Objective·To systematically review the effectiveness of actigraphy on the evaluation of circadian rhythm characteristics in patients with depression.Methods·A systematic literature search was conducted in PubMed,Embase,Web of Science,Cochrane Library,PsycINFO,CNKI,WanFang Data,and Chinese biomedical literature database(CBM),from the inception of each database to May 5th,2023.Case control studies that used actigraphy to evaluate circadian rhythms in patients with depression and compared them with healthy controls were collected.Literature was screened according to the inclusion and exclusion criteria,and the quality of the included literature was evaluated by using the Newcastle-Ottawa Scale.The meta-analysis was performed by using RevMan 5.4 software.Results·A total of 9 articles were included,including 390 patients with depression and 288 healthy controls.The meta-analysis showed that the MESOR(midline statistic of rhythm)(SMD=-0.29,95%CI-0.51 ?-0.07,P=0.009)of the circadian cosine function in patients with depression was lower than that in healthy controls;sleep onset(MD=33.06,95%CI 14.90 ? 51.23,P=0.000)and sleep offset(MD=53.80,95%CI 22.38 ? 85.23,P=0.000)were later in patients with depression than those in healthy controls;no statistical difference was found in the activity level of the most active 10 hours(SMD=-0.26,95%CI-0.52 ? 0.01,P=0.060)between patients with depression and healthy controls,although there was a trend for lower activity in patients with depression;no statistical difference was found in the acrophase(MD=25.33,95%CI-12.41 ? 63.06,P=0.190)of the circadian cosine function between patients with depression and healthy controls;no clear statistical significance of the difference was found in the amplitude(SMD=-0.14,95%CI-0.42 ? 0.14,P=0.340)and the activity level of the least active 5 hours(SMD=0.31,95%CI-0.10 ? 0.71,P=0.140)between patients with depression and healthy controls.Conclusion·Actigraphy can reflect circadian rhythm disruption in patients with depression to some extent,but the limited number of included studies and inconsistencies in the study populations and methodologies have affected the quality and results of the analyses.More high-quality clinical trials are needed to provide evidence.

Objective:To explore the clinical characteristics of interleukin-6 (IL-6) and interleukin-8 (IL-8) in cerebrospinal fluid (CSF) of children with bacterial meningitis (BM) and provide reference for clinical diagnosis and treatment of BM.Methods:The clinical data of BM children hospitalized in Women and Children′s Medical Center Affiliated to Guangzhou Medical University from December 2019 to March 2022 were collected and retrospectively analyzed in this case series study.Cytokines in CSF of these children were detected at least twice during the treatment. t test, Mann-Whitney test or analysis of variance were carried out for statistical analysis. Results:There were 40 patients included in this study.The age of onset was 2(1, 8) months, ranging from 2 days to 8 years, and the length of time from onset to hospitalization was (15±17) days, ranging from 1 day to 69 days.The main symptoms at the onset were fever (40 cases, 100%), poor mental state (16 cases, 35.0%), convulsion (9 cases, 22.5%), and vomiting (9 cases, 22.5%).According to pathogens, the patients were divided into the Streptococcus agalactia group (GBS group, 9 cases), Streptococcus pneumoniae group (SP group, 9 cases), other bacteria group (9 cases), and unknown bacteria group (13 cases).The levels of cytokines in the CSF of BM children were increased, along with significantly elevated levels of IL-6 and IL-8 within 1 st week of BM, followed by the peak at 2 nd-3 rd weeks, and then levels of IL-6 and IL-8 presented an overall decreasing trend with the progression of BM.The level of IL-6 in CSF of 10 cases significantly decreased in the 4 th week of BM [within 2 weeks: 773.5(164.1, 1 781.2) ng/L vs. 4 th week: 10.8(2.2, 21.1) ng/L, P=0.005].Such statistical differences didn′t occur to the level of IL-8 [within 2 weeks 182.9(33.6, 657.7) ng/L vs. 4 th week: 92.9(22.6, 226.6) ng/L, P=0.303].After effective antibiotic therapy, 6 patients had elevated white blood cell count in CSF during the 4 th-20 th weeks, with or without repeating intermittent fever.Among them, 4 cases of GBS and 1 case of SP were negative for pathogens in CSF during the retest after treatment, and the levels of IL-6 and IL-8 [(149.1-4 218.6) ng/L and (124.2-1 890.3) ng/L, respectively] in CSF were elevated.Low-dose glucocorticoid was administered for anti-inflammatory treatment, with additional gamma globulin for 1 case and Ibuprofen instead for 1 case.Subsequently, the fever completely subsided.The white blood cell count in CSF decreased significantly ( P=0.024). Conclusions:The levels of IL-6 and IL-8 in CSF increase significantly in the acute phase of BM and generally decrease with the progression of BM.If they are still significantly elevated in the later course of BM, it should be noted that an intracranial hyperinflammatory response may occur, especially when the pathogenic bacteria are GBS or SP.

