Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

ObjectiveTo explore the possible mechanisms by which ligustilide （LIG） exerts neuroprotective effects on ischemic stroke （IS） by inhibiting the release of neutrophil extracellular traps （NETs）， promoting blood-brain barrier repair， and alleviating post-ischemic neuroinflammation， thereby providing a new direction for IS treatment. MethodsA middle cerebral artery occlusion （MCAO） model was established in rats. The rats were divided into the sham operation （Sham） group， model （Model） group， low- and high-dose LIG groups （20， 40 mg·kg^-1）， and the NET inhibitor CI-amidine group （CI-amidine， 10 mg·kg^-1）. Drug treatments were administered for 3 days. Neurological injury after ischemia was evaluated by 2，3，5-triphenyltetrazolium chloride （TTC） staining， neurological deficit scoring， and brain index measurement. Flow cytometry and Western blot were used to analyze changes in neutrophil expression. Immunofluorescence was used to observe the fluorescence intensity of the NET marker citrullinated histone H3 （H3Cit）. Western blot was performed to detect the expression of blood-brain barrier tight junction-related proteins and inflammatory factors， including interleukin-18 （IL-18） and interleukin-1β （IL-1β）. ResultsCompared with the Sham group， the Model group exhibited significant brain tissue injury （P<0.05）， significantly increased neutrophil numbers and NET expression （P<0.05）， significantly impaired blood-brain barrier permeability （P<0.05）， and significantly increased expression of inflammatory factors （P<0.05）. Compared with the Model group， both low- and high-dose LIG significantly alleviated brain tissue injury in rats （P<0.01）， inhibited neutrophil numbers and NET expression （P<0.01）， reduced blood-brain barrier damage （P<0.01）， and suppressed the expression of inflammatory factors IL-18 and IL-1β （P<0.01）， thereby ultimately exerting a neuroprotective effect. ConclusionThe neuroprotective effect of LIG in rats with cerebral ischemia-reperfusion injury may be related to inhibition of neutrophils and the NETs induced by them.

OBJECTIVE To form an expert consensus addressing clinical issues regarding the use of parenteral direct thrombin inhibitors （DTIs） in special populations. METHODS Led by the Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital（the Affiliated Hospital of UESTC）， a multidisciplinary working group was formed comprising experts from multiple fields， including clinical pharmacy， cardiac surgery， obstetrics， pediatrics and evidence-based medicine. Through literature review and the Delphi method， clinical questions regarding the efficacy and safety of parenteral DTIs used in special populations were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” （PICO） framework；systematic searches were conducted in CJFD， PubMed， Embase and other databases. Relevant evidence from randomized controlled trials，cohort studies and systematic reviews were included and synthesized. Evidence quality was assessed using the Grading of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through three rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven clinical questions were ultimately selected （with a consensus rate exceeding 90%）， resulting in the formulation of seven recommendations on the use of parenteral DTIs in special populations， including children， pregnant women， patients with hepatic or renal impairment， patients with mesenteric venous thrombosis， and individuals with thrombophilia. These recommendations clarify the preferred agents， dosing ranges， monitoring parameters， and safety management strategies for parenteral DTIs in these special populations. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in special populations.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Based on previous research on the promoting effect of dendrobium officinale polysaccharides (DOP) on hair growth, this study aimed to regulate the skin keratin penetration and hair follicle targeting ability of DOP through molecular weight and nano-carriers to enhance its therapeutic effect on androgenetic alopecia (AGA). Three molecular weight polysaccharides, namely high (DOP), medium (MDOP), and low (LDOP), were prepared by mannanase hydrolysis, and the corresponding liposomes (DOP-lip/MDOP-lip/LDOP-lip) were constructed. Studies have shown that DOP liposomes can effectively achieve follicular targeted delivery and promote efficient uptake by human dermal papilla cells through caveolin-mediated pathways. In the testosterone-induced AGA mouse model, LDOP-lip demonstrated excellent therapeutic effects, restoring the number and morphology of hair follicles to nearly normal levels. In summary, DOP liposomes show significant potential for promoting hair follicle repair through precise delivery and efficient cellular uptake.

