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.

Objective: To investigate the association of special family structure and physical activity with psychological sub health among secondary vocational school students, so as to provide reference to inform mental health promotion in the population. Methods: From September to December 2024, a convenience sample was drawn from 16 schools including 5 141 secondary vocational school students across 8 provinces (municipalities) in China (Fujian, Chongqing, Guangdong, Guangxi, Hubei, Jiangxi, Shanghai, Zhejiang). A self developed questionnaire, Multidimensional Sub health Questionnaire of Adolescents and International Physical Activity Questionnaire Short Form were used to investigate and evaluate basic information, family structure, psychological sub health status and physical activity. Descriptive statistics and Logistic regression analysis were performed to explore relationships of special family structures and physical activity with psychological sub health in secondary vocational school students. Results: The detection rate of psychological sub health among secondary vocational school students was 11.0%. The reporting rates for secondary vocational school students who lost their father or lost their mother, whose parents divorced, whose parents remarried, and those from special family structures were 2.8%, 0.8%, 11.8%, 3.9%, and 14.7%, respectively. Moreover, the detection rates of psychological sub health and its sub dimensions significantly differed among secondary vocational school students grouped by family type (divorced parental families, remarried parental families and special family structures)( χ 2=5.90-22.67, all P <0.05). Binary Logistic regression indicated that maternal bereavement was associated with a higher risk of conduct problems [ AOR ( 95% CI )= 2.90(1.15-7.33)], and parental divorce was associated with a higher risk of psychological sub health ( AOR= 2.71 , 95%CI =1.04- 7.06 ) among secondary vocational school students (both P <0.05). Interaction analysis showed that both students with a special family structure and insufficient physical activity [ AOR (95% CI )=1.99(1.44-2.75)] and those with a non-special family structure and insufficient physical activity [ AOR (95% CI )=1.81(1.48-2.22)] were associated with increased risks of psychological sub health among secondary vocational school students (both P <0.01). Conclusion Special family structure and physical activity are associated with psychological sub health among secondary vocational school students; early identification and assessment based interventions for those with a special family structure should be strengthened, while school based physical activity should be implemented to increase physical activity levels,thereby reducing the risk of psychological sub health.

Panretinal photocoagulation(PRP)is the first-line treatment for severe non-proliferative diabetic retinopathy and proliferative diabetic retinopathy(PDR).Its therapeutic efficacy varies due to multiple patient-specific systemic and ocular factors. Despite standardized PRP, some patients fail to show adequate regression of neovascularization and subsequently develop vitreous hemorrhage(VH). In such cases, pars plana vitrectomy(PPV)effectively clears the hemorrhage, restores transparency of the ocular media, supplement PRP, and delays the progression of PDR, thus becoming a critical intervention. With recent advances in surgical techniques, concepts, and equipment, early PPV intervention for VH following PRP has emerged as a growing research focus. Nevertheless, consensus remains lacking regarding its indications, optimal timing, and surgical protocols. This article systematically reviews relevant domestic and international studies, summarizing the surgical timing, approaches, and prognoses of PPV for VH in PDR patients after PRP, aiming to provide evidence-based reference for clinical decision-making and reduce the risk of PDR-related blindness.

