OBJECTIVE To explore the independent risk factors of voriconazole （VCZ）-related liver injury in elderly patients with hypoproteinemia. METHODS Elderly patients with invasive fungal infection and hypoproteinemia who were hospitalized in the respiratory intensive care unit of our hospital and treated with VCZ from August 2020 to July 2023 were selected. They were divided into group A （liver injury group） and group B （non-liver injury group） based on whether the liver injury occurred after using VCZ. Pearson correlation analysis was used to analyze the correlation between minimum concentration （cmin） of VCZ and inflammatory factor[C-reactive protein （CRP）， procalcitonin （PCT）， interleukin-6 （IL-6）]， as well as liver function [alanine transaminase （ALT）， aspartate transaminase （AST）， alkaline phosphatase （ALP）， gamma-glutamyl transpeptidase （GGT）， total bilirubin （TBIL）]； univariate analysis was performed by using χ 2 test； Logistic regression analysis was used to analyze the independent risk factors affecting the occurrence of liver injury. RESULTS A total of 320 patients were included in the study， of whom 56 developed liver injury， with an incidence of 17.50%. The VCZ cmin in group A was significantly higher than group B （P＝ 0.021）. CRP， PCT， IL-6， and TBIL were correlated with VCZ cmin （P＜0.05）. CRP， PCT， IL-6， and TBIL had a significant impact on VCZ cmin （P＜0.05）. VCZ cmin， PCT， and TBIL were independent risk factors for liver injury （P＜0.05）. The patients with VCZ cmin≥3.76 mg/L had a significantly increased risk of liver injury. CONCLUSIONS VCZ cmin， PCT， and TBIL are independent risk factors for the occurrence of liver injury in elderly patients with hypoproteinemia. For patients with high PCT and TBIL， VCZ cmin and liver function should be closely monitored during VCZ treatment to reduce the risk of liver injury.

Guillain-Barré syndrome (GBS) defines a kind of Immune-mediated acute inflammatory peripheral neuropathy. Miller-Fisher Syndrome (MFS) is a special variant of GBS, with mostly one-way course and rare clinical recurrence. Only a few recurrent cases have been reported in China. Here we report a case of a young male patient with double vision and progressive aggravation of limb numbness, acute onset, with symptoms of upper respiratory tract infection before onset, accompanied by pupil abnormalities and autonomic nervous dysfunction, who was was admitted to our hospital for similar symptoms 3 years ago and was improved by immunotherapy. The patient had a triad of “ataxia, areflexia and ophthalmoplegia”. Cerebrospinal fluid showed protein-cell separation. Serum anti-Sulfatides antibody IgM, anti-GT1a antibody IgG, anti-GQ1b antibody IgG and anti-GM3 IgM were positive. Recurrent MFS was diagnosed and the symptoms improved after immunotherapy. This case suggests that MFS is clinically heterogeneous, a few patients can present with relapse and generally have a better prognosis with immunotherapy. Pre-existing infection and anti-GQ1b antibody production may be predisposing factors for MFS recurrence.

Objective:To analyze the clinical phenotype, copy number variation, treatment and follow-up characteristics of children with typical 16p11.2 deletion syndrome.Methods:The clinical data of 10 children with typical 16p11.2 deletion syndrome who were treated in the Department of Neurology, Children′s Hospital of Fudan University from August 2011 to December 2021 were retrospectively collected, and their clinical phenotype, copy number variation, treatment and follow-up were summarized.Results:Among the 10 children, 4 are female and 6 are male, all with epilepsy. Nine patients had epilepsy in infancy, and the age of onset was 6.0 (4.0, 8.5) months. Four cases had focal seizures (1 with fever), 4 had generalized tonic-clonic seizures, and 2 had focal seizures with generalized tonic-clonic seizures. Eight cases had cluster seizures (more than 2 to 10 seizures within 24 hours), and 1 case had 1 status epilepticus. Nine children did not show obvious developmental delay at the onset of epilepsy, and 1 child had developmental delay at the onset of epilepsy at 14 months of age. One child had parallel toes at left foot, and 1 had macrocephaly and low limb muscle tone. Genetic testing found that 10 children carried typical 16p11.2 heterozygous deletion, the starting position of the deletion fragment was Chr16:29478119-29675016, the ending position was Chr16:30125670-30206112, and the deletion length was 525-712 kb, all of which were considered pathogenic variants. In the antiepileptic drug treatment, 4 children were treated with oxcarbazepine, 2 with sodium valproate, 2 was switched to oxcarbazepine after levetiracetam was ineffective, 1 with levetiracetam combined with sodium valproate, and 1 with levetiracetam in combination with sodium valproate and ketogenic diet, and all 10 children had no seizures. One patient developed episodic exercise-induced dyskinesia at school age, and the seizures decreased after treatment with oxcarbazepine. Follow-up of 10 children found that 9 children had different degrees of developmental delay (language was significantly affected), 3 cases were combined with autism-like manifestations, and 1 case had poor comprehension, learning difficulties, and repeated grades after entering regular primary schools.Conclusion:The typical 16p11.2 microdeletion syndrome has the deletion of gene fragments in the proximal region of 16p11.2, characterized by drug-responsive cluster seizures with onset in infancy, which may be accompanied by language delay, autism spectrum disorder and nonspecific malformations.

