[Clinical analysis of 9 children with refractory N-methyl-D-aspartate receptor antibody encephalitis children treated with tocilizumab].

Objective: To analyze the clinical features of children with refractory N-methyl-D-aspartate (NMDA) receptor antibody encephalitis treated with tocilizumab. Methods: Demographic and clinical manifeatations, immunotherapy and prognosis data of 9 children with refractory NMDA receptor antibody encephalitis who received tocilizumab in the Department of Pediatrics Neurology, XiangYa Hospital of Central South University from August 2021 to September 2023 were collected retrospectively. Prognosis was evaluated using the modified Rankin scale at initial diagnosis, at the initiation of tocilizumab treatment, and at the last follow-up. Treatment related complications, neuroimaging, and electroencephalography data were analyzed. Results: Among the 9 children, 6 were male and 3 were female, with an onset age of 4.2 (2.8, 8.7) years. At the onset of the disease, 9 children had a modified Rankin scale score of 5. When tocilizumab treatment was initiated, 7 children had a score of 5, and 2 children had a score of 4. The interval between the onset and initiation of tocilizumab treatment was 12 (5, 27) months, and the treatment frequency was 8 (5, 13) times. The follow-up time was 2.8 (1.5, 3.7) years. At the last follow-up, the symptoms of 9 children, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction, were improved to varying degrees, and none of them had seizures. At the last follow-up, 4 cases with a modified Rankin scale score of 0, 1 case with a score of 1, 2 cases with a score of 3, 1 case with a score of 4 and 1 case with a score of 5. The modified Rankin scale at the last follow-up was significantly different from that at the start of tocilizumab (Z=-2.56, P=0.014). All children had no serious adverse reactions during the treatment. Conclusions: After treatment with tocilizumab, the symptoms in patients with refractory NMDA receptor antibody encephalitis, including movement disorder, sleep disorder, consciousness disorder, silence and autonomic dysfunction were improved, and none of them had seizures. The modified Rankin scale were improved, and the safety was good.

Interventions to promote the implementation of pressure injury prevention measures in nursing homes: A scoping review.

AIMS: To identify studies and the content of the interventions that have facilitated the implementation of pressure injury (PI) prevention measures in nursing home settings. DESIGN AND METHOD: A scoping review methodology was employed. The author has carried out the following steps successively: Identified this scoping review's questions, retrieved potentially relevant studies, selected relevant studies, charted the data, summarised the results, and consulted with stakeholders from nursing homes in China. DATA SOURCES: Six electronic databases and three resources of grey literature-PubMed, CINAHL, Web of Science Core Collection, Embase, Cochrane Central Register of Controlled Trials, Psych INFO, Open Grey, MedNar, ProQuest Dissertations, and Theses Full Texts were searched from January 2002 through May 2022. RESULTS: Forty articles were included, among which the primary interventions were quality improvement, training and education, evidence-based practice, device-assisted PI prophylaxis, nursing protocols, and clinical decision support systems. Twenty-three outcome indicators were summarised in 40 articles, which included 10 outcome indicators, seven process indicators, and six structural indicators. Furthermore, only five articles reported barriers in the process of implementing interventions. CONCLUSION: The common interventions to promote the implementation of PI prevention measures in nursing homes are quality improvement, training, and education. Relatively limited research has been conducted on evidence-based practice, clinical decision support systems, device-assisted PI prophylaxis, and nursing protocols. In addition, there is a paucity of studies examining the impediments to implementing these measures and devising targeted solutions. Therefore, it is recommended that future studies include analysis and reporting of barriers and facilitators as part of the article to improve the sustainability of the intervention. IMPACT: This article reminds nursing home managers that they should realise the importance of implementation strategies between the best evidence of PI prevention and clinical practice. Also, this review provides the types, contents, and outcome indicators of these strategies for managers of nursing homes to consider what types of interventions to implement in their organisations. TRIAL AND PROTOCOL REGISTRATION: The protocol of this scoping review was published as an open-access article in June 2022 (Yang et al., 2022).

[Efficacy of fenestrated atrial septal defect occulders on pulmonary hypertension dogs].

