This study examined the effect of islet macrophages on β-cell function changes during type 2 diabetes mellitus (T2DM) progression based on the traditional Chinese medicine theory that " moderate fire generating qi, hyperactive fire consuming qi" . T2DM is closely associated with chronic low-grade inflammation, with islet macrophages playing a central role in this process. Under physiological conditions, islet macrophages secrete anti-inflammatory and growth factors to regulate the immune response, promote cell proliferation, and support islet β-cell survival and function, reflecting the concept of " moderate fire generating qi" . However, during the pathological process of T2DM, islet macrophages become over-activated and dysfunctional, secreting large amounts of pro-inflammatory factors that trigger severe inflammatory responses and oxidative stress. This process damages islet β-cells, disrupts the islet microenvironment and blood supply, exacerbates local inflammation and structural damage, and worsens the survival environment of β-cells. Ultimately, this leads to fewer β-cells and function loss, aligning with the " hyperactive fire consuming qi" theory, where excessive fire depletes qi and blood. This study enhances the understanding and application of traditional Chinese medicine theories in modern medicine, offering a new perspective on T2DM prevention and treatment. Regulating islet macrophage function and reducing their pro-inflammatory responses may become key strategies for preserving β-cell function and slowing T2DM progression.

Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.

Cholesterol is an essential molecule for the biosynthesis of cell membranes and cell proliferation and differentiation， and the liver plays a central role in cholesterol metabolism and is responsible for the synthesis， uptake， secretion， and transport of cholesterol. The initial stages of cholesterol synthesis in the liver are particularly important， and abnormalities in such stages are closely associated with the progression of various liver diseases. Studies have shown that as a key rate-limiting enzyme in cholesterol biosynthesis， 3-hydroxy-3-methylglutaryl-coenzyme A reductase （HMGCR） has well-defined regulatory properties and has been confirmed as an important target for the regulation of various liver diseases. This article reviews the process of cholesterol metabolism， the degradation and regulatory mechanisms of HMGCR， and the application of inhibitors， as well as the role of HMGCR in liver diseases， in order to provide new insights for scientific research and the clinical prevention and treatment of liver diseases.

ObjectiveTo investigate the mechanism by which Mingshi prescription regulates the retinal melanopsin-dopamine （Opn4-DA） axis in myopic mice to inhibit endoplasmic reticulum （ER） stress in the retina and sclera， thereby delaying axial elongation associated with myopia. MethodsSixty 4-week-old male SPF-grade C57BL/6J mice were randomly divided into a normal group， a form-deprived myopia group （FDM group）， an intrinsically photosensitive retinal ganglion cells ablation group （ipRGCs group）， a Mingshi Prescription group （MSF group， 5.2 g·kg^-1）， and an ipRGCs + MSF group （5.2 g·kg^-1）. Except for the normal group， all other groups underwent FDM modeling. Additionally， the ipRGCs and ipRGCs + MSF groups received retinal ipRGC ablation. Three weeks after modeling， the MSF and ipRGCs + MSF groups were administered Mingshi prescription via continuous gavage for six weeks. After refraction and axial length were measured in all mice， eyeballs were collected along with retinal and scleral tissues. Pathological and morphological changes in the retina， choroid， and sclera were observed using periodic acid-Schiff （PAS） staining. Western blot was employed to detect the relative protein expression levels of dopamine D1 receptor （DRD1）， C/EBP homologous protein （CHOP）， and glucose-regulated protein 78 （GRP78） in the retina， and CHOP and GRP78 in the sclera. Real-time PCR was used to detect the relative mRNA expression of Opn4， CHOP， and GRP78 in the retina， and CHOP and GRP78 in the sclera. Immunofluorescence staining （IF） was performed to detect the expression of Opn4 and DRD1 in retinal tissues. ResultsCompared with the normal group， the FDM group showed a significant myopic shift in refraction （P<0.05） and a significant increase in axial length （P<0.05）. The retinal layers were thinner， the number of ganglion cells was reduced， and collagen fibers in the sclera were loosely arranged with evident gaps. Opn4 and DRD1 protein and mRNA expression in the retina were significantly decreased （P<0.05）， while CHOP and GRP78 protein and mRNA expression in both retinal and scleral tissues were significantly increased （P<0.05）. Compared with the FDM group， the ipRGCs group exhibited further increases in myopic refraction and axial length （P<0.05）， more pronounced thinning and looseness in the retinal， choroidal， and scleral layers， lower expression of Opn4 and DRD1 protein and mRNA in the retina （P<0.05）， and higher expression of CHOP and GRP78 protein and mRNA in the retina and sclera （P<0.05）. Compared with the FDM group， the MSF group showed significantly reduced refractive error and axial length （P<0.05）， with improved cellular number， arrangement， and thickness in ocular tissues， increased Opn4 and DRD1 protein and mRNA expression in the retina （P<0.05）， and reduced CHOP and GRP78 protein and mRNA expression in both retina and sclera （P<0.05）. Similarly， the ipRGCs + MSF group showed significant improvements in terms of the above items compared with the ipRGCs group （P<0.05）. ConclusionMingshi Prescription delays myopic axial elongation and refractive progression by regulating the Opn4-DA axis in the retina of myopic mice， thereby inhibiting ER stress in the retina and sclera. This intervention promotes Qi and blood nourishment of the eyes， softens the fascia， and restores ocular rhythm.