Diabetic retinopathy （DR） is one of the most important microvascular complications of diabetes mellitus， which can lead to blindness in severe cases. Both traditional drug therapy and surgical treatment have certain limitations. Literature review indicates that the main pathogenesis of DR is related to inflammation and apoptosis induced by oxidative stress， and changes in growth factors， hormones， etc. Monomer of traditional Chinese medicine （chlorogenic acid）， single medicine （Panax notoginseng， Typha angustifolia， Pueraria montana root， Matrimony vine， etc.）， prescription （modified Buyang huanwu decoction and Liujunzi decoction， modified Xuefu zhuyu decoction， Simiaoyong’an decoction， etc.） and Chinese patent medicine （Ligustrazine injection， Furong tongmai capsule， Qiju dihuang pill， etc.） can provide beneficial supplement for the treatment of DR. Its mechanism of action mainly involves antioxidant， anti-inflammatory， anti-apoptosis， decreasing the expression of vascular endothelial growth factor， improving hormone levels and so on.

Background Lipid metabolism in liver shows circadian-dependent profiles. The hepatotoxicity of environmental chemicals is dependent on circadian time. Objective To observe the effects of bisphenol A (BPA) exposure at different zeitgeber time (ZT) on hepatic and blood lipid metabolism and decipher the underlying mechanisms related to circadian rhythm in mice. Methods Thirty-five female C57BL/6J mice were sacrificed every 4 h in a light-dark cycle (12 h/12 h). The liver tissues were collected to describe the circadian profiles of hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels within 24 h. Thirty female mice were divided into 6 groups by the timing (ZT3 represents the 3 h after light on, ZT15 represents the 3 h after light off) and dose (50 or 500 μg·kg⁻¹·d⁻¹) of BPA exposure to observe hepatotoxicity. Mice were gavaged with designed doses of BPA once per day for 4 weeks. Mice were maintained with ad libitum access to food and water and measured body weight weekly. After the experiment, mice were euthanatized and liver tissues were separated to determine the biochemical indicators of lipid metabolism and lipid metabolism- and circadian-related gene mRNA expressions. Results Hepatic Rev-erba, Bmal1, Clock, Srebp1c, and Chrebp mRNA expression levels were rhythmic during a 24 h period in mice. At ZT3 and ZT15, BPA did not alter body weight, plasma glucose, plasma total cholesterol, plasma low density lipoprotein cholesterol, and plasma triglycerides (P>0.05). The plasma high density lipoprotein cholesterol decreased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT3 by 14.56% compared with the control group (P<0.05). The liver triglycerides increased in the 50 μg·kg⁻¹·d⁻¹ BPA group at ZT15 by 115.20% compared with the control group (P<0.05). BPA decreased Srebp1c mRNA expression level when dosing at ZT3 and increased Chrebp, Srebp1c, and Acc1 mRNA expression levels when dosing at ZT15 compared with the control group (P<0.05). BPA increased Bmal1 mRNA expression level and decreased Rev-erbα mRNA expression level at ZT3 exposure and decreased Bmal1 and increased Rev-erbα mRNA expression level at ZT15 exposure (P<0.05). Conclusion BPA exposure at light or dark period has different effects on hepatic lipid metabolism in mice. Hepatic lipid deposit appears when BPA is dosed at dark period. Rev-erbα-Bmal1 regulation circuits and the subsequent upregulation of Srebp1c and Chrebp and the target gene Acc1 may be involved.