Objective: To explore the short-term efficacy of fenestrated atrial septal defect (ASD) occulders in the treatment of pulmonary arterial hypertension (PAH). Methods: Thirty-six healthy dogs were divided into the balloon atrial septostomy (BAS)+fenestrated ASD occulders group (n=12), BAS group (n=12) and non-septostomy group (n=12). PAH was induced by intra-atrial injection of dehydrogenized monocrotaline (1.5 mg/kg) in all dogs. Animals in the BAS+fenestrated ASD occulders group underwent atrial septal puncture and fenestrated ASD occulders implantation. Animals in the BAS group underwent balloon atrial septostomy. The non-septostomy group received no surgical intervention. The hemodynamic indexes and blood N-terminal pro-B-type natriuretic peptide (NT-proBNP) of dogs were measured before modeling, 2 months after modeling, 1, 3, and 6 months after surgery, respectively. Echocardiography was performed to observe the patency of the shunt and atrial septostomy of the dogs in the BAS+fenestrated ASD occulders group and BAS group at 1, 3, and 6 months after surgery. Three dogs were sacrificed in each group at 1, 3, and 6 months after surgery, respectively. Atrial septal tissue and fenestrated ASD occulders were removed to observe the patency and endothelialization of the device. Lung tissues were obtained for hematoxylin-eosin (HE) staining to observe the inflammatory cells infiltration and the thickening and narrowing of the pulmonary arterials. Results: Among 36 dogs, 2 dogs died within 24 hours after modeling, and 34 dogs were assigned to BAS+fenestrated ASD occulders group (n=12), BAS group (n=11), and non-septostomy group (n=11). Compared with BAS group, the average right atrial pressure (mRAP) and NT-proBNP of dogs in the BAS+fenestrated ASD occulders group were significantly reduced at 3 months after surgery (P<0.05), and the cardiac output (CO) was significantly increased at 6 months after surgery, arterial oxygen saturation (SaO2) was also significantly reduced (P<0.05). Compared with non-septostomy group, dogs in the BAS+fenestrated ASD occulders group had significantly lower mRAP and NT-proBNP at 1, 3, and 6 months after surgery (P<0.05), and higher CO and lower SaO2 at 6 months after surgery (P<0.05). Compared with the non-septostomy group, the dogs in the BAS group had significantly lower mRAP and NT-proBNP at 1 month after surgery (P<0.05), and there was no significant difference on mRAP and NT-proBNP at 3 and 6 months after surgery (P>0.05). Echocardiography showed that there was a minimal right-to-left shunt in the atrial septum in the BAS group at 1 month after the surgery, and the ostomy was closed in all the dogs in the BAS group at 3 months after the surgery. There was still a clear right-to-left shunt in the dogs of BAS+fenestrated ASD occulders group. The shunt was well formed and satisfactory endothelialization was observed at 1, 3 and 6 months after surgery. The results of HE staining showed that the pulmonary arterials were significantly thickened, stenosis and collapse occurred in the non-septostomy group. Pulmonary microvascular stenosis and inflammatory cell infiltration in the pulmonary arterials were observed in the non-septostomy group. Pulmonary arterial histological results were comparable between BAS+fenestrated ASD occulders group and non-septostomy group at 6 months after surgery. Conclusions: The fenestrated ASD occulder has the advantage of maintaining the open fistula hole for a longer time compared with simple balloon dilation. The fenestrated ASD occulder can improve cardiac function, and it is safe and feasible to treat PAH in this animal model.

[Application of diffusion-weighted magnetic resonance imaging in evaluating the efficacy of radiotherapy and chemotherapy for esophageal cancer].

This study was a prospective single arm trial conducted in Zhejiang Jinhua Guangfu hospital from February 2018 to June 2020. A total of 39 patients (32 males and 7 females) with esophageal cancer, aged from 44 to 82 (69±9) years were enrolled. Diffusion weighted magnetic resonance imaging(MR-DWI) was implemented to evaluate the changes of apparent diffusion coefficient(ADC) value before and after chemoradiotherapy. The results showed that the ADC value after chemoradiotherapy was higher than that before treatment[(2.03±0.42)×10⁻³ mm 2/s vs (1.60±0.28)×10⁻³ mm2/s], and there was a positive correlation between the increase of ADC value and the prognosis of patients.

An incremental feeding pattern for Guangdong Small-ear Spotted gilts during gestation: effects on stillbirth rate and muscle weight of progeny.

