly in the rat models.Treatment with Wendan Decoction effectively alleviated hepatic pathology,reduced body weight and abdominal circumference,improved glucose and lipid metabolic profiles and gut microbiota structure,and reversed the changes in hepatic and ileal protein expressions.Correlation analysis revealed that Firmicutes and Lachnospiraceae_NK4A136_group were positively correlated while Bacteroidetes,Megamonas and Bacteroides were negative correlated with the levels of isohyodeoxycholic acid and hyodeoxycholic acid.Conclusion Wendan Decoction can significantly improve metabolic profiles in rats with phlegm syndrome of MS possibly by regulating the intestinal flora-bile acid axis to modulate the intestinal flora structure and maintain bile acid homeostasis via the FXR signaling pathway.

Objective:To investigate the impact of tumor origin (ventral pancreatic origin and dorsal pancreatic origin) on prognosis in patients with pancreatic head cancer.Methods:A retrospective analysis was performed on the clinical data of 150 patients with pancreatic head cancer who received surgical treatment at the First Affiliated Hospital of the Naval Medical University from October 2014 to December 2017. Among these patients, 92 were male and 58 were female, aged (61.2±8.8) years. The 150 patients were divided into two groups based on tumor origin: the ventral pancreatic cancer group ( n=72) and the dorsal pancreatic cancer group ( n=78). A comparative analysis of clinical, pathological, and imaging charac-teristics was conducted between the two groups. Univariate and multivariable Cox proportional hazards models were used to analyze the association between pancreatic head cancer origin and overall survival (OS). Results:Patients with pancreatic head carcinoma arising from the ventral and dorsal pancreas accounted for 48%(72/150) and 52%(78/150) of the study cohort, respectively. Pancreatic head carcinoma arising from the dorsal pancreas were more likely to show pathological features of pancreatic parenchymal atrophy [73.1%(57/78) vs. 47.2%(34/72), χ2=10.49, P=0.001] and pancreatitis [44.9%(35/78) vs. 29.2%(21/72), χ2=3.95, P=0.047]. In contrast, patients with pancreatic head carcinoma arising from the ventral pancreas was more frequently associated with contact with the superior mesenteric artery [25.0%(18/72) vs. 1.3%(1/78), χ2=19.04, P<0.001], perineural invasion [100%(72/72) vs. 88.5%(69/78), χ2=8.84, P=0.003], and positive surgical margins [15.3%(11/72) vs. 2.6%(2/78), χ2=7.65, P=0.006], with all differences statistically significant. The ventral pancreatic cancer group demonstrated cumulative survival rates of 33.2% and 0 at 1-year and 2-year postoperative intervals, respectively, while the dorsal pancreatic cancer group exhibited rates of 56.7% and 24.8% at the corresponding timepoints. Comparison of Kaplan-Meier survival curves between the two groups showed a statistically significant difference ( χ2=6.00, P=0.014). Multivariable Cox proportional hazards analysis identified dorsal pancreatic origin pancreatic head cancer as an independent predictor of increased mortality risk compared to ventral origin tumors ( HR=2.75, 95% CI: 1.52-4.98, P=0.001). Conclusion:The embryonic origin of pancreatic head cancer determines its clinical, pathological, and imaging heterogeneity, and pancreatic head cancer arising from the ventral pancreas demonstrates significantly worse prognostic outcomes compared to dorsal pancreatic origin.

Venetoclax (Ven) is now widely used for both acute myeloid leukaemia (AML) and high-risk myelodysplastic syndrome (MDS), yet there is no consensus on salvage regimens after Ven failure. This study retrospectively evaluated the efficacy and safety of selinexor combined with subcutaneous decitabine (DAC) in 10 patients with AML or MDS with excess blasts (MDS-EB1/2) who had experienced prior Ven treatment failure. A literature review was also performed. Among the 7 patients with AML, 1 achieved complete remission (CR), 2 achieved CR with incomplete hematologic recovery (CRi), 1 achieved partial remission (PR), 2 had no remission, and 1 experienced disease progression (PD). Among the 3 patients with MDS, 2 achieved marrow CR and 1 had stable disease (SD). The median duration of response among the 6 responding patients was 2 months (range, 0.5-6 months). All 10 patients experienced varying degrees of myelosuppression. Five patients had mild gastrointestinal reactions, all of which were manageable. The overall tolerability was good, and no treatment-related deaths occurred. These findings suggest that selinexor combined with subcutaneous decitabine offers a novel and well-tolerated therapeutic option for patients with myeloid malignancies who have previously failed venetoclax-based therapy.

Here we report the case of a CBF-AML patient with KIT p.D816V mutation who failed avapritinib induction therapy and subsequently underwent bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT), along with a literature review. The patient was a 64-year-old male who did not achieve remission after induction therapy with the DA regimen (Daunorubicin + Cytarabine). After reinduction with avapritinib combined with the DCHG regimen (Decitabine + Homoharringtonine + Cytarabine + Granulocyte colony-stimulating factor), he attained complete remission (CR) and flow cytometry minimal residual disease (MRD) negativity, but the RUNX1::RUNX1T1 fusion gene remained positive. During consolidation therapy, flow MRD reappeared, and the fusion gene level progressively increased. The patient then underwent a 9/10 HLA-matched unrelated donor allo-HSCT. Post-transplant, the fusion gene persisted, prompting treatment with the "ITI" regimen (with dose adjustments, including sequential addition of interferon and interleukin-2, pomalidomide incorporation, and standard vs. escalated dosing of "ITI" regimen). Currently, MRD negativity has been maintained for over 5 months, with good treatment tolerance. This finding suggest that the "ITI" regimen may serve as a novel and well-tolerated therapeutic option for CBF-AML patients with persistent RUNX1::RUNX1T1 fusion gene positivity after allo-HSCT and KIT p.D816V mutation, particularly in cases of avapritinib treatment failure.