Objective:To investigate the clinical characteristics of infantile cholestasis caused by IFT122 gene variants and the molecular mechanism underlying its impact on primary cilia.Methods:The clinical data of an infant with cholestasis from the Children′s Hospital of Fudan University in September 2022 were retrospectively analyzed. The whole-exome sequencing was performed to identify candidate variants, which were validated by Sanger sequencing in the family. Immortalized cell lines were generated using lentiviral infection, followed by immunofluorescence staining to assess the impact of the variants on primary cilia. Intergroup comparisons were performed using the independent sample t-test and Mann-Whitney U test .Results:The proband was a 4-month-old male infant presenting with jaundice, distinctive facial features, and sagittal craniosynostosis. Blood biochemistry indicated elevated direct bilirubin, total bile acids, and transaminases, with markedly increased γ-glutamyltransferase (GGT). Liver pathology demonstrated giant cell hepatitis with cholestasis and bile duct dysplasia. Genetic analysis identified compound heterozygous variants in IFT122 (NM_052989.3) gene c.88G>C (p.Ala30Pro) and c.240G>C (p.Trp80Cys), which co-segregated with the disease in the family. Immunofluorescence analysis demonstrated that the IFT122 gene compound heterozygous missense variants not only significantly reduced the proportion of cilia-positive cells but also led to aberrant ciliary localization of ADP-ribosylation factor-like protein 13B (ARL13B).In addition, ciliary deposition with phosphatidylinositol polyphosphate 5-phosphatase type Ⅳ (INPP5E) was reduced. All differences were statistically significant (all P<0.05). Conclusion:The compound heterozygous missense variants in IFT122 gene not only impair ciliogenesis but also disrupt the ciliary localization of ARL13B and INPP5E, ultimately resulting in high-GGT infantile cholestasis.

Objective:To investigate the clinical characteristics of infantile cholestasis caused by IFT122 gene variants and the molecular mechanism underlying its impact on primary cilia.Methods:The clinical data of an infant with cholestasis from the Children′s Hospital of Fudan University in September 2022 were retrospectively analyzed. The whole-exome sequencing was performed to identify candidate variants, which were validated by Sanger sequencing in the family. Immortalized cell lines were generated using lentiviral infection, followed by immunofluorescence staining to assess the impact of the variants on primary cilia. Intergroup comparisons were performed using the independent sample t-test and Mann-Whitney U test .Results:The proband was a 4-month-old male infant presenting with jaundice, distinctive facial features, and sagittal craniosynostosis. Blood biochemistry indicated elevated direct bilirubin, total bile acids, and transaminases, with markedly increased γ-glutamyltransferase (GGT). Liver pathology demonstrated giant cell hepatitis with cholestasis and bile duct dysplasia. Genetic analysis identified compound heterozygous variants in IFT122 (NM_052989.3) gene c.88G>C (p.Ala30Pro) and c.240G>C (p.Trp80Cys), which co-segregated with the disease in the family. Immunofluorescence analysis demonstrated that the IFT122 gene compound heterozygous missense variants not only significantly reduced the proportion of cilia-positive cells but also led to aberrant ciliary localization of ADP-ribosylation factor-like protein 13B (ARL13B).In addition, ciliary deposition with phosphatidylinositol polyphosphate 5-phosphatase type Ⅳ (INPP5E) was reduced. All differences were statistically significant (all P<0.05). Conclusion:The compound heterozygous missense variants in IFT122 gene not only impair ciliogenesis but also disrupt the ciliary localization of ARL13B and INPP5E, ultimately resulting in high-GGT infantile cholestasis.

