ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory， Qijia Rougan prescription， combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted， and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis （CHB-HF） who met the diagnosis and inclusion criteria were randomly assigned to an observation group （Qijia Rougan prescription + entecavir） and a control group （entecavir）. The treatment duration was 24 weeks. Liver stiffness measurement （LSM）， fibrosis-4 index （FIB-4）， portal vein diameter， hepatitis B serology， biochemical indicators， hepatic fibrosis markers in serum ［hyaluronic acid （HA）， laminin （LN）， procollagen Ⅲ peptide （PⅢP）， and type Ⅳ collagen （Ⅳ-C）］， and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis， with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment， the observation group showed a significant reduction in LSM and FIB-4 （P<0.01）， as well as notable improvements in LN， Ⅳ-C， and various TCM syndrome scores （P<0.05， P<0.01）. When compared to the control group after treatment， the observation group demonstrated significant improvements in LSM， FIB-4， and various TCM syndrome score indicators （P<0.05， P<0.01）， indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment， the observation group had better improvement in regression of stages F2 and F3 （P<0.05）. When compared to the control group after treatment， the observation group exhibited superior improvement in regression of stage F3 （P<0.05）. No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone， the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3， which is a potential “interception” point of the “Zhu Ke Jiao” theory.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic obstructive pulmonary disease （COPD） is a chronic respiratory disease that poses a significant threat to global health， exhibiting high morbidity， disability and mortality rate， with its prevention and treatment situation becoming increasingly critical. The pathogenesis of COPD is complex， and the underlying cellular and molecular biological mechanisms remain incompletely elucidated. Programmed cell death （PCD） is the process wherein cells actively undergo demise to maintain internal environmental stability in response to certain signals or specific stimuli. Contemporary medical research indicates that the dysregulation of PCD patterns such as apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis is closely related to the onset and progression of COPD. Clarifying the molecular mechanisms of PCD in COPD may provide novel perspectives for in-depth understanding and prevention of the disease. Traditional Chinese medicine （TCM） is characterized by holistic regulation. In recent years， extensive research has been conducted in the TCM field focusing on modulating apoptosis， necroptosis， pyroptosis， autophagy， and ferroptosis for the treatment of COPD， yielding remarkable achievements. Therefore， this study systematically explored the molecular mechanism of PCD in COPD and reviewed the potential mechanisms and intervention status of TCM targeting PCD in COPD， aiming to provide insights and references for the clinical prevention， treatment and in-depth research of COPD.

Chronic mucocutaneous candidiasis (CMC) is an infectious phenotype characterized by recurrent or persistent infections caused by Candida species that affect the skin, nails, oral, and genital mucosae for a duration exceeding six months. Current research suggests that CMC is an immunodeficiency disease with a complex pathogenesis. Patients with CMC have various defects in nonspecific and/or specific immunity against Candida infection, resulting in the inability of patients to defend themselves against Candida infection. CMC can be stratified into primary CMC and secondary CMC based on etiology. Primary CMC is often associated with genetic mutations leading to immunodeficiencies in T helper cell 17 and interleukin-17, whereas secondary CMC is frequently linked to factors such as human immunodeficiency virus infection, diabetes mellitus, and immunosuppressive therapy. Primary CMC typically manifests as Candida infections, with distinct genetic mutations often correlating to varied concomitant symptoms. Secondary CMC may present with not only superficial mucosal Candida infections and manifestations of the underlying primary disease but also with invasive fungal infections. Diagnosing CMC requires an integration of medical history and clinical presentation, supplemented by the outcomes of auxiliary diagnostic procedures, including microscopic examination of fungal smear, fungal culture, immunological testing, and genetic sequencing and analysis. Furthermore, confirming primary CMC requires exclusion of the aforementioned secondary factors. At present, antifungal drugs such as triazoles, echinocandins, and polyenes are the main treatment for CMC. Moreover, immunotherapy with biologics such as Janus kinase (JAK) inhibitors provides more options for the clinical treatment of patients with CMC. Gene therapy also has potential clinical application value. In this review, we discuss the etiologies, pathogenesis, clinical manifestations, diagnosis, and treatments of CMC, aiming to provide a reference for the clinical diagnosis and treatment of CMC.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