While an appropriate feed intake is crucial for the reproductive performance of sows, there is a lack of recommendations currently for feed allowance of Guangdong Small-ear Spotted gilts during gestation. The effects of 2 different feeding patterns during gestation on the reproductive performance of Guangdong Small-ear Spotted gilts were investigated by assigning 80 gilts to 2 feeding pattern groups with a randomized complete block design in accordance with initial body weight and back fat thickness, followed by treatment with an incremental feeding pattern (IFP) and a concaved feeding pattern, respectively, with no difference in total feed intake. The IFP group showed a significant decrease in the stillbirth rate (P < 0.05) and an upward trend in piglet mean birth weight (P = 0.06). Furthermore, the IFP group exhibited an increase in the weights of stomach, supraspinatus tendon, triceps, and psoas minor in neonatal piglets (P < 0.05). Overall, the results of the present investigation showed that IFP could significantly reduce the stillbirth rate of Guangdong Small-ear Spotted gilts and increase the muscle weight of progeny.

[Impact of transcatheter aortic valve replacement on renal function in patients with severe aortic stenosis].

Objective: To explore the impact of transcatheter aortic valve replacement (TAVR) on renal function in patients with severe aortic stenosis. Methods: This is a single-center retrospective study. Consecutive patients with severe aortic valve stenosis and received TAVR in Zhongshan Hospital from December 2014 to December 2019 were included. The patients were divided into four groups according to the estimate glomerular filtration rate (eGFR) measured at one day before TAVR, namely eGFR>90 ml·min-1·1.73m-2 group, 6090 ml·min-1·1.73m-2 group, 60

[Fudan experience of neoadjuvant treatment for rectal cancer].

Neoadjuvant chemoradiotherapy is the standard treatment for locally advanced rectal cancer. Fudan University Shanghai Cancer Center has carried out multiple series of studies to explore the optimization of the neoadjuvant therapy since 2005. On the one hand, the "addition" method refers to a higher intensity treatment at the neoadjuvant stage to obtain better tumor regression. On the other hand, the "subtraction" method reduces some unnecessary treatment from the current triad of surgery, radiotherapy and chemotherapy to improve the quality of life of patients. However, locally advanced rectal cancer is associated with great heterogeneity, and therefore, any single treatment mode will not be optimal for all. Notably, the treatment decision-making should be based on clinical presentations, imaging findings, and molecular biology to precisely stratify patients. Besides, the scheme should be dynamically adjusted according to the therapeutic response, so as to realize the dual goals of prolonging patients' life and improving their quality of life. Meanwhile, the treatment decision-making for target population under the guidance of biomarker should be dynamically and self-adaptively adjusted based on the therapeutic effect. This approach will become the future development direction and objective for the precise medical treatment for rectal cancer.

[Clinical analysis of 71 cases of anti-N-methyl-D-aspartate receptor encephalitis in children].

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; χ(2)=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).

[Dynamic visual analysis of neutrophils chemotaxis in peritoneal cavity of schizophrenic model in mice].

OBJECTIVE: To compare the differences of neutrophils chemotaxis ability in peritoneal cavity between normal rats and schizopherenic rats with cell dynamic visualization system. METHODS: In the study,18 healthy Kunming rats were randomly divided into 3 groups which were control group (n=6), 0.3 mg/kg MK-801 treatment group (n=6), 0.6 mg/kg dizocilpine maleate (MK-801) treatment group(n=6), extracted neutrophils separately, and observed the morphology and counted under a microscope. Each group of cells was divided into two parts for chemotactic experiment, called chemokine agent treatment group and no chemokine agent treatment group respectively, indicating control 1, 0.3 mg/kg MK-801 treatment 1,0.6 mg/kg MK-801 treatment 1 and control 2, 0.3 mg/kg MK-801 treatment 2,0.6 mg/kg MK-801 treatment 2. The dynamic migration of cells was recorded using the NIS-Elements software, and TAXIScan Analyzer 2 software was used to select 30 cells (n=30) in each group of cells and analyze cells migration trajectory, speed and distance, and use pair test and One-Way analysis of variance for statistical analysis. RESULTS: The number of neutrophils in control group, 0.3 mg/kg MK-801 treatment group and 0.6 mg/kg MK-801 treatment group were(1.00±0.03)×104/mL,(0.05±0.02)×104/mL,(0.32±0.01)×104/mL respectively, the differences of results were statistically significant(P<0.05).Under the effect of chemotactic agent,the directional migration capability of neutrophils in control group 1, 0.3 mg/kg MK-801 treatment group 1 and 0.6 mg/kg MK-801 treatment group 1 were(0.85±0.11) radian,(1.00±0.11) radian,(0.96±0.10) radian respectively (P<0.05); the migration velocities of neutrophils were (0.09±0.02) µm/s,(0.12±0.01) µm/s,(0.14±0.01) µm/s respectively (P<0.05);the migration distances of neutrophils were (94.26±0.02) µm,(134.61±0.01) µm,(156.19±0.01) µm respectively(P<0.05). CONCLUSION: Compared with neutrophils in peritoneal cavity of control group, the neutrophils in peritoneal cavity of schizophrenic rats have stronger chemotactic movement ability.