Objective To systematically analyze the trends in life expectancy and healthy life expectancy in China from 1990 to 2023, identify the factors influencing changes in life expectancy, and provide scientific evidence for the Healthy China Strategy. Methods Based on the most recent authoritative data from the Global Burden of Disease Study 2023 (GBD 2023), the United Nations Population Division, the World Bank, and Our World in Data, complete life tables and cause-deleted life tables were constructed. Analytical methods including Joinpoint regression and ARIMA forecasting were comprehensively applied to systematically evaluate life expectancy, survival probability, and the burden of diseases and risk factors. Results From 1990 to 2023, life expectancy at birth in China exhibited sustained and rapid growth (average annual percentage change, AAPC = 0.63%), with a growth rate significantly higher than those observed in the United States, Japan, and the global average (AAPC = 0.12%, 0.21%, and 0.45%, respectively). Survival probability improved across all age groups, with particularly notable gains in children and the oldest-old. Interprovincial and sex-based disparities persisted. Cause-deleted analysis revealed that cardiovascular disease (CVD) accounted for the greatest loss in life expectancy at birth. From 2004 to 2020, years of life lost due to CVD increased annually, reaching 8.70 years in 2020 for the zero-age group in China. Neoplasm ranked second in causing life expectancy loss, which remained relatively stable at approximately 3 years over the study period. Among risk factors, tobacco use, hypertension, air pollution, dietary risks, and high fasting plasma glucose were identified as prominent contributors to life expectancy loss. Strong positive correlations were observed between health resources, economic growth, and life expectancy. Conclusion China has made remarkable progress in extending lifespan and improving quality of life, but it still faces challenges such as chronic diseases limiting lifespan and life quality, diverse health risks, and disparities in health levels and life expectancy across regions and populations.

Objective To explore the factors affecting the prognosis of patients with carbapenem-resistant Ente-robacterales(CRE)healthcare-associated infection(HAI)after neurosurgical procedure,construct and validate a nomogram prediction model.Methods Data of patients with CRE infection after neurosurgical procedure in a tertia-ry hospital in Shanghai from 2018 to 2023 were collected,patients were divided into death group and survival group based on prognosis.LASSO regression and multivariate COX regression analysis were adopted to screen indepen-dent risk factors and construct nomogram prediction model.Receiver operating characteristic(ROC)curve,calibra-tion curve,and decision curve analysis(DCA)were drawn based on Bootstrap internal validation method to evaluate the effectiveness of the model.Results A total of 241 patients were included in analysis,with 221 in the survival group and 20 in the death group.The LASSO and COX regression analysis results showed that gender,length of hospital stay＞30 days,decreased monocyte percentage(MONO％),and elevated creatinine(Cr)were independent risk factors for death in patients with CRE HAI after neurosurgical procedure.The nomogram prediction model for risk of death in CRE patients after neurosurgical procedure was established based on these findings.The model vali-dation results showed that at the 30th day,the calibration curve approached the ideal curve,the area under the ROC curve was 0.981(95％CI:0.947-1.000),the DC A curve showed that when the threshold of risk of death excee-ded 8.36％,there was a higher net benefit value.Conclusion The nomogram prediction model for prognosis during hospitalization in CRE HAI patients after neurosurgical procedure constructed based on LASSO-COX regression analysis has good goodness of fit and predictive performance,which can provide reference for early screening of high-risk patients and implementation of intervention measures in clinical practice.