In liver tumor surgery, owing to the characteristics such as the abundant blood supply of the liver and the abnormal hyperplasia of tumor blood vessels, the risk of intraoperative hemorrhage is significantly elevated. Frequently, it is necessary to rely on allogeneic blood transfusion to maintain hemodynamic stability. It is well established that allogeneic blood transfusion poses risks such as immunosuppression and transmission of infectious agents, which may compromise postoperative recovery and long-term patient outcomes. Intraoperative autologous blood transfusion (IOABT) serves as a crucial strategy for blood conservation. The use of allogeneic blood can be effectively reduced by recovering, washing, and centrifuging blood from the patient's surgical field before transfusion to the patient. This article provides an overview of the application and research advancements in IOABT technology within the context of liver tumor surgery. It outlines the evolution of blood salvage techniques, core operational principles, and strategies to mitigate tumor cell dissemination, including the use of leukocyte filters and irradiation. Furthermore, it examines the clinical efficacy and safety of IOABT in both liver resection and liver transplantation, with particular attention to the potential risk of tumor cell reinfusion. Current evidence does not indicate an increased risk of tumor recurrence associated with this technique. Looking ahead, the integration of emerging technologies such as artificial intelligence, nanobiotechnology, and immunotherapy holds promise for further enhancing IOABT, ultimately enabling safer and more precise perioperative blood management strategies for patients undergoing liver tumor surgery.

Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Myopia is a significant global health issue,and its exact causes are still not fully understood,leaving a lack of effective and propaqable treatment options.The prevalence of myopia among children and adolescents in China remains high,posing challenges for prevention and control efforts.According to the"theory of imbalance of essence and tendon",an imbalance in the essential elements and tendons can impede the passage of eye essence and blood,resulting in delayed expansion and contraction of the eye meridians and tendons,leading to blurred vision.Modern research indicates that during the development of myopia,there are notable changes in the microstructure,activation range,and signaling of various brain regions,providing a biological basis for the"brain-eye"mechanism.Moreover,abnormal activity in the brain nucleus contributes to alterations in choroid blood flow and the impairment of eye muscle regulation,thereby accelerating the progression of myopia,this phenomenon represents the manifestation of the brain-eye imbalance.Consequently,strategies for myopia prevention and control should prioritize nourishing kidney essence,replenishing brain marrow,promoting liver and blood health,and softening the meridians.These measures aim to optimize the functioning of the brain and eyes,maintain the flexibility of eye tendons,enhance eye regulation,sustain the strength of eye tendons,and delay the advancement of eye axis growth and myopia.By enriching the scientific understanding of the appropriate application of traditional Chinese medicine techniques to prevent and control myopia through the brain,this research provides valuable insights for future explorations in this field.

Objective To elucidate the mechanisms of interface disruption between the actin filament and membrane of the cell pseudopodium that occurs during the breakage of the pseudopodium.Methods Time-lapse images of the behavior of actin filaments and membranes during the rupture process of cell pseudopodia were captured using the confocal microscopy.A theoretical model of the fracture of a cylindrical interface was developed to analyze the interface damage between the actin filament and the membrane during the breakage of the cell pseudopodium.Molecular dynamics simulations were employed to simulate the breaking process of the cell pseudopodium for comparison with the theoretical results.A finite element model considering the coupling of the tensile and torsional deformation of actin filaments was developed to simulate the torsional deformation of actin filaments under tension,both in the presence and absence of a membrane.Results The theoretical results indicated an exponential relationship between the critical load for the broken interface and crack length.The critical load increased with the interfacial strength.The effect of the fiber diameter on the critical load depended on the crack length,exhibiting different effects for small and large crack lengths.Finite element analysis suggested that the membrane substantially constrained torsional movement when the actin filament was extended.Conclusions This study revealed the breaking process of cell pseudopodia and the mechanical aspects underlying the disruption of the interface between the actin filament and the membrane.These results provide theoretical support for exploring cellular behaviors associated with pseudopodium breakage,such as the release of extracellular vesicles.