Dracorhodin perchlorate inhibits biofilm formation and virulence factors of Candida albicans.

OBJECTIVE: The aim of this study was to investigate the antifungal activity of dracorhodin perchlorate (DP) against planktonic growth and virulence factors of Candida albicans. METHODS: Microdilution method based on CLSI-M27-A3 was used to test the antifungal susceptibility of DP. The activity of DP against biofilm formation and development of C. albicans was quantified by XTT assay and visualized by confocal laser scanning microscope. The effect of DP on the morphological transition of C. albicans induced by four kinds of hyphal-inducing media at 37°C for 4hours was observed under microscope. The rescue experiment by adding exogenous cAMP analog was performed to investigate the involvement of cAMP in the yeast to hyphal transition and biofilm formation of C. albicans. Egg yolk emulsion agar was used to determine the inhibition of DP on the phospholipase production of C. albicans. Human JEG-3 and HUVEC cell lines, as well as the nematode Caenorhabditis elegans was used to assess the toxicity of DP. RESULTS: The minimum inhibitory concentration (MIC) of DP is 64µM while the antifungal activity was fungistatic. As low as a concentration at 16µM, DP could inhibit the yeast to hyphal transition in liquid RPMI-1640, Spider, GlcNAc and 10% FBS-containing Sabouroud Dextrose medium, as well as on the solid spider agar. Exogenous cAMP analog could rescue part of biofilm viability of C. albicans. DP could inhibit the production of phospholipase. The toxicity of DP against human cells and C. elegans is low. CONCLUSION: DP could inhibit the planktonic growth and virulent factors in multiple stages, such as yeast to hyphal transition, adhesion, biofilm formation and production of phospholipase of C. albicans.

Vascular endothelial growth factor gene is associated with hypertensive cerebellar hemorrhage and rehabilitative treatment.

Early rehabilitative therapy is important for patients with hypertensive cerebral hemorrhage to improve long-term function of the extremities. Vascular endothelial growth factor (VEGF) is closely associated with the pathogenesis of hypertension. To identify the markers contributing to the genetic susceptibility to hypertensive cerebellar hemorrhage (HCH) and rehabilitative treatment, we examined the potential association between HCH and 12 single nucleotide polymorphisms of the VEGF gene. Participants included 244 patients with HCH and 251 healthy controls from our rehabilitation department. The T allelic frequencies of the rs3025020 (intron 6) and rs3025039 (3'-UTR) polymorphisms were significantly higher in the patients with HCH than in the healthy controls (rs3025020 T allele: P = 0.0002, OR = 1.619, 95%CI = 1.256-2.088; rs3025039 T allele: P = 0.001, OR = 1.682, 95%CI = 1.246-2.270). Strong linkage disequilibrium was observed in three blocks (D' > 0.9), and significantly more C-G-C (rs3025020, rs3025030, and rs3025039) haplotypes (P = 0.001) were found in the controls in block 3. Significantly more T-G-C haplotypes were found in the patients with HCH (P = 0.046). Further genotype and clinical phenotype correlation study of the rs3025039 carriers showed that Fugl-Meyer and Barthel index scores were lower in the patients with the TT genotype relative to CT + CC genotypes (P < 0.01). These findings point to a role for VEGF polymorphism in HCH, and may be informative for future investigations on the pathogenesis of rehabilitative treatment.

Antimicrobial activity of recombinant mature bovine neutrophil ß-defensin 4 on mycobacterial infection.

