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.

Objectives:To explore the antitumor effects of redox-responsive nanoparticles containing platinum(Ⅳ)—NP@Pt(Ⅳ) in ovarian cancer.Methods:Redox-responsive polymer carriers were synthesized. Polymer carriers and platinum(Ⅳ)—Pt(Ⅳ) can self-assemble into NP@Pt(Ⅳ). Inductively coupled plasma mass spectrometry was performed to detect the platinum release from NP@Pt(Ⅳ) in reducing environment and the platinum content in ovarian cancer cells ES2 treated with cisplatin, Pt(Ⅳ) and NP@Pt(Ⅳ). The proliferation ability of the ovarian cancer cells were detected by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cellular apoptosis was assessed by flow cytometry. Collection of primary ovarian cancer tissues from patients with primary high-grade serous ovarian cancer who were surgically treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from October to December 2022. The high-grade serous ovarian cancer patient-derived xenograft (PDX) mice were intravenously injected with Cy7.5 labeled NP@Pt(Ⅳ) followed by in vivo imaging system. Mice were treated with PBS, cisplatin and NP@Pt(Ⅳ). Tumor volume and weight were measured in each group. Necrosis, apoptosis and cell proliferation of tumor tissues were detected by hematoxylin-eosin (HE) staining, TUNEL fluorescence staining and Ki-67 immunohistochemistry staining. Body weight and HE staining of heart, liver, spleen, lung and kidney of mice in each group were measured.Results:The platinum release of NP@Pt(Ⅳ) after 48 hours in reducing environment was 76.29%, which was significantly higher than that of 26.82% in non-reducing environment ( P<0.001). The platinum content in ES2 cells after 4 hours and 7 hours of treatment with NP@Pt(Ⅳ) (308.59, 553.15 ng/million cells) were significantly higher than those of Pt(Ⅳ) (100.21, 180.31 ng/million cells) and cisplatin (43.36, 50.36 ng/million cells, P＜0.05). The half inhibitory concentrations of NP@Pt(Ⅳ) in ovarian cancer cells ES2, A2780, A2780DDP were 1.39, 1.42 and 4.62 μmol/L, respectively, which were lower than those of Pt(IV) (2.89, 7.27, and 16.74 μmol/L) and cisplatin (5.21, 11.85, and 71.98 μmol/L). The apoptosis rate of ES2 cells treated with NP@Pt(Ⅳ) was (33.91±3.80)%, which was significantly higher than that of Pt(Ⅳ) [(16.28±2.41)%] and cisplatin [(15.01±1.17)%, P＜0.05]. In high-grade serous ovarian cancer PDX model, targeted accumulation of Cy7.5 labeled NP@Pt(Ⅳ) at tumor tissue could be observed. After the treatment, the tumor volume of mice in NP@Pt(IV) group was (130±98) mm 3, which was significantly lower than those in control group [(1 349±161) mm 3, P<0.001] and cisplatin group [(715±293) mm 3, P=0.026]. The tumor weight of mice in NP@Pt(IV) group was (0.17±0.09)g, which was significantly lower than those in control group [(1.55±0.11)g, P<0.001] and cisplatin group [(0.82±0.38)g, P=0.029]. The areas of tumor necrosis and apoptosis in mice treated with NP@Pt(Ⅳ) were higher than those in mice treated with cisplatin. Immunohistochemical staining revealed that there were low expressions of Ki-67 at tumor tissues of mice treated with NP@Pt(Ⅳ) compared with cisplatin. The change in body weight of mice in NP@Pt(Ⅳ) group was not significantly different from that of the control group [(18.56±2.04)g vs.(20.87±0.79)g, P=0.063]. Moreover, the major organs of the heart, liver, spleen, lung, and kidney were also normal by HE staining. Conclusion:Redox-responsive NP@Pt(Ⅳ), produced in this study can enhance the accumulation of cisplatin in ovarian cancer cells and improve the efficacy of ovarian cancer chemotherapy.

