AIM:To investigate the effect of apoptosis stimulation protein 2(ASPP2)on the development of traumatic proliferative vitreoretinopathy(PVR)in a rabbit model.METHODS:A total of 30 New Zealand white rabbits were selected, and the right eyes of all rabbits were inflicted with a scleral penetrating wound of approximately 6 mm. Then rabbits were randomly and evenly divided into experimental and control group. The experimental group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with lentivirus-ASPP2, while the control group received an intravitreal injection of 0.1 mL of ARPE-19 cell suspension transfected with negative control lentivirus. At 1, 2, 3, and 4 wk after PVR modeling, a handheld tonometer was used to measure the intraocular pressure. Moreover, fundus photography and ocular ultrasound examination were performed to detect the retinal proliferation. At 4 wk after modeling, hematoxylin-eosin staining was used to observe the morphological retinal changes, and Western blot was used to determine the protein expressions of ASPP2 and the epithelial-mesenchymal transition(EMT)marker Vimentin in the rabbit retinas.RESULTS:At 1, 2, 3, and 4 wk after modeling, there were no significant changes in intraocular pressure within the experimental and control group of rabbit eyes, either before or after PVR modeling, the success rate of PVR modeling in the experimental group was lower than that in the control group(P<0.05), and the retinal proliferation and structural disorder was less severe in the experimental group. At 4 wk after modeling, the retinal protein expression level of ASPP2 in the experimental group was significantly higher than that in the control group(t=3.193, P=0.033), while the Vimentin protein expression level was significantly lower in the experimental group(t=-3.599, P=0.023).CONCLUSION:ASPP2 may be involved in regulating the process of EMT in retinal pigment epithelial cells, thereby delaying the development and progression of traumatic PVR in rabbit eyes.

Neurocritical care involves complex pathophysiological mechanisms, and its incidence is higher, injuries are more severe, and treatment is more challenging in high-altitude environments. This consensus, based on the latest domestic and international evidence-based medical data, establishes a standardized, goal-oriented framework for neurocritical care management applicable in high-altitude regions and nationwide. The consensus was developed following international standards for evidence quality assessment and underwent two rounds of Delphi expert consultation, resulting in 32 recommendation statements covering three parts: management systems, monitoring and assessment, and core strategies. Key updates include: advocating for the establishment of independent neurocritical care units and implementing precise tiered diagnosis and treatment based on the "Five Differences in Critical Care" concept; constructing a "trinity" multimodal brain monitoring system centered on cerebral blood flow, cerebral oxygenation, and brain function, emphasizing routine bedside transcranial Doppler ultrasound, cerebral oximetry, and continuous electroencephalography monitoring; shifting management strategies from mild hypothermia therapy to targeted temperature management, and defining the "446" target management pathway for the supercritical stage; emphasizing the assessment of static and dynamic cerebrovascular autoregulation functions through multimodal methods to achieve individualized optimal mean arterial pressure management; elevating cerebrospinal fluid management goals to the level of "glymphatic system" function maintenance; implementing a multidisciplinary collaborative, whole-process management model focusing on patients' long-term neurological functional outcomes; de-escalation criteria include multidimensional indicators such as recovery of brain structure, restoration of cerebrovascular autoregulation, improvement in cerebrospinal fluid dynamics, and reduction in biomarker levels; and integrating cutting-edge technologies like artificial intelligence into post-critical care management and rehabilitation planning. This consensus systematically integrates the entire process of neurocritical care management, reflecting the modern connotation of goal-oriented, dynamic, and multimodal integration in neurocritical care medicine. It aims to adapt to new trends such as deepening understanding of pathophysiological mechanisms, the integration of medicine and engineering, and the empowerment of artificial intelligence, thereby further advancing the discipline of critical care medicine.

The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Objective The data related to adverse drug reaction of trastuzumab deruxtecan(T-DXd)were mined to provide references for its clinical management and adverse event handling.Methods Based on the Food and Drug Administration Adverse Event Reporting System(FAERS)database,the data reported from the post-marketing period of T-DXd until the fourth quarter of 2024 were extracted.The proportion imbalance method,specifically the reporting odds ratio(ROR)method,was used to mine and analyze the data related to adverse events of T-DXd.Results A total of 13 134 cases of adverse events related to T-DXd were obtained from the FAERS database.Gastrointestinal disorders were the most common,with 2348 adverse reaction signals,accounting for 17.88％.The most frequent adverse reactions were nausea(n=809),interstitial lung disease(n=732),and fatigue(n=579).The one with the highest ROR value was Listeriosis gastroenteritis(ROR=1228.74).The highest number of deaths were from interstitial lung disease(226),pneumonitis(90),and nausea(67).Conclusion By mining data on real-world adverse drug reaction related to T-DXd,suggests that pulmonary function,cardiac function,complete blood count and other parameters should be closely monitored during treatment for early diagnosis and treatment of corresponding complications.

