Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.

Using the amorphous solid dispersion (ASD) technology, poorly water-soluble drugs can be formulated into high-energy amorphous forms. After oral administration, a kinetic supersaturated solution is formed in the gastrointestinal tract, and oral bioavailability is thus effectively improved. As important components of ASDs, pharmaceutical excipients affect the supersaturation of ASDs. Therefore, it is significant to clarify the effects of various types of pharmaceutical excipients on the supersaturated solutions for the development of ASDs. This paper reviews the effects of polymers, small-molecule excipients, and porous materials on the supersaturated solutions formed after dissoptlution of ASD with an emphasis on the mechanisms of various types of pharmaceutical excipients on the supersaturated solutions, providing theoretical guidance for the rational selection of medicinal excipients in the development of ASDs.

Farnesoid X receptor (FXR) is widely accepted as a promising target for various liver diseases; however, panels of ligands in drug development show limited clinical benefits, without a clear mechanism. Here, we reveal that acetylation initiates and orchestrates FXR nucleocytoplasmic shuttling and then enhances degradation by the cytosolic E3 ligase CHIP under conditions of liver injury, which represents the major culprit that limits the clinical benefits of FXR agonists against liver diseases. Upon inflammatory and apoptotic stimulation, enhanced FXR acetylation at K217, closed to the nuclear location signal, blocks its recognition by importin KPNA3, thereby preventing its nuclear import. Concomitantly, reduced phosphorylation at T442 within the nuclear export signals promotes its recognition by exportin CRM1, and thereby facilitating FXR export to the cytosol. Acetylation governs nucleocytoplasmic shuttling of FXR, resulting in enhanced cytosolic retention of FXR that is amenable to degradation by CHIP. SIRT1 activators reduce FXR acetylation and prevent its cytosolic degradation. More importantly, SIRT1 activators synergize with FXR agonists in combating acute and chronic liver injuries. In conclusion, these findings innovate a promising strategy to develop therapeutics against liver diseases by combining SIRT1 activators and FXR agonists.

Objective:To understand the knowledge attitude and practice (KAP) on vaccination among children's parents in Jiangxi, Shanghai, and Qinghai and explore the factors influencing KAP.Methods:The study selected two counties/districts in Jiangxi, Shanghai, and Qinghai, respectively, by stratified sampling and used a unified questionnaire to investigate the parental KAP of vaccination. A structural equation model (SEM) was used to explore factors influencing parental KAP, as well as the relationship between knowledge and behavior.Results:Of the 760 valid questionnaires, the knowledge of vaccination among children's parents was better, and the vaccination knowledge of parents in Qinghai and Shanghai were slightly better than those in Jiangxi. Parents mainly obtained vaccination knowledge through medical staff and vaccination manuals. The fitting degree of SEM was relatively good; the root mean square error of approximation of the model is 0.033. The higher the parents' education level, the better their knowledge of vaccination ( β?=0.082). Parental vaccination knowledge could influence whether the vaccinated children stay for half an hour in the clinics ( β?=0.541). It could also impact whether parents giving up vaccinating their children in the face of media reports about the adverse effects of vaccinations ( β?=0.515). Conclusions:The knowledge of vaccination among the parents in Jiangxi, Shanghai, and Qinghai was quite good. Moreover, we should pay more attention to the mass media programs and vaccination knowledge among parents with low or middle education backgrounds. Vaccination knowledge can be disseminated through medical staff, vaccination manuals, or mobile applications.

Betacoronavirus ; Coronavirus Infections ; Humans ; Pandemics ; Pneumonia, Viral ; Single-Cell Analysis

