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.

OBJECTIVE To provide references for ensuring the safety of prescription preparation， dispensing， and use of parenteral nutrition solution， as well as for expanding the scope of pharmaceutical services provided by pharmacists in the Pharmacy Intravenous Admixture Services （PIVAS）. METHODS Under the guidance of PIVAS pharmacists， the rules for reviewing medical orders of parenteral nutrition in the PIVAS system and the information displayed on the infusion labels of finished parenteral nutrition solutions were refined. The process management of dispensing parenteral nutrition solution was strengthened， and detailed quality control and inspection rules were formulated. Additionally， Clinical Safety Monitoring Form for Finished Parenteral Nutrition Infusions was designed to conduct clinical monitoring and inspections for abnormalities in the finished infusions， infusion operations， and complications that may arise during the use of finished parenteral nutrition infusions. The implementation effects of the aforementioned optimization/inspection measures were evaluated by comparing data on the efficiency of medical order review for parenteral nutrition， the rate of irrational medical orders， the compliance rate of vascular access selection and infusion rate standardization， the rate of dispensing error， as well as the abnormalities occurring during clinical use， before and after the optimization/inspection initiatives were put into place. RESULTS The optimized prescription review system achieved automatic review of medical orders for parenteral nutrition， enhancing the efficiency of order review. The average time taken to review one parenteral nutrition medical order was reduced from approximately 1 minute to 10 seconds. The irrational rate of parenteral nutrition orders decreased by 31.87%. The dispensing error rate of parenteral nutrition decreased by 56.55%. The standard rate of vascular access selection and standard rate of infusion speed were increased by 13.29% and 3.54%， respectively. The PIVAS pharmacists identified and intervened in 5 abnormal cases out of 298 cases examined for use of parenteral nutrition solutions. CONCLUSIONS By optimizing the prescription review system， improving labeling information， and strengthening quality control inspections during both preparation and administration processes， PIVAS pharmacists have enhanced the safety of compounded parenteral nutrition solutions. This initiative has expanded the scope and depth of pharmaceutical care provided by dispensing pharmacists.

Computational approaches for predicting drug-target interactions (DTIs) are pivotal in advancing drug discovery. Current methodologies leveraging heterogeneous networks often fall short in fully integrating both local and global network information. To comprehensively consider network information, we propose DHGT-DTI, a novel deep learning-based approach for DTI prediction. Specifically, we capture the local and global structural information of the network from both neighborhood and meta-path perspectives. In the neighborhood perspective, we employ a heterogeneous graph neural network (HGNN), which extends Graph Sample and Aggregate (GraphSAGE) to handle diverse node and edge types, effectively learning local network structures. In the meta-path perspective, we introduce a Graph Transformer with residual connections to model higher-order relationships defined by meta-paths, such as "drug-disease-drug", and use an attention mechanism to fuse information across multiple meta-paths. The learned features from these dual perspectives are synergistically integrated for DTI prediction via a matrix decomposition method. Furthermore, DHGT-DTI reconstructs not only the DTI network but also auxiliary networks to bolster prediction accuracy. Comprehensive experiments on two benchmark datasets validate the superiority of DHGT-DTI over existing baseline methods. Additionally, case studies on six drugs used to treat Parkinson's disease not only validate the practical utility of DHGT-DTI but also highlight its broader potential in accelerating drug discovery for other diseases.

