Objective:To study the phenotypes and genotypes of neonatal nonketotic hyperglycinemia (NKH).Methods:A neonate with severe NKH admitted to our hospital was retrospectively analyzed. Using keywords 'glycine cleavage enzyme', 'glycine decarboxylase', 'nonketotic hyperglycinemia' and 'glycine encephalopathy' (both in Chinese and English), multiple medical databases were searched until December 31, 2022. The clinical phenotypes and genotypes of neonatal NKH were summarized.Results:For our case, the neonate was lethargy and had no appetite on the second day of life, followed by recurrent seizures and irregular breathing, requiring mechanical ventilation. She died at 3 weeks of age. Two compound heterozygous variants were found in GLDC gene from whole exome sequencing , one was c.848C>G(p.A283G) of maternal origin and one was c.1607G>A(p.R536Q) of paternal origin. The former was a novel mutation. A total of 54 cases (including this case) were collected. The main clinical manifestations included poor feeding, decreased muscle tone, hiccups, progressive lethargy, irregular breathing, apnea and neonatal seizures. 42 cases (77.8%) had GLDC gene mutations, 9 cases (16.7%) had AMT gene mutations, 2 cases (3.7%) had LIAS gene mutations and 1 case (1.9%) had GCSH gene mutations. Conclusions:Neurological manifestations are most common in neonatal NKH with wide clinical variations. GLDC gene mutations are the predominant pathogenic mutations.

Humans ; Stroke/therapy* ; Thrombectomy ; Treatment Outcome ; Brain Ischemia/therapy* ; Retrospective Studies

Objective:To prepare a phase-change lipid nanoparticle modified by tumor homing membrane-penetrating peptide (tLyP-1) and carrying paclitaxel (PTX) engineered by metal polyphenol network (TA-Fe 3+ ), and evaluate the therapeutic effects of tumor targeting, ultrasound/photoacoustic imaging and photothermal combined chemotherapy in vitro. Methods:Phase-change lipid nanoparticles (t-P@TFP) with TA-Fe 3+ engineered PTX mediated by tLyP-1 were prepared by solvent replacement method, thin film hydration method and double emulsification method. Its detection and characterization, in vitro targeting ability, photothermal conversion ability, in vitro photoacoustic and ultrasonic imaging ability, CCK-8 method, cell live and death double staining method and flow cytometry method were used to detect the safety of nanoparticles and the killing effects of different nanoparticles on 4T1 cells. Results:t-P@TFP nanoparticles were successfully prepared. Transmission electron microscopy showed that the nanoparticles were spherical with uniform shape and size, with a particle size of (209.8±1.56)nm and a potential of (-25.9±1.36)mV. Laser confocal scanning microscopy showed that t-P@TFP nanoparticles could gather around 4T1 cells in a targeted manner. It had an efficient photothermal conversion effect, and nanoparticles could quickly become microbubbles after being irradiated by near-infrared laser, which enhanced the in vitro ultrasonic imaging effect; The photoacoustic signal of nanoparticles increased with the increase of concentration. CCK-8 method, double staining of living and dead cells and flow cytometry showed that t-P@TFP combined photothermal chemotherapy had the best anti-tumor effect. Conclusions:t-P@TFP nanoparticles are successfully prepared. The nanoparticles have good targeting ability for photoacoustic and ultrasonic imaging and have good photothermal effect, killing breast cancer cells, which is expected to realize the integration of diagnosis and treatment.

Objective:To construct an extended care programme for type 2 diabetes patients based on the App and "hospital-community-family" linkage.Methods:Through literature review and qualitative interviews, an extended care programme for type 2 diabetes patients based on the App "Hospital-community-family" linkage was initially constructed, and two rounds of expert consultation were used to evaluate the usability and adjust the program.Results:This extended care program is led by a diabetes specialist nurse, mediated by a diabetes App, and based on the mechanism of "hospital-community-family" linkage. The intervention included two stages: establishment of patient health records, comprehensive assessments, discharge plan formulation, discharge referrals before discharge, and health monitoring and reminders, health education and consultation, health follow-up, health assessment, consultation and referral after discharge.Conclusion:The construction process of this protocol is scientific and feasible, which can realize continuous and personalized management of patients and promote "integration of resources and complementary advantages".

