This study aimed to identify ideal pharmaceutical candidates featuring strong anti-HIV-1 activity and desirable drug-like characteristics. Our endeavor involved the implementation of a bioisosterism strategy, leading to the discovery of an assemblage of halogen-containing biphenyl-diarylpyrimidines as potent HIV-1 non-nucleoside reverse transcriptase inhibitors. Notably, compound A12 demonstrated exceptional efficacy against both WT HIV-1 (EC₅₀ = 1.9 nmol/L) and seven mutant strains (EC₅₀ = 1.7-157 nmol/L), surpassing that of the lead compound 6 and comparable to etravirine. Furthermore, this analog exhibited minimal adverse effects with significantly reduced cytotoxicity (CC₅₀ = 195 μmol/L) and a high selectivity index (SI = 102,608), superior to those of etravirine (CC₅₀ > 4.6 μmol/L, SI > 1436) and rilpivirine (CC₅₀ = 3.98 μmol/L, SI = 3989). It displayed low inhibition of CYP (IC₅₀ = 6.99-25 μmol/L) and hERG (IC₅₀ > 40 μmol/L), indicating a safer profile compared to etravirine and rilpivirine. No acute toxicity or organ pathological damage was observed at a single dose of 2 g/kg. Additionally, A12 exhibited favorable oral bioavailability (F = 29.2%) and an extended elimination half-life (T _1/2 = 13.56 h), enabling convenient oral administration at minimal doses. These findings indicated that A12 could serve as a promising drug candidate for HIV treatment.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Objective:To evaluate the application value of artificial intelligence (AI) and robot of stereotactic surgery (ROSS)-assisted ultra-early thalamic hematoma drainage in elderly patients with minor thalamus and internal capsule hematoma (TICH) and severe hypoperfusion in the internal capsule area.Methods:A retrospective cross-sectional study was performed; 278 patients with TICH and severe hypoperfusion in the internal capsule area identified by AI medical imaging diagnostic system were enrolled from Department of Neurosurgery, Xingtai Central Hospital from January 2023 to August 2024. Among them, 134 patients (study group) received AI and ROSS-assisted ultra-early thalamic hematoma drainage, and 144 patients (control group) received drug treatment. Differences in baseline data and therapy efficiency between the two groups of patients were compared. Multivariate Logistic regression analysis was used to screen the independent influencing factors for prognosis in the study group 180 days after onset (good prognosis: modified Rankin scale scores of 0-3).Results:Compared with the control group, the study group had significantly higher Glasgow coma scale (GCS) score and regional cerebral blood flow (rCBF) in the internal capsule area 14 days after onset, and statistically higher therapy efficiency and good prognosis rate 180 days after onset ( P<0.05). In the study group, 84 patients had a good prognosis and 50 had a poor prognosis 180 days after onset; compared with the good prognosis group, the poor prognosis group had significantly higher proportion of patients with hyper-homocysteinemia history, lower GCS score on admission, larger volume of thalamic hematoma, higher proportions of patients with combined intraventricular hemorrhage and shunt-dependent hydrocephalus, and lower rCBF in the internal capsule area on admission ( P<0.05). Multivariate Logistic regression analysis showed that thalamic hematoma volume ( OR=2.527, 95% CI: 1.504-4.247, P<0.001), combined intraventricular hemorrhage ( OR=2.325, 95% CI: 1.460-3.703, P<0.001), shunt dependent hydrocephalus ( OR=2.371, 95% CI: 1.267-4.078, P=0.006), and rCBF in the internal capsule area on admission ( OR=0.672, 95% CI: 0.314-1.025, P<0.001) were independent risk factors for prognosis of patients in the study group. Conclusion:AI and ROSS-assisted ultra-early thalamic hematoma drainage is effective for elderly patients with minor TICH and severe hypoperfusion in the internal capsule area; patients with large thalamic hematoma volume, combined intraventricular hemorrhage, shunt-dependent hydrocephalus, and low rCBF in the internal capsule area on admission are prone to have a poor prognosis.