Objective:To investigate the changes of Toll-like receptor 4(TLR4) level in peripheral blood of endometriosis (EMT) patients with infertility and its relationship with clinicopathological types and pregnancy outcomes.Methods:A total of 150 patients with EMT complicated with infertility (study group) admitted to Huangzhou District People′s Hospital of Huanggang City from May 2019 to March 2021 and 50 healthy married women (control group) who participated in physical examination during the same period were selected as the research objects. Reverse transcription polymerase chain reaction (RT-PCR) was used to determine the level of TLR4 in peripheral blood of the two groups, and different pathological types of EMT were compared. The receiver operating characteristic (ROC) curve was used to evaluate the predictive efficacy of TLR4 expression for postoperative pregnancy in EMT patients with infertility. At the same time, the relationship between changes in TLR4 level in peripheral blood and pregnancy outcomes was analyzed according to the TLR4 cut-off value.Results:The expression of TLR4 mRNA in peripheral blood in the study group was higher than that in the control group: 98.65 ± 10.63 vs. 1.27 ± 0.20, there was statistical difference ( t = 64.66, P<0.01). After treatment, the expression of TLR4 mRNA in peripheral blood of patients with simple peritoneal type, internal cystic type and adenomyosis type EMT complicated were decreased :81.13 ± 8.89 vs. 64.31 ± 6.44, 103.58 ± 10.01 vs. 85.40 ± 8.78, 118.69 ± 12.76 vs. 96.38 ± 9.96, There were statistical differences ( P<0.05); No matter before or after treatment, the expression of TLR4 mRNA in peripheral blood of patients with adenomyosis was higher than that of patients with internal cystic type and simple peritoneal type, while the expression of TLR4 mRNA in peripheral blood of patients with internal cystic type was higher than that of simple peritoneal type, and there were statistical differences ( P<0.05). The results of ROC curve analysis showed that when the area under the curve (AUC) was 0.787(95% CI 0.701 - 0.863, P<0.05) and the best cut-off value was 41.75, the sensitivity, specificity and accuracy of TLR4 mRNA expression in peripheral blood to predict postoperative pregnancy in EMT patients with infertility were 80.12%, 81.57% and 80.30%, respectively. Using the peripheral blood TLR4 mRNA expression of 41.75 as the cut-off value, 143 patients with EMT and infertility with complete follow-up data were divided into high expression group (58 cases, TLR4 mRNA≥41.75) and low expression group (85 cases, TLR4 mRNA < 41.75). The postoperative intrauterine pregnancy rate and total pregnancy rate in the high expression group were lower than those in the low expression group: 44.83% (26/58) vs. 70.59% (60/85), 58.62% (34/58) vs. 81.18% (69/85), and there were statistical differences ( χ2 = 9.54, 8.71, P<0.05). Conclusions:There is abnormal expression of TLR4 in peripheral blood of EMT patients with infertility, and its high expression is closely related to adverse clinicopathological features and pregnancy outcomes. Effective intervention of treatment and postoperative recovery according to the expression level of TLR4 mRNA can further improve the natural pregnancy rate of such patients.

With accumulating dysregulated circular RNAs(circRNAs)in pathological processes,the regulatory functions of circRNAs,especially circRNAs as microRNA(miRNA)sponges and their interactions with RNA-binding proteins(RBPs),have been widely validated.However,the collected information on experimentally validated circRNA-disease associations is only preliminary.Therefore,an updated CircR2Disease database providing a comprehensive resource and web tool to clarify the relationships between circRNAs and diseases in diverse species is necessary.Here,we present an updated CircR2Disease v2.0 with the increased number of circRNA-disease associations and novel characteristics.CircR2Disease v2.0 provides more than 5-fold experimentally validated circRNA-disease associations compared to its previous version.This version includes 4201 entries between 3077 circRNAs and 312 disease subtypes.Secondly,the information of circRNA-miRNA,circRNA-miRNA-target,and circRNA-RBP interactions has been manually collected for various diseases.Thirdly,the gene symbols of circRNAs and disease name IDs can be linked with various nomenclature databases.Detailed descriptions such as samples and journals have also been integrated into the updated version.Thus,CircR2Disease v2.0 can serve as a platform for users to systematically investigate the roles of dysregulated circRNAs in various diseases and further explore the posttranscriptional regulatory function in diseases.Finally,we propose a computational method named circDis based on the graph convolutional network(GCN)and gradient boosting decision tree(GBDT)to illustrate the applications of the CircR2Disease v2.0 database.

Objective:To explore the relationship between symptom burden and hematologic responses after treatment with interferon and/or hydroxyurea in patients with polycythemia vera (PV) .Methods:Hematologic responses after continuous treatment with interferon and/or hydroxyurea for six months were evaluated in 190 patients with PV using the Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-10 score) . In all patients, the PV diagnosis was based on the 2016 World Health Organization diagnostic definitions.Results:The study cohort comprised 93 (48.9% ) male and 97 (51.1% ) female patients. The median age at the time of MPN-10 assessment was 60 (32-82) years. The median MPN-10 score of the entire cohort was 9 (range, 0-67) . The median MPN-10 score of patients treated with interferon plus hydroxyurea ( n=27) was 11 (0-67) , which was significantly higher than those of patients treated with interferon only ( n=64) (6[0-56], P=0.019) or hydroxyurea only ( n=99) (9[0-64], P=0.047) , whereas the median MPN-10 score was not significantly different between those treated with interferon only and hydroxyurea only ( P=0.421) . The rate of severe symptom burden (i.e., any single symptom burden score ≥ 7 and/or total score ≥ 44) was 28.9% (55/190) in the entire cohort, whereas the rate of severe symptom burden was not significantly different among the interferon only (23.4% ) , hydroxyurea only (29.3% ) , and interferon plus hydroxyurea (40.7% ) groups ( P>0.05 for all two-group comparisons) . When evaluating MPN-10 score, 37.4% (71/190) of the patients achieved complete hematologic remission (CHR) . Only 28.9% (55/190) patients had adequate disease control, defined as CHR without severe symptom burden. Reasons for inadequate disease control were evaluating blood counts alone, severe symptom burden alone, and evaluating blood counts accompanied with severe symptom burden in 42.1% (80/190) , 8.4% (16/190) , and 20.5% (39/190) of the patients, respectively. Compared to the patients with a platelet count ≤ 400×10 9/L, those with a platelet count > 400×10 9/L had a significantly higher rate of severe symptom burden (40.8% [20/49] vs 24.8% [35/141], P=0.044) and a higher median MPN-10 score (14[0-67] vs 7[0-56], P=0.038) . Platelet count > 400×10 9/L was associated with an increased risk of severe symptom burden (hazard ratio, 2.089; 95% confidence interval, 1.052-4.147, P=0.035) . Conclusions:Symptoms related to disease after treatment with interferon and/or hydroxyurea were rather universal in patients with PV. Some patients still experienced severe symptom burden despite achieving CHR. Platelet count > 400×10 9/L was associated with an increased risk of severe symptom burden in patients with PV treated with interferon and/or hydroxyurea.