Objective:To understand the continuing care needs of patients based on the App and "hospital-community-home" linkage.Methods:With descriptive qualitative research, a semi-structured in-depth interview was conducted in 15 patients with type 2 diabetes in Gongli Hospital, Pudong New Area, Shanghai City, and community hospital from January to February 2020. Thematic analysis and the software NVivo 10.0 were used for data analysis.Results:Five themes were extracted: desire a "hospital-led,community-implemented, family-supported" model of continuing care; desire an appropriate, convenient and personalized access to information and follow-up; expect continuous, comprehensive, professional health guidance; expect to receive continuing care service led by specialized nurses and managed by multidisciplinary team; expect diabetes App to be simple and practical, satisfying various needs such as post-hospitalization condition monitoring, assessment feedback, health education and health intervention,ensure information security and free use.Conclusions:Patients have a strong willingness to receive continuing care based on the App and "hospital-community-family" linkage. A mechanism of "hospital-community-family" linkage continuing care service with clear division of labor should be established, multidisciplinary cooperation should be strengthened, and team advantages should be utilized. Providing comprehensive, professional and evidence-based continuing care services for patients, while further optimizing software functions and focusing on information security construction and following evidence-based guidelines to standardize App content in order to adapt to more patient characteristics and needs.

Objective    By applying the mutual corroboration in the diagnosis, we aimed to improve the accuracy of preoperative imaging diagnosis, select the appropriate timing of operation and guide the follow-up time for patients with pulmonary nodules. Methods    Clinical data of 1 368 patients with pulmonary nodules undergoing surgical treatment in our department from July 2016 to October 2019 were summarized. There were 531 males and 837 females at age of 44 (21-67) years. The intraoperative findings, images and pathology were classified and analyzed. The imaging pathology and pathological changes of pulmonary nodules were shown as a dynamic process through mutual collaboration and interaction. Results    Of 1 368 patients with pulmonary nodules, 376 (27.5%) were pure ground-glass nodules, 729 (53.3%) were mixed ground-glass nodules and 263 (19.2%) were solid nodules. Among the pure ground-glass nodules, adenocarcinoma in situ (AIS) accounted for the highest proportion (156 patients), followed by microinvasive adenocarcinoma (MIA, 90 patients), atypical adenomatous hyperplasia (AAH, 85 patients), and benign tumors (20 patients). Among mixed ground-glass nodules, 495 patients were invasive adenocarcinoma (IA) and 207 patients of MIA. no patient was featured by AAH, AIS or MIA. Conclusion    The mutual collaboration and interaction can improve the accuracy of preoperative diagnosis of pulmonary nodules, and it supports the choice of operation timing and the judgment of follow-up time.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular event that often is followed by permanent brain impairments. It is necessary to explore the pathogenesis of secondary pathological damages in order to find effective interventions for improving the prognosis of SAH. Blockage of brain lymphatic drainage has been shown to worsen cerebral ischemia and edema after acute SAH. However, whether or not there is persistent dysfunction of cerebral lymphatic drainage following SAH remains unclear. In this study, autologous blood was injected into the cisterna magna of mice to establish SAH model. One week after surgery, SAH mice showed decreases in fluorescent tracer drainage to the deep cervical lymph nodes (dcLNs) and influx into the brain parenchyma after injection into the cisterna magna. Moreover, SAH impaired polarization of astrocyte aquaporin-4 (AQP4) that is a functional marker of glymphatic clearance and resulted in accumulations of Tau proteins as well as CD3⁺, CD4⁺, and CD8⁺ cells in the brain. In addition, pathological changes, including microvascular spasm, activation of glial cells, neuroinflammation, and neuronal apoptosis were observed in the hippocampus of SAH mice. Present results demonstrate persistent malfunction of glymphatic and meningeal lymphatic drainage and related neuropathological damages after SAH. Targeting improvement of brain lymphatic clearance potentially serves as a new strategy for the treatment of SAH.
Animals ; Apoptosis ; Aquaporin 4 ; Astrocytes ; Brain ; Brain Ischemia ; Cisterna Magna ; Drainage ; Edema ; Hippocampus ; Lymph Nodes ; Mice ; Neuroglia ; Neurons ; Prognosis ; Spasm ; Subarachnoid Hemorrhage ; tau Proteins