Triple-negative breast cancer (TNBC) represents a distinctive subtype, characterized by the absence of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor 2 (HER2). Due to its high inter-tumor and intra-tumor heterogeneity, TNBC poses significant chanllenges for personalized diagnosis and treatment. The advant of clustered regular interspaced short palindromic repeats (CRISPR) technology has profoundly enhanced our understanding of the structure and function of the TNBC genome, providing a powerful tool for investigating the occurrence and development of diseases. This review focuses on the application of CRISPR/Cas technology in the personalized diagnosis and treatment of TNBC. We begin by discussing the unique attributes of TNBC and the limitations of current diagnostic and treatment approaches: conventional diagnostic methods provide limited insights into TNBC, while traditional chemotherapy drugs are often associated with low efficacy and severe side effects. The CRISPR/Cas system, which activates Cas enzymes through complementary guide RNAs (gRNAs) to selectively degrade specific nucleic acids, has emerged as a robust tool for TNBC research. This technology enables precise gene editing, allowing for a deeper understanding of TNBC heterogeneity by marking and tracking diverse cell clones. Additionally, CRISPR facilitates high-throughput screening to promptly identify genes involved in TNBC growth, metastasis, and drug resistance, thus revealing new therapeutic targets and strategies. In TNBC diagnostics, CRISPR/Cas was applied to develop molecular diagnostic systems based on Cas9, Cas12, and Cas13, each employing distinct detection principles. These systems can sensitively and specifically detect a variety of TNBC biomarkers, including cell-specific DNA/RNA and circulating tumor DNA (ctDNA). In the realm of precision therapy, CRISPR/Cas has been utilized to identify key genes implicated in TNBC progression and treatment resistance. CRISPR-based screening has uncovered potential therapeutic targets, while its gene-editing capabilities have facilitated the development of combination therapies with traditional chemotherapy drugs, enhancing their efficacy. Despite its promise, the clinical translation of CRISPR/Cas technology remains in its early stages. Several clinical trials are underway to assess its safety and efficacy in the treatment of various genetic diseases and cancers. Challenges such as off-target effects, editing efficiency, and delivery methods remain to be addressed. The integration of CRISPR/Cas with other technologies, such as 3D cell culture systems, human induced pluripotent stem cells (hiPSCs), and artificial intelligence (AI), is expected to further advance precision medicine for TNBC. These technological convergences can offer deeper insights into disease mechanisms and facilitate the development of personalized treatment strategies. In conclusion, the CRISPR/Cas system holds immense potential in the precise diagnosis and treatment of TNBC. As the technology progresses and becomes more costs-effective, its clinical relevance will grow, and the translation of CRISPR/Cas system data into clinical applications will pave the way for optimal diagnosis and treatment strategies for TNBC patients. However, technical hurdles and ethical considerations require ongoing research and regulation to ensure safety and efficacy.

Objective:To investigate the different expression levels of programmed cell death 1 ligand 1 (PD-L1) in non-small cell carcinoma (NSCLC) of distribution characteristics of TCM constitutions and prognosis.Methods:The clinical data of 355 NSCLC patients who had been treated with immune checkpoint inhibitors (ICIs) from January 2019 to June 2023 in the Cancer Medical Center of the First Affiliated Hospital of Hunan University of Chinese Medicine were retrospectively analyzed, and their TCM constitutions were determined. According to the expression level of PD-L1, they were divided into three groups: low expression group (TPS≤1%), medium expression group (1% < TPS < 49%) and high expression group (TPS≥50%). Overall survival (OS) of patients was followed up, and the median OS were compared. Kaplan-Meier method was used to draw survival curves, and Log-rank test was used to compare the difference of survival curves. The independent risk factors of OS were analyzed by COX regression.Results:The distribution of different TCM constitutions showed statistical significance across the three groups ( P<0.05). The median OS for the medium and high expression groups were 21.082 months and 25.714 months, respectively, both significantly higher than the 14.437 months for the low expression group ( P<0.05). The survival curve of TCM constitutions showed that the constitutions significantly correlated with the prognosis of ICIs treatment were qi deficiency, phlegm dampness, and blood stasis ( P<0.05 or P<0.01). The median OS from high to low was 44.971 months for phlegm-dampness constitution, 23.297 months for qi-deficiency constitution, and 11.763 months for blood-stasis constitution. COX regression analysis indicated that medium PD-L1 expression ( HR=0.622, 95% CI=0.459,0.844, P=0.002), high PD-L1 expression ( HR=0.509, 95% CI=0.361,0.718, P<0.001), phlegm-dampness constitution ( HR=0.556, 95% CI=0.335,0.924, P=0.024), and blood-stasis constitution ( HR=2.952, 95% CI=1.929,4.518, P<0.001) were independent prognostic factors. Conclusions:The higher the expression level of PD-L1 in NSCLC patients, the better the prognosis of ICIs treatment. The prognosis of ICIs treatment is better for people with phlegm-dampness constitution and poor for those with blood stasis constitution.

