AIM: To explore the factors associated with significant corneal astigmatism during the perioperative period in patients with pterygium. METHODS: Patients with primary pterygium presenting at Shanxi Eye Hospital between February and June 2025 were enrolled. All patients underwent medical history collection. Pre- and postoperative data were obtained using Pentacam, anterior segment photography, Image J software, and anterior segment optical coherence tomography(AS-OCT). All patients underwent pterygium excision combined with autologous bulbar conjunctival flap transplantation under local infiltration anesthesia. RESULTS: A total of 76 patients(76 eyes)with pterygium were finally enrolled(30 males, 46 females)with a mean age of 62.2±8.2 y. The mean length of corneal invasion by pterygium was 3.61±0.89 mm, the mean depth of invasion into the anterior corneal surface was 0.15±0.09 mm, and the median area of corneal invasion was 10.25(6.90, 18.75)mm2. The median preoperative corneal astigmatism was 1.50(0.70, 5.45)D. Median astigmatism was 0.8(0.40, 1.28)D at 2 wk postoperatively and 0.60(0.30, 1.15)D at 1 mo postoperatively. Patient age showed a positive correlation with preoperative astigmatism, and with residual astigmatism at 2 wk and 1 mo postoperatively(all P<0.05). The length of corneal invasion was positively correlated with preoperative astigmatism and residual astigmatism at both postoperative timepoints(P<0.01). The depth of invasion showed no significant linear correlation with astigmatism at any stage(P=0.250, 0.761, 0.686). The area of corneal invasion was positively correlated with astigmatism at all stages(P<0.01). Patients were grouped based on significant astigmatism(≥1.0 D)and non-significant astigmatism(<1.0 D), after adjusting for other variables, age(P=0.031)and the area of corneal invasion(P=0.004)were identified as risk factors for significant astigmatism. Pterygium invasion length was not significant factors(P>0.05). Receiver operating characteristic(ROC)analysis showed the highest area under the curve(AUC)for the invasion area(AUC=0.915). CONCLUSION: Significant preoperative corneal astigmatism in pterygium patients is correlated with patient age, the length of corneal invasion, and the area of invasion. The area of pterygium invasion into the cornea is the strongest predictor of significant preoperative corneal astigmatism.

BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

BACKGROUND:During bone remodeling,bone formation and bone resorption are spatially and temporally coordinated,involving intricate interactions between osteoclasts and osteoblasts.Isoginkgetin,a flavonoid found in Ginkgo biloba,has a wide range of anticancer activity and anti-reactive oxygen species activity;however,the effect of isoginkgetin on osteoclast differentiation is unknown.OBJECTIVE:To study the effect and mechanism of action of isoginkgetin on osteoclastogenesis.METHODS:In vitro studies were performed on mouse bone marrow-derived macrophages,and cell counting kit-8 cytotoxicity assay was used to detect the effect of isoginkgetin on cell viability of bone marrow-derived macrophages.Macrophage colony-stimulating factor and receptor activator of nuclear factor kappa-B ligand were used to induce the differentiation of bone marrow-derived macrophages to osteoclasts.Network pharmacology and molecular docking and molecular dynamics simulations were used to predict the processes and targets of the effects of isoginkgetin on the differentiation of osteoclasts.Tartrate-resistant acid phosphatase staining and F-actin staining were used to detect the effects of isoginkgetin on the differentiation and function of osteoclasts.Western blot and RT-PCR were used to detect the effects of isoginkgetin on the expression of genes and proteins related to osteoclast differentiation,reactive oxygen species,and PI3K/AKT pathways.Fluorescent probes were used to detect cellular and mitochondrial reactive oxygen species levels.Flow cytometry technology was used to detect reactive oxygen species levels in cells.RESULTS AND CONCLUSION:(1)Network pharmacology results showed that isoginkgetin affected osteoporosis mainly through the PI3K-AKT pathway and cellular response to drugs and hypoxia,and GSK3β,ESR1,MCL1 and CCNA2 were the key targets.