ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg^-1）， free Cur group（8 mg·kg^-1）， free SSD group（10 mg·kg^-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.

As a pivotal strategy to alleviate the shortage of organ donors, xenotransplantation has achieved remarkable advances in both pre-clinical and clinical studies in recent years, driven by continuous optimization of gene modification techniques and immunosuppressive regimens. Nevertheless, clinical translation still confronts formidable challenges, including rejection and heightened infection risks, which severely compromise long-term graft survival. Consequently, the role of immunosuppressive regimens in xenotransplantation has become increasingly prominent. This article summarizes the mechanisms underlying xenogeneic immune rejection, the latest developments in immunosuppressive regimens, cutting-edge strategies for inducing immune tolerance and the major hurdles facing clinical xenotransplantation. It delves into potential optimization strategies and directions for future clinical research, aiming to offer theoretical insights and practical guidance for the safe and effective application of clinical xenotransplantation.

ObjectiveTo evaluate the efficacy and possible mechanism of Wei's Huoxue Tongluo Formula （韦氏活血通络方，WHTF） in treating atrophic-stage non-arteritic anterior ischemic optic neuropathy （NAION） with qi deficiency and blood stasis. MethodsA total of 82 atrophic-stage NAION patients with qi deficiency and blood stasis were randomly divided into a treatment group and a control group， with 41 cases in each group. The treatment group was given oral administration of WHTF twice a day plus acupoint injection of distilled water 2 ml at Taiyang （EX-HN5） once daily， while the control group received injection of compound anisodine injection 2 ml at Taiyang （EX-HN5） once daily and oral administration of WHTF placebo twice a day. Both groups received treatment for a course of 14 days. The best-corrected visual acuity （BCVA）， optic disc perfusion density （PD）， flux index （FI）， macular superficial PD， vascular density （VD）， and traditional Chinese medicine （TCM） syndrome scores were compared between groups before treatment and on day 7 and day 14 of treatment. Additionally， mean defect （MD） and mean sensitivity （MS） of visual fields were measured before treatment and on day 14， along with safety evaluation. ResultsAfter treatment， both groups showed significant improvement in BCVA， visual field MD and MS， and TCM syndrome scores （P＜0.05 or P＜0.01）. On day 14 of treatment， the TCM syndrome score in the treatment group was significantly lower than that in the control group （P＜0.05）. There was no significant improvement in optic disc PD and FI， and macular superficial PD and VD after treatment in either group （P＞0.05） except that on day 7 the macular superficial foveal PD in the control group was significantly better than that in the treatment group （P＜0.05）. During the treatment period， no serious adverse events occurred in either group. ConclusionWHTF can improve the visual function indicators including visual acuity and visual field， as well as TCM syndrome scores in atrophic-stage NAION patients with qi deficiency and blood stasis. It shows clinical safety， although it does not appear to have a significant effect on optic disc or macular blood flow.

Organ transplantation faces the challenge of a shortage of donors. Although xenotransplantation holds great potential, it is limited by rejection. Extracellular histones, as key members of damage-associated molecular patterns, have been proven in recent years to play a crucial role in transplant rejection by activating innate immunity, regulating the coagulation-inflammation network, and modulating adaptive immune responses. However, the specific functions and key mechanisms remain to be clarified. Therefore, this article reviews the structural characteristics of histones, their release pathways, the biological functions of extracellular histones, and their potential roles in xenotransplantation. It summarizes the latest research progress of extracellular histones in xenotransplantation, analyzes the shortcomings of existing research and the direction for future research, with the expectation of providing references for the application of extracellular histones in xenogeneic kidney transplantation.

Acute myocardial infarction and acute upper gastrointestinal bleeding are both critical internal medicine conditions. The incidence of acute upper gastrointestinal bleeding in patients with acute myocardial infarction ranges from 5.31% to 8.90%, with a mortality rate as high as 20.50% to 35.70%. The pathogenesis may be related to the use of antiplatelet and anticoagulant drugs, as well as stress-induced injury. In treatment, the contradiction between antiplatelet/anticoagulation therapy and bleeding has made this disease a significant challenge in modern medicine. Therefore, re-exploring the etiology, pathogenesis, treatment principles, and methods of traditional Chinese medicine(TCM) for acute myocardial infarction and acute upper gastrointestinal bleeding is of great clinical importance. The research team has been working year-round in the coronary care unit(CCU), managing a large number of such severe patients. By revisiting classic texts and delving into the foundational theories of TCM and historical medical literature, it has been found that this disease falls under the category of "distant blood" in the Synopsis of the Golden Chamber. In terms of etiology, it is primarily associated with weakness of healthy Qi and damage caused by drug toxicity. In terms of pathogenesis, in the acute stage, it mainly manifests as insufficient spleen Yang, deficiency of spleen Qi, and failure of the spleen to control blood. In the remission stage, it is characterized by deficiency of both heart Qi and spleen blood. For treatment, during the acute stage, Huangtu Decoction is used to warm Yang and restrain blood, while in the remission stage, Guipi Decoction is administered to tonify Qi and nourish blood. During the treatment process, for patients with acute myocardial infarction complicated with acute upper gastrointestinal bleeding, it is crucial to flexibly apply the treatment principles of "Nil per os" in western medicine and "where there is stomach Qi, there is life; where there is no stomach Qi, there is death" in TCM. Early intervention with Huangtu Decoction can also prevent bleeding, with large doses being key to achieving hemostasis. It is important to address the pathogenesis of heat syndrome in addition to the core pathogenesis of Yang deficiency bleeding and to emphasize the follow-up treatment with Guipi Decoction for a successful outcome.
Humans ; Gastrointestinal Hemorrhage/etiology* ; Myocardial Infarction/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Acute Disease

ObjectiveTo investigate the optimal ratio of goat horn replacing antelope horn in Fufang Lingjiao Jiangya pills and the blood pressure-lowering mechanism of this medicine. MethodsThe blood pressure-lowering efficacy of Fufang Lingjiao Jiangya pills with varying proportions of goat horn replacing antelope horn was evaluated on spontaneous hypertensive rats （SHR）. In this experiment， 50 SHR rats were randomly grouped as follows： model （n=8）， captopril （0.01 g·kg^-1） （n=6）， low-dose blank Fufang Lingjiao Jiangya pills （0.342 g·kg^-1） （n=6）， high-dose blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1） （n=6）， low-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， high-dose antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）， low-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.378 g·kg^-1） （n=6）， and high-dose goat horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1） （n=6）. Additionally， 8 WKY rats were used as the normal group. Drugs were administered by gavage for 4 weeks while an equal volume of distilled water was administered for the normal and model groups. Blood pressure was measured before administration， 3 h post administration， and biweekly thereafter. In the experiment for Fufang Lingjiao Jiangya pills with goat horn replacing antelope horn in different proportions， 48 SHR rats were randomly grouped as follows： model， blank Fufang Lingjiao Jiangya pills （0.684 g·kg^-1）， antelope horn-containing Fufang Lingjiao Jiangya pills （0.756 g·kg^-1）， 2× goat horn-containing Fufang Lingjiao Jiangya pills （0.824 g·kg^-1）， 4× goat horn Fufang Lingjiao Jiangya pills （0.969 g·kg^-1）， and 6× goat horn Fufang Lingjiao Jiangya pills （1.112 g·kg^-1）. The normal group included 8 WKY rats， and the normal group and model group received an equal volume of distilled water. The treatment lasted for 2 weeks， and blood pressure was recorded at various time points （pre-administration， 3 h post administration， and on days 4， 7， 10， and 14 of administration）. Serum levels of angiotensin-converting enzyme （ACE）， angiotensin Ⅱ（Ang Ⅱ）， renin， and interleukin-6 （IL-6） were measured by enzyme-linked immunosorbent assay. Histopathological changes in the heart， kidney， and thoracic aorta were observed by hematoxylin-eosin staining. The protein levels of ACE2， angiotensin Ⅱ type 1 receptor （AT1R）， and angiotensinogen （AGT） in the kidney tissue were determined by Western blot， while the expression of nuclear factor （NF）-κB p65 and Toll-like receptor 4 （TLR4） in the thoracic aorta tissue was assessed by immunohistochemistry. ResultsCompared with the model group， all treatment groups showed lowered blood pressure （P<0.05， P<0.01）， and the 6× goat horn-containing Fufang Lingjiao Jiangya pills group showed consistent blood pressure-lowering effect with the antelope horn-containing Fufang Lingjiao Jiangya pills group. Compared with the normal group， the model group showed elevated serum levels of ACE， Ang Ⅱ， renin， and IL-6， while the elevations were declined in the Fufang Lingjiao Jiangya pills groups （P<0.05， P<0.01）. Pathological changes in the heart， kidney， and thoracic aorta were alleviated in all the treatment groups， with the 6× goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups exhibited the best effect. Western blot and immunohistochemistry results showed that all the treatment groups exhibited down-regulated protein levels of AT1R， AGT， NF-κB p65， and TLR4 and up-regulated protein levels of ACE2 （P<0.05， P<0.01） compared with model group， with the 6×goat horn- and antelope horn-containing Fufang Lingjiao Jiangya pills groups showcasing the best effect. ConclusionReplacing antelope horn with 6×goat horn in Fufang Lingjiao Jiangya pills can achieve consistent blood pressure-lowering effect with the original prescription. The prescription may exert the effect by inhibiting the renin-angiotensin-aldosterone system （RAAS） and TLR4/NF-κB signaling pathways.