Objective:To explore predictors of overall survival (OS) in Chinese patients with polycythemia vera (PV) .Methods:A total of 906 consecutive newly diagnosed patients with PV seen at the Blood Diseases Hospital, Chinese Academy of Medical Sciences, from June 2007 to February 2020 were included, and their data were collected. PV was diagnosed according to 2016 World Health Organization (WHO) diagnostic definitions. OS and prognostic factors were retrospectively analyzed.Results:Among the 906 patients, 439 were male (48.5%) and 467 were female (51.5%) . The median age was 57 years (range: 18-91 years) . 31.6% (276/874) of the patients had a thrombosis history at diagnosis, and 4.6% (25/541) of the patients had abnormal cytogenetics. The median follow-up was 54 months (95% confidence interval [ CI] 8-130 months) . The 5- and 10-year cumulative deaths were 5.8% (95% CI 4.8%-6.7%) and 11.1% (95% CI 9.3%-12.9%) , respectively. Univariate analysis showed that age ≥60 years, thrombosis history, white blood cells (WBC) ≥15×10 9/L, platelet (PLT) ≥450×10 9/L, and platelet distribution width (PDW) ≥15 fl significantly correlated with worse OS, and palpable spleen correlated with better OS. Multivariate analysis showed that age ≥60 years ( HR=4.3, 95% CI 2.1-9.2, P<0.001) and PDW ≥15 fl ( HR=2.1, 95% CI 1.1-4.0, P=0.023) were independent prognostic factors for worse OS. The 5-year cumulative death for patients with PDW ≥15 fl or PDW<15 fl was 8.6% (95% CI 5.9%-11.3%) or 4.4% (95% CI 3.4%-5.4%) , respectively. The 5-year cumulative death for patients defined as low-, intermediate-, and high-risk patients by international working group score system for PV (IWG-PV) were 0.8% (95 CI 0.2%-1.4%) , 4.0% (95% CI 2.7%-5.3%) , and 12% (95% CI 9.6%-14.4%) , respectively, with a significant difference among the three cohorts ( P<0.05) . PDW ≥ 15 fl significantly affected OS for intermediate- and high-risk patients ( HR=2.3, 95% CI 1.2-4.2, P=0.009) defined by IWG-PV score system, but not for low-risk patients ( HR=3.1, 95% CI 0.2-52.0, P=0.405) . Conclusions:Age ≥60 years and PDW ≥15 fl were independent prognostic factors for worse OS in PV. IWG-PV score system effectively predicted OS for Chinese patients with PV.

