[Effect on ankylosing spondylitis at early-middle stage and bone marrow edema of sacroiliac joint treated with acupuncture and governor vessel moxibustion].

OBJECTIVE: To observe the efficacy of the combined treatment with acupuncture and governor vessel moxibustion on ankylosing spondylitis (AS) at early-middle stage and investigate the effect on bone marrow edema of sacroiliac joint. METHODS: Seventy patients of AS at early-middle stage were randomized into an observation group (35 cases) and a control group (35 cases, 1 case dropped off ). In the control group, the recombinant human tumor necrosis factor receptor-antibody of type Ⅱ fusion protein for injection was injected subcutaneously, 25 mg each time, once on every Monday and Friday, consecutively for 3 weeks. In the observation group, on the base of the intervention as the control group, acupuncture combined with governor vessel moxibustion were provided. Acupuncture was applied to Dazhui (GV 14), Changqiang (GV 1), Zhibian (BL 54), Baihui (GV 20), etc.; the thermal needling technique was adopted at Dazhui (GV 4) and Changqiang (GV 1) for promoting the circulation of the governor vessel, and the ginger-isolated moxibustion on the governor vessel was combined. Such intervention measure was provided once daily. One treatment session contained 7 treatments and 3 sessions were required. Before and after treatment, the scores of Spondyloarthritis Research Consortium of Canada (SPARCC), Bath ankylosing spondylitis disease activity index (BASDAI) and Bath ankylosing spondylitis functional index (BASFI) and Bath ankylosing spondylitis patient global score (BAS-G) were observed in the two groups separately. The efficacy and adverse effects were assessed in the two groups after treatment. RESULTS: The scores of SPARCC, BASDAI, BASFI and BAS-G were all reduced after treatment compared with those before treatment in the two groups (P<0.05), and those in the observation group were lower than the control group (P<0.05). The total effective rate was 97.1% (34/35) in the observation group, higher than 82.4% (28/34) in the control group (P<0.05). There were 4 cases of gastrointestinal reactions and 1 case of skin rashes in the control group; and 3 cases of local skin redness and pruritus after governor vessel moxibustion, no any drug adverse effect was found in the observation group. CONCLUSION: Based on the western medicine treatment, the combined therapy of acupuncture and governor vessel moxibustion may relieve bone marrow edema of sacroiliac joint in patients with AS at early-middle stage, control the progression of disease and improve the daily life activity. This therapy is relatively safe and effective.

Study on serum Tau protein level and neurodevelopmental outcome of placental abruption with neonatal hypoxic-ischemic encephalopathy.

Objective: The aim of this study was to explore differences in serum Tau protein levels and neurodevelopmental prognoses of placental abruption or umbilical cord around neck with hypoxic-ischemic encephalopathy (HIE).Methods: Forty neonates with moderate/severe HIE divided into placental abruption with HIE group (placental abruption with hypoxic-ischemic encephalopathy (PA-HIE) group) (n = 18) and umbilical cord around the neck with HIE group (umbilical cord around the neck with hypoxic-ischemic encephalopathy (UCAN-HIE) group) (n = 22). Healthy term newborns comprised the control group (n = 35). Serum Tau protein levels were measured using an enzyme-linked immunosorbent assay 24 hours (3.50 hours [1.00-24.00]) after birth. Neurodevelopment outcomes were assessed based on the Gesell Developmental Scale at 9 months of age.Results: Serum Tau protein levels were significantly higher in 40 cases (1013 pg/ml [538.04-1190.42]) than in the control group (106.41 pg/ml [64.55-154.71], p = .0001). Serum Tau protein levels in the PA-HIE group (1024.46 pg/ml [657.88-1190.42]) were significantly higher than those in the UCAN-HIE group (892.78 pg/ml [538.04-1179.50], p = .0149). The development quotient score in the PA-HIE group (67.0 [47.0-90.0]) was significantly lower than that in the UCAN-HIE group (81.5 [52.6-100.0]) (p = .0028). The component ratio of neurodevelopmental retardation in the PA-HIE group (44.45%) was significantly higher than that in the UCAN-HIE group (22.73%) (X2 = 13.3138, p = .0013).Conclusions: Compared with the UCAN-HIE group, the serum Tau protein level and the component ratio of neurodevelopmental retardation were significantly higher in the PA-HIE group.

A Case Report of Primary Neonatal Hypocholinesterase Caused by Homozygous Frameshift Mutation of the utyrylcholinesterase (BCHE) Gene and Review of Literature.

BACKGROUND: Primary neonatal hypocholinesterase is rare; its genetic pattern and mutation still need to be further studied. METHODS: The patient and his parents are studied using next-generation sequencing technology. RESULTS: A boy one day after birth is admitted to the Neonatal Intensive Care Unit at our hospital after experiencing intermittent vomiting for 12 hours. The patient's serum cholinesterase level (113 - 283 U/L) is lower than normal value (4,000 - 12,600 U/L). Many factors of low serum cholinesterase are excluded. We highly suspect that it may be related to congenital factors. Molecular genetic test results show that the patient carried the BCHE gene (NM_000055.2) and has homozygous frameshift mutations at exon 2 c.401dupA (p.Asn134fs) of chromosome 3q26. It is a pathogenicity mutation. This locus mutation belongs to a novel pathogenic mutation. As a result of this mutation, the 134th amino acid Asn began to frameshift and the translation is terminated early. It can cause the Encoding of protein to truncate and lose its normal function. His parents' serum cholinesterase levels (father: 5,135 U/L; mother: 4,367 U/L) are in the normal value range, but his parents carried a heterozygous BCHE gene. CONCLUSIONS: This study suggests that gene sequence detection should be carried out early in hypocholinesterase of nknown cause in neonates. This study can not only improve understanding of the etiology and pathological mechanism of hypocholinesterase, but also it can enlarge the hypocholinesterase gene mutation spectrum.