Objective:To compare the long-term oncological outcomes between laparoscopic and abdominal surgery in stage Ⅰa1 （lymph-vascular space invasion-positive, LVSI +）- Ⅰb1 cervical cancer patients with different tumor sizes. Methods:Based on the Big Database of Clinical Diagnosis and Treatment of Cervical Cancer in China (1538 project database), patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who treated by laparoscopic or abdominal surgery were included. The 5-year overall survival (OS) and 5-year disease-free survival (DFS) between the two surgical approaches were compared under 1∶1 propensity score matching (PSM) in different tumor diameter stratification. Results:(1) A total of 4 891 patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer who underwent laparoscopy or laparotomy from January 1, 2009 to December 31, 2016 were included in the 1538 project database. Among them, 1 926 cases in the laparoscopic group and 2 965 cases in the abdominal group. There were no difference in 5-year OS and 5-year DFS between the two groups before matching. Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.367, 95% CI: 1.105-1.690, P=0.004). After 1∶1 PSM matching, 1 864 patients were included in each group, and there was no difference in 5-year OS between the two groups （94.1% vs 95.4%, P=0.151）. While, the inferior 5-year DFS was observed in the laparoscopic group (89.0% vs 92.3%, P=0.004). And the laparoscopic surgery was associated with lower 5-year DFS ( HR=1.420, 95% CI: 1.109-1.818, P=0.006). (2) In stratification analysis of different tumor sizes, and there were no difference in 5-year OS and 5-year DFS between the laparoscopic group and abdominal group in tumor size ≤1 cm, >1-2 cm and >2-3 cm stratification (all P>0.05). Cox multivariate analysis showed that laparoscopic surgery were not related to 5-year OS and 5-year DFS ( P>0.05). In the stratification of tumor size >3-4 cm, there was no difference in 5-year OS between the two groups ( P>0.05). The 5-year DFS in the laparoscopic group was worse than that in the abdominal group (75.7% vs 85.8%, P=0.025). Cox multivariate analysis suggested that laparoscopic surgery was associated with lower 5-year DFS ( HR=1.705, 95% CI: 1.088-2.674, P=0.020). Conclusions:For patients with stage Ⅰa1 （LVSI +）-Ⅰb1 cervical cancer, laparoscopic surgery is associated with lower 5-year DFS, and the adverse effect of laparoscopic surgery on oncology prognosis is mainly reflected in patients with tumor size >3-4 cm. For patients with tumor sizes ≤1 cm, >1-2 cm and >2-3 cm, there are no difference in oncological prognosis between the two surgical approaches.

Objective: To investigate the health effects of air pollution on elementary school students with the indicator of absenteeism caused by respiratory symptoms and diseases, and to provide a reference for improving their physical health. Methods: Absenteeism, air pollutants, and meteorological data during Sep. 2015 to Jun. 2017 in Pudong, Shanghai were collected. Generalized additive model was used to estimate the effects of air pollution on students’ absenteeism caused by respiratory symptom and diseases, time trends, day of week and meteorological factors were controlled. Results: Totally 47 723 person-days of elementary school students’ absenteeism caused by respiratory symptoms and diseases were recorded during Sep.2015 to Jun. 2016 in Pudong, Shanghai, and the absenteeism rate was 0.07%. The PM2.5 concentration on lag0 and SO2 concentration on lag2 showed the most significant effects, the elementary school students’ absenteeism raised for 1.43% (95%CI=0.25%~2.62%)and 6.79% (95%CI=0.25%~13.32%) respectively with every 10 μg/m3 increment of PM2.5 and SO2. Conclusion Air pollution in Pudong new area have made a influence on the elementary school student’s respiratory symptoms and absenteeism, and the prevention work of air pollution should be strenghthened.

Objective To explore the preoperative localization diagnosis and surgical techniques of intractable occipital lobe epilepsy.Methods Retrospectively studied 37 patients diagnosed as occipital lobe epilepsy and underwent focal occipital resections for epilepsy.The semiology,scalp electroencephalography,MRI,fluorodeoxyglucose-positron emission tomography(FDG-PET),and intracranial EEG monitoring were used to localize the epileptogenic zones.The long-term seizure outcomes were assessed according to the Engel classification scheme.Results Visual symptoms were present in 25 patients preoperatively in this series.MRI displayed occipital lobe lesions in 15 patients,and FDG-PET revealed hypometabolism in or adjacent to epileptogenic zones.And 30 patients' epileptogenic zones and functional areas were defined by intracranial EEG monitoring.Visual field deficits were present in 35.3% of patients preoperatively,and 61% had new or aggravated visual field deficits after surgery.After a mean follow-up of 41 months,81.1% of the patients were seizure free or rarely had seizures.Conclusion The curative effect of the surgery on the medically intractable occipital lobe epilepsy is good.Intracranial EEG monitoring with electrodes extensively covering the occipital lobe and adjacent areas can be useful to demarcate the epileptogenic zones and the visural cortex,and it may prevent aggravation of the visual field deficits as much as possible.