Objective:To investigate the clinical effect of vortioxetine in the treatment of patients with first-episode depression.Methods:From January 2018 to January 2019, 100 patients with depression in outpatients or inpatients of Wenzhou Kangning Hospital were enrolled in the study.According to different treatment methods, they were divided into control group and observation group according to the random digital table method, with 50 cases in each group.The control group was given fluoxetine 20-40mg, qd, and the observation group was treated with vortioxetine.Both two groups were treated for 8 weeks.The pre-treatment subjective cognitive function of the two groups was evaluated.Brain-derived neurotrophic factor(BDNF), homocysteine (Hcy), tumor necrosis factorα(TNF-α), 1, 25-hydroxyl vitamin D 3[1, 25-(OH) 2D 3] were detected in two groups.The electrophysiological indicators event-related potential P300 were detected.The Hamilton Depression Scale(HAMD) was used to evaluate the mental anxiety, mood and physical anxiety of patients before and after treatment in the two groups.The clinical effects of the two groups were evaluated and the adverse reactions were recorded. Results:After treatment for 4 weeks and 8 weeks, the cognitive function scores of the control group were (24.96±2.85)points and (26.18±3.16)points, respectively, which of the observation group were (28.65±3.32)points and (32.66±3.81)points, respectively, which were significantly higher than before treatment(control group: F=14.821; observation group: F=10.632, all P<0.01). The cognitive function scores of the two groups after treatment for 8 weeks were significantly higher than treatment for 4 weeks (control group: t=2.027, P=0.045, observation group: t=5.611, P=0.000). After treatment, the levels of BDNF, Hcy, TNF-α, 1, 25-(OH) 2D 3 in the control group were (29.74±3.62)ng/L, (18.46±2.34)μmol/L, (314.11±15.87)ng/L, (30.69±4.17)ng/mL, respectively, which in the observation group were (34.22±2.85)ng/L, (14.55±2.17)μmol/L, (286.55±10.11)ng/L, (34.92±4.28)ng/m, respectively, the differences between the two groups were statistically significant( t=6.876, 8.663, 10.357, 5.005, all P<0.01). After treatment, the P300 latency and P300 amplitude of the control group were (426.94±4.72)ms, (0.62±-4.31)μV, respectively.which of the observation group were (413.65±3.66)ms, (0.84±-4.76)μV, respectively, the differences between the two groups were statistically significant( t=15.734, 3.048, all P<0.01). After treatment, the HAMD score of the observation group[(10.72±1.53) points] was significantly lower than that of the control group[(12.93±1.84)points]( t=6.530, P<0.01). The effective rate of the observation group was 88.0%(44/50), which of the control group was 86.0%(43/50), the difference between the two groups was not statistically significant( P>0.05). Conclusion:The application of vortioxetine in the treatment of patients with first-episode depression can improve the cognitive function and clinical symptoms of patients, and can also reduce the biochemical indicators of patients.However, the therapeutic effect is similar to that of fluoxetine, but it has less adverse reactions, so it is worthy of promoting.

Objective: To investigate the therapeutic effect of long-acting paliperidone palmitate on schizophrenia and the expression of miR-132 and miR-320 in serum of patients with schizophrenia. Methods: From January 2016 to December 2018, 68 patients with schizophrenia in Wenzhou Kangning Hospital were selected as treatment group.Sixty healthy people were selected as control group.The blood was taken before treatment and 12 months after treatment.The positive and negative symptom scales (PANSS) was recorded and evaluated, and the effect of long-acting injection of paliperidone palmitate on the expression of miR-132 and miR-320 in serum of patients with schizophrenia was detected by RT-PCR. Results: Three months after treatment, the PANSS scores of the treatment group were significantly lower than those of the case group [(60.2±5.4)points vs.(84.5±4.7)points, t=12.02, 22.52, 27.16, 33.32, all P<0.01]. With the prolongation of treatment time, the treatment effect was most obvious at 12 months[(38.2±1.8)points]. The results of RT-PCR showed that compared with the control group [(1.74±0.92)%, (1.43±1.01)%], the expression of serum miR-132 and miR-320 in the treatment group was significantly decreased [(0.47±0.32)%, (0.53±0.37)%, t=13.96, 14.93, all P<0.01]. The long-acting injection of paliperidone palmitate significantly increased the expression of miR-132 and miR-320 in serum of patients with schizophrenia[(0.96±0.58), (1.16±1.07), t=11.08, 8.45, all P<0.01]. Conclusion Long-acting paliperidone palmitate has a certain therapeutic effect on schizophrenia and can up-regulate the expression of miR-132 and miR-320 in serum of patients with schizophrenia.

Objective: To investigate the relationship between the erythrocyte membrane protein gene mutations and the clinical severity of hereditary spherocytosis (HS). Methods: Targeted sequencings were performed on 25 HS patients, correlation between HS mutations and patients’ clinical characteristics were evaluated. Results: A total of 25 HS patients were enrolled, including 13 males and 12 females with median age of 20 (4-55) years, including 9 compensatory hemolysis patients, 9 patients with mild anemia, 3 patients with moderate anemia and 4 patients with severe anemia. Of them, 18 patients (72%) harbored HS-related mutations, including ANK1 mutation in 6 cases, SLC4A1 mutation in 6 cases, SPTB mutation in 5 cases and 1 case with EPB41 mutation. Seven patients (28%) didn’t carry common HS mutations. SPTB and SLC4A1 mutations mainly affected male patients. There was no significant difference between the age of diagnosis (P=0.130) and HGB level (P=0.585) in patients with HS mutation and those without mutation, however, the EMA binding fluorescence intensity (P=0.015), AGLT50 (P=0.032) and EOF minimal hemolytic concentration (P=0.027) were significantly different in these two groups of HS patients. Conclusion To screen erythrocyte membrane protein coding gene mutations could favor the diagnosis of HS, and patients without mutations have mild clinical phenotype.