Serum levels of PIICP, PIIANP, and PIIBNP are decreased in patients with an endemic osteochondropathy, Kashin-Beck disease.

BACKGROUND: Kashin-Beck disease (KBD) is an endemic, chronic, degenerative osteoarthropathy. KBD is usually diagnosed by using X-ray image and clinical symptoms, lacking of serological biomarkers. The serum level of PIICP, PIIANP, and PIIBNP can specifically reflect the damage of the cartilage. So, in this study, the serum levels of PIICP, PIIANP, and PIIBNP were detected in order to determine whether they can be used as potential biomarkers for the diagnosis of KBD. METHOD: Using a status survey, the survey sites were selected in the KBD historical endemic areas and non-endemic areas in Jilin and Heilongjiang provinces. All local residents have undergone clinical examination, X-ray examination of the hands and knees, and questionnaire survey. A total of 554 people were surveyed, and 184 residents who are eligible for inclusion criteria were selected as our subjects. Fifty-six cases were diagnosed as KBD and 63 individuals were included as internal control and 65 subjects were included as external control. And blood samples of surveyed subjects were collected, and the serum was separated to detect the levels of PIICP, PIIANP, and PIIBNP by ELISA. Statistical analysis was performed using the SPSS software. RESULTS: There were no statistically significant differences in age and sex among the three groups. The Kruskal-Wallis H test showed that the serum levels of PIICP, PIIANP, and PIIBNP were significantly different among the three groups. Multiple comparisons using Dunnett's T3 test revealed that serum levels of PIICP, PIIANP, and PIIBNP were significantly lower in KBD patients than in internal and external control. However, there was no significant difference between the internal and external control. CONCLUSIONS: The results preliminarily indicated that the levels of PIICP, PIIANP, and PIIBNP in serum could reflect the abnormal synthesis of type II collagen in KBD patients and suggested that these indicators might be used as potential biomarkers for the diagnosis of KBD.

SATB2-Associated Syndrome: a Case Report of a De Novo Nonsense Mutation in SATB2 from China and Review of Literature.

BACKGROUND: To study the clinical and genetic features from a Chinese child with SATB2-associated syndrome (SAS) and review of literature. METHODS: The girl, 2 years 3 months old, is admitted to the Department of Pediatric Rehabilitation in our hospital. This patient has mental retardation, language development disorder, cleft palate II0, micrognathia, malocclusion, irritability and bilateral oblique palpebral fissure as a clinical manifestation and is treated for 3 months. RESULTS: Gesell Development Scale (GDS) evaluation displays the patient's action capacity: gross motor 13.4, DQ 41%; fine motor 14.1, DQ 44%; adaptive behavior: DA 15.2, DQ 47%; speech capacity: DA 8.8; DQ 27%; person capacity: DA 11.7, DQ, 36%. Bayley Scale evaluation displays MDI < 50 and PDI < 50. Sleep EEG showed bilateral frontal pole - frontal - central - anterior temporal area presents in sharp wave, sharp and slow wave synchronization issue. A brain MRI showed that signal T2 is strengthened in the internal capsule hind leg. Flake T2FLATR high signal can been showed in the periventricular area of the parietal lobe in bilateral hemisphere. Molecular studies showed the patient carries a de novo nonsense mutation c.1285G>A (p.R429X) in SATB2. CONCLUSIONS: SATB2 mutation is not detected in the parents of the subjects. This study is important to further study the clinical features of SATB2-associated syndrome and to enlarge the SATB2 mutation spectrum.

Prevalence of hand osteoarthritis and knee osteoarthritis in Kashin-Beck disease endemic areas and non Kashin-Beck disease endemic areas: A status survey.

Osteoarthritis (OA) is a considerable health problem worldwide, and the prevalence of OA varies in different regions. In this study, the prevalence of OA in Kashin-Beck disease (KBD) and non-KBD endemic areas was examined, respectively. According to monitoring data, 4 types of regions (including none, mild, moderate and high KBD endemic areas) in Heilongjiang and Jilin provinces were selected. All local residents were eligible for inclusion criteria have undergone X-ray images of hands and anteroposterior image of knees. A total of 1673 cases were collected, 1446 cases were analyzed after removing the KBD patients (227). The overall hand OA and knee OA detection rates were 33.3% (481/1446) and 56.6% (818/1446), respectively. After being standardized by age, the detection rate of hand OA in the KBD endemic areas was significantly higher than that in the non-endemic endemic areas. Differently, there was no significant difference in the detection rates of knee OA between the KBD endemic areas and the non-endemic area. The correlation coefficient between the severity of OA and the severity of knee OA was 0.358 and 0.197 in the KBD and non-KBD endemic areas, respectively. Where the KBD historical prevalence level was higher, the severity of the residents' hand OA was more serious. The detection rates of hand OA and knee OA increased with age. The detection rate of knee OA increased with the increase in body mass index. The prevalence of hand OA was closely related to the pathogenic factors of Kashin-Beck disease, and the prevalence of knee OA had no significant correlation with KBD pