A 19-year-old male patient with a history of congenital left oval window defect has had recurrent admissions to a children’s hospital for bacterial meningitis since the age of 7. Investigations revealed a left-sided type 1 incomplete partition deformity of the left ear with a congenital oval window defect, leading to communication between the cranium and the middle ear. The patient underwent a left canal wall down mastoidectomy and oval window defect repair, remaining well for 3 years. He experienced two more episodes of bacterial meningitis as he got older, prompting repeated exploratory tympanotomy and repair of the cerebrospinal fluid (CSF) leak after each episode. Recently, he was referred again for recurrent meningitis. Investigations showed a recurrent oval window defect. After undergoing left external ear canal transection, mastoid and middle ear obliteration, and left Eustachian tube obliteration, he remained well without further leaks or meningitis. Congenital oval window defect is rare and may present with recurrent bacterial meningitis secondary to spontaneous CSF leak via the oval window. Radiology plays a crucial role in identifying the source of the CSF leak, facilitating more precise preoperative counseling and surgical intervention.

A 19-year-old male patient with a history of congenital left oval window defect has had recurrent admissions to a children’s hospital for bacterial meningitis since the age of 7. Investigations revealed a left-sided type 1 incomplete partition deformity of the left ear with a congenital oval window defect, leading to communication between the cranium and the middle ear. The patient underwent a left canal wall down mastoidectomy and oval window defect repair, remaining well for 3 years. He experienced two more episodes of bacterial meningitis as he got older, prompting repeated exploratory tympanotomy and repair of the cerebrospinal fluid (CSF) leak after each episode. Recently, he was referred again for recurrent meningitis. Investigations showed a recurrent oval window defect. After undergoing left external ear canal transection, mastoid and middle ear obliteration, and left Eustachian tube obliteration, he remained well without further leaks or meningitis. Congenital oval window defect is rare and may present with recurrent bacterial meningitis secondary to spontaneous CSF leak via the oval window. Radiology plays a crucial role in identifying the source of the CSF leak, facilitating more precise preoperative counseling and surgical intervention.

A 19-year-old male patient with a history of congenital left oval window defect has had recurrent admissions to a children’s hospital for bacterial meningitis since the age of 7. Investigations revealed a left-sided type 1 incomplete partition deformity of the left ear with a congenital oval window defect, leading to communication between the cranium and the middle ear. The patient underwent a left canal wall down mastoidectomy and oval window defect repair, remaining well for 3 years. He experienced two more episodes of bacterial meningitis as he got older, prompting repeated exploratory tympanotomy and repair of the cerebrospinal fluid (CSF) leak after each episode. Recently, he was referred again for recurrent meningitis. Investigations showed a recurrent oval window defect. After undergoing left external ear canal transection, mastoid and middle ear obliteration, and left Eustachian tube obliteration, he remained well without further leaks or meningitis. Congenital oval window defect is rare and may present with recurrent bacterial meningitis secondary to spontaneous CSF leak via the oval window. Radiology plays a crucial role in identifying the source of the CSF leak, facilitating more precise preoperative counseling and surgical intervention.

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Objective In this study,Knoevenagel derivatives of curcumin were synthesized,and their oil-water partition coefficient were determined.Our aim is to provide an experimental basis for further development of curcumin derivatives.Methods Two Knoevenagel derivatives of curcumin,including 4-(thiophen-2-ylidene)curcumin(3a)and 4-(pyridine-4-ylidene)curcumin(3b),were obtained by using the methylene group of curcumin as the modification site and purified by column chromatography.The structures of these derivatives were confirmed by nuclear magnetic resonance spectroscopy(NMR),infrared(IR)and high-resolution liquid mass spectrometry(HRLC-MS).The oil-water partition coefficient of the derivatives in n-octanol aqueous solution was determined by quantitative analysis using HPLC.Results Knoevenagel derivatives of curcumin were successfully synthesis.The oil-water partition coefficients(lgPap)of curcumin derivatives 3a and 3b are 0.96 and 0.82,respectively.Compared with the oil-water partition coefficient of curcumin(lgPap=3.85),it suggested that curcumin derivatives showed better water solubility than curcumin.Conclusion Compared to the curcumin prototype,Knoevenagel derivatives of curcumin increased water solubility and improved bioavailability.Thus,it may provide experimental basis for introducing heteroarylene moiety of the methylene position of curcumin to enhance pharmacological activity.

Objective:To analyze and evaluate the equity of children's health in countries along the"the Belt and Road",promote further attention to children's health in countries along the route,and promote cooperation and exchanges on children's health between China and countries along the"the Belt and Road".Methods:Using concentration index and concentration curve to measure overall equity,and using the Thiel index for intraregional and interregional euqity measurement.Results:The under-five mortality concentration index is 0.349 7,the concentration curve is below the absolute fair line.The Thiel index shows that inequality in low-income countries,lower-middle-income countries,upper-middle-income countries and high-income countries is the leading cause of child health inequities in the"the Belt and Road"countries.Conclusion:There is inequity in the health of children in countries along"the Belt and Road Initiative",countries along the"the Belt and Road"should take comprehensive measures to reduce the under-five mortality rate,at the same time strengthen international cooperation to further promote equity in children's health in"Belt and Road"countries.