Objective:This study investigated the independent risk factors for lymph node metastasis（LNM）in high-risk prostate cancer（HRPCa）patients undergoing robot-assisted radical prostatectomy（RARP），and constructed a nomogram model based on clinical data to improve the accuracy and clinical practicality of preoperative prediction of LNM.Methods:A retrospective analysis was conducted on the clinical data of 218 HRPCa patients who received RARP treatment at the First Medical Center of the PLA General Hospital from January 2020 to March 2025 as the modeling group. The age of the modeling group was（66.91±6.94）years old. 75 cases（34.40%）had a history of smoking，and 48 cases（22.02%）had a history of drinking. There were a body mass index（BMI）of 25.55（23.58，27.00）kg/m 2，a total prostate-specific antigen（tPSA）of 20.59（10.42，30.61）ng/ml，a free prostate-specific antigen（fPSA）of 1.87（1.04，3.26）ng/ml，a prostate volume（PV）of（41.19±21.00）ml，a prostate-specific antigen density（PSAD）of 0.52（0.30，0.84）ng/ml 2. Among the patients，60 cases（27.52%）had a preoperative biopsy Gleason score >8，and the percentage of positive biopsy cores（PPBC）was 50%（31%，80%）. Thirty-one patients（14.22%）were staged clinically as >T 2c. The diagnostic criteria for high-risk prostate cancer（HRPCa）were defined as meeting any one of the following：PSA >20 ng/ml，Gleason score on prostate biopsy ≥8，or clinical stage ≥T 3. Among the 218 patients in the modeling cohort，67 cases（30.73%）met two of the criteria，and 7 cases（3.21%）met all three criteria. All 218 patients underwent RARP，and based on postoperative pathology，they were divided into the LNM group and the non-LNM group. The relationship between the number of diagnostic criteria met and the occurrence of LNM was analyzed. An external validation cohort included 42 HRPCa patients who underwent RARP at the Third，Fifth Medical Centers of the PLA General Hospital between January 2023 and May 2025. Their mean age was（66.79±5.92）years. Eighteen patients（42.86%）had a smoking history，and nine（21.43%）had a history of alcohol consumption. The median BMI was 26.00（23.80，27.13）kg/m 2. The median tPSA level was 17.34（8.97，27.30）ng/ml. The median fPSA was 1.51（0.83，2.52）ng/ml，and the median PV was（35.57 ± 15.25）ml. The median PSAD was 0.57（0.23，0.87）ng/ml 2，and the median PPBC was 58%（36%，71%）. Three patients（7.14%）had a clinical stage >T 2c，and 12 patients（28.57%）had a Gleason score >8 on preoperative biopsy. Univariate and multivariate binary logistic regression analyses were used to identify independent risk factors for LNM，and a nomogram model was constructed based on these factors. The predictive performance of the model was evaluated using receiver operating characteristic（ROC）curves and calibration plots，and the model was validated in the external cohort. Result:According to postoperative pathology，45 patients were classified into the LNM group，and 173 into the non-LNM group. The probability of LNM increased proportionally with the number of diagnostic criteria met for HRPCa（meeting two criteria： OR = 4.762，95% CI 2.323-9.761， P < 0.01；meeting three criteria： OR = 10.667，95% CI 2.187-52.025， P=0.003）. Binary logistic regression analysis revealed that age（ OR=0.913，95% CI 0.859-0.971， P = 0.004），tPSA（ OR=1.039，95% CI 1.018-1.061， P<0.01），PPBC（ OR = 5.656，95% CI 1.101-29.056， P = 0.038），and clinical T stage（T 2c stage： OR=2.945，95% CI 0.888-9.769， P=0.077；>T 2c stage OR = 18.351，95% CI 4.790-70.306， P < 0.01）were independent risk factors for postoperative LNM in HRPCa patients after RARP. The ROC curve of the nomogram model based on these factors showed an area under the curve（AUC）of 0.853（95% CI 0.790-0.917）. In the external validation cohort，the nomogram achieved an AUC of 0.743（95% CI 0.556-0.929）. The calibration plots demonstrated good agreement between the predicted probabilities and actual observations. Conclusions:Age，tPSA，PPBC，and clinical T stage were independent predictors of postoperative LNM in HRPCa patients undergoing RARP. The greater the number of HRPCa diagnostic criteria met，the higher the likelihood of postoperative LNM. The nomogram developed in this study could effectively predict the risk of LNM in HRPCa patients after RARP.