Objective To explore the effect of cancer related anemia on the abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood.Methods A total of 34 HLA-A*11∶01 positive patients with middle-and late-stage tumors admitted in the Rocket Force Medical Center of PLA from June to July 2023 were enrolled in this study.According to hemoglobin(HGB)level,they were divided into non anemia group(≥120 g/L,n=14),mild anemia group(90～120 g/L,n=14),and moderate to severe anemia group(＜90 g/L,n=6).After their peripheral blood mononuclear cells were isolated,memory CD8+T cells were stimulated by the epitopes of SARS-CoV-2 and then expanded.Positive epitopes were screened using enzyme-linked immunosorbent spot(ELISP OT)assay,and then MHC-peptide Tetramers were constructed.The proportion and number of Tetramer+cells and the number of ELISPOT spots were detected in the expanded cells to reflect the abundance of SARS-CoV-2 specific memory CD8+T cells.The relevance of patients'HGB level with the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed.The differences of the proportion and number of Tetramer+cells and the number of ELISPOT spots was analyzed in different groups.Results Among the 34 patients,there were 25 males and 9 females,at an age range of 36～78(median 57)years.The proportion and number of Tetramer+cells and the number of ELISPOT spots were positively correlated with HGB level(P＜0.05).The proportion and number of Tetramer+cells and the number of ELISPOT spots were significantly decreased in patients with moderate to severe anemia than the non anemia patients(P＜0.05).Conclusion The abundance of SARS-CoV-2 specific memory CD8+T cells in peripheral blood is positively correlated with patients'HGB level,indicating that CRA may increase the susceptibility of patients to viruses by reducing the abundance of memory CD8+T cells in peripheral blood.

OBJECTIVE: To explore the genetic basis for a child with myopathy and cerebellar atrophy with ataxia. METHODS: Clinical examinations and laboratory testing were carried out for the patient. The proband and the parents' genomic DNA was extracted from peripheral blood samples and subjected to trio whole-exome sequencing. Candidate variant was validated by Sanger sequencing. RESULTS: The 1-year-and-8-month-old boy manifested motor developmental delay, ataxia, hypomyotonia, increased serum creatine kinase. Cranial MRI showed cerebellar atrophy with progressive aggravation. Genetic testing revealed that the patient has harbored compound heterozygous variants of the MSTO1 gene, namely c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile), which were respectively inherited from his mother and father. The former was unreported previously and was predicted to be likely pathogenic, whilst the latter has been reported previously and was predicted to be of uncertain significance. CONCLUSION The compound heterozygous c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile) variants probably underlay the disease in the proband. Above finding has enriched the spectrum of MSTO1 gene variants underlying mitochondrial myopathy and cerebellar atrophy with ataxia.
Ataxia/genetics* ; Atrophy/genetics* ; Cell Cycle Proteins/genetics* ; Child ; Cytoskeletal Proteins/genetics* ; Humans ; Infant ; Male ; Mitochondrial Myopathies ; Mutation ; Neurodegenerative Diseases ; Whole Exome Sequencing

Objective To investigate the efficacy and safety of apatinib monotherapy as subsequent-line therapy on patients with advanced ESCC. Methods We included 56 patients with advanced ESCC who were administered with apatinib monotherapy. The initial dosage of apatinib was 500mg or 250mg daily. Clinicopathological characteristics, adverse reaction and prognosis of the patients were analyzed. The primary endpoint of this study was PFS, the secondary endpoints were ORR, DCR, OS and safety of apatinib administration. Results All the 56 patients with ESCC corresponded with the eligibility criteria and were available for the evaluation of efficacy and adverse reaction. The ORR of the 56 patients who received apatinib monotherapy was 8.9% (95%CI: 3.0%-19.6%) and DCR was 64.3% (95%CI: 50.4%-76.6%). The median PFS was 3.7 months (95%CI: 3.19-4.21) and the median OS was 6.3 months (95%CI: 3.53-9.08). The common adverse reactions were hypertension (50.0%), fatigue (41.1%), loss of appetite (35.7%), hand-foot syndrome (30.4%) and diarrhea (26.8%). Conclusion Apatinib monotherapy demonstrates potential efficacy and tolerable safety as the further-line treatment for the patients with advanced ESCC. And the conclusion should be validated in prospective clinical studies subsequently.

