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.

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.

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 introduce the formulation and effect evaluation of performance appraisal scheme for pharmacists in comprehensive pharmacy.Methods A comprehensive evaluation method formulated by critical event method and grade scoring method was adopted to evaluate the workload,work ability,learning ability,and work discipline.Results From September 2022 to August 2023,the average score of monthly pharmacist assessment increased from 73.9 to 87.9,the satisfaction rate increased from(7.5±1.52)to(11.5±2.66)(P＜0.05),and the number of patients with drug consultation increased from 5 cases to 61 cases.Conclusion The performance appraisal scheme can significantly improve the work ability and enthusiasm of pharmacists.

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