Salvianolic acid B alleviates autoimmunity in Treg-deficient mice via inhibiting IL2-STAT5 signaling.

Regulatory T cell (Treg) deficiency leads to immune dysregulation, polyendocrinopathy, enteropathy, and X-linked (IPEX) syndrome, which is a CD4+ T cell-driven autoimmune disease in both humans and mice. Despite understanding the molecular and cellular characteristics of IPEX syndrome, new treatment options have remained elusive. Here, we hypothesized that salvianolic acid B (Sal B), one of the main active ingredients of Salvia miltiorrhiza, can protect against immune disorders induced by Treg deficiency. To examine whether Sal B can inhibit Treg deficiency-induced autoimmunity, Treg-deficient scurfy (SF) mice with a mutation in forkhead box protein 3 were treated with different doses of Sal B. Immune cells, inflammatory cell infiltration, and cytokines were evaluated by flow cytometry, hematoxylin and eosin staining and enzyme-linked immunosorbent assay Kits, respectively. Moreover, RNA sequencing, western blot, and real-time PCR were adopted to investigate the molecular mechanisms of action of Sal B. Sal B prolonged lifespan and reduced inflammation in the liver and lung of SF mice. Moreover, Sal B decreased plasma levels of several inflammatory cytokines, such as IL-2, IFN-γ, IL-4, TNF-α, and IL-6, in SF mice. By analyzing the transcriptomics of livers, we determined the signaling pathways, especially the IL-2-signal transducer and activator of transcription 5 (STAT5) signaling pathway, which were associated with Treg deficiency-induced autoimmunity. Remarkably, Sal B reversed the expression of gene signatures related to the IL-2-STAT5 signaling pathway in vitro and in vivo. Sal B prolongs survival and inhibits lethal inflammation in SF mice through the IL-2-STAT5 axis. Our findings may inspire novel drug discovery efforts aimed at treating IPEX syndrome.

Effects of adjunctive Chinese patent medicine on outcome of viral encephalitis in children: A multicenter retrospective study in China.

BACKGROUND: Some patients with viral encephalitis in China seek treatment with Chinese patent medicine (CPM) to improve their symptoms, but few studies have focused on the impact of CPM on the prognosis of viral encephalitis (VE). The aim of this multicenter retrospective study was to assess the benefit of adjunctive CPM therapy on the outcome of children with VE in China. METHODS: This study retrospectively included 834 children with viral encephalitis who were hospitalized at five medical institutions from 2018 to 2021. Univariate and multivariate logistic regression was used to assess the effect of CPM on sequelae in patients with VE. 1:1 propensity score matching was used to exclude the effect of confounding factors. Forest plots were used to observe the effect of CPM on the prognosis of VE in different subgroups. RESULTS: There were fewer patients with sequelae in the group of patients using CPM regardless of whether they were matched or not. The results of multivariate logistic regression analysis showed that the use of CPM was an independent protective factor for the development of sequelae in VE patients (OR = 0.063, 95 % CI: 0.011-0.350, p = 0.002). Subgroup analyses showed that CPM was a protective factor for the development of sequelae regardless of the presence or absence of coma and comorbidities. In addition, we evaluated other outcome indicators and found shorter duration of illness, fever and headache in children with EV in the CPM group. CONCLUSION: Adjunctive CPM therapy may significantly reduce sequelae in children with VE, as well as effectively alleviate patients' clinical symptoms. However, more prospective studies and clinical trials are needed to further evaluate its efficacy and safety.

Four new species of the genus Eophileurus Arrow, 1908 (Coleoptera: Scarabaeidae: Dynastinae) from Thailand and Vietnam, with notes on some Indochinese species.