Objective:To investigate the variation of T, B, NK lymphocyte subgroup in children with anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis and their clinical significance.Methods:This was a prospective and control study.Forty children primarily diagnosed with anti-NMDAR encephalitis in the department of neurology in Guangzhou Women and Children′s Medical Center from January 2017 to August 2019 served as patient group, 20 healthy children served as control group.Absolute counts and percentages of T, B and NK lymphocytes in whole blood were detected before and 1 month after treatment in patient group.Serum immunoglobulin G(IgG), IgA and IgM were measured before treatment.The blood levels of T, B, NK lymphocyte subgroup were detected with flow cytometer.NMDAR antibody titers of serum and cerebrospinal fluid were detected in patient group.The differences between patient group at different time points and control group were compared.The patients were divided into two groups according to the response to treatment after 2 weeks and the absolute counts of T, B and NK lymphocytes before treatment were compared between groups.Results:Compared with control group, the blood absolute count of B lymphocyte in patient group were significantly higher before and after treatment( P<0.05). There was no significant difference of B lymphocyte in patient group between before and after treatment.After treatment, T cells(including T inhibitory cells and T helper cells)were significantly increased compared with those before treatment and those in control group( P<0.05), but there was no significant difference between patient group and control group before treatment.These with poor response to treatment after 2 weeks had higher level of B, T lymphocyte subgroup compared to those with good response( P<0.05). The level of IgG, IgA, IgM in patient group showed no significant difference with control group.There was no significant correlation between B lymphocyte count in blood and NMDAR antibody titer in cerebrospinal fluid( r=0.282, P>0.05). Conclusion:B lymphocytes increase greatly in children with anti-NMDAR encephalitis, and the level of B lymphocyte subgroup before treatment are associated with treatment response, and T lymphocytes increase greatly after treatment.There is no significant correlation between the titer of NMDAR antibody in cerebrospinal fluid and B lymphocyte level.

Objective:To explore the clinical technique and method of reconstruction large soft tissue defect of plantar by skin soft tissue dilatation combined with thigh cross leg flap to improve the weight-bearing function of plantar standing.Methods:From February 2015 to June 2019, 8 cases with plantar soft tissue defects were repaired with cross leg flap expanded from the healthy side of the thigh. Right foot in 4 cases, left foot in 3 cases and bilateral in 1 case. There were 5 males and 3 females. Ages ranged from 16 to 56, with an average age of 31. Clinical features: scar ulcer in 4 cases, bone-sticking scar in 4 cases, bone exposure in 1 case. After debridement, the area of skin and soft tissue defect was 9 cm×16 cm-12 cm×29 cm, the area of harvest expanded flap was 11 cm×18 cm-14 cm×30 cm. All flaps were fixed by cross-leg with pedicle. The pedicle division were performed one month after the skin flap transmission.Results:Of the 9 flaps transferred, 8 survived, 1 died in the distal part of the flap and was repaired by secondary expanded flap, and the donor site healed in linear scar stage. After 6-24 months follow-up, the plantar flap was in good shape and could walk with weight-bearing, without ulceration, and the protective tactile sensation was gradually restored in 12 months.Conclusions:The large-area soft tissue defect of plantar was repaired with the expanded cross leg flap in the healthy thigh, which also provide sufficient thickness of soft tissue to increase the ability of bearing weight and wearing resistance of the sole. It is a good alternative method to repair large area soft tissue defect of plantar under the condition of limited transfer of perforator flap and free flap.

Objective:To explore the clinical technique and method of reconstruction large soft tissue defect of plantar by skin soft tissue dilatation combined with thigh cross leg flap to improve the weight-bearing function of plantar standing.Methods:From February 2015 to June 2019, 8 cases with plantar soft tissue defects were repaired with cross leg flap expanded from the healthy side of the thigh. Right foot in 4 cases, left foot in 3 cases and bilateral in 1 case. There were 5 males and 3 females. Ages ranged from 16 to 56, with an average age of 31. Clinical features: scar ulcer in 4 cases, bone-sticking scar in 4 cases, bone exposure in 1 case. After debridement, the area of skin and soft tissue defect was 9 cm×16 cm-12 cm×29 cm, the area of harvest expanded flap was 11 cm×18 cm-14 cm×30 cm. All flaps were fixed by cross-leg with pedicle. The pedicle division were performed one month after the skin flap transmission.Results:Of the 9 flaps transferred, 8 survived, 1 died in the distal part of the flap and was repaired by secondary expanded flap, and the donor site healed in linear scar stage. After 6-24 months follow-up, the plantar flap was in good shape and could walk with weight-bearing, without ulceration, and the protective tactile sensation was gradually restored in 12 months.Conclusions:The large-area soft tissue defect of plantar was repaired with the expanded cross leg flap in the healthy thigh, which also provide sufficient thickness of soft tissue to increase the ability of bearing weight and wearing resistance of the sole. It is a good alternative method to repair large area soft tissue defect of plantar under the condition of limited transfer of perforator flap and free flap.