OBJECTIVE: To investigate the anthropometric parameters that can accurately predict the diameter of the hamstring tendon graft, and to examine the correlation between disease etiology, duration, and graft diameter. METHODS: A retrospective analysis was conducted on data from 166 patients who underwent anterior cruciate ligament reconstruction using hamstring tendon autografts (semitendinosus and gracilis tendon) between January 2013 and December 2023. The cohort conprised 135 males and 31 females;the age ranged from 14 to 62 years old with an average of (28.87±10.46) years old. Pearson correlation coefficients, partial correlation coefficients, and stepwise multiple linear regression analysis were utilized to elucidate the relationship between the outcome variable (diameter of hamstring tendon grafts) and predictive variables (e.g., height). RESULTS: Correlation analysis revealed significant associations between the diameter of hamstring tendon grafts and height (r=0.379, P<0.001), weight (r=0.225, P=0.002), male gender (r=0.302, P<0.001), age(r=-0.218, P=0.002), and sports injury etiology (r=0.167, P=0.016). No significant correlations were found with surgical side, body mass index (BMI), or injury duration (P>0.05). Stepwise multiple linear regression analysis using a backward elimination method indicated that height was the sole significant predictive variable (R²=0.144, P<0.001), with the optimal predictive equation being:Graft size =2.636+0.029×Height (cm). Partial correlation analysis, after controlling for height, showed no significant association between age, gender, weight, and injury etiology with graft diameter. CONCLUSION Height is an effective predictive factor for the diameter of autologous hamstring tendon grafts. Factors such as gender, age, surgical side, body weight, and BMI are not influential to the diameter of the hamstring tendon grafts. Under the condition of the same height, there is no significant difference in the influence of these factors on the graft diameter. Preoperative physical activity level and the duration of injury do not significantly affect the diameter of the hamstring tendon grafts obtained during surgery. It is recommended to use the formula 'Graft Diameter=2.636 + 0.029 × Height (cm)' for preoperative prediction.
Humans ; Male ; Female ; Adult ; Middle Aged ; Retrospective Studies ; Adolescent ; Young Adult ; Transplantation, Autologous ; Anthropometry ; Anterior Cruciate Ligament Reconstruction ; Tendons/anatomy & histology* ; Autografts ; Hamstring Tendons/transplantation* ; Quadriceps Muscle/surgery*