Four new species of the genus Eophileurus Arrow, 1908 are described: E. minor Yang Pathomwattananurak, new species (Thailand and Vietnam), E. prelli Yang Pathomwattananurak, new species (Vietnam), E. quadratifovealis Yang Pathomwattananurak, new species and E. sidereus Yang Pathomwattananurak, new species (both Thailand). Two new junior synonyms are proposed: E. confinis Prell, 1913 = E. takakuwai Yamaya Muramoto, 2008, new synonym and E. felschei Prell, 1913 = E. grossepunctatusDupuis, 2014, new synonym. Lectotypes for E. andamanicus Arrow, 1914 and E. siamensis Arrow, 1914 are designated. Taxonomic problems regarding E. confinis and E. malyi Endrdi, 1978 are discussed. Type material of E. andamanicus, E. confinis, E. decipiens Prell, 1913, E. felschei, E. gracilis Prell, 1913, E. grossepunctatus, E. malyi, E. nicobarensis Endrdi, 1978 and E. siamensis is illustrated. A distribution map of the new species and their closest relatives is also provided.

Safety and efficacy of Yupingfeng granules in children with recurrent respiratory tract infection: A randomized clinical trial.

Importance: Recurrent respiratory tract infection (RRTI) is common in children. Inappropriate RRTI treatment will lead to asthma and other diseases, thereby seriously affecting the growth and physical health of children. Immune function modulation can prevent and alleviate childhood RRTI. Yupingfeng (YPF), a patented traditional Chinese medicine (TCM), has immunomodulatory effects and is widely used in China to treat children with RRTI. Objective: To evaluate the safety and efficacy of YPF monotherapy in treating children with RRTI. Methods: This multicenter, randomized, double-blind, double-simulation, noninferiority clinical trial was conducted from January 2015 to August 2017, with an 8-week treatment period and 52-week follow-up after the drug withdrawal. Children aged 2-6 years with RRTI meeting the inclusion and exclusion criteria were enrolled in 13 hospitals in China and divided randomly into three groups (2:2:1 ratio) to receive YPF, pidotimod, or placebo. The primary outcome was the proportion of RRTI returning to normal standard level during the follow-up. The secondary outcomes were reduction in the number of RRTI recurrences, effect on clinical symptoms (in accord with TCM practice), effect per symptom, and safety. The trial was registered at the Chinese Clinical Trials Registry (www.chictr.org.cn) under the unique identifier ChiCTR-IPR-15006847. Results: Three hundred and fifty-one children were enrolled and randomly assigned to 3 groups; 124, 125, and 61 children in the YPF, pidotimod, and placebo groups, respectively, had completed the trial. During the follow-up, the proportion of RRTI returning to normal standard level was 73.13%, 67.15%, and 38.81% with YPF, pidotimod, and placebo, respectively (P < 0.0001). The proportion of cases who returned to normal standard level in the YPF group was 34.32% higher than that in the placebo group. The safety profile did not significantly differ among the groups. Interpretation: YPF granules were noninferior to the active control drug pidotimod oral solution for the treatment of RRTI in children, and were superior to placebo, with a high safety profile.

[The preliminary report of investigation: Using mask for cardiopulmonary exercise testing in Chinese children may result misinterpretation and misdiagnosis].

Objective: Observe the increased anatomical dead space of the mask, summarize the law of exercise induced oscillatory breathing (EIOB) in the results of CPET's new 9 figure, and analyze its incidence and age groups that are prone to oscillatory breathing. Methods: After signed the informed consent form by guardian, 501 children from pre-school to middle-school, aged 3~14 year, performed Harbor-UCLA standard protocol CPET with strict quality control in the CPET laboratory of Liaocheng Children's Hospital since 2014. CPET data was interpreted second by second from the breath by breath collection, averaged by 10s and then display by 9 plots. We analyzed the trends, pattern, incidence and age difference for EIOB and gas leakage. Results: The incidence of EIOB was the highest in the 3 to 6-year-old group, which was 42%. The 7 to 10-year-old group was 29.4% and the 11- to 14-year-old group was 29.9%. The three groups were tested by chi-square (x2=7.512), and the difference was statistically significant (P<0.05). 14 out of 508 children had air leakage during CPET, the incidence rate was 2.7%. Conclusion: The phenomenon of oscillatory breathing (OB) in children may be caused by the increased anatomical dead space of the mask, and it is not caused by disease. To improve the quality of CPET and to reduce clinical misdiagnosis, it is recommended to use a mouthpiece to decrease the dead space rather than the musk.