Objective: To investigate the clinical characteristics, treatment and prognosis of relapsed demyeli-nating disease (RDD) associated with myelin oligodendrocyte glycoprotein antibodies (MOG abs) children in southern China. Methods: Children with RDD associated with MOG abs at Department of Neurology in Guangzhou Women and Children′s Medical Center from January 2015 to December 2018 were retrospectively analyzed.The annualized relapse rates (ARRs) and expand disability status scale (EDSS) were used to assess the recurrence frequency and neurological dysfunction respectively. Results: Ten children were included with the age of (6.4±3.6) years old, and male to female ratio was 4∶6.(1)Clinical phenotype: all children had 24 episodes during follow-up, with acute disseminated encephalomyelitis (ADEM)(7/10 cases) and neuromyelitis optica spectrum disorders (NMOSD)(3/10 cases) on the first episode.Among 14 recurrent episodes, ADEM (9/14 times) was the most common, followed by optic neuritis(ON)(3/14 times)and brainstem encephalitis (2/14 times). By the final follow-up, the final diagnosis was multiphasic disseminated encephalomyelitis(MDEM)(6/10 cases), NMOSD(3/10 cases), ADEM-ON(1/10 case), respectively.(2)Laboratory examination: all the children had positive serum MOG abs in the acute stage.The serum MOG abs titer high group(≥1∶640)(6 cases)on the first episode complicated ON (3 cases) and long segment myelitis (3 cases) more common than those of low group(1∶320)(4 cases). (3)Imaging changes: 25 times of bain magnetic resonance imaging (MRI) were performed in the acute stage, MRI changes mostly involved the cortex and subcortical white matter.Four cases had abnormal spinal cord MRI.(4)Treatment and prognosis: intravenous methylprednone (IVMP) combined with intravenous immunoglobulin (IVIG) were administrated in acute stage.Rituximab (2/10 cases), mycophenolate mofetil (4/10 cases), IVIG (2/10 cases) monthly and low dose prednisone orally (2/10 cases) were given respectively in maintains stage.ARRs decreased from 1.4 to 0 and EDSS score improved significantly after these treatments above.Seven cases had residual neurological dysfunction with 3 cases of NMOSD, 3 cases of MDEM and 1 case of ADEM-ON, including motor dysfunction, learning disability and inattention, symptomatic epilepsy and visual impairment. Conclusions ADEM is the most common form of RDD associated with MOG abs in children.Those with high serum MOG abs titer on the first episode are prone to have ON or long segment myelitis.Immunomodification therapy is effective in the relapsed patients, residual neurological sequelae were related to the type of repeated demyelination.

Objective To investigate the relationship between body composition and adequacy of dialysis,and analyze the related risk factors for inadequate delivery of hemodialysis.Methods In a prospective clinical trial,two different methods determining dialysis dose were simultaneously applied:Kt/Vdau (conventional method with Daugirdas' formula) and Kt/Vbem [online clearance monitoring (OCM) measurement with Ⅴ measured by body composition monitor (BCM)].Using the value of 1.27 as the boundary,the patients were divided into two groups:Kt/Vbcm ＜ 1.27 group and Kt/Vbcm≥ 1.27 group.Clinical indices were compared between the two groups.Multiple linear regression was applied to analyze the potential impact factors of the difference between Kt/V values calculated by the two methods.Receiver operator characteristic (ROC) curve was applied to analyze meaningful factors.Results A total of 138 maintenance hemodialysis patients with age of (54.9±12.7) years old were enrolled,and 55.1％ of them were males.There was no significant difference between Kt/Vdau and Kt/Vbcm [1.432(1.235,1.718) vs 1.434 (1.244,1.642),P=0.823].Kt/Vdau was incidentally prone to falsely high values due to operative errors,whereas in these cases OCM-based measurement Kt/Vbcm delivered realistic values.An excellent correlation was observed between Kt/Vdau and Kt/Vbcm;the mean difference was 0.07,95％CI (-0.66-0.79);the correlation coefficient was 0.842(0.821-0.862).The patients in Kt/Vbcm≥ 1.27 group had older age,lower body mass index (BMI),lower height and weight,lower total body water (TBW),lower extracellular water,lower intracellular water,and lower lean tissue index (LTI) compared to those in Kt/Vbcm ＜ 1.27 group.Excellent correlations were observed between Kt/Vbcm and TBW or LTI (r=-0.834,P ＜ 0.001;r=-0.721,P ＜ 0.001).ROC curve analysis showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 87.1％ and 86.5％,with a threshold of 30 L for TBW.It also showed that the sensitivity and specificity of predicting inadequate delivery of hemodialysis were 60.4％ and 94.6％,with a threshold of 11.05 kg/m2 for LTI.Conclusions BCM can give more accurate parameters of urea distribution volume,thus modifying the result of Kt/V.TBW and LTI are important risk influencing factors for inadequately dialysis,and special attention should be paid to patients with TBW ＞ 30 L or LTI ＞ 11.05 kg/m2.