Objective To evaluate the application value of stereotactic robotic surgery driven by a multi scenario AI system in the elderly with severe hypoperfusion in the internal capsule area and minor HTH.Methods A retrospective analysis was conducted on 101 minor HTH patients com-plicated with severe hypoperfusion in the internal capsule area identified by an AI diagnostic sys-tem in our department from January to October 2024.Among them,48 cases who underwent ster-eotactic robotic drainage with AI system support were assigned into the study group,and 53 cases of conventional drug treatment were into the control group.The general clinical data were com-pared between the two group.Improvement rate of rCBF 14 d after treatment,effective rate 90 d after treatment,favorable prognosis rate,and incidence of shunt dependent hydrocephalus were compared between the two groups to evaluate the application value of AI-assisted stereotactic ro-botic surgery in these patients.Results The study group had significantly higher improvement rate of rCBF 14 d after treatment,better effective rate and larger ratio of favorable prognosis 90 d after treatment when compared with the control group(60.4％vs 39.6％,P＜0.05;62.5％vs 41.5％,P＜0.05;64.6％vs 43.4％,P＜0.05).Conclusion Stereotactic robotic assisted drainage driven by multi scenario AI system can significantly improve the prognosis of the elderly minor HTH patients complicated with severe hypoperfusion in the internal capsule area.

Objective To evaluate the application value of stereotactic robotic surgery driven by a multi scenario AI system in the elderly with severe hypoperfusion in the internal capsule area and minor HTH.Methods A retrospective analysis was conducted on 101 minor HTH patients com-plicated with severe hypoperfusion in the internal capsule area identified by an AI diagnostic sys-tem in our department from January to October 2024.Among them,48 cases who underwent ster-eotactic robotic drainage with AI system support were assigned into the study group,and 53 cases of conventional drug treatment were into the control group.The general clinical data were com-pared between the two group.Improvement rate of rCBF 14 d after treatment,effective rate 90 d after treatment,favorable prognosis rate,and incidence of shunt dependent hydrocephalus were compared between the two groups to evaluate the application value of AI-assisted stereotactic ro-botic surgery in these patients.Results The study group had significantly higher improvement rate of rCBF 14 d after treatment,better effective rate and larger ratio of favorable prognosis 90 d after treatment when compared with the control group(60.4％vs 39.6％,P＜0.05;62.5％vs 41.5％,P＜0.05;64.6％vs 43.4％,P＜0.05).Conclusion Stereotactic robotic assisted drainage driven by multi scenario AI system can significantly improve the prognosis of the elderly minor HTH patients complicated with severe hypoperfusion in the internal capsule area.

Objective:To evaluate the application value of artificial intelligence (AI) and robot of stereotactic surgery (ROSS)-assisted ultra-early thalamic hematoma drainage in elderly patients with minor thalamus and internal capsule hematoma (TICH) and severe hypoperfusion in the internal capsule area.Methods:A retrospective cross-sectional study was performed; 278 patients with TICH and severe hypoperfusion in the internal capsule area identified by AI medical imaging diagnostic system were enrolled from Department of Neurosurgery, Xingtai Central Hospital from January 2023 to August 2024. Among them, 134 patients (study group) received AI and ROSS-assisted ultra-early thalamic hematoma drainage, and 144 patients (control group) received drug treatment. Differences in baseline data and therapy efficiency between the two groups of patients were compared. Multivariate Logistic regression analysis was used to screen the independent influencing factors for prognosis in the study group 180 days after onset (good prognosis: modified Rankin scale scores of 0-3).Results:Compared with the control group, the study group had significantly higher Glasgow coma scale (GCS) score and regional cerebral blood flow (rCBF) in the internal capsule area 14 days after onset, and statistically higher therapy efficiency and good prognosis rate 180 days after onset ( P<0.05). In the study group, 84 patients had a good prognosis and 50 had a poor prognosis 180 days after onset; compared with the good prognosis group, the poor prognosis group had significantly higher proportion of patients with hyper-homocysteinemia history, lower GCS score on admission, larger volume of thalamic hematoma, higher proportions of patients with combined intraventricular hemorrhage and shunt-dependent hydrocephalus, and lower rCBF in the internal capsule area on admission ( P<0.05). Multivariate Logistic regression analysis showed that thalamic hematoma volume ( OR=2.527, 95% CI: 1.504-4.247, P<0.001), combined intraventricular hemorrhage ( OR=2.325, 95% CI: 1.460-3.703, P<0.001), shunt dependent hydrocephalus ( OR=2.371, 95% CI: 1.267-4.078, P=0.006), and rCBF in the internal capsule area on admission ( OR=0.672, 95% CI: 0.314-1.025, P<0.001) were independent risk factors for prognosis of patients in the study group. Conclusion:AI and ROSS-assisted ultra-early thalamic hematoma drainage is effective for elderly patients with minor TICH and severe hypoperfusion in the internal capsule area; patients with large thalamic hematoma volume, combined intraventricular hemorrhage, shunt-dependent hydrocephalus, and low rCBF in the internal capsule area on admission are prone to have a poor prognosis.