BACKGROUND: Previous studies have shown that human cathelicidin and defensins have effective antimicrobial activity against Mycobacterium spp. OBJECTIVE: To investigate the antimycobacterial effect of mature bovine neutrophil ß-defensin (mBNBD) 4 against Mycobacterium spp. infection for the first time. DESIGN: mBNBD4 protein was expressed in Pichia pastoris GS115. We used immunofluorescent assay to detect whether the recombinant mBNBD4 had entered the macrophages. The antimycobacterial activity of mBNBD4 was tested through colony-forming unit (cfu) assay. Morphological changes in the cell wall of M. bovis treated with mBNBD4 were observed by scanning electron microscope. RESULTS: mBNBD4 was expressed and successfully purified from P. pastoris with intact antimicrobial activity. The recombinant protein was able to enter Raw 264.7 macrophages and exhibited potent in vitro bactericidal activity against M. smegmatis and M. bovis. The cell wall of M. bovis was disrupted after interaction with mBNBD4. Exogenous addition of mBNBD4 to both Raw 264.7 and THP-1 derived macrophages reduced the intracellular survival of M. bovis and M. tuberculosis relative to control cells. CONCLUSION: Our data show that mBNBD4 plays an important role in inhibiting mycobacterial growth and in controlling intracellular survival of mycobacteria. mBNBD4 could therefore an effective antimycobacterial molecule in combination with other measures.

Association of dietary intake of folate and MTHFR genotype with breast cancer risk.

We conducted a hospital-based case-control study to investigate the associations of dietary intake of folate and MTHFR C677T and A1298C polymorphisms with breast cancer in a Chinese population. A 1:1-matched case-control study was conducted. Two hundred and thirty patients who were newly diagnosed and histologically confirmed breast cancer and 230 controls were enrolled from Xinxiang Central Hospital. Folate intake was calculated by standard portion size and relative size for each food item in the questionnaire. Genotyping of MTHFR C677T and A1298C was performed by PCR-RFLP. MTHFR 677TT (OR = 2.26, 95%CI = 1.09-4.87, P = 0.02) and T allele (OR = 1.40, 95%CI = 1.03-1.90, P = 0.03) had an increased risk of laryngeal cancer when compared with the CC genotype. We found any interaction between MTHFR C677T and folate intake (P for interaction = 0.02). In conclusion, our study demonstrated that MTHFR C677T polymorphism and folate are associated with risk of breast cancer.

Electric-field control of nonvolatile magnetization in Co40Fe40B20/Pb(Mg(1/3)Nb(2/3))(0.7)Ti(0.3)O3 structure at room temperature.

We report a large and nonvolatile bipolar-electric-field-controlled magnetization at room temperature in a Co(40)Fe(40)B(20)/Pb(Mg(1/3)Nb(2/3))(0.7)Ti(0.3)O(3) structure, which exhibits an electric-field-controlled looplike magnetization. Investigations on the ferroelectric domains and crystal structures with in situ electric fields reveal that the effect is related to the combined action of 109° ferroelastic domain switching and the absence of magnetocrystalline anisotropy in Co(40)Fe(40)B(20). This work provides a route to realize large and nonvolatile magnetoelectric coupling at room temperature and is significant for applications.

RhoA and NF-κB are involved in lipopolysaccharide-induced brain microvascular cell line hyperpermeability.

PURPOSE: The aim of this study was to investigate the signaling mechanisms surrounding changes in tight junction (TJ) and the permeability of brain microvascular cell lines induced by lipopolysaccharide (LPS). METHODS: To confirm that LPS induces endothelial barrier hyperpermeability by disrupting tight junction, Bend.3 cells were exposed to LPS, and changes in endothelial permeability (transendothelial electrical resistance (TEER) assay), F-actin dynamics (Rhodamine-Phalloidin staining) and tight junction protein expression (western blot or immunofluorescence) were monitored. Moreover, to ensure that both RhoA and NF-κB participated in the regulatory mechanisms, Bend.3 cells were transfected with n19RhoA and DNMu-IκBα plasmids, and the above experiments were repeated. To clarify the relationship between RhoA and NF-κB in the process, the activities of NF-κB (via luciferase reporter assays) and RhoA (via pull-down assays) were detected in transfected and untreated Bend.3 cells. Lastly, to investigate whether RhoA and NF-κB regulate MLC phosphorylation, we measured changes in myosin light chain (MLC) phosphorylation in untreated and transfected Bend.3 cells by western blot. RESULT: LPS caused RhoA and NF-κB activation, MLC phosphorylation, F-actin rearrangement, tight junction disruption and barrier dysfunction. These effects were suppressed by inhibitors of RhoA or NF-κB; inhibiting RhoA was more efficient. Inactivating RhoA prohibited LPS-induced NF-κB activation, but the inverse was not true. CONCLUSIONS: LPS induces brain microvascular endothelial barrier hyperpermeability by disrupting TJs, in part through RhoA and NF-κB activation, in which RhoA is the positive upstream regulator for NF-κB.