Objective: To investigate the clinical features, treatment strategies and long term outcomes of children with anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis. Methods: The data of clinical features, auxiliary examinations, treatments and prognosis in children with anti-NMDAR encephalitis in Xiangya Hospital of Central South University from March 2014 to October 2017 were collected and retrospectively analyzed. A total of 71 patients were enrolled, including 33 males and 38 females. The youngest age of onset was 4 months old, and the age of onset was (9±4) years. The first-line immunotherapy treatment for anti-NMDAR encephalitis was short course corticosteroid (high-dose impulse therapy and oral maintenance therapy for 1 month in acute period) and (or) immunoglobulin. The clinical evaluation was performed 2 weeks after first-line immunotherapy treatment. The second-line immunotherapy treatment, including rituximab and (or) cyclophosphamide, would be started if the symptoms did not improve significantly and the modified Rankin scale (mRS) score ≥3. All patients were followed up and evaluated for prognosis. T-test, Mann-Whitney U, Chi square test and Fisher′s exact probability method were used for comparison between good outcome group and poor outcome group, first-line immunotherapy group and first-line immunotherapy combined with second-line immunotherapy group. Results: The more common clinical manifestations were psychiatric symptoms (n=61, 86%), dyskinesia (n=55, 77%) and convulsions (n=51, 72%). Two cases (3%) had tumors. Electroencephalogram (EEG), cerebro-spinal fluid (CSF) and brain magnetic resonance imaging (MRI) studies were abnormal in 83% (59/71), 39% (27/69) and 38% (27/71) patients, respectively. For the treatment regimens, all the 71 patients underwent first-line immunotherapy, resulting in improvement within 14 days in 40 cases (56%), and 1 case (1%) died. The rest 30 cases (42%) received second-line immunotherapy. The patients were followed up for 5.0-41.8 months, with a median of 19.3 months. At the last follow-up, 49 cases (69%) recovered completely, 15 cases (21%) had mild disability, 6 cases (8%) had severe disability, 1 case (1%) died and 3 cases (4%) had relapse. There were significant differences between the groups with good prognosis and poor prognosis on admission to pediatric intensive care unit (PICU) and consciousness disorder (10/64 vs. 5/7, 39/64 vs. 7/7, P=0.047, 0.004). There were significant differences between first-line immunotherapy group and the first-line combined second-line immunotherapy group on admission to PICU, consciousness disorder, sleep disorder and first mRS score (12% (5/41) vs. 33% (10/30), 44% (18/41) vs. 93% (28/30), 56% (23/41) vs. 90% (27/30), 3 (1-5) vs. 4 (3-5), respectively; χ²=4.645, 18.555, 9.560, Z=5.184, P=0.031, <0.01, 0.002, <0.01, respectively). Conclusions Anti-NMDAR encephalitis can occur in all ages of children. The most common clinical manifestations are psychotic symptoms, dyskinesia and convulsions. Paraneoplastic cases are less common in children. Immunotherapy is effective. The second-line immunotherapy should be given after the failure of first-line therapy (mRS score≥3).