Analysis of enterovirus genotypes in the cerebrospinal fluid of children associated with aseptic meningitis in Liaocheng, China, from 2018 to 2019.

BACKGROUND: Aseptic meningitis is most often caused by enteroviruses (EVs), but EVs associated with aseptic meningitis have not yet been reported in Liaocheng. The aim of this study was to determine the prevalence and genetic characteristics of EVs causing aseptic meningitis in children in Liaocheng. METHODS: We reviewed the epidemiological and clinical characteristics of 504 paediatric cases of aseptic meningitis in Liaocheng from 2018 to 2019 and analysed the phylogeny of the predominant EV types causing this disease. RESULTS: A total of 107 children were positive for EV in cerebrospinal fluid samples by nested PCR. Most of the positive patients were children 13 years old or younger and had symptoms such as fever, headache and vomiting (P < 0.05). The seasons with the highest prevalence of EV-positive cases were summer and autumn. The 107 EV sequences belonged to 8 serotypes, and echovirus types 18, 6 and 11 were the three dominant serotypes in Liaocheng during the 2-year study period. Phylogenetic analyses demonstrated that the E18 and E6 isolates belonged to subgenotype C2, while the E11 isolates belonged to subgenotype D5. VP1 analysis suggested that only one lineage of these three types was cocirculating in the Liaocheng region. CONCLUSIONS: This study demonstrated the diverse EV genotypes contributing to a large outbreak of aseptic meningitis in Liaocheng. Therefore, large-scale surveillance is required to assess the epidemiology of EVs associated with aseptic meningitis and is important for the diagnosis and treatment of aseptic meningitis in Liaocheng.

[Value of N-terminal pro-brain natriuretic peptide in evaluating early septic cardiac dysfunction in neonates].

OBJECTIVE: To investigate the significance of N-terminal pro-brain natriuretic peptide (NT-proBNP) in the early assessment of neonatal cardiac dysfunction in sepsis. METHODS: The children diagnosed with neonatal sepsis and common infection neonates admitted to the department of pediatric neonatal intensive care unit (NICU) of Liaocheng People's Hospital from January 2016 to January 2019 were enrolled. Data of clinical sign, laboratory results, bedside echocardiography and survival data were collected, and the differences of clinical indexes were compared among sepsis patients with and without cardiac dysfunction and common infection. The risk factors of sepsis with cardiac dysfunction were analyzed by multivariate Logistic regression, and the early prediction value of NT-proBNP for neonatal septic cardiac dysfunction was evaluated by the receiver operating characteristic (ROC) curve. RESULTS: There were 112 neonates with sepsis (49 with cardiac dysfunction and 63 without cardiac dysfunction) and 67 children with common infection included in the analysis. The onset time of neonates in septic cardiac dysfunction group was significantly earlier than that of septic non-cardiac dysfunction group and common infection group [hours: 52.9 (0, 180.3) vs. 53.9 (0, 183.6), 81.0 (45.6, 202.4), both P < 0.05]. Compared with the general infection group, albumin (ALB), white blood cell count (WBC), left ventricular ejection fraction (LVEF) in septic cardiac dysfunction group significantly decreased, NT-proBNP, hypersensitive C-reactive protein (hs-CRP)/ALB, pulmonary artery systolic pressure (PASP) significantly increased, while right ventricular (RV) and Tei index significantly increased [ALB (g/L): 24.1±3.8 vs. 27.8±3.6, WBC (×109/L): 12.7 (3.7, 18.9) vs. 15.4 (9.9, 23.2), LVEF: 0.626±0.123 vs. 0.700±0.021, NT-proBNP (ng/L): 20 230.6 (15 890.0, 35 000.0) vs. 7 324.5 (2 426.5, 13 890.0), hs-CRP/ALB: 0.33 (0.29, 0.81) vs. 0.06 (0.00, 0.21), PASP (mmHg, 1 mmHg = 0.133 kPa): 52.25±14.12 vs. 41.07±27.73, RV (mm): 10.74±2.42 vs. 8.55±1.41, Tei index: 0.52±0.03 vs. 0.30±0.04, all P < 0.05]. NT-proBNP and Tei index in septic cardiac dysfunction group were significantly higher than those in septic non-cardiac dysfunction group [NT-proBNP (ng/L): 20 230.6 (15 890.0, 35 000.0) vs. 13 057.6 (8 946.0, 35 000.0), Tei index: 0.52±0.03 vs. 0.39±0.02, both P < 0.05], and LVEF was significantly lower than that in septic non-cardiac dysfunction group (0.626±0.123 vs. 0.671±0.086, P < 0.05). Multivariate Logistic regression analysis showed that NT-proBNP, Tei index and hs-CRP/ALB were independent risk factors for cardiac dysfunction in sepsis neonates [odds ratio (OR) and 95% confidence interval (95%CI) were 8.73 (1.54-5.67), 1.97 (1.26-2.87), 1.87 (1.03-3.40) respectively, all P < 0.05]. ROC curve analysis showed that NT-proBNP, Tei index and hs-CRP/ALB had good predictive value for the occurrence of cardiac dysfunction in septic neonates, the area under ROC curve (AUC) was 0.81 (95%CI was 0.84-0.91), 0.78 (95%CI was 0.65-0.79) and 0.77 (95%CI was 0.61-0.77), respectively. The sensitivity and specificity of NT-proBNP were 80.0% and 79.0% respectively with 12 291.5 ng/L as the cut-off value, the sensitivity and specificity of Tei index were 74.0% and 77.0% respectively with 0.45 as the cut-off value, and the sensitivity and specificity of hs-CRP/ALB were 76.0% and 76.3% respectively with 0.10 as the cut-off value. CONCLUSIONS: NT-proBNP can be used as a diagnostic marker of early cardiac dysfunction, and for rapid diagnosis of neonatal cardiac dysfunction in sepsis. The application may guide clinicians to use drugs better to improve cardiac function and treatment effect.