The anterior disc displacement (ADD) leads to temporomandibular joint osteoarthritis (TMJOA) and mandibular growth retardation in adolescents. To investigate the potential functional role of fibrocartilage stem cells (FCSCs) during the process, a surgical ADD-TMJOA mouse model was established. From 1 week after model generation, ADD mice exhibited aggravated mandibular growth retardation with osteoarthritis (OA)-like joint cartilage degeneration, manifesting with impaired chondrogenic differentiation and loss of subchondral bone homeostasis. Lineage tracing using Gli1-CreER⁺; Tm^fl/-mice and Sox9-CreER⁺;Tm^fl/-mice showed that ADD interfered with the chondrogenic capacity of Gli1⁺ FCSCs as well as osteogenic differentiation of Sox9⁺ lineage, mainly in the middle zone of TMJ cartilage. Then, a surgically induced disc reposition (DR) mouse model was generated. The inhibited FCSCs capacity was significantly alleviated by DR treatment in ADD mice. And both the ADD mice and adolescent ADD patients had significantly relieved OA phenotype and improved condylar growth after DR treatment. In conclusion, ADD-TMJOA leads to impaired chondrogenic progenitor capacity and osteogenesis differentiation of FCSCs lineage, resulting in cartilage degeneration and loss of subchondral bone homeostasis, finally causing TMJ growth retardation. DR at an early stage could significantly alleviate cartilage degeneration and restore TMJ cartilage growth potential.
Animals ; Mice ; Osteogenesis ; Zinc Finger Protein GLI1 ; Fibrocartilage ; Temporomandibular Joint ; Disease Models, Animal ; Osteoarthritis ; Stem Cells ; Growth Disorders

Objective:To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus (GEFS + ) caused by the KCNT2 gene mutation and review the literature. Methods:Clinical data of a child with GEFS + and his family members who visited Department of Pediatric Neurology, Guangzhou Women and Children′s Medical Center in May 2019 were collected.DNA samples were collected from the peripheral blood of the proband, his parents, his elder brother, and his maternal grandparents, and genetic analysis and verification were performed using the next-generation sequencing technique.Using " KCNT2" as the key word, literature was retrieved from PubMed, China National Knowledge Infrastructure and Wanfang databases (up to August 2019). Results:The proband was a 3-year-old boy who was admitted to Guangzhou Women and Children′s Medical Center because of frequent epileptic seizures in the past 5 months.He presented with a binocular gaze and experienced 3 to 8 times of extremities myoclonic-spastic epileptic attacks every day.He had a history of 3 times of febrile seizures at the age of 2 years old.His seizures were refractory to Sodium valproate, Topiramate, Nitrazepam and Levetiracetam.His elder brother and mother had a history of childhood febrile seizures.Other members in the family had no history of convulsion.Ictal electroencephalogram showed general 1 Hz high voltage spike-slow waves.A heterozygous nonsense mutation of KCNT2 gene c. 574C>T(p.Q192X) that was never reported previously was detected in the proband, his brother, mother and maternal grandmother.Furthermore, no other family members carried the mutation at the c. 574 locus of the KCNT2 gene.No article in Chinese was found, and 2 articles in a language other than Chinese provided the complete data of 3 sporadic cases.Together with 4 cases in the family studied in this article, there were 7 cases and 4 mutation sites in KCNT2 gene.Of these mutations, there were 3 missense mutations and 1 nonsense mutation.Three sporadic patients presented with early infantile epileptic encephalopathy.The family of this study was characterized with febrile seizures and febrile seizures plus. Conclusions:A de novo mutation and phenotype of the KCNT2 gene is found in a family with GEFS + .It would expand the gene mutation spectrum and provide basis for family genetic counseling. KCNT2 mutation induced GEFS + is refractory to antiepileptic drugs.

