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 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 explore the feasibility and effectiveness of repairing surgical defect in pharyngo-laryngeal malignant tumor with free rectus femoris flap. METHODS: The clinical data of 34 patients with surgical defects in pharyngo-laryngeal malignant tumor who met the selection criteria between July 2014 and August 2024 were retrospectively analyzed. There were 25 males and 9 females, aged 25-82 years, with a median age of 54 years. The disease duration ranged from 2 months to 2 years, with a median of 7 months. The tumor locations included the oropharynx, hypopharynx, cervical esophagus, and larynx. Pathological types included squamous cell carcinoma (29 cases), myoepithelial carcinoma (2 cases), adenoid cystic carcinoma (1 case), and diffuse large B-cell lymphoma (2 cases). TNM staging: 16 cases of T ₄N ₁M ₀, 3 cases of T ₄N ₂M ₀, 3 cases of T ₄N ₀M ₀, 10 cases of T ₃N ₁M ₀, and 2 cases of T ₃N ₀M ₀. The 2017 American Joint Committee on Cancer (AJCC) staging was stage Ⅲ in 2 cases and stage Ⅳ in 32 cases. The blood supply of the proximal rectus femoris muscle was observed by enhanced CT of the lower limb vessels before operation, and the surgical defects ranged from 3.0 cm×2.0 cm to 12.0 cm×8.5 cm. The blood supply and perforators of rectus femoris muscle were explored during operation, and the free rectus femoris flap pedicled with the direct vascular stem of rectus femoris muscle was used to repair the defect. For the patients with pharyngeal fistula or obvious neck swelling after operation, the blood supply of the flap was analyzed by vascular enhanced CT to determine the corresponding strategies of nutritional support, anti-infection, dressing change and drainage. Radiotherapy and chemotherapy were supplemented in 27 patients with lymph node metastasis after operation. RESULTS: All the 34 patients were followed up 1-10 years, with an average of 3 years. The flap was found to be necrotic by fibrolaryngoscopy at 1 week after operation in 2 cases, and the incision healed after dressing change and nutritional support, and no reoperation was performed. The flap was in good condition at 1 week after operation in 4 cases, and the signs of gradual necrosis of the flap were found within 1 month after operation, of which 2 cases were healed after dressing change, 1 case was removed the necrotic tissue by reoperation, and 1 case was healed after pectoralis major myocutaneous flap was used to repair the pharyngeal tissue defect. The flaps survived in 28 cases, including 4 cases of pharyngeal fistula, which healed by dressing change. Twenty-two cases achieved satisfactory results in swallowing or phonation. Two patients with total laryngectomy and voice reconstruction underwent reoperation to seal the voice tube because of postoperative aspiration. During the follow-up, 1 case had tracheal stomal recurrence, 2 cases had bone metastasis, and 1 case had bone and lung metastasis. CONCLUSION The free rectus femoris flap has good flexibility, the volume of the flap is easy to adjust, and the incision of the donor site is concealed, which is expected to become a new choice for the repair of the surgical defect in pharyngo-laryngeal malignant tumor.
Humans ; Male ; Middle Aged ; Female ; Aged ; Adult ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Laryngeal Neoplasms/pathology* ; Aged, 80 and over ; Pharyngeal Neoplasms/pathology* ; Free Tissue Flaps/blood supply* ; Quadriceps Muscle/transplantation* ; Surgical Wound/surgery* ; Treatment Outcome

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 investigate the clinical, cytopathological characteristics, and differential diagnosis of metastatic clear cell renal cell carcinomas (CCRCC).Methods:Nine cases of metastatic CCRCC cytologically diagnosed in the Department of Pathology, the First Affiliated Hospital of Air Force Medical University from July 2021 to December 2024 were collected. The HE staining, May-Grunewald-Giemsa staining, liquid-based slides, cell block preparation, and immunocytochemistry of EnVision two-step staining were performed. The clinical and cytopathological features, treatments and follow-up data were analyzed in combination with literature review.Results:Among the 9 cases of metastatic CCRCC, there were 7 males and 2 females. The age range was 43-78 years, and the average age was 63.6 (57.5, 72.5) years. The metastatic sites were lymph node in 3 cases (2 cases of mediastinal lymph nodes and 1 case of left cervical lymph node), bone in 3 cases (pubis, thoracic vertebrae and femur, respectively), thyroid in 2 cases, and adrenal gland, lung and pancreas in 1 case, respectively. Two of the 9 cases had two metastatic sites (case 8 had metastases of lung and mediastinal lymph nodes; case 9 had metastases of thyroid and cervical lymph nodes). The median time from the diagnosis to metastasis was 9.4 years (range 1.1 to 13.8 years). The tumor cells were arranged in papillary, acinar, sheet, cluster or single scattered pattern. Most cases had uniform nuclei with mild atypia and inconspicuous nucleoli, while some cases had variable nuclei with prominent nucleoli. The cytoplasm of the tumor cells was abundant. Some cases showed clear cytoplasm with small vacuoles, while some of them showed eosinophilic and granular cytoplasm. Immunocytochemically, the tumor cells were positive for CKpan(AE1/AE3,6/6), PAX8 (9/9), CAⅨ (9/9), CD10 (9/9), and vimiten (8/8). Patients were treated primarily with targeted therapy and/or immunotherapy and curettage and radiation therapy for bone lesions. The follow-up time ranged from 1.0 month to 41.5 months (median, 20 months), and all patients survived at the end of follow-up.Conclusions:The cytology of metastatic CCRCC often shows uniform cell size, abundant and clear cytoplasm, low nuclear/cytoplasmic ratio, and mild nuclear atypia. Its cytological diagnosis is challenging because it occurs in various sites and needs to be differentiated from primary tumors of these sites. Emphasis should be placed on the morphological recognition of CCRCC, and immunocytochemical staining should be used to improve diagnosis. When necessary, molecular testing can be employed for diagnosis. Meanwhile, the medical history should be carefully inquired by pathologists to avoid missed diagnosis and misdiagnosis.

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 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.

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.