This study analyzed the characteristics of 118 738 seasonal migrants who were aged 65 and under management by the Health Statistics Center of Hainan Health Commission.Our study revealed that approximately 51.6％of elderly seasonal migrants were male,with around 75.2％aged below 75 years.Elderly seasonal migrants originating from the Northeast region constituted roughly 36.3％of the total,and the majority of them settled in Haikou,Chengmai and Dongfang(each representing over 10％of the total).Of the nine prevalent health conditions surveyed,about 27.6％of the elderly seasonal migrants suffered at least one condition.Haikou,Wanning,Qionghai,and Dongfang received more than 3 000 elderly seasonal migrants with health issues.Considering the availability of healthcare resources,there exists a negative correlation between the distribution of elderly seasonal migrants and the hospitalization service load of doctors in various destination areas.This study recommends Hainan Province further improving the seasonal migrants dynamic survey system,scientifically arranging healthcare resources and services,and systematically enhancing the health service experience of the seasonal migrants.

Objective:To explore the association between cognitive function and the level of gamma-amino-butyric acid(GABA)in anterior cingulate cortex(ACC)before and after treatment in patients with major depres-sion disorder.Methods:Totally 31 medication-naive patients with major depression disorder meeting the criteria of the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition(DSM-5)and 33 normal controls were col-lected.Each eligible patient received treatment with selective serotonin reuptake inhibitor agents for 8 weeks.The MATRICS Consensus Cognitive Battery(MCCB)was used to evaluate the cognitive function.By means of 1H magnetic resonance spectroscopy,anterior cingulate cortex GABA concentrations were measured.Results:At base-line,the concentration of ACC GABA relative to water(GABA+/W)was lower in the patient group than in the control group(P＜0.05)and increased after treatment(P＜0.05).ACC GABA+/W was negatively associated with verbal learning and visual memory score in patient group at baseline(correlation coefficient and P value were r=-0.40,P＜0.05;r=-0.42,P＜0.05,respectively).The ACC GABA+/W difference resulted of treatment in patient group was positively associated with the difference of working memory score and the difference of reasoning and problem-solving score(correlation coefficient and P value were r=0.58,P＜0.05;r=0.66,P＜0.05,respec-tively).Conclusion:The cognitive dysfunction of patients with major depression disorder may not be related to the degree of depression and anxiety.And improvement of cognitive function may be associated with increase of ACC GABA concentrations.

Objective To explore the application value of emergency temporal body surface positioning for single drain dual-target thalamic hematoma ventricular drainage in the treatment of thalamic hemorrhage breaking into ventricle with hydrocephalus.Methods A retrospective analysis was conducted on 223 patients with thalamic hemorrhage breaking into the ventricles with hydrocephalus,including a study group of 115 cases who underwent emergency single drain dual-target thalamic hematoma ventricular drainage surgery with temporal body surface positioning,and a control group of 108 cases who underwent emergency ventricular drainage first and then underwent stereotactic thalamic hematoma drainage surgery after the condition stabilized.Compare the differences in postoperative complications and treatment outcomes between two groups of patients,and evaluate the application value of temporal surface positioning for single drain dual-target thalamic hematoma ventricular drainage surgery in the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus.Results The postoperative rebleeding rates,hematoma clearance and death were 5.2％,87.5％±7.3％and 13.9％in the study group and 4.7％,90.2％±8.5％and 15.7％in control group,respectively.There was no significant difference between the two groups(P＞0.05).The tube time,postoperative intracranial infection,Shunt dependent hydrocephalus,effective treatment and favorable prognosis of and the control group were(75.5±18.4)h,3.5％,19.1％,53.9％and 51.3％in the study group and(130.8±22.9)h,13.9％,35.1％,38.7％and 38.0％,respectively.The difference between the two groups was statistically significant(P＜0.05).Conclusion Body surface landmark-guided emergency single drain dual-target thalamic hematoma ventricular drainage surgery for the treatment of thalamic hemorrhage breaking into the ventricle with hydrocephalus is safe and reliable,and can improve the patient's prognosis.

Target trail emulation is an observational research method, which can use real-world data (such as observational data and historical data) to carry out research design according to the design principles of randomized controlled trials (RCT) when RCT cannot be carried out. The intervention group and the control group were classified by simulating random grouping. Finally a high-reliable conclusion similar to RCT can be obtained. This paper summarizes the basic concepts and application process of target trail emulation based on the effect of statins on the prognosis of myocardial infarction in diabetic patients to provide reference for the application of this method in real world.