ObjectivePancreatic ductal adenocarcinoma (PDAC) exhibits a limited response to current treatments due to its dense fibrotic stroma and highly immunosuppressive tumor microenvironment. In recent years, advancements in cellular immunotherapy, particularly chimeric antigen receptor macrophage (CAR-M) therapy, have offered new hope for pancreatic cancer treatment. Although CAR-M therapy demonstrates dual potential in directly killing tumor cells and remodeling the immune microenvironment, it still faces challenges such as complex in vitro preparation processes and low in vivo targeting and delivery efficiency. Therefore, developing strategies for efficient and targeted in vivo delivery of CAR genes has become crucial for overcoming current therapeutic limitations. This study aims to develop an orally administrable nano-gene delivery system for the targeted delivery of CAR genes to pancreatic tumor sites. MethodsCore nano-gene particles (PNP/pCAR) were constructed by loading plasmid DNA encoding CAR (pCAR) with cationic polypeptides (PNP). Subsequently, PNP/pCAR was surface-modified with β-glucan to prepare the targeted nanoparticles (βGlus-PNP/pCAR). The loading efficiency of PNP for pCAR was quantitatively assessed by gel retardation assay. The particle size, Zeta potential, morphology, and storage stability of PNP/pCAR were characterized using a Malvern particle size analyzer and transmission electron microscopy. At the cellular level, RAW 264.7 macrophages were selected. The cytotoxicity of PNP/pCAR was evaluated using the CCK-8 assay. The cellular uptake efficiency and lysosomal escape ability of the nanoparticles were assessed via flow cytometry and confocal microscopy. Transfection efficiency was quantitatively evaluated by detecting the expression of the reporter gene GFP using flow cytometry. At the in vivo level, an orthotopic pancreatic cancer mouse model was established. Cy7-labeled βGlus-PNP/pCAR nanoparticles were administered orally, and the fluorescence distribution in mice was dynamically monitored at 1, 2, 4, 8, and 16 h post-administration using a small animal in vivo imaging system. Forty-eight hours after oral gavage, the mice were euthanized, and pancreatic tumor tissues were collected for further analysis of intratumoral fluorescence signals using the imaging system. Additionally, βGlus-PNP/pCAR-GFP nanoparticles loaded with the reporter gene (GFP) were administered orally. Forty-eight hours post-administration, pancreatic tumor tissues were harvested to prepare frozen sections, and GFP expression was observed and analyzed under a fluorescence microscope. ResultsThe PNP carrier exhibited a high loading capacity for pCAR. The successfully prepared PNP/pCAR nanoparticles were regular spheres with a hydrodynamic diameter of approximately (120±10) nm and a Zeta potential of about +(6±1) mV. They maintained good structural stability after incubation in PBS buffer for 7 d. Cell experiments demonstrated that PNP/pCAR exhibited no significant cytotoxicity in RAW 264.7 cells while being efficiently internalized and effectively escaping lysosomal degradation. The transfection positive rate of PNP/pCAR-GFP in RAW 264.7 cells reached (25±3)%, surpassing that of Lipofectamine 2000-loaded pCAR-GFP (Lipo/pCAR-GFP), which was (20±1)%.In vivo experiments revealed that, compared to unmodified PNP/pCAR, βGlus-PNP/pCAR exhibited strongerin situ pancreatic tumor targeting ability after oral administration. Furthermore, oral administration of βGlus-PNP/pCAR-GFP resulted in significant GFP protein expression detectable within pancreatic tumor tissues. ConclusionThis study successfully constructed and validated an orally administrable, pancreatic cancer-targeting polypeptide-based nano-gene delivery system. It provides an important technological foundation in delivery systems and experimental basis for the subsequent development of in situ CAR-M-based therapeutic strategies for pancreatic cancer.

Objective To construct a dynamic prediction model for JC polyomavirus (JCV) reactivation after kidney transplantation. Methods A retrospective analysis was conducted on the clinical data of 128 recipients who met the inclusion criteria and received kidney transplantation in Nanfang Hospital, Southern Medical University, from June 2021 to December 2024. Dynamic Cox regression and dynamic restricted mean survival time (RMST) regression based on the landmark method were adopted to establish the dynamic prediction models, and Monte Carlo cross-validation was used to evaluate model performance. Results The dynamic models could predict the incidence and onset time of JCV reactivation within the subsequent 3 months according to covariates at each landmark time point from the 1st to the 6th month after transplantation. Remuzzi score, body mass index and warm ischemia time were independent risk factors for JCV reactivation, while a history of urinary BK polyomavirus reactivation served as a protective factor. The median values of the area under the curve, C-index and Brier score of the dynamic Cox model were 0.873, 0.851 and 0.065 respectively, and the C-index of the dynamic RMST model was 0.829, all of which were superior to those of the static model. Conclusions The landmark-based dynamic models exhibit excellent predictive performance, which may integrate baseline data and post-transplant follow-up information to realize dynamic assessment of the risk and time window of JCV reactivation, thereby providing evidence for optimizing post-operative monitoring and individualized intervention strategies.