Flavone inhibited proliferation of T-ALL by promoting c-Cbl-induced ubiquitinylation and degradation of Notch1.

Aberrant activation of Notch1 signaling frequently occurs in T-cell acute lymphoblastic leukemia (T-ALL). Notch1 activation causes release of intracellular Notch1 (ICN1, the activated form of Notch1) from cell membrane to cytoplasm. As a transcription factor, ICN1 must be transferred into nucleus and bind to the promoters of its downstream target genes. E3 ubiquitin ligase induces ICN1 degradation in cytoplasm, which blocks ICN1 transfer into the nucleus. Flavone is a natural plant polyphenol, demonstrated to have anti-cancer effects in vitro and in vivo in breast and colon cancers. However, the effects of flavone on leukemia have not been reported. In this study, we demonstrated that flavone inhibited cell proliferation by down-regulating Notch1 signal pathway in CCRF-CEM and Molt-4 T-ALL cells. Flavone-mediated upregulation of c-Cbl level results in the increase in its interaction with ICN1, further caused ICN1 ubiquitinylation and degradation. Knockdown of c-Cbl reversed flavone-induced down-regulation of ICN1 and inhibition of cell proliferation in T-ALL cells. In short, this study indicated that flavone exerted resistance to T-ALL by promoting c-Cbl-induced ubiquitinylation and degradation of ICN1.

Early Premature Infant Oral Motor Intervention Improved Oral Feeding and Prognosis by Promoting Neurodevelopment.

OBJECTIVE: This study aimed to explore the clinical significance of early premature infant oral motor intervention (PIOMI) in the prognosis of premature infants. STUDY DESIGN: Infants were randomly divided into an intervention group (n = 78) and a control group (n = 73). PIOMI was given to the intervention group 15 to 30 minutes before feeding once a day for 14 days. The whole procedure lasted 15 minutes, including oral stimulation and nonnutritive sucking. Oral feeding ability and neuromotor development were evaluated using the Preterm Infant Oral Feeding Readiness Assessment (PIOFRA) scale and Infant Neurological International Battery (Infanib) scale. RESULTS: The PIOFRA score was higher in the intervention group and increased with time, showing a group-time interaction effect. The intervention group exhibited a higher feeding efficiency, a shorter transition time from assisted oral feeding to independent oral feeding, and lower body weight at achievement of independent oral feeding. The percentages of infants with a normal score on the Infanib scale were higher in the intervention group at 3 and 6 months of age, and an abnormal ratio was lower in the intervention group at 6 months (p < 0.01). CONCLUSION: PIOMI promoted neuromotor coordination by improving neurodevelopment, thereby improving the oral feeding ability and prognosis of preterm infants.