Background and purpose:Primary adrenal intravascular large B-cell lymphoma(IVLBCL)is rare and highly aggressive.Unfortunately,comprehensive and sufficient understanding of the disease is lacking.This study investigated the clinicopathological and molecular genetic characteristics of adrenal IVLBCL.Methods:Adrenal IVLBCL cases diagnosed from 2012 to 2023 were collected from Department of Pathology,Fudan University Shanghai Cancer Center.The clinical and histopathological features,immunophenotype,treatment and prognosis were analyzed.The molecular genetic characteristics were detected using next-generation sequencing(NGS).This study was approved by the Ethics Committee of Fudan University Shanghai Cancer Center(Ethics number:050432-4-2307E).Results:All of the 5 patients were male,with median age 52 years(ranged 50-82 years).Two cases had low-grade fever,1 case had abdominal pain,1 case was found by physical examination,and the information of the remaining one was unknown.Peripheral blood test showed elevated serum lactate dehydrogenase in 2 cases and adrenal dysfunction in 2 cases.On initial diagnosis,imaging tests displayed adrenal enlargement or masses with increased fluorodeoxyglucose(FDG)uptake.Bilateral adrenal glands were involved in 4 cases and only the right adrenal gland was involved in the other case.Morphologically,large atypical lymphocytes were confined to blood vessels,and fibrinous necrosis was observed in some cases.Immunohistochemical study revealed that CD20 was positive in all cases.Ki-67 proliferation index was high,all above 80%.80%(4/5)of the cases were of non-germinal-center B-cell-like(non-GCB)phenotype,100%(4/4)of the cases had MYC/BCL2 double expression.Endothelial cell markers staining indicated that most of the tumor cells were confined within the blood vessels in all cases.Follow-up data were available in 3 patients.One patient who underwent only surgical resection died 5 months after diagnosis,one achieved complete remission after surgery plus R-CHOP,and the other diagnosed by biopsy achieved a partial remission after R-CHOP.The 1-year overall survival rate was 66.7%,and overall survival was 5-87 months.NGS testing in 1 case showed missense mutations in MYD88 V217F,TP53,CDH1,ARID1B,MSH3,MLH3,PTPRK,CD22 and FLCN.Conclusion:Adrenal IVLBCL is rare and tends to occur in the middle-aged and elderly male.The majority of our patients were non-GCB phenotype,often accompanied by MYC/BCL2 double expression,and MYD88 non-L265P mutation was detected.Early diagnosis of adrenal IVLBCL is difficult due to its diverse clinical symptoms and lack of specificity.It is of great importance to accumulate more cases and further understand the clinicopathological and molecular genetic characteristics of this rare disease,which might not only help with early diagnosis,timely treatment and improvement of prognosis,but also provide a theoretical basis for further understanding the pathogenesis and development of the disease and exploring therapeutic targets.

Objective:To explore the optimal pulse oxygen saturation (SpO 2) range during hospitalization for patients with sepsis. Methods:A case-control study design was employed. Demographic information, vital signs, comorbidities, laboratory parameters, critical illness scores, clinical treatment information, and clinical outcomes of sepsis patients were extracted from the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ). A generalized additive model (GAM) combined with a Loess smoothing function was employed to analyze and visualize the nonlinear relationship between SpO 2 levels during hospitalization and in-hospital all-cause mortality. The optimal range of SpO 2 was determined, and Logistic regression model along with Kaplan-Meier curve were utilized to validate the association between the determined range of SpO 2 and in-hospital all-cause mortality. Results:A total of 5?937 patients met the inclusion criteria, among whom 1?191 (20.1%) died during hospitalization. GAM analysis revealed a nonlinear and U-shaped relationship between SpO 2 levels and in-hospital all-cause mortality among sepsis patients during hospitalization. Multivariable Logistic regression analysis further confirmed that patients with SpO 2 levels between 0.96 and 0.98 during hospitalization had a decreased mortality compared to those with SpO 2 < 0.96 [hypoxia group; odds ratio ( OR) = 2.659, 95% confidence interval (95% CI) was 2.190-3.229, P < 0.001] and SpO 2 > 0.98 (hyperoxia group; OR = 1.594, 95% CI was 1.337-1.900, P < 0.001). Kaplan-Meier survival curve showed that patients with SpO 2 between 0.96 and 0.98 during hospitalization had a higher probability of survival than those patient with SpO 2 < 0.96 and SpO 2 > 0.98 (Log-Rank test: χ2 = 113.400, P < 0.001). Sensitivity analyses demonstrated that, with the exception of subgroups with smaller sample sizes, across the strata of age, gender, body mass index (BMI), admission type, race, heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, respiratory rate, body temperature, myocardial infarction, congestive heart failure, cerebrovascular disease, chronic liver disease, diabetes mellitus, sequential organ failure assessment (SOFA), simplified acute physiology score Ⅱ (SAPSⅡ), systemic inflammatory response syndrome score (SIRS), and Glasgow coma score (GCS), the mortality of patients with SpO 2 between 0.96 and 0.98 was significantly lower than those of patients with SpO 2 < 0.96 and SpO 2 > 0.98. Conclusions:During hospitalization, the level of SpO 2 among sepsis patients exhibits a U-shaped relationship with in-hospital all-cause mortality, indicating that heightened and diminished oxygen levels are both associated with increased mortality risk. The optimal SpO 2 range is determined to be between 0.96 and 0.98.