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.

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

OBJECTIVE: To explore and quantify the association of hot night exposure during the sperm development period (0-90 lag days) with semen quality. METHODS: A total of 6,640 male sperm donors from 6 human sperm banks in China during 2014-2020 were recruited in this multicenter study. Two indices (i.e., hot night excess [HNE] and hot night duration [HND]) were used to estimate the heat intensity and duration during nighttime. Linear mixed models were used to examine the association between hot nights and semen quality parameters. RESULTS: The exposure-response relationship revealed that HNE and HND during 0-90 days before semen collection had a significantly inverse association with sperm motility. Specifically, a 1 °C increase in HNE was associated with decreased sperm progressive motility of 0.0090 (95% confidence interval [ CI]: -0.0147, -0.0033) and decreased total motility of 0.0094 (95% CI: -0.0160, -0.0029). HND was significantly associated with reduced sperm progressive motility and total motility of 0.0021 (95% CI: -0.0040, -0.0003) and 0.0023 (95% CI: -0.0043, -0.0002), respectively. Consistent results were observed at different temperature thresholds on hot nights. CONCLUSION Our findings highlight the need to mitigate nocturnal heat exposure during spermatogenesis to maintain optimal semen quality.
Humans ; Male ; Semen Analysis ; Adult ; Sperm Motility ; Hot Temperature/adverse effects* ; China ; Middle Aged ; Spermatozoa/physiology* ; Young Adult

Objective To investigate the relationship between different body position fixation tech-niques,umbilical plane volume change(ΔV),body weight change rate(ΔW%),and radiotherapy setup errors in cervical cancer patients,and to provide recommendations for determining the margin of planning target vol-ume(MPTV).Methods A retrospective analysis was performed on the clinical data of 57 cervical cancer pa-tients who underwent radiotherapy at this hospital from June 2022 to May 2023.Patients were divided into the observation group(fixed with body membrane+thermoplastic pad,n=24)and the control group(fixed with body membrane alone,n=33)based on different positioning fixation methods.They were also further strati-fied by median BMI into BMI≥23.82 kg/m2 and BMI<23.82 kg/m2 patients.Setup errors in the left-right(X),cranio-caudal(Y),and anterior-posterior(Z)directions were recorded.Meanwhile,the umbilical plane volume on the first CT positioning image and the patient's body weight before positioning were recorded,as well as umbilical plane volume of cone-beam CT(CBCT)verification images during weekly radiotherapy and body weight before scan,the ΔV and ΔW%were calculated.Setup errors were compared between two groups,and correlations between ΔV,ΔW%and setup errors were analyzed in all patients,in two groups(the obser-vation group and the control group)and in two BMI subgroups.MPTV values in X,Y,and Z directions were calculated,and receiver operating characteristic(ROC)curve determined the cut off values of ΔV and ΔW%when setup errors met the department's MPTV criteria.Results Compared with the control group,the ob-servation group showed significantly smaller setup errors in X,Y,and Z directions(P<0.05).Both ΔV and ΔW%were positively correlated with setup errors in X and Y direction in all patients,patients in the control group,and patients with BMI≥23.82 kg/m2(P<0.05).In the observation group,ΔW%was positively corre-lated with setup errors in Z direction in patients with BMI<23.82 kg/m2(P<0.05);In the control group,ΔV and ΔW%were positively correlated with setup errors in X and Y direction in patients with BMI≥23.82 kg/m2.ROC curve analysis showed that when setup errors in Y direction reached the department's MPTV criteria(8.41 mm),the cutoff values ΔV and ΔW%were 8.045 cm2 and 4.12%,respectively.Conclusion The body membrane+thermoplastic pad fixation technique reduces setup errors and mitigates the impact of ΔV and ΔW%on setup errors in X and Y directions.When ΔV or ΔW%exceeds the cutoff values,increasing CBCT verification frequency and re-fabricating the body membrane are recommended.

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.

Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To develop a treatment-related quality of life scale for Chinese patients with multiple myeloma (MM) and to test its reliability and validity.Methods:The initial scale was constructed through a literature search, Delphi expert correspondence, and cognitive testing. This study conducted a preliminary survey of 379 patients with MM and a formal survey of 865 patients from the hematology departments of 155 hospitals nationwide from February 2024 to March 2024. The final scale was obtained after conducting item analysis and reliability and validity tests on the initial scale.Results:The constructed scale contains 36 items covering six domains: physiological, psychological, social, treatment side effects, general health, and others. In the preliminary survey, the Cronbach’s alpha coefficient of each item ranged from 0.597 to 0.939, and the test-retest reliability was 0.747 ( P<0.001). Exploratory factor analysis extracted eight common factors with a cumulative variance contribution of 60.058%. In the formal survey, the Cronbach’s alpha coefficient of each item ranged from 0.484 to 0.930, and the test-retest reliability was 0.835 ( P<0.001). Confirmatory factor analysis revealed a comparative fit index of 0.750, a root-mean-square error of approximation of 0.090, and a root-mean-square residual of 0.067. Conclusion:The treatment-related quality of life scale for Chinese patients with MM designed in this study exhibited good reliability and validity, reflecting the impact of treatment on the quality of life of patients. This scale can provide a reference to clinicians for assessing the disease status of patients.

Objective:To investigate the significance of urinary 8-oxo-7, 8-dihydroguanosine(8-oxoGuo)in assessing the short-term prognosis of sepsis in frail elderly patients.Methods:We conducted a cross-sectional study involving 62 frail elderly patients diagnosed with sepsis who were admitted to the Emergency Intensive Care Unit(EICU)at Beijing Hospital between March 2021 and March 2022.Based on their 28-day prognosis, the patients were categorized into two groups: those who died and those who survived.Upon admission, we collected urine samples and clinical data from both groups.We employed isotope dilution high-performance liquid chromatography-mass spectrometry to measure the levels of the RNA oxidation marker 8-oxoGuo in the urine.Results:A total of 62 frail elderly patients[aged(85.1±6.3)years]diagnosed with sepsis were included in the study, comprising 36 patients in the 28-day mortality group and 26 patients in the survival group.Univariate analysis revealed that the survival group had significantly lower body temperature, blood calcitonin(PCT)levels, sequential organ failure assessment(SOFA)scores, and urinary 8-oxoGuo levels compared to the mortality group.Additionally, the survival group exhibited a higher mean arterial pressure(MAP)than the mortality group, with all differences reaching statistical significance(all P<0.05).Spearman correlation analysis indicated that urinary 8-oxoGuo levels were positively correlated with both PCT and SOFA scores in frail elderly sepsis patients( r=0.426, 0.768, both P<0.05).Furthermore, logistic regression analysis identified urinary 8-oxoGuo and SOFA as independent risk factors for 28-day mortality in this population( OR=1.936, 1.427; P=0.006, 0.002).The area under the receiver operating characteristic curve(AUC)for urinary 8-oxoGuo and SOFA in predicting the 28-day prognosis of frail elderly sepsis patients was 0.761 and 0.741, respectively, both demonstrating statistical significance(both P<0.001). Conclusions:Our findings suggest that urinary 8-oxoGuo possesses strong predictive value for the short-term prognosis of sepsis in this vulnerable population.