Chinese guidelines for the diagnosis and treatment of hand, foot and mouth disease (2018 edition).

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease in childhood caused by an enterovirus (EV), and which is principally seen in children under 5 years of age. To promote diagnostic awareness and effective treatments, to further standardize and strengthen the clinical management and to reduce the mortality of HFMD, the guidelines for diagnosis and treatment have been developed. METHODS: National Health Commission of China assembled an expert committee for a revision of the guidelines. The committee included 33 members who are specialized in diagnosis and treatment of HFMD. RESULTS: Early recognition of severe cases is utmost important in diagnosis and treatment of patients with HFMD. The key to diagnosis and treatment of severe cases lies in the timely and accurate recognition of stages 2 and 3 of HFMD, in order to stop progression to stage 4. Clinicians should particularly pay attention to those EV-A71 cases in children aged less than 3 years, and those with disease duration less than 3 days. The following indicators should alert the clinician of possible deterioration and impending critical disease: (1) persistent hyperthermia; (2) involvement of nervous system; (3) worsening respiratory rate and rhythm; (4) circulatory dysfunction; (5) elevated peripheral WBC count; (6) elevated blood glucose and (7) elevated blood lactic acid. For treatment, most mild cases can be treated as outpatients. Patients should be isolated to avoid cross-infection. Intense treatment modalities should be given for those severe cases. CONCLUSION: The guidelines can provide systematic guidance on the diagnosis and management of HFMD.

Clinical characteristics and etiology of bacterial meningitis in Chinese children >28 days of age, January 2014-December 2016: A multicenter retrospective study.

OBJECTIVE: To explore the clinical characteristics and etiology of bacterial meningitis (BM) in Chinese children. METHOD: BM cases in children 28days to 18 years old were collected from January 2014-December 2016 and screened according to World Health Organization standards. Clinical features, pathogens, and resistance patterns were analyzed. RESULTS: Overall, 837 cases were classified into five age groups: 28 days-2 months (17.0%), 3-11 months (27.8%), 12-35 months (24.0%), 3-6 years (13.9%), and >6years (17.3%). Major pathogens were Streptococcus pneumoniae (S. pneumoniae, n=136, 46.9%), group B Streptococcus (GBS, n=29, 10.0%), and Escherichia coli (E. coli, n=23, 7.9%). In infants <3 months old, GBS (46.5%) and E. coli (23.3%) were most common; in children >3 months old, S. pneumoniae (54.7%), which had a penicillin non-susceptibility rate of 55.4% (36/65), was most frequent. The resistance rates of S. pneumoniae and E. coli to cefotaxime and ceftriaxone were 14.0%/40.0% and 11.3%/68.4%, respectively. All GBS isolates were sensitive to penicillin. CONCLUSIONS: The occurrence of BM peaked in the first year of life, while S. pneumoniae was the predominant pathogen in children >3months of old. The antibiotic resistance of S. pneumoniae was a concern.

Fulminant Type 1 Diabetes in Children: A Multicenter Study in China.