Introduction: Severe hypertriglyceridemia during pregnancy is a rare yet potentially life-threatening disorder. It is frequently linked to acute pancreatitis and poses considerable risks for both maternal and fetal morbidity. Case: We report a 35-year-old G4P3 female at 33 + 6 weeks gestation with underlying type 2 diabetes mellitus who presented with acute abdominal pain, nausea, vomiting, and poor oral intake, initially mistaken for preterm labor and sepsis. Further evaluation revealed profound hypertriglyceridemia (triglycerides 79.1 mmol/L) with markedly elevated total cholesterol (>32 mmol/L) and raised serum amylase, consistent with hypertriglyceridemia-induced acute pancreatitis. She was managed in a multidisciplinary setting with intravenous insulin infusion, dextrose supplementation, aggressive fluid resuscitation, and empiric antibiotics. Due to clinical deterioration and ongoing risk of maternal complications, she underwent emergency lower segment caesarean section and exploratory laparotomy at 34 weeks of gestation. Intraoperative findings included inflammatory intra-abdominal fluid and a bulky pancreas, supporting the diagnosis. Rapid biochemical improvement was observed following treatment, with triglyceride levels decreasing by approximately 70% within 24 hours (79.1– 24.0 mmol/L) and achieving >90% reduction over 10 days. Postpartum management included initiation of omega-3 fatty acids, fibrate, and statin therapy, resulting in sustained lipid control. Ophthalmologic examination demonstrated lipemia retinalis, further confirming severe dyslipidemia. Conclusion This case highlights the importance of early recognition of severe hypertriglyceridemia in pregnancy, particularly in patients with metabolic risk factors such as diabetes. Prompt initiation of insulin therapy can achieve rapid triglyceride reduction and may obviate the need for plasmapheresis in selected cases. Delivery should be considered in the setting of maternal instability. Long-term lipid management postpartum is essential for preventing recurrence and reducing future metabolic risk. A multidisciplinary approach remains critical in optimizing both maternal and fetal outcomes in this rare but serious condition.
Female ; Pregnancy ; Acute Disease ; Pancreatitis

The self-remodeling of scleral extracellular matrix(ECM)is a significant characteristic alterationin the development of myopia, and it also influences the progression of myopia. The mechanisms of scleral remodeling are intricate, with transforming growth factor-β(TGF-β)and its associated signaling pathways playing a pivotal role. This review systematically summarizes the major metabolic changes in scleral ECM, the molecular mechanisms of the TGF-β signaling pathway, and its regulatory effects on scleral remodeling during myopic development, aiming to provide new insights and potential strategies for the treatment and prevention of myopia.

Objective: To analyze the demographic evolution of China over the forthcoming decade (2026-2035) and to systematically evaluate its potential implications for voluntary blood donation practices and the equilibrium of clinical blood supply and demand. Methods: Leveraging comprehensive blood collection and utilization data from 2021 to 2025 at the national, provincial (Shandong), and municipal (Zibo) levels, we identified and examined critical determinants influencing blood management systems. The DeepSeek-V3.2 large language model was deployed to project future population age structures, and to generate quantitative estimates for hospitalization volumes, clinical blood requirements, available blood supply, and donation frequencies for the target years 2030 and 2035, thereby furnishing an evidence base for strategic planning and priority-setting. Results: DeepSeek-derived projections indicate that the proportion of China's population aged 60 years and above will surpass 27% (370 million/1 380 million) by 2030 and exceed 30% (400 million/1 350 million) by 2035, signaling a marked acceleration in population aging. This demographic shift is projected to reduce the proportion of the national population eligible to donate blood from 59.2% (835 million out of 1.41 billion) to 52% (710 million out of 1.36 billion), while the demand for blood is expected to increase by 87.8% relative to 2024, rising from 26.927 million units to 50.56 million units. Sustaining blood supply-demand balance will necessitate progressive annual increases in donation rates. Under prevailing policy frameworks, the required blood donation rate among the eligible population in Shandong Province would need to rise by 122.57% by 2035 [from 20.07‰ (1.1641 million person-times/58 million people) to 44.67‰ (2.189 million person-times/49 million people)] to potentially satisfy projected clinical requirements. Conclusion: By integrating DeepSeek-V3.2, AI predictive models, and blood donation incentive measures, it is possible to monitor population demographics, forecast clinical blood demand, manage blood supplies, and ensure the long-term sustainability of clinical blood availability. It must be acknowledged, however, that the present analysis is constrained by a limited data foundation (comprising only five annual observation points); accordingly, the projections should be interpreted as directional trend indicators or methodological illustrations rather than definitive quantitative forecasts.