Objective: To investigate the prevalence of co-occurrence of common diseases among junior high school students in Yunnan Province and to identify latent comorbidity patterns and analyze their associated factors, so as to provide evidence for the comprehensive prevention and control of common diseases among students. Methods: From September to November 2025, a stratified cluster sampling method was employed to survey 71 791 students in grades 7-9 recruited from 258 junior high schools in Yunnan Province. Information on six common diseases, including screening myopia, dental caries, overweight/obesity, malnutrition, elevated blood pressure, and abnormal spinal curvature, was collected through physical examinations and questionnaire surveys, along with data on demographic characteristics, physical activity, and sleep. Latent class analysis (LCA) was used to identify comorbidity patterns of common diseases, and multinomial Logistic regression was performed to analyze the factors associated with each pattern. Results: The detection rates of screening myopia, dental caries, overweight/obesity, elevated blood pressure, malnutrition, and abnormal spinal curvature among junior high school students were 65.2%, 62.1%, 22.4%, 10.9% , 8.2%, and 5.7%, respectively. LCA identified three latent comorbidity patterns of common diseases: a high prevalence screening myopia-dental caries-spinal curvature abnormality pattern (C1, 63.8%), an overweight/obesity elevated blood pressure pattern (C2, 24.1%), and a relatively low burden pattern (C3, 12.0%). With C3 as the reference, multinomial Logistic regression showed that girls were more likely than boys to be assigned to C1 and C2 [ OR (95% CI )=2.12(2.02-2.23), 1.31(1.23-1.38)]; non-Han students were less likely than Han students to belong to C1 and C2 [ OR (95% CI )=0.88(0.83-0.92), 0.81(0.77-0.86)]; students in grades 8 and 9 were more likely than those in grade 7 to belong to C1 and C2, with the highest likelihood observed among grade 9 students [ OR (95% CI )=1.43(1.35-1.52), 1.27(1.19-1.36)]; insufficient sleep was associated with increased odds of belonging to C1 and C2 [ OR (95% CI )=1.15(1.09-1.22), 1.25(1.18-1.33)] (all P <0.05). Compared with students who engaged in outdoor activities during breaks, those who stayed indoors, either inside the teaching building but outside the classroom or inside the classroom, were more likely to belong to C1 [ OR (95% CI )=1.09(1.02-1.16), 1.17(1.09-1.26)] and C2 [ OR (95% CI )=1.13(1.05-1.21), 1.25(1.15-1.35)]; students not living with their parents were less likely to belong to C1 and C2 [ OR (95% CI )=0.83(0.77-0.90), 0.74(0.68-0.81)] (all P <0.05). Conclusions The co-occurrence of common diseases is relatively prominent among junior high school students in Yunnan Province, with distinct latent stratification patterns. Tiered and precise comprehensive interventions should be implemented targeting key populations to promote the prevention and control of common diseases among students.

Objective: To evaluate the risk of donation-related adverse reactions, donation behavior, and contributions to the blood supply among donors aged 56-65 years following extension of the upper age limit for voluntary blood donation, and to provide real-world evidence for optimizing blood donation age policies in China. Methods: A multicenter retrospective cohort was established using blood donation databases from Hainan, Shenzhen, and Jiangxi. A total of 1 180 767 donors contributing 2 020 407 whole-blood and apheresis donations were included. Donations were classified by donor age at each donation into the 18-55-year and 56-65-year groups. Generalized estimating equation (GEE) models were used to compare the risks of overall, local, and systemic donation-related adverse reactions between the two age groups. Restricted cubic spline analysis was used to assess the continuous association between donor age and the risk of overall adverse reactions. Poisson GEE models were used to compare annual donation frequency, and donation participation and contributions to the blood supply among donors aged 56-65 years were evaluated. The study was approved by the Ethics Committee of the Institute of Blood Transfusion, Chinese Academy of Medical Sciences (No.2025012) and registered with the Chinese Clinical Trial Registry (ChiCTR2500114960). Results: A total of 1 960 711 donations were included in the 18-55-year group and 59 696 in the 56-65-year group. The overall donation-related adverse reaction rates were 3.890‰and 0.704‰, respectively. Multivariable GEE analysis showed that, compared with donors aged 18-55 years, those aged 56-65 years had lower risks of overall adverse reactions (adjusted OR=0.294, 95%CI: 0.217-0.398, P<0.001) and systemic adverse reactions (adjusted OR=0.163, 95%CI: 0.101-0.263, P<0.001), whereas no statistically significant difference was observed in the risk of local adverse reactions (adjusted OR=1.337, 95%CI: 0.487-3.670, P=0.573). Donor age was nonlinearly associated with the risk of overall adverse reactions (P overall<0.001, P nonlinear<0.001), with the risk generally decreasing with increasing age between 18 and 65 years. The mean annual donation frequency was higher among donors aged 56-65 years than among those aged 18-55 years (1.63 vs 1.24 donations per year; adjusted IRR=1.34, 95%CI: 1.30-1.39, P<0.001). During the study period, donors aged 56-65 years contributed 2.95% of all donations; their whole-blood donations and whole-blood collection volume accounted for 2.36% and 2.37% of the corresponding totals, respectively. Conclusion: Under current health screening and standardized donor management, donors aged 56-65 years did not show an increased risk of short-term donation-related adverse reactions and demonstrated a higher annual donation frequency, together with a measurable contribution to the blood supply. These findings support appropriately extending the upper age limit for voluntary blood donation under strict health screening to broaden the donor pool and supplement the blood supply.

ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

Network pharmacology has gained widespread application in drug discovery, particularly in traditional Chinese medicine (TCM) research, which is characterized by its "multi-component, multi-target, and multi-pathway" nature. Through the integration of network biology, TCM network pharmacology enables systematic evaluation of therapeutic efficacy and detailed elucidation of action mechanisms, establishing a novel research paradigm for TCM modernization. The rapid advancement of machine learning, particularly revolutionary deep learning methods, has substantially enhanced artificial intelligence (AI) technology, offering significant potential to advance TCM network pharmacology research. This paper describes the methodology of TCM network pharmacology, encompassing ingredient identification, network construction, network analysis, and experimental validation. Furthermore, it summarizes key strategies for constructing various networks and analyzing constructed networks using AI methods. Finally, it addresses challenges and future directions regarding cell-cell communication (CCC)-based network construction, analysis, and validation, providing valuable insights for TCM network pharmacology.
Medicine, Chinese Traditional/methods* ; Artificial Intelligence ; Network Pharmacology/methods* ; Humans ; Drugs, Chinese Herbal/chemistry* ; Drug Discovery

Objective:To explore the feasibility of the multiple-choice auditory graphical interactive check（MAGIC） screening module in childhood hearing screening in children aged 3 to 6 years. Methods:A hearing screening was conducted on 366 children（732 ears） aged between 3 and 6 years. The screening methods included MAGIC, DPOAE, and acoustic immittance.The cooperation, screening time, pass rate, and correlation of the three screening methods were compared. Results:There was a statistically significant difference in the degree of cooperation among the three screeningmethods（P=0.004）.The MAGIC pure tone screening method was 98.6%, the screening DPOAE was 99.5%,and the acoustic immittance screening was 100%. For the screening duration, the MAGIC pure tone screening method was（116.3±59.1）s, the screening DPOAE was（27.2±19.7）s, and the acoustic impedance screening was（24.6±14.6）s. There was a significant statistical significance differences among the three or two groups（P<0.01）. The passing rates of MAGIC pure tone screening,screening DPOAE and acoustic immittance screening were 64.7%, 65.4%, and 69.3%, respectively, and there was no significant statistical difference among the three or two groups（P>0.05）. There was no significant difference between MAGIC pure tone screening method and screening DPOAE（P=0.827>0.05）, and acoustic impedance（P=0.653>0.05）, while the difference between screening DPOAE and acoustic impedance was statistically significant（P<0.01）. Conclusion:MAGIC pure sound screening method has good feasibility, can comprehensively reflect the hearing level of screened children, and can be promoted for hearing screening in children aged between 3 and 6 years.
Humans ; Child, Preschool ; Child ; Female ; Male ; Audiometry, Pure-Tone ; Mass Screening/methods* ; Feasibility Studies ; Acoustic Impedance Tests/methods* ; Hearing Loss/diagnosis* ; Hearing Tests/methods*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

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