Although the neuropathologic changes and diagnostic criteria for the neurodegenerative disorder Alzheimer′s diseasehave been established, the clinical symptoms are very different largely.The clinical symptoms of its special type frontal lobe variant and behavioral variant frontotemporal dementia are very similar, which brings great challenges to the differential diagnosis.Therefore, we report a patient with progressive cognitive impairment, early significant executive dysfunction and abnormal behavior, and magnetic resonance imaging showed significant frontotemporal atrophy.It is easy to be misdiagnosed as behavioral variant frontotemporal dementia.However, multimodal functional neuroimaging results show that neuropathological changes are more likely to be frontal variant Alzheimer′s disease.This study shows that the use of detailed neuropsychological tests, biological markers and multimodal neuroimaging to identify these atypical syndromes will help to improve the accuracy of diagnosis and patient management.

Objective:To investigate the effects of meditation therapy on fear of disease progress and mental health among acute myocardial infarction (AMI) patients.Methods:Totally, 120 cases of acute myocardial infarction patients admitted to Affiliated Hospital of Jiangnan University were divided into experimental group and control group according to the enrolled time. 60 patients with AMI treated from June to November 2018 served as the control group and 60 patients with AMI treated from January to May 2019 served as the experimental group. The patients in the control group received routine nursing, the experimental group carried out 4-week meditation therapy based on the routine nursing. Before and after intervention, the effect was assessed by Fear of Progression Questionnaire-Short Form (FoP-Q-SF) and Symptom Checklist-90 (SCL-90), respectively.Results:After intervention, the physical health and social family function dimension scores in FoP-Q-SF as well as total FoP-Q-SF scores were (12.78±3.47), (10.45±2.44), (23.24±4.25) points, significantly lower than in the control group (14.33±2.72), (11.59±2.82), (25.91±3.89) points, the difference was statistically significant ( t values were 2.623, 2.277, 3.499, P<0.05); the scores of somatization, compulsion, anxiety, depression and total SCL-90 were (1.26±0.19), (1.42±0.23), (1.19±0.28), (1.20±0.16) and (121.81±9.59) points, significantly lower than (1.83±0.25), (1.68±0.37), (1.82±0.41), (1.71±0.33) and (145.85±9.12) points in the control group, the difference was statistically significant ( t values were from 4.580 to 13.659, P<0.001). Conclusion:Meditation therapy can effectively decrease disease progress and promote mental health in patients with acute myocardial infarction.

Objective: To analyze the epidemiological history, clinical manifestations, treatment and the short-term prognosis of 31 cases of 2019 novel coronavirus(2019-nCoV) infection in children from six provinces (autonomous region) in northern China. Methods: A retrospective analysis of the epidemiological history, clinical symptoms, signs, laboratory examinations, chest imaging, treatment and the short-term prognosis of 31 cases of 2019-nCoV was conducted. The patients were diagnosed between January 25th, 2020 and February 21st, 2020 in 21 hospitals in 17 cities of six provinces(autonomous region) of Shaanxi, Gansu, Ningxia, Hebei, Henan and Shandong. Results: The age of the 31 children with 2019-nCoV infection was 7 years and 1 month (6 months -17 years). Nine cases (29%) were imported cases. Other 21 cases (68%) had contact with confirmed infected adults. One case (3%) had contact with asymptomatic returnees from Wuhan. Among the 31 children, 28 patients (90%) were family cluster cases. The clinical types were asymptomatic type in 4 cases (13%), mild type in 13 cases (42%), and common type in 14 cases (45%). No severe or critical type existed. The most common symptom was fever (n=20, 65%), including 1 case of high fever, 9 cases of moderate fever, 10 cases of low fever. Fever lasted from 1 day to 9 days. The fever of fifteen cases lasted for ≤3 d, while in other 5 cases lasted > 3 d. Other symptoms included cough (n=14, 45%), fatigue (n=3, 10%) and diarrhea (n=3, 9%). Pharyngalgia, runny nose, dizziness, headache and vomiting were rare. In the early stage, the total leukocytes count in peripheral blood decreased in 2 cases (6%), the lymphocytes count decreased in 2 cases (6%), and the platelet count increased in 2 cases (6%).Elevation of C-reactive protein (10%, 3/30), erythrocyte sedimentation rate(19%,4/21), procalcitonin(4%,1/28), liver enzyme(22%, 6/27) and muscle enzyme (15%, 4/27) occurred in different proportions. Renal function and blood glucose were normal. There were abnormal chest CT changes in 14 cases, including 9 cases with patchy ground glass opacities and nodules, mostly located in the lower lobe of both lungs near the pleural area. After receiving supportive treatment, the viral nucleic acid turned negative in 25 cases within 7-23 days. Among them, 24 children (77%) recovered and were discharged from hospital. No death occurred. Conclusions In this case series, 2019-nCoV infections in children from six provinces (autonomous region) in northern China are mainly caused by close family contact. Clinical types are asymptomatic, mild and common types. Clinical manifestations and laboratory examination results are nonspecific. Close contact history of epidemiology, nucleic acid detection and chest imaging are important bases for diagnosis. After general treatment, the short-term prognosis is good.