(2)Cell counting kit-8 and tartrate-resistant acid phosphatase staining results showed that isoginkgetin at 8 μmol/L had the most significant inhibitory effect on osteoclastogenesis in vitro,and F-actin results showed that isoginkgetin inhibited osteoclast cytoskeletal actin ring formation in a concentration-dependent manner.(3)Molecular dynamics simulations showed that isoginkgetin bound well to osteoclastogenesis marker proteins(NFATc1,c-Fos,CTSK,and MMP9).Western blot and RT-PCR results indicated that isoginkgetin inhibited the expression of osteoclastogenesis marker proteins and genes(NFATc1,c-Fos,CTSK,and MMP9).(4)Western blot results showed that isoginkgetin inhibited the phosphorylation level of PI3K/AKT/GSK3β and suppressed osteoclastogenesis by activating the PI3K-AKT-GSK3β pathway.(5)The results of reactive oxygen species assay showed that isoginkgetin significantly reduced receptor activator of nuclear factor kappa-B ligand-induced cellular and mitochondrial reactive oxygen species production,and inhibited the differentiation of bone marrow-derived macrophages to osteoclasts.

BACKGROUND:β-Caryophyllene has a variety of pharmacological activities such as antioxidant,anti-inflammatory and anti-apoptotic,which may have a better therapeutic effect on osteoarthritis.OBJECTIVE:To investigate the effect and mechanism of β-caryophyllene on mouse osteoarthritis.METHODS:Forty C57BL/6J mice were randomly divided into sham group,model group,low-dose β-caryophyllene group and high-dose β-caryophyllene group,with 10 mice in each group.Hulth method was used to construct an osteoarthritis model in the latter three groups.Four weeks after modeling,70 and 140 mg/kg/d β-caryophyllene was intragastrically given in the low-and high-dose β-caryophyllene groups,respectively,and normal saline was given by gavage in the sham group and the model group,once a day,for 4 weeks.After administration,knee joint morphological changes were observed by hematoxylin-eosin staining,serum levels of inflammatory factors(tumor necrosis factor-α,interleukin-1β,interleukin-6,and interleukin-10)were detected by ELISA,and oxidative stress indexes(glutathione peroxidase,superoxide dismutase,and malondialdehyde)were detected by chemiluminescence.The expression levels of key proteins in the Sonic hedgehog(Shh)/glioma associated oncogene homolog 1(Gli1)signaling pathway were detected by immunohistochemistry and western blot.RESULTS AND CONCLUSION:(1)Compared with the sham group,a large number of inflammatory cells infiltrated in the knee joint of mice in the model group,cartilage tissue was seriously damaged,serum levels of tumor necrosis factor-α,interleukin-1β,interleukin-6,interleukin-10 and malondialdehyde were significantly increased(P＜0.01),the activities of glutathione peroxidase and superoxide dismutase were significantly decreased(P＜0.01),and the relative expression levels of Shh and Gli1 in the knee joint were significantly increased(P＜0.01).(2)Compared with the model group,in the low-and high-dose β-caryophyllene groups,inflammatory cell infiltration in the mouse knee joint was decreased,cartilage tissue injury was alleviated,serum levels of tumor necrosis factor-α,interleukin-1 β,interleukin-6 and malondialdehyde were significantly decreased(P＜0.05),the activities of glutathione peroxidase and superoxide dismutase were significantly increased(P＜0.01),and the expression levels of Shh and Gli1 in the knee joint were significantly decreased(P＜0.01).The above-mentioned improvements were more significant in the high-dose β-caryophyllene group than the low-dose β-caryophyllene group.To conclude,β-caryophyllene can improve osteoarthritis,and its mechanism may be related to reducing inflammation and oxidative stress damage by regulating the Shh/Gli1 signaling pathway.

Background/Aims: Liver transplantation (LT) following total hepatectomy is a life-saving treatment for hepatocellular carcinoma (HCC). The HCC recurrence after LT hinders the effectiveness of the procedure. The objective of this study is to develop a pre-operative risk stratification model based on a liquid biopsy. Methods: We conducted a comprehensive multi-omics study of 260 HCC patients from three centers, including clinical data, low-coverage whole-genome sequencing of cell-free DNA (cfDNA) from plasma, as well as whole-exome, single-nucleus RNA, and spatial transcriptomics from matched tumor and non-tumor tissues. Results: We identified cfDNA-derived copy number alteration (CNA) signatures associated with post-transplant recurrence. By integrating cfDNA-derived CNA profiles with single-cell transcriptomic data, we traced recurrence-associated cfDNA to a distinct subpopulation of malignant cells within the primary tumor. These cells were embedded in a pro-metastatic microenvironment of specialized endothelial subtypes and cancer-associated fibroblasts. Notably, most recurrence-associated lesions were detectable in cfDNA prior to liver transplantation (LT). Building on these insights, we developed the ZJU Criteria based on CNA fragments and tumor markers, a pre-LT risk prediction tool that integrates conventional clinical factors with cfDNA-derived CNA signatures, and validated it using internal and independent external cohorts. Conclusion Our findings suggest that post-transplant recurrence commonly originates from advanced subclones that emerge late during tumor evolution. The ZJU Criteria provides an accurate, non-invasive strategy that significantly improves pre-LT risk stratification and clinical decision-making for patients with HCC.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To clarify the current development status of clinical pharmacist training bases and the pharmacist workforce in China， and to provide evidence for standardizing base construction and promoting the high-quality development of hospital pharmacy. METHODS Questionnaires were distributed to all clinical pharmacist training bases for urgently-needed health professionals and clinical pharmacist training bases under the Chinese Hospital Association that had been approved by the end of 2023 to collect data including base profiles and pharmacist staffing conditions. Expert teams carried out field investigations to verify the collected data. Descriptive statistical analyses were conducted on the quantity， type and regional distribution of training bases， and the influencing factors of pharmacist staffing in the bases were analyzed. RESULTS Field surveys were completed covering 297 training bases across 31 provincial-level administrative regions. Among the base hospitals， 87.88% were Grade A tertiary general hospitals， and 65.32% were located in provincial capitals. The eastern region had the largest number of bases （136， accounting for 45.79%）， followed by the western region （79， 26.60%）. Great disparities existed among provinces in terms of base quantity and hospital scale. The median proportion of pharmaceutical technical personnel in base hospitals was 4.05%， and the median number of clinical pharmacists per 100 hospital beds was 0.53. Both indicators reached the highest in the eastern region （0.57， 4.43%） and the lowest in the northeastern region （0.45， 3.01%）. A total of 3 627 full-time clinical pharmacists were employed in all surveyed bases， among whom 83.68% held clinical pharmacist training certificates， 35.43% possessed senior professional titles， and 78.19% had postgraduate or higher educational background. The total annual training capacity of the surveyed bases was 4 291 trainees， with obvious differences in annual training capacity across regions and provinces. Training specialties covered 19 specialized disciplines plus one general discipline， and no province could deliver training for all 20 specialties simultaneously. Multivariate Logistic regression analysis showed that geographic region exerte d a significant impact on the proportion of pharmaceutical technical personnel （≥4%） （ P ＜0.05）， while the approval time of training bases and hospital scale had significant effects on the number of clinical pharmacists per 100 beds （≥0.6） （ P ＜0.05）. CONCLUSIONS China’s clinical pharmacist training system has basically matured and taken initial shape. The distribution of clinical pharmacist training resources is generally consistent with regional population and economic development levels. However， the allocation of pharmaceutical staff and clinical pharmacists has not yet met national standards and clinical service demands.