Objective To investigate the influence of down-regulation NEK-2 level on the radiosensitivity of A549 cells.Methods NEK-2 siRNA was transfected to A549 cells with liposome and NEK-2 expression level was inspected by Western blot.The radiosensitivity was detected by clone formation experiment.Cell cycle and cell apoptosis were analyzed by flow cytometry.Immunofluorescence experiment was used to detect the DNA double strand break and repair.Results NEK-2 siRNA successfully suppressed NEK-2 expression in A549 cells and resuced the cell proliferation ability after irradiation compared to the blank control group and the negative control group.It can improve the radiosensitivity of A549 cells (The radiosensitivity of A549 cells enhanced significantly.).The D0 values declined form 1.80 Gy to 1.40 Gy,and the sensitizing enhancement ratio was 1.32.After irradiation,compared to negative control group,the apoptosis rate was significantly improved (7.85％ to 17.17％),cells in G2/M phase were obviously increased (9.23％ to 30.16％),the DNA double strand break rate was increased (100％ to 165％) and the DNA damage repair rate was reduced (100％ to 48％) in NEK-2 siRNA group.The comparisons among the groups wer statistically significant (P＜0.05).Conclusions NEK-2 siRNA reduced the proliferation and increased the radiosensitivity of A549 cell line,probably by affecting the cell cycle,promoting cell apoptosis and suppressing DNA damage repair.

Objective: To investigate the inhibitory effect of 17AAG-Cypate micelles on the non-small cell lung cancer A549 cells in nude mice and to explore its possible mechanism. Methods: A549 lung adenocarcinoma tumor-bearing nude mice were established. The nude mice were treated with saline ( saline group), X-ray (X-ray group), 17AAG micelles+ X-ray (17AAG-M/X group) and 17AAG-Cypate micelles+ laser/X-ray (17AAG-Cypate-M/L+ X group), respectively. The growth of xenograft tumors in different groups was measured on a regular basis to delineate the growth curve. The expression of proliferating cell nuclear antigen (PCNA) was measured by immunohistochemistry. The microvascular density was detected. The apoptosis of xenograft tissues was observed by TUNEL staining. The expression levels of p-ERK1/2 and p-AKT were quantitatively measured by Western blot. Results: Compared with the saline group, varying degrees of inhibition of tumor growth were observed in the X-ray, 17AAG-M/X-ray and 17AAG-Cypate-M/L+ X groups, particularly in the 17AAG-Cypate-M/L+ X group (all P<0.05). In all groups, the expression levels of PCNA were significantly down-regulated (all P<0.05), the microvascular density was remarkably reduced (all P<0.05) and the expression levels of p-ERK1/2 and p-AKT were considerably down-regulated (all P<0.05). Conclusions 17AAG-Cypate micelles can inhibit the growth of human non-small cell lung cancer in nude mice, probably by reducing the activity of p-ERK1/2 and p-AKT, thereby weakening the activation of the MAPK-ERK and PI3K-AKT signaling pathways.

Objective To investigate the abnormal change of gray matter volume in patients with euthymic bipolar disorder Ⅰ (BD-Ⅰ),and to elucidate the relationship between the use of different mood stabilizers and brain structure variations.Methods Voxel-based morphometry (VBM) was used to analyze the volume of local gray matter in 35 patients with BD-Ⅰ and 30 healthy controls(HC).The patients were divided into BD-Ⅰ with lithium group and BD-Ⅰ with valproate group according to different mood stabilizers.The volume differences of gray matter of the three groups were compared by one-way ANOVA.Results Compared with HC,BD-Ⅰ patients showed significantly reduced gray matter volume in the medial frontal cortex (MNI (x,y,z):2,34,-18),orbital frontal cortex (MNI(x,y,z):-32,22,-4),frontal operculum (MNI(x,y,z):38,18,4) and insula cortex (MNI(x,y,z):-32,22,-4) (P＜0.05).There was no significant difference in thevolume of gray matter between BD-Ⅰ with lithium group and BD-Ⅰ with valproate group(P＞0.05).Conclusion Emotional disturbance in patients with BD-Ⅰ may be associated with reduced gray matter volume in the medial frontal cortex,orbital frontal cortex,frontal operculum and insula cortex.There are not significant difference about the effects of lithium carbonate and valproate on cerebral gray matter volume in patients with BD-Ⅰ.