Objective:To investigate the effects of dexmedetomidine combined with butorphanol for sedation and analgesia on postoperative intracranial pressure and prognosis in patients with severe traumatic brain injury.Methods:A prospective randomized controlled study was conducted on 60 patients with severe traumatic brain injury who were admitted to the ICU after emergency craniotomy surgery at the South Campus of Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University from August 2020 to December 2023. The patients were randomly assigned to two groups: the control group (C group, n = 30) and the dexmedetomidine combined with butorphanol group (DB group, n = 30). Based on the treatment recommendations from the 2016 Guidelines for the Management of Severe Traumatic Brain Injury, the DB group received a combination of dexmedetomidine and buprenorphine for sedation and analgesia. Dexmedetomidine was administered via intravenous infusion at a loading dose of 1 μg/kg over 10 minutes, followed by a continuous infusion of 0.4-0.7 μg/kg per hour. Butorphanol was given with a loading dose of 10 μg/kg, followed by a continuous infusion of 10-20 μg/kg per hour. The infusion rate was adjusted to maintain a target Richmond Agitation-Sedation Scale (RASS) score of -3 to -4 to ensure adequate sedation. Patients in the C group received a continuous infusion of an equal amount of 0.9% sodium chloride injection. RASS scores were evaluated in both groups every 4 hours and maintained for 72 hours. The blood pressure, heart rate, central venous pressure, intracranial pressure, RASS sedation scores, and Numerical Verbal Pain Scale pain scores were observed at each time point: upon admission to the ICU (T 1) as well as 24 hours (T 2), 48 hours (T 3), and 72 hours (T 4) after surgery. The number of ventilator days, length of stay in the ICU, and Glasgow Outcome Scale prognosis score at discharge were recorded for all patients. Additionally, the incidence of adverse events such as secondary pulmonary infections, rebleeding, secondary surgeries, and death during hospitalization was recorded. Results:The mean arterial pressure ( F = 69.02, P < 0.001), heart rate ( F = 127.19, P < 0.001), and intracranial pressure ( F = 53.36, P < 0.001) in the DB group were significantly lower compared with those in the C group. The RASS scores ( F = 8.00, P = 0.006) and Numerical Verbal Pain Scale scores ( F = 420.02, P < 0.001) in the DB group were significantly lower than those in the C group. Central venous pressure in the DB group was significantly higher than that in the C group ( F = 6.34, P = 0.015). In terms of clinical outcomes, the mortality rate in the DB group was significantly lower than that in the C group ( χ2 = 4.36, P = 0.037), and the Glasgow Outcome Scale prognosis score was significantly higher in the DB group ( t = 3.03, P = 0.004). The number of ventilator days ( t = 6.10, P < 0.001) and the length of stay in the ICU ( t = 7.71, P < 0.001) were significantly shorter in the DB group compared with the C group (both P < 0.05). There were no statistically significant differences in the incidence of pulmonary infections, rebleeding events, or secondary surgeries between the two groups (all P > 0.05). Conclusions:The combination of dexmedetomidine and butorphanol can effectively decrease postoperative intracranial pressure in patients with severe traumatic brain injury and improve their prognosis.

Alzheimer's disease(AD)is a progressive neurodegenerative disease with hidden onset.Recent researches have shown that apolipoprotein E4(APOE4)is a high-risk genetic factor of AD,and the clinical symptoms in APOE4 genotype AD patients are closely related to metabolic disorders.This paper reviewed the role of APOE4 in the pathogenesis of AD,and it is indicated that APOE4 contributes to the injury of the cerebral blood-brain barrier,is associated with the disorder of cerebral glucose and lipid metabolism,and leads to the damage of the scavenging ability of microglia.Moreover,this paper explored the approach of early intervention of AD with traditional Chinese medicine(TCM)based on the APOE4 pathogenesis.Based on the pathogenesis of AD being deficiency in origin and excess in superficiality,and under the guidance of the principle of prevention before illness in TCM,it is proposed that early TCM intervention for APOE4 genotype AD patients with metabolic disorders can be performed through improving the phlegm-dampness constitution,by focusing on insulin resistance-related indicators,and with traditional Chinese drug therapy based on syndrome differentiation alone or together with comprehensive management of exercises,diet control and drug interventions,thus to reduce or delay the onset of APOE4 genotype AD.

Abstract Tumor immune escape represents a pivotal determinant of cancer immunotherapy failure. It's mechanistically linked to immunosuppressive tumor microenvironment(TME). The TME comprises tumor cells, immune cells, stromal components and extracellular matrix. These components interact synergistically to suppress antitumor immunity through multiple pathways, thereby promoting immune evasion. As crucial chromosomal stability regulators, centromere proteins(CENPs) remodel the TME via multifaceted mechanisms to potentiate immune evasion. This review synthesizes current knowledge on CENPs' role in tumor immune evasion, offering novel insights for cancer diagnostics and immunotherapy.