Objective: To investigate the effect of hypertensive disorder complicating pregnancy (HDCP) on the mortality and early complications of premature infants. Methods: The general clinical data of preterm infants with gestational age 24-36^{+ 6} weeks were collected from the cooperative units in the task group from January 1, 2013 to December 31, 2014.According to the severity of HDCP, the infants were divided into 4 groups: HDCP group, preeclampsia group, eclampsia group and non HDCP group, the mortality and major complications of preterm infants were compared, and the influencing factors were analyzed. Results: The mortality rate of preterm in the HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=9.970, P=0.019). Eclampsia had a highest fatality rate (4.8%) in the early stage, compared with non HDCP group (2.2%), and the difference was statistically significant.Comparison of HDCP group (1.8%) and eclampsia group (3.2%) suggested that there was no statistically significant difference.The incidence of respiratory distress syndrome (RDS) in preterm in HDCP group was significantly higher than that of non HDCP group, and there was statistical significance (χ²=13.241, P=0.004). Eclampsia group showed the highest incidence (35.4%), compared with non HDCP group (16.2%), the difference was statistically significant, but compared with HDCP group (19.9%), preeclampsia group (17.1%), there was no significant diffe-rence.The incidence of bronchopulmonary dysplasia (BPD) in preterm in HDCP group was significantly higher than that of non HDCP group (χ²=9.592, P=0.022), the highest incidence showed up in eclampsia group (9.7%), compared with non HDCP group (2.0%) and HDCP group (1.7%), the difference was statistically significant.But there was no statistically significant difference, compared with preeclampsia group.As the degree of HDCP aggravated, the incidence of BPD gradually rose.There was no significant impact on necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), intraventricular hemorrhage (IVH) and sepsis of HDCP (χ²=7.054, 7.214, 0.358, 3.852; P=0.070, 0.065, 0.949, 0.278). Considering the overall outcome of the child, that was, whether the child died or survived, he had at least one complication, and HDCP had an effect on it (χ²=15.697, P=0.001), so the incidence increased while the degree of HDCP rose gradually.After adjusting gestational age, birth weight, sex, way of delivery, placental abruption and front placenta, prenatal hormonal, gestational diabetes, neonatal asphyxia and other factors, the results displayed that HDCP was the factor leading to the death of premature baby (OR=2.159, 95%CI: 1.093-4.266), and comparison between preeclampsia and eclampsia showed no statistical difference (P=0.714, 0.389); HDCP had no significant influence on RDS, BDP, ICH, NEC, ROP and sepsis. Conclusions HDCP leads to increased risk of premature death, but also leads to the increased incidence of RDS and BPD, but it had no obvious effect on NEC, ROP, IVH, sepsis and other complications.

Objective To investigate the precipitating factors,clinical manifestations,magnetic resonance imaging (MRI) features and prognoses of children with posterior reversible encephalopathy syndrome (PRES) during the treatment of hematological diseases,and to improve the understanding of the diseases.Methods A total of 9 children with PRES,admitted to our hospital from January 2012 to December 2016,were chosen.The clinical data,including precipitating factors,clinical manifestations,MRI features and prognoses,were retrospectively analyzed.Results (1) Precipitating factors:6 patients with acute lymphoblastic leukemia occurred PRES during remission induction therapy (6/9,66.7％) and 3 occurred PRES during oral cyclosporine A after hematopoietic stem cell transplantation or autoimmune diseases (3/9,33.3％).(2) Clinical manifestations:all of them were acute onset,and the main symptoms were seizures (8/9,88.9％) and hypertension (7/9,77.8％);some patients suffered from headache,vomiting,visual disturbances,disturbance of consciousness and poor mental symptoms.(3) Features of head MR imaging:the lesions were mainly located in the parietal-occipital lobe,showing patchy long T1 and long T2 signals,and bilateral imperfect symmetry;FLAIR imaging showed high signal distinctly,and other parts of brain could also been involved in.(4) Prognoses:7 children (77.8％) recovered well,one (11.1％) left frequent seizures during 2 years of follow up,one (11.1％) left mental retardation.Conclusion Methotrexate,cyclosporine A and other agents are important incentives in children with PRES during the treatment of hematological diseases;seizures and hypertension are the main clinical manifestations;MR imaging is important in diagnosing the disease;and PRES is not completely reversible.