Objective·To compare the clinical features between different subtype bipolar patients with first mania episode, and to contribute to early identification of bipolar disorder. Methods·This study was based on the database named as National Bipolar Mania Pathway Survey (BIPAS). From November 2012 to January 2013, bipolar patients from 26 mental health facilities in China were enrolled in current study. The clinical features were compared between mania patients of different subtypes, including hypomania (groupⅠ), mania without psychotic symptoms (groupⅡ), mania with psychotic symptoms (group Ⅲ) and mixed state (group Ⅳ). Results·There was significant difference in the percentage of clinical symptoms between different subtype bipolar patients with first mania episode, especially the mania and anxiety related symptoms. Group Ⅰ, Ⅲ , Ⅳ were further compared with groupⅡ, which was considered as the typical bipolar disorder. The results showed that the mania related symptoms was significantly higher in group Ⅱ, but anxiety related symptoms was significantly higher in group Ⅰ, Ⅲ, Ⅳ. Moreover, Logistic regression analysis revealed that more eloquent or humor and unusually restless could be in favor of the diagnosis of hypomania; younger and mania or hypomania as first episode might be in favor of the diagnosis of mania with psychotic symptoms; older, national minorities and unusually restless could be in favor of the diagnosis of mixed state. Conclusion·The clinical features between different subtype bipolar patients with first mania episode are various, and analysis of the clinical features can contribute to early identification of bipolar disorder.

Objective To investigate the radiosensitizing effect of 17AAG-cypate micelles on human non-small cell lung cancer A549 cells and its possible mechanism.Methods (1) A single-hit multi-target model formula was used to analyze the radiosensitizing effects of 17AAG-M and 17AAG-cypate-M.(2) The effects of 17AAG-cypate-M on the viability of A549 cells under laser and X-ray irradiation were analyzed by MTT assay.(3) The effect of the drugs on the cell senescence was observed by β-galactosidase staining assay.(4) The effects of different treatment conditions on DNA damage repair were analyzed by γ-H2AX immunofluorescence staining assay.(5) The expression of p-Erk1/2 and p-Akt was measured by Western blot.The paired t test was used for analyzing the differences between groups.Results Compared with the X-ray irradiation group,the X-ray+17AAG-cypate-M group had a lower mean lethal dose and a sensitization enhancement ratio greater than 1,indicating that 17AAG-cypate-M had a radiosensitizing effect.Compared with the 17AAG-M group,the 17AAG-cypate-M group showed significantly lower cell viability (P<0.01),a significantly higher percentage of aging cells (P<0.01),and significantly further delayed DNA damage repair (P<0.01).And the 17AAG-cypate-M group had lower expression of p-Erk1/2 and p-Akt than the 17AAG-M group.Conclusions Compared with 17AAG-M,17AAG-cypate-M has a higher radiosensitizing effect on A549 cells.The mechanism might be inducing the cell senescence,delaying DNA damage repair,and inhibiting the expression of p-Erk1/2 and p-Akt.

ObjectiveTo determine thallium in whole blood by atomic absorption detection method, and to investigate the eliminating effect of hemoperfusion (HP) for thallium in blood.Methods The blood of Beagle dogs which had not exposed to thallium before were obtained for preparation of thallium nitrate (TlNO3)-containing solution in three concentrations according to the conversion formula based on animal weight and volume of blood. HP was performed in the simulated in vivo environment. The content of TlNO3 in blood of the next group was determined on the amount of TlNO3 for the last HP of the former dose group. Thallium quantity in different samples was measured with atomic absorption spectrometer blood samples before and after HP. Finally, the thallium concentration in blood was analyzed statistically.Results Thallium concentrations showed a good linear relationship in the range of 0-200μg/L (r = 0.998 4). The intra-day precision (RSD) was lower than 4.913%, the intra-day recovery rate was 96.2%-111.9%; the inter-day precision (RSD) was lower than 7.502%, the inter-day recovery rate was 89.6%-105.2%. The concentration of thallium in blood was significantly reduced after HP per time in high, middle, and low dose groups [(453.43±27.80) mg/L to (56.09±14.44) mg/L in high dose group,F = 8.820,P = 0.003;(64.51±13.60) mg/L to (3.19±0.23) mg/L in middle dose group,F = 36.312,P = 0.000; (5.40±0.98) mg/L to (0.38±0.25) mg/L in low dose group,F = 46.240,P = 0.000]. The adsorption rate of four times of HP in high, middle and low dose group were (87.63±2.48)%, (95.06±1.54)% and (92.76±4.87)%, respectively, without significant difference (F = 4.231,P = 0.070 ).Conclusions The method for measuring thallium was established, and it shows a very stable, simple, sensitive for determination of thallium. HP can effectively remove thallium from blood. Thallium concentration can be reduced by 90% after four times of HP. HP is also effective even when thallium concentration is not high.