OBJECTIVE To evaluate the levels of evidence and analyze the rationality for off-label use of tacrolimus in the kidney diseases in adults. METHODS By systematically reviewing the drug instructions, clinical guidelines and medical literature of tacrolimus in the kidney diseases in adults, screening the highest level of evidence, and an evaluation table based on evidence-based medical for off-label use of tacrolimus in the kidney diseases in adults was established. Based on the evaluation table, collect adult patients from the Department of Nephrology in Zhongda Hospital Southeast University who had a medication history of off-label use of tacrolimus from January 1, 2021 to December 31, 2022, and evaluated the rationality of application for tacrolimus. RESULTS A total of 19 indications for off-label use of tacrolimus in the kidney diseases in adults were listed, and their recommended levels were determined based on evidence. Among them, the recommended levels for common types of kidney diseases were higher. In addition, 194 adult patients with off-label use of tacrolimus were selected from the Department of Nephrology in Zhongda Hospital Southeast University, and their application recommended levels with "strongly recommended""moderately strongly recommended""weakly recommended" and "not recommended", were 67.0%, 12.9%, 15.0% and 5.1%, respectively. CONCLUSION Tacrolimus has a wide range of indications for off-label use in the kidney diseases in adults, but the evidence for most common types of kidney diseases are relatively sufficient and their use are reasonable.

Abstract Allergic diseases can occur in all systems of the body, covering the whole life cycle, from children to adults and to old age, can be lifelong onset and even fatal in severe cases. Children account for the largest proportion of the victims of allergic disease, Children s allergies start from scratch, ranging from mild to severe, from less to more, from single to multiple systems and systemic performance, so the prevention and treatment of allergic diseases in children is of great importance, which can not only prevent high risk allergic conditions from developing into allergic diseases, but also further block the process of allergy. At present, there is no consensus on the management system of allergic children in kindergartens and primary schools. The "Consensus on Allergy Management and Prevention in Kindergartens and Primary Schools", which includes the organizational structure, system construction and management of allergic children, provides evidence informed recommendations for the long term comprehensive management of allergic children in kindergartens and primary schools, and provides a basis for the establishment of the prevention system for allergic children.

Microglial surveillance plays an essential role in clearing misfolded proteins such as amyloid-beta, tau, and α-synuclein aggregates in neurodegenerative diseases. However, due to the complex structure and ambiguous pathogenic species of the misfolded proteins, a universal approach to remove the misfolded proteins remains unavailable. Here, we found that a polyphenol, α-mangostin, reprogrammed metabolism in the disease-associated microglia through shifting glycolysis to oxidative phosphorylation, which holistically rejuvenated microglial surveillance capacity to enhance microglial phagocytosis and autophagy-mediated degradation of multiple misfolded proteins. Nanoformulation of α-mangostin efficiently delivered α-mangostin to microglia, relieved the reactive status and rejuvenated the misfolded-proteins clearance capacity of microglia, which thus impressively relieved the neuropathological changes in both Alzheimer's disease and Parkinson's disease model mice. These findings provide direct evidences for the concept of rejuvenating microglial surveillance of multiple misfolded proteins through metabolic reprogramming, and demonstrate nanoformulated α-mangostin as a potential and universal therapy against neurodegenerative diseases.

Objective:To investigate the correlations of endoscopic evaluation results with laboratory indices and clinical disease activity in Crohn disease (CD) patients with different intestinal involvement.Methods:Data of 147 patients diagnosed as having CD who visited the Department of Gastroenterology, Zhongnan Hospital of Wuhan University from July 1, 2017 to June 30, 2022 were collected retrospectively. According to the involvement of intestinal segment, patients were divided into three groups: the group with isolated small intestinal involvement ( n=55), the group with both small intestinal and large intestinal involvement ( n=48), and the group with isolated large intestinal involvement ( n=44). Correlations of endoscopic evaluation (based on CDEIS) with laboratory indices and clinical disease activity (based on Harvey-Bradshaw index) were analyzed. Results:C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) could be used for the prediction of endoscopic disease activity. The areas under curve (AUC) of receiver operator characteristic (ROC) were 0.677 (0.506-0.849) and 0.744 (0.597-0.890), respectively. In terms of determing clinical disease activity, clinical Harvey-Bradshaw index was consistent with endoscopic CDEIS score in 65.3% (96/147) patients, showing a low positive correlation ( r=0.260, P<0.05). In subgroup analysis for patients with isolated small intestinal involvement, CRP showed no predictive value for clinical disease activity [AUC (95% CI): 0.617 (0.461-0.773), P=0.148], while for endoscopic activity neither CRP nor ESR showed predictive value [AUC (95% CI): 0.537 (0.146-0.929), P=0.829; AUC (95% CI): 0.571 (0.153-0.990), P=0.680]. Furthermore, for patients with isolated small intestinal involvement and both small intestinal and large intestinal involvement, no correlation was found between clinical Harvey-Bradshaw index and endoscopic CDEIS score ( r=0.222, P=0.092; r=0.142, P=0.322). Conclusion:For CD patients with small intestinal involvement, especially isolated small intestinal involvement, laboratory indices and clinical disease activity cannot accurately reflect endoscopic disease activity. Great importance should be attached to evaluation of the extent and activity of intestinal lesions by endoscopy, especially enteroscopy.