Objective To explore the molecular mechanism by which SOS Ras/Rac guanine nucleotide exchange factor 1-intronic transcript 1(SOS1-IT1)affects enhancer of zeste homolog 2(EZH2)protein expression in endometrial cancer cells Ishikawa and RL95-2.Methods Lentiviral transfection of short hairpin RNA(shRNA)and overexpression plasmid were used in Ishikawa and RL95-2 cell lines to knock down and overexpress SOS1-IT1.The mechanism of EZH2 expression regulation was studied using Real-time PCR,Western blotting,and chromatin immunoprecipitation.Results The expression of SOS1-IT1 and EZH2 genes was positively correlated in endometrial cancer tissues.Knocking down SOS1-IT1 significantly reduces the expression of EZH2,inhibited the proliferation and migration of Ishikawa and RL95-2 cells,and could reduced the acetylation of histone H3 at position 27(H3K27)and the enrichment of CREB binding protein(CBP)in the EZH2 gene promoter region.Overexpression of SOS1-IT1 could increased the expression of EZH2 and enhance the acetylation of H3K27 and the enrichment of CBP.CBP could bind to SOS1-IT1 RNA,and this binding ability was weakened when CBP was knocked down.Conclusion SOS1-IT1 can promote the expression level of EZH2 in endometrial cancer cells Ishikawa and RL95-2 by regulating the acetylation modification level of the EZH2 gene promoter region,thereby affecting the proliferation and migration ability of endometrial cancer cells.

Objective To discuss the application of partial antiplatelet drug genotype detection and thromboelastography-platelet mapping(TEG-PM)in guiding the selection of antiplatelet regimens in patients with intracranial aneurysms(IAs)after receiving stenting.Methods A total of 106 patients with IAs in the First Affiliated Hospital of Kunming Medical University,who underwent implantation of stent and received the testings of platelet-endothelial aggregation receptor 1(PEAR 1)and clopidogrel-related gene-cytochrome P450 enzyme 2C19(CYP2C19),and some of whom received TEG-PM testing from January 2019 to August 2022,were collected for this study.The patients were divided into group A(gene detection group,according to the drug-related gene detection results to adjust the medication)and group B(combination group,according to the two testing results to guide the medication).The patient's gender,age,testing data were collected,and the occlusion of IAs,stent intimal hyperplasia,drug-related hemorrhagic and ischemic complications during follow-up period were recorded.Results A total of 123 IAs lesions in 106 patients were treated.The patient's mean age was(53.67±6.66)years,67 patients were female.Group A had 41 patients and group B had 65 patients.No statistically significant differences in the baseline data,IAs features,stent types used,and medication regimen existed between the two groups(all P＞0.05).In Group A,the ischemic complications and hemorrhagic complications occurred in two patients each.In Group B,no ischemic complications occurred and 4 patients developed hemorrhagic complications.The difference in the incidence of related complications between the two groups was not statistically significant(P=0.287 and P=0.782 respectively).There were no statistically significant differences in the postoperative one-month and 3-month intimal hyperplasia grade and the aneurysm occlusion rate between the two groups(all P＞0.05).The postoperative 6-month overall intimal hyperplasia grade in Group A was slightly higher than that in Group B,and the difference was statistically significant(P=0.034).Conclusion In order to improve the precision and individualized treatment of antiplatelet therapy,it is suggested that clinicians should adopt TEG-PM-guided conventional double-antibody therapy first when making selection of testing items.For patients with insufficient inhibition rate indicated by TEG-PM,testing of the genes associated with antiplatelet drugs should be used.Based on the genetic test results it is necessary to determine the reasons for the insufficient inhibition rate as well as to adjust the medication promptly according to the specific situation of the patient,so as to ensure the effectiveness of antiplatelet therapy and achieve the purpose of individualized precision therapy.