Objective:To explore the effect of hyperthermic intraperitoneal chemotherapy (HIPEC) on postoperative immune function and tumor marker levels in patients with advanced gastric adenocarcinoma.Methods:A prospective cohort study was conducted, enrolling 72 patients with stage ⅢA-ⅢC gastric adenocarcinoma admitted to Jinjiang Hospital from August 2022 to December 2023. Patients were divided into the HIPEC group ( n=36, radical resection+ HIPEC within 3 days after surgery) and the control group ( n=36, radical resection alone) using the random number table method. The HIPEC protocol was perfusion with raltitrexed (4 mg in 4, 000 ml normal saline, at 43 ℃) for 60 minutes. Peripheral blood immune cells (CD3 +, CD4 +, CD8 +, CD4 + /CD8 + ratio) before treatment and 7 days after treatment, and serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 72-4 (CA72-4) 30 days after treatment were compared between the two groups. Results:Before treatment, there were no statistically significant differences in CD3 +, CD4 +, CD8 +, or CD4 + /CD8 + levels between the two groups (all P>0.05). Seven days after treatment, the HIPEC group had higher levels of CD3 +, CD4 +, and CD4 + /CD8 + ratio, and a lower CD8 + level than the control group, with statistically significant differences (all P<0.05). Before treatment, there were no significant differences in CEA, CA19-9, or CA72-4 levels between the two groups (all P>0.05). Thirty days after treatment, the HIPEC group had lower levels of CEA, CA19-9, and CA72-4 than the control group, with statistically significant differences (all P<0.05). Conclusions:HIPEC can significantly improve the postoperative immune function of patients with advanced gastric adenocarcinoma (by increasing the CD4 + /CD8 + ratio and immune cell activity) and effectively reduce tumor marker levels, which may provide a new strategy for preventing postoperative recurrence.

BACKGROUND:Patients with Alzheimer's disease have severe brain energy disorders.In recent years,brain energy rescue strategies based on ketone body intervention have attracted more and more attention in the treatment of Alzheimer's disease.OBJECTIVE:To investigate whether β-hydroxybutyric acid can improve energy dysfunction by improving mitochondrial bioenergy function in HT22 cells of mouse hippocampal neurons induced by amyloid-β protein 1-42 (Aβ1-42).METHODS:HT22 cells were divided into four groups:Control,β-hydroxybutyric acid,Aβ1-42,Aβ1-42+β-hydroxybutyric acid.Related detection kits were respectively used to detect HT22 cell survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,mitochondrial membrane potential,and reactive oxygen species levels.RESULTS AND CONCLUSION:Compared with the control group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly decreased (P<0.05),and the level of reactive oxygen species was significantly increased (P<0.05) in the Aβ1-42 group.Compared with the Aβ1-42 group,the survival rate,adenosine triphosphate level,α-ketoglutarate dehydrogenase activity,Na+K+-ATPase activity,and mitochondrial membrane potential of HT22 cells were significantly increased (P<0.05),and the reactive oxygen species level was significantly decreased (P<0.05) in the Aβ1-42+β-hydroxybutyric acid group.These results showed that β-hydroxybutyric acid improved mitochondrial bioenergetic function and ultimately improved Aβ1-42-induced energy impairment and survival rate in HT22 cells.