BACKGROUND: To investigate the hospital-based incidence of FT1D in Chinese children and compare the clinical feature with classical T1DM. METHODS: A cross-sectional study with sixteen hospitals involved. We obtained 23 FT1D cases as group 1, acute-onset T1DM as group 2, and typical T1DM as group 3. RESULTS: The incidence of FT1D was 1.56% in 16 participating hospitals. The mean age at the onset of group 1 was 2.00 (1.08, 6.51) years old, much younger than that of group 2 (6.11 (3.92, 9.50)) and group 3 (6.92 (4.17, 10.03)). In addition, significant differences were found between three groups: mean BMI and flu-like symptoms with fever and abdominal pain. Follow-up comparison of three groups from Beijing Children's Hospital for at least one year showed that there is no significant difference between the three groups in terms of mean HbA1c levels and insulin injection dosages. CONCLUSION: FT1D onset age is much younger than that of classical T1D patients. The hospital-based incidence of FT1D in Chinese children was 1.56% in all new-onset T1DM. For the diagnosis, making FT1D alone into a subtype within type 1 diabetes may be meaningful. However, for the treatment and prognosis, such classification should not be helpful to the clinic.

Intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar protective immunity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine.

Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) are the two major causative agents of hand, foot and mouth disease (HFMD), which erupts in the Asia-Pacific regions. A bivalent vaccine against both EV71 and CVA16 is highly desirable. In the present study, on the bases that an experimental bivalent vaccine comprising of inactivated EV71 and CVA16 induces a balanced protective immunity against both EV71 and CVA16, we compare the immunogenicity and reactogenicity of one fourth of a full dose of an intradermal vaccine administered by needle-free liquid jet injector with a full dose of an intramuscular vaccine administered by needle-syringe in monkeys. The results suggest that intradermal injection of a fractional dose of an inactivated HFMD vaccine elicits similar immunogenicity and reactogenicity to intramuscular inoculation of a full dose of an Al(OH)3-adjuvanted vaccine, regardless of whether monovalent or bivalent vaccines were used. Our results support the use of an intradermal bivalent vaccine strategy for HFMD vaccination in order to satisfy the requirements and reduce the costs.

Effects of erythropoietin on neonatal hypoxia-ischemia brain injury in rat model.

BACKGROUND: Hypoxic-ischemic (HI) injury to the developing brain remains a major cause of morbidity. To date, few therapeutic strategies could provide complete neuroprotection. Erythropoietin (EPO) has been shown to be beneficial in several models of neonatal HI. This study examines the effect of treatment with erythropoietin on postnatal day 2 (P2) rats introduced with HI injury. METHOD: Rats at P2 were randomized into four groups: sham, bilateral carotid artery occlusion (BCAO), BCAO + early EPO, and BCAO + late EPO groups. Pups in each group were injected with either saline or EPO (5000U/kg) intraperitoneally once at immediately (early) or 48h (late) after HI induction. Body weight was assessed at P2 before and day 7 after HI. Mortality Rate was assessed at 24h, 48h and 72h after HI and brain water content was assessed at 72h. Brain weight and expression of myelin basic protein (MBP) were assessed at day 7 and day 14. At day 31 to 35 following HI insult, neurological behavior function was assessed via Morris water maze (MWM) test. RESULT: HI cause significant higher mortality in male than in female (P=0.0445). Among the surviving animal, HI affect significantly the body growth, brain growth, MBP expression, and neurological behavior. EPO treatments at both early and late time points significantly benefit the rats in injury recovery, in which they promoted weight gains, reduced brain edema, as well as improved spatial learning ability and memory. CONCLUSION: We demonstrated a single dose of EPO at 5000U/kg immediately or 48h after HI injury had significant benefit for the P2 rats in injury recovery, and there was no adverse effect associated with either EPO treatment.

Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line.

OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. RESULTS: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. CONCLUSION: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia.

Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line.

OBJECTIVES: To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. MATERIALS AND METHODS: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. RESULTS: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. CONCLUSION: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia[PARANDCO1].

Application of Glutamine-enriched nutrition therapy in childhood acute lymphoblastic leukemia.

