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.

Based on the theoretical framework of "grease-turbidity-heat toxin"， this paper elucidates the patholo-gical evolution pattern underlying the alternation between active and remission phases of inflammatory bowel disease （IBD）. It is proposed that the active phase of IBD represents a progressive and explosive process characterized by internal accumulation of grease turbidity， constraint transforming into heat， and exuberant heat generating toxin. During the remission phase， the pathogenic process manifests as subsidence of heat toxin， depletion of qi and yin， latent retention of residual turbidity， and a state of coexistence between deficiency of healthy qi and lingering pathogenic factors. Accordingly， a staged therapeutic strategy with dynamic intervention and targeted modulation has been established. During the active phase， treatment follows the sequential principle of unblocking， clearing， and resolving pathogenic factors. In the early stage， the therapeutic approach focuses on regulating qi movement， fortifying the spleen， and resolving turbidity， using Tongxie Essential Formula （痛泻要方） and Shenling Baizhu Powder （参苓白术散） to regulate qi and fortify spleen. In the middle stage， the strategy emphasizes clearing heat， eliminating dampness， and dispersing pathogenic accumulation through downward and outward pathways， and Gegen Qinlian Decoction （葛根芩连汤） combined with Banxia Xiexin Decoction （半夏泻心汤） is used to clear and resolve damp-heat. In the late stage， treatment aims to resolve toxin， restrain sore， cool blood， and stabilize collaterals， using Baitouweng Decoction （白头翁汤）， Shaoyao Decoction （芍药汤）， and Xijiao Dihuang Decoction （犀角地黄汤） to eliminate toxins and cool blood. During the remission phase， the principle of reinforcing， consolidating， and penetrating is adopted to restore internal balance and clear the source， using Sishen Pills （四神丸） and Sijunzi Decoction （四君子汤） to reinforce healthy qi and venting pathogens.

Based on the theory of Zi Wu Liu Zhu （子午流注， the ebb and flow of midnight and midday） and the clinical characteristics of diarrhea-predominant irritable bowel syndrome （IBS-D） that its symptoms mainly occur during chou （丑） period （01：00—03：00）， mao （卯） period （5：00—7：00）， and si （巳） period （9：00—11：00）， this paper proposes a temporal pathogenesis chain of "liver constraint during chou period， intestinal stagnation during mao period， and spleen deficiency during si period". Within this chain， liver constraint serves as the initiating factor， and intestinal stagnation manifests as the branch， while spleen deficiency constitutes the root of the disease. Accordingly， a chronotherapeutic principle of "soothing the liver， regulating the intestines， and fortifying the spleen" is proposed， establishing a corresponding time-based syndrome differentiation and treatment system. During chou period， the treatment should focus on soothing the liver to relieve constraint and calming the mind to tranquilize the spirit， thereby blocking the mechanism of liver constraint overacting on the spleen. During mao period， the focus is regulating qi to resolve dampness and harmonizing the intestine to alleviate the branch symptoms of morning abdominal pain and diarrhea. During si period， the suggested method is fortifying the spleen and supplementing qi to drain dampness and stop diarrhea， thereby restoring the pivot of spleen-stomach transportation and transformation. These methods are complemented by strategies to optimize medication compliance， thereby providing a new chronotherapeutic approach for clinical diagnosis and treatment of IBS-D.

Based on the theoretical framework of "grease-turbidity-heat toxin"， this paper elucidates the patholo-gical evolution pattern underlying the alternation between active and remission phases of inflammatory bowel disease （IBD）. It is proposed that the active phase of IBD represents a progressive and explosive process characterized by internal accumulation of grease turbidity， constraint transforming into heat， and exuberant heat generating toxin. During the remission phase， the pathogenic process manifests as subsidence of heat toxin， depletion of qi and yin， latent retention of residual turbidity， and a state of coexistence between deficiency of healthy qi and lingering pathogenic factors. Accordingly， a staged therapeutic strategy with dynamic intervention and targeted modulation has been established. During the active phase， treatment follows the sequential principle of unblocking， clearing， and resolving pathogenic factors. In the early stage， the therapeutic approach focuses on regulating qi movement， fortifying the spleen， and resolving turbidity， using Tongxie Essential Formula （痛泻要方） and Shenling Baizhu Powder （参苓白术散） to regulate qi and fortify spleen. In the middle stage， the strategy emphasizes clearing heat， eliminating dampness， and dispersing pathogenic accumulation through downward and outward pathways， and Gegen Qinlian Decoction （葛根芩连汤） combined with Banxia Xiexin Decoction （半夏泻心汤） is used to clear and resolve damp-heat. In the late stage， treatment aims to resolve toxin， restrain sore， cool blood， and stabilize collaterals， using Baitouweng Decoction （白头翁汤）， Shaoyao Decoction （芍药汤）， and Xijiao Dihuang Decoction （犀角地黄汤） to eliminate toxins and cool blood. During the remission phase， the principle of reinforcing， consolidating， and penetrating is adopted to restore internal balance and clear the source， using Sishen Pills （四神丸） and Sijunzi Decoction （四君子汤） to reinforce healthy qi and venting pathogens.

ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

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.

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.