OBJECTIVE To investigate the current status of quality management in clinical pharmacist training bases in China， and to provide references for the standardized development and improvement of these bases. METHODS A combined approach of questionnaire survey and on-site investigation was adopted， targeting the healthcare highly sought-after talent （clinical pharmacist） training bases in 31 provinces of China as well as the clinical pharmacist training bases affiliated with the Chinese Hospital Association. A training quality management evaluation index system consisting of 25 tertiary indicators was established. Investigations were conducted from two dimensions： structural quality of training and quality management of training processes. Data were statistically analyzed using descriptive statistical methods. RESULTS On-site investigations were completed for 297 clinical pharmacist training bases across the 31 provinces， among which 284 were affiliated with the Chinese Hospital Association and 271 were healthcare highly sought-after talent （clinical pharmacist） training bases. In terms of structural quality， the core indicator compliance rate for hospital-level training systems exceeded 80%， the rate of special fund utilization for designated purposes reached 80.13%， and the overall compliance rate for software and hardware facilities surpassed 88%. A total of 1 348 preceptors were employed across the training bases， among whom those with senior professional titles and full-time specialist clinical pharmacists as lead preceptors accounted for 62.91% and 94.36%， respectively. Regarding process quality， the compliance rate for “establishment of clinical practice teaching groups in accordance with regulations during clinical department rotations” was 85.19%， and 79.80% and 76.09% of the bases were found to implement strict confidentiality in theoretical examinations and meet the required scale of assessment cases， respectively. However， formal documents of corresponding training management regulations were formulated in only 57.91% of the bases， and the completeness and standardization rate of training manual completion was merely 47.47%. In addition， considerable disparities in quality management levels were observed among provinces， with issues in training process quality being particularly prominent. CONCLUSIONS The management system， hardware facilities， and preceptor staffing of clinical pharmacist training bases in China are relatively well-established， yet notable variations in quality management exist among training bases across different provinces.

Intelligence encompasses various abilities, including logical reasoning, comprehension, self-awareness, learning, planning, creativity, and problem-solving. Extensive research and practical experience suggest that there are sex differences in intellectual development, with females typically maturing earlier than males. However, the key genes and molecular network mechanisms underlying these sex differences in intellectual development remain unclear. To date, Genome-Wide Association Studies (GWAS) have identified 507 genes that are significantly associated with intelligence. This study first analyzed RNA sequencing data from different stages of brain development (from BrainSpan), revealing that during the late embryonic stage, the average expression levels of intelligence-related genes are higher in males than in females, while the opposite is observed during puberty. This study further constructed interaction networks of intelligence-related genes with sex-differential expression in the brain, including the prenatal male network (HELP-M: intelligence genes with higher expression levels in prenatal males) and the pubertal female network (HELP-F: intelligence genes with higher expression levels in pubertal females). The findings indicate that the key genes in both networks are Ep300 and Ctnnb1. Specifically, Ep300 regulates the transcription of 53 genes in both HELP-M and HELP-F, while Ctnnb1 regulates the transcription of 45 genes. Ctnnb1 plays a more prominent role in HELP-M, while Ep300 is more crucial in HELP-F. Finally, this study conducted sequencing validation on rats at different developmental stages, and the results indicated that in the prefrontal cortex of female rats during adolescence, the expression levels of the intelligence genes in HELP-F, as well as key genes Ep300 and Ctnnb1, were higher than those in male rats. These genes were also involved in neurodevelopment-related biological processes. The findings reveal a sex-differentiated intelligence gene network and its key genes, which exhibit varying expression levels during the neurodevelopmental process.
Female ; Intelligence/physiology* ; Male ; Sex Characteristics ; Animals ; Brain/growth & development* ; E1A-Associated p300 Protein/physiology* ; beta Catenin/physiology* ; Transcriptome ; Rats ; Gene Expression Profiling ; Genome-Wide Association Study