BACKGROUND: We investigated the effects of glutamine (Gln)-enriched nutritional therapy during chemotherapy on the nutritional status and immune function of children with acute lymphoblastic leukemia (ALL). METHODS: We enrolled 48 children who were newly diagnosed with ALL in our department during the period of 2013.1-2014.12. The patients (follow random number table) were randomly divided into the control group (peptamen) and the treatment group (peptamen + glutamine), 24 cases in each group. The remission induction regimens were all based on VDLP (D) chemotherapy (VCR (Vincrisstine), DNR (Daunomycin), L-ASP (L-Asparagiase), Prednisolone and Dexamethasone). The treatment group received Gln-enriched nutritional therapy every day during the full course of chemotherapy,and the control group is as same as the treatment group except without glutamine. The indicators of general nutritional status, such as weight, height, and triceps skinfold thickness, and the indicators of biochemical tests, such as serum albumin, prealbumin, creatinine-height index, retinol binding protein, and urinary hydroxyproline index, were compared between the two groups at the end of the first, second, third and the fourth week when the chemotherapy was completed. And in the fourth week, flow cytometry was applied to detect the levels of T cell subsets and the activities of natural killer (NK) cells in peripheral blood of the two groups. RESULTS: 1. after 4 weeks nutritional therapy, there is no significant difference (p > 0.05) between the two groups of children in weight, height and other indicators. 2. At the end of 2 weeks treatment, the level of prealbumin (PA) and retinol-binding protein (RBP) is higher in treatment group than that in the control group (P <0.05), at the end of 3 weeks treatment, the thickness of triceps skinfold is higher (P <0.05) than that in the control group; 3. At the end of 3 and 4 weeks, the concentrations serum ALB, PA, RBP and UHI were higher than in the control group (P <0.05); 4. There is statistically significant (p < 0.05) between the two groups in edema incidence; 5. At the end of treatment (4 weeks), the percentages of CD3 +, CD4 +, CD4 +/CD8 +, NK cell are significantly decreased in the two groups (P <0.05). CONCLUSION: Gln-enriched nutritional therapy can effectively improve the systemic nutritional status of children with leukemia, improve immune function.

Knockdown of USP39 by lentivirus-mediated RNA interference suppresses the growth of oral squamous cell carcinoma.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is a frequently diagnosed life-threatening oral cancer worldwide and has become one of the leading causes of cancer-related mortality. However, the pathogenesis of this disease is very limited. OBJECTIVE: In this study, we aimed to investigate the functional relationship between OSCC and a potential tumor related gene ubiquitin-specific proteases 39 (USP39). METHODS: The lentivirus-based RNA interference was utilized to knock down USP39 expression in human OSCC CAL27 cells. The effect of USP39 on cell proliferation was detected by MTT and colony formation assays. RESULTS: The results uncovered that the proliferation rate was significantly decreased in specific USP39-targeting lentivirus infected cells compared to control lentivirus infected cells. The colony formation capacity was also attenuated in CAL27 cells after USP39 knockdown. Moreover, knockdown of USP39 arrested CAL27 cells in S and G1/M phases of the cell cycle. Furthermore, USP39 silencing induced apoptosis of CAL27 cells via activations of Caspase 3 and PARP. CONCLUSIONS: In conclusion, the inhibition of USP39 in CAL27 cells suppressed cell growth probably via induction cell cycle arrest and apoptosis. USP39 might act as an oncogenic factor in OSCC and could be a potential molecular target for OSCC gene therapy.

[The diagnostic value of high-sensitivity C-reactive protein/albumin ratio in evaluating early-onset infection in premature].