Objective:To analyze the risk factors for clinically relevant delayed gastric emptying (CR-DGE) following laparoscopic pancreaticoduodenectomy (LPD) and to develop a model to predict the postoperative CR-DGE after LPD using the machine-learning approach with multi-model comparison.Methods:Clinical data of 278 patients with tumors located in the pancreatic head and periampullary region undergoing LPD at People’s Hospital of Zhengzhou University from January 2019 to December 2023 were retrospectively analyzed, including 167 males and 111 females, aged 59 (53, 66) years. According to the occurrence of DGE, patients were divided into the CR-DGE group ( n=94) and the non-CR-DGE group ( n=184). Main clinical characteristics were compared between the groups, including pancreatic duct diameter, intraoperative blood loss and operative time. The perioperative indicators were selected using the least absolute shrinkage and selection operator (LASSO) algorithm. Following variable selection, 278 patients were allocated into a training set ( n=222) and a validation set ( n=56) in an 8∶2 ratio. Eight machine learning models were selected to model the training set: random forest, adaptive boosting, light gradient boosting, multilayer perceptron, support vector machine, K-nearest neighbor algorithm, decision tree and complementary set plain bayes. The area under the curve (AUC) of receiver operating characteristic curve of the validation set was utilized to identify the optimal model. The predictive performance of the optimal model was evaluated using calibration plots and decision curve analysis (DCA). The contribution of each feature to the prediction is assessed using Shapley additive explanation (SHAP). Results:Univariate analysis showed statistically significant differences between the CR-DGE and non-CR-DGE groups in terms of age [66(62, 69) years vs. 56(51, 60), years], diabetes [42.6%(40/94) vs. 11.4%(21/184)], level of fibrinogen [3.43(2.74, 4.18) g/L vs. 3.84(3.19, 4.68) g/L], pancreatic duct diameter [2.00(1.50, 2.70) mm vs. 3.40(1.60, 5.00) mm], intraoperative blood loss [300(200, 600) ml vs. 200(150, 300) ml], operative time [472(430, 502) min vs. 430(365, 475) min], clinically relevant postoperative pancreatic fistula [34.0%(32/94) vs. 3.8%(7/184)], abdominal fluid accumulation [46.8%(44/94) vs. 12.5%(23/184)], postoperative hemorrhage [20.2%(19/94) vs. 3.3%(6/184)], abdominal infection [28.7%(27/94) vs. 11.4% (21/184)] and duration of postoperative gastrointestinal decompression [4.00 (2.00, 6.00) d vs. 3.00 (2.00, 5.00) d] (all P<0.05). The eleven variables selected via LASSO were incorporated into each of the eight machine learning models. Results demonstrated that the random forest model achieved the highest performance in the validation set, with an AUC of 0.894 (95% CI: 0.800-0.985), accuracy of 0.820 and sensitivity of 0.606. Calibration plots and DCA confirmed the robustness of the random forest model. SHAP analysis indicated that age, pancreatic duct diameter and preoperative aspartate aminotransferase were important predictors in the random forest model. Conclusion:The random forest model developed in this study demonstrated a good predictive performance for CR-DGE after LPD and may assist in the early identification of high-risk patients in clinical practice.

Traditional Chinese medicine(TCM) is the pillar for the development of motherland medicine, and animal medicine has a long history of application in China, characterized by wide resources, strong activity, definite efficacy, and great benefits. It has significant potential and important status in the consumption market of raw materials of TCM. In the context of global climate change, farming system alterations, and low renewability, the depletion of wild medicinal animal resources has accelerated. Accordingly, the conservation and sustainable utilization of wild resources of animal medicinal materials has become a problem that garners increasing attention and urgently needs to be solved. This paper summarizes the current situation of domestic and foreign medicinal animal breeding and research progress in industrial application in recent years and points out the issues related to standardized breeding, germplasm selection and breeding, and quality evaluation standards for medicinal animals. Furthermore, this paper discusses standardized breeding, quality standards, resource protection and utilization, and the search for alternative resources for rare and endangered medicinal animals. It proposes that researchers should systematically carry out in-depth basic research on animal medicine, improve the breeding scale and level of medicinal animals, employ modern technology to enhance the quality standards of medicinal materials, and strengthen the research and development of alternative resources. This approach aims to effectively address the relationship between protection and utilization and make a significant contribution to the sustainable development of medicinal animal resources and the animal-based Chinese medicinal material industry.
Animals ; Breeding ; China ; Medicine, Chinese Traditional ; Conservation of Natural Resources

Homo- or heterodimeric compounds that affect dimeric protein function through interaction between monomeric moieties and protein subunits can serve as valuable sources of potent and selective drug candidates. Here, we screened an in-house dimeric natural product collection, and panepocyclinol A (PecA) emerged as a selective and potent STAT3 inhibitor with profound anti-tumor efficacy. Through cross-linking C712/C718 residues in separate STAT3 monomers with two distinct Michael receptors, PecA inhibits STAT3 DNA binding affinity and transcription activity. Molecular dynamics simulation reveals the key conformation changes of STAT3 dimers upon the di-covalent binding with PecA that abolishes its DNA interactions. Furthermore, PecA exhibits high efficacy against anaplastic large T cell lymphoma in vitro and in vivo, especially those with constitutively activated STAT3 or STAT3^Y640F. In summary, our study describes a distinct and effective di-covalent modification for the dimeric compound PecA to disrupt STAT3 function.