OBJECTIVES: Near vision loss (NVL) is one of the leading causes of visual impairment worldwide, exerting a profound impact on individual quality of life and socio-economic development. This study aims to analyze the burden of NVL in China by sex and age groups from 1990 to 2021 and to project trends over the next 15 years. METHODS: Using data from the Global Burden of Disease (GBD) 2021 database, we conducted descriptive analyses of NVL prevalence in China, calculated age-standardized prevalence rates (ASPR) and age-standardized disability-adjusted life years rates (ASDR) to compare burden differences between sexes and age groups, and applied an autoregressive integrated moving average (ARIMA) model to predict NVL trends for the next 15 years. The model selection was based on best-fit criteria to ensure reliable projections. RESULTS: From 1990 to 2021, China's ASPR of NVL rose from 10 096.24/100 000 to 15 624.54/100 000, and ASDR increased from 101.75/100 000 to 158.75/100 000. In 2021, ASPR (16 551.70/100 000) and ASDR (167.69/100 000) were higher among females than males (14 686.21/100 000 and 149.76/100 000, respectively). China ranked highest globally in both NVL cases and disability-adjusted life years (DALYs), with female burden significantly exceeding male burden. Projections indicated this trend and sex gap will persist until 2036. Compared with 1990, the prevalence cases and DALYs increased by 239.20% and 238.82%, respectively in 2021, with the highest burden among females and the 55-59 age group. The ARIMA model predicted continued increases in prevalence and DALYs by 2036, with females maintaining a higher burden than males. CONCLUSIONS This study reveals a marked increase in the NVL burden in China and predicts continued growth in the coming years. Public health policies should prioritize NVL prevention and control, with special attention to women and middle-aged populations to mitigate long-term societal and health impacts.
Humans ; China/epidemiology* ; Male ; Female ; Prevalence ; Middle Aged ; Disability-Adjusted Life Years ; Adult ; Global Burden of Disease ; Adolescent ; Quality-Adjusted Life Years ; Aged ; Sex Factors ; Child ; Young Adult ; Child, Preschool ; Cost of Illness ; Infant ; Aged, 80 and over ; Vision Disorders/epidemiology*

Loss-of-function variants in CSDE1 have been strongly linked to neuropsychiatric disorders, yet the precise role of CSDE1 in neurogenesis remains elusive. In this study, we demonstrate that knockout of Csde1 during cortical development in mice results in impaired neural progenitor proliferation, leading to abnormal cortical lamination and embryonic lethality. Transcriptomic analysis revealed that Csde1 upregulates the transcription of genes involved in the cell cycle network. Applying a dual thymidine-labelling approach, we further revealed prolonged cell cycle durations of neuronal progenitors in Csde1-knockout mice, with a notable extension of the G1 phase. Intersection with CLIP-seq data demonstrated that Csde1 binds to the 3' untranslated region (UTR) of mRNA transcripts encoding cell cycle genes. Particularly, we uncovered that Csde1 directly binds to the 3' UTR of mRNA transcripts encoding Cdk6, a pivotal gene in regulating the transition from the G1 to S phases of the cell cycle, thereby maintaining its stability. Collectively, this study elucidates Csde1 as a novel regulator of Cdk6, sheds new light on its critical roles in orchestrating brain development, and underscores how mutations in Csde1 may contribute to the pathogenesis of neuropsychiatric disorders.
Animals ; Neurogenesis/genetics* ; Cell Cycle/genetics* ; Mice, Knockout ; Mice ; Neural Stem Cells/metabolism* ; DNA-Binding Proteins/metabolism* ; Cyclin-Dependent Kinase 6/genetics* ; Cell Proliferation ; 3' Untranslated Regions ; Cerebral Cortex/embryology* ; RNA-Binding Proteins ; Mice, Inbred C57BL