OBJECTIVE: To observe the diagnostic value of high-sensitivity C-reactive protein/albumin ratio (hs-CRP/ALB) in early-onset infection in premature and its clinical significance. METHODS: Clinical data of premature patients with high risk factors of intrauterine infection admitted to neonatal intensive care unit (NICU) of Liaocheng People's Hospital in Shandong Province from July 2013 to July 2015 were analyzed retrospectively. They were divided into infection and non-infection groups, as well as survival and death groups according to the outcome of the premature babies. The pre-albumin (PA), ALB, white blood cell count (WBC), platelet count (PLT), and hs-CRP at the moment of NICU admission (0 hour) and 24, 48 and 72 hours after NICU admission were compared. The receiver operating characteristic (ROC) curve was plotted for evaluation of the predictive value of serum hs-CRP/ALB ratio for the babies during hospitalization. RESULTS: A total of 214 cases of premature infants were enrolled, with 102 cases in infection group, and 112 in non-infection group. In infection neonates, 97 of them survived, and 5 died. (1) The level of hs-CRP after NICU admission was increased in infection and non-infection groups, and it was significantly higher at 48 hours in infection group than that of the non-infection group [mg/L: 22.0 (7.6, 40.4) vs. 18.3 (12.9, 23.4),Z = 5.257,P = 0.038]. Then hs-CRP was decreased in non-infection, but it was persistently increased in infection group, and it was significantly higher at 72 hours in infection group than that of the non-infection group [mg/L: 25.5 (9.8, 43.5) vs. 12.2 (1.9, 22.1), Z = 5.879, P = 0.042]. The levels of ALB and WBC in infection group was significantly lower than those of the non-infection group [ALB (g/L): 27.9±2.7 vs. 29.1±2.9, t = 5.178, P = 0.026; WBC (×109/L): 13.7±7.1 vs. 16.1±7.9, t = 4.368, P = 0.037], and at 48 hours hs-CRP/ALB in infection group was significantly higher than that of non-infection group [0.16 (0.08, 0.57) vs. 0.07 (0.00, 0.23), Z = 3.436, P = 0.042]. There was no significant difference in PA and PLT between infection and non-infection groups. (2) In premature patients with infection, ALB in non-survival group was decreased (g/L: 20.4±6.9 vs. 29.6±7.5, t = 7.859, P = 0.003), and 48-hour hs-CRP and hs-CRP/ALB ratio was significantly increased when compared with that of survival group [hs-CRP (mg/L): 25.8 (15.6, 54.8) vs. 18.2 (12.9, 36.2), Z = 4.067, P = 0.043; hs-CRP/ALB: 0.31 (0.28, 0.76) vs. 0.06 (0.00, 0.21), Z = 6.102, P = 0.011].(3) It was shown by ROC curve analysis that the area under ROC curve (AUC) of 48-hour hs-CRP/ALB ratio for evaluating infection was 0.765, when the cut-off of 48-hour hs-CRP/ALB ratio was 0.08, the sensitivity was 84.2%, and the specificity was 76.3%. CONCLUSIONS: The values of hs-CRP and ALB can be used as effective indexes in early diagnosis of intrauterine bacterial infection, and increase in 48-hour hs-CRP/ALB can improve the sensitivity of the diagnosis. Hs-CRP/ALB can be combined to guide rational use of antibiotics.

Relationship Between Serum Albumin Levels and Infections in Newborn Late Preterm Infants.

BACKGROUND: We aimed to evaluate the clinical value of serum albumin levels for the evaluation and prognosis of late preterm infants with infections. MATERIAL/METHODS: This was a retrospective study performed in late preterm infants admitted at the neonatal intensive care unit (NICU) of the Liaocheng People's Hospital between July 2012 and March 2013. Data, including laboratory test results, neonatal critical illness score (NCIS), perinatal complications and prognosis, were analyzed. The newborn infants were divided into 3 groups according to their serum albumin levels, (≥30 g/L, 25-30 g/L and ≤25 g/L for high, moderate, and low, respectively). RESULTS: Among 257 patients, birth weight was 2003±348 g, gestational age was 35.7±2.3 weeks, and 59.1% were male. In addition, 127 (49.4%) were in the low albumin group. There were 32 patients with sepsis, 190 with infections, and 35 without infection, and their rates of hypoalbuminemia were 86.0%, 50.5%, and 30.7%, respectively (P<0.05). Albumin levels of the patients who survived were higher than those of the patients who died. In the low albumin group, the number of individual-event-critical NCIS cases and the frequency of multiple organs injuries were 63.8% and 28.3%, respectively, and were higher than in the 2 other groups. Mortality was higher in patients with sepsis. Hypoalbuminemia was associated with severe adverse outcomes (odds ratio=6.3, 95% confidence interval: 3.7-10.9, P<0.001). CONCLUSIONS: Hypoalbuminemia was frequent among neonates with sepsis. Lower albumin levels might be associated with a poorer prognosis. Albumin levels could be appropriate for the diagnosis and prognosis of late preterm neonates with infections.