Objective: To explore refractive development of primary school students in Jinshan district of Shanghai during the past five years. Methods: A total of 201 first grade pupils enrolled in 2013 were followed up for 5 years. Annual examination of non-cycloplegic refraction and axial length (AL) was implemented and analyzed. Results: The mean spherical equivalents (SEs) of boys at each grade was (0.22±0.53)(-0.04±0.64)(-0.36±0.92)(-0.74±1.23)(-1.14±1.67)D, respectively; for girls, (0.26±0.88)(-0.03±1.02)(-0.28±1.02)(-0.64±1.32)(-1.13±1.65)D, respectively. The mean ALs of boys at each grade was (22.94±0.60)(23.13±0.68)(23.45±0.69)(23.65±0.81)(24.03±0.93)mm, respectively and was (22.40±0.67)(22.67±0.70)(22.95±0.74)(23.14±0.79)(23.59±0.90)mm for girls at each grade, respectively. There were negative correlations between dioptres and ALs in each grade(r=-0.26, -0.35, -0.41, -0.53, -0.59, P<0.05). Conclusion The dioptre and AL among primary school students in Jinshan district of Shanghai increased gradually and results in developing into myopia. The dioptre negatively associates with AL, which should be both paid attention to among primary school students.

Objective: To investigate the radiographic manifestations and clinical relevance to central nervous system complications of leukemia (CNSCL)in children. Methods: The CT and magnetic resonance imaging(MRI) fin-dings and clinical features of 49 pediatric patients with CNCSL in Shanghai Children′s Medical Center Affiliated to Shanghai Jiaotong University School of Medicine from May 2010 to June 2018 were retrospectively analyzed. Results: (1) Cerebrovascular abnormalities in 23 cases included hemorrhage(20 cases), infarction(2 cases) and sinus thrombosis(1 case). One case of epidural hematoma and 19 cases of intracerebral multiple bleeding were seen in the hemorrhage group, which demonstrated high-density on CT and different signal on MRI as time went by.Microhe-morrhage displayed as low signal on susceptibility weighted imaging.(2) Among 23 cases of leukemic infiltration, the dura and/or skull were involved in 18 cases, which presented as fusiform or mass, with high density on CT, low signal on T1WI, intermediate signal on T2WI and strong enhancement; 6 leptomeningeal infiltration demonstrated as meningeal thickening and enhancement; 2 parenchymal involvement manifested with high-density mass; 2 oculomotor nerve and 1 optic nerve infiltration demonstrated thickening and enhancement.(3)White matter disease was seen in 2 cases, with hyper-intensity on T2WI.(4) One case of secondary tumor was glial tumor in the brainstem. Conclusions The radiographic manifestations of CNCSL in children are various.CT and MRI are of important diagnostic values.Choosing the best imaging examination method and sequence according to clinical symptoms and test results can provide more valuable information for clinical diagnosis and treatment.