Objective To explore the factors affecting the prognosis of patients with carbapenem-resistant Ente-robacterales(CRE)healthcare-associated infection(HAI)after neurosurgical procedure,construct and validate a nomogram prediction model.Methods Data of patients with CRE infection after neurosurgical procedure in a tertia-ry hospital in Shanghai from 2018 to 2023 were collected,patients were divided into death group and survival group based on prognosis.LASSO regression and multivariate COX regression analysis were adopted to screen indepen-dent risk factors and construct nomogram prediction model.Receiver operating characteristic(ROC)curve,calibra-tion curve,and decision curve analysis(DCA)were drawn based on Bootstrap internal validation method to evaluate the effectiveness of the model.Results A total of 241 patients were included in analysis,with 221 in the survival group and 20 in the death group.The LASSO and COX regression analysis results showed that gender,length of hospital stay＞30 days,decreased monocyte percentage(MONO％),and elevated creatinine(Cr)were independent risk factors for death in patients with CRE HAI after neurosurgical procedure.The nomogram prediction model for risk of death in CRE patients after neurosurgical procedure was established based on these findings.The model vali-dation results showed that at the 30th day,the calibration curve approached the ideal curve,the area under the ROC curve was 0.981(95％CI:0.947-1.000),the DC A curve showed that when the threshold of risk of death excee-ded 8.36％,there was a higher net benefit value.Conclusion The nomogram prediction model for prognosis during hospitalization in CRE HAI patients after neurosurgical procedure constructed based on LASSO-COX regression analysis has good goodness of fit and predictive performance,which can provide reference for early screening of high-risk patients and implementation of intervention measures in clinical practice.

Deep proximal lesions with significant defects and subgingival margins exceeding cementoenamel junction are common clin-ical scenarios.With the development of materials and bonding dentistry,along with the popularization of the concept of minimally inva-sive dentistry,deep margin elevation is becoming an option for its minimal invasion and less time-consuming.Even though deep margin elevation seems a valuable technique,clinicians have not extensively applied it limited to its technical sensitivity.Current research is mainly in vitro and lacks high-quality clinical randomized controlled trails,or even standardized clinical process.This review summari-zes the concept,procedure and clinical performance of deep margin elevation.

Objective:To explore the chain mediating effect of coping style and illness perception between intolerance of uncertainty and fear of disease progression in patients with intracranial aneurysm.Methods:A total of 270 patients with intracranial aneurysms admitted to the neurosurgery department of 2 hospitals in Guangzhou from October 2023 to June 2024 were selected by convenience sampling method. The general information questionnaire, intolerance of uncertainty scale-12, the brief disease perception questionnaire, medical coping mode questionnaire(MCMQ) and fear of progression questionnaire-short form were used to investigate the subjects. Statistical description and Spearman correlation analysis were performed using IBM SPSS 25.0 software, and AMOS 23.0 software was used to test and correct the structural equation models.Results:The total score of fear of disease progression in patients with intracranial aneurysms was 27.50(20.00, 34.00). The total score of intolerance of uncertainty was 23.50(19.75, 29.00). The sores of confrontation, avoidance and submission in MCMQ were 18.69±5.44, 12.00(10.00, 15.00) and 7.00(5.00, 9.00), respectively.The total score of illness perception was 37.23±11.60. Fear of disease progression was positively correlated with intolerance of uncertainty, submission and illness perception ( r=0.614, 0.696, 0.680, all P<0.01). The direct effect of intolerance of uncertainty on fear of disease progression was significant in patients with intracranial aneurysms ( β=0.431, P<0.001). Intolerance of uncertainty indirectly affected fear of disease progression through submission ( β=0.181, P<0.001) and illness perception ( β=0.092, P<0.001). Submission and illness perception played chain-mediating effect in the relationship between intolerance of uncertainty and fear of disease progression ( β=0.103, P<0.001). Conclusion:The intolerance of uncertainty in patients with intracranial aneurysms can positively predict the fear of disease progression. Submission and illness perception played a chain mediating role between intolerance of uncertainty and fear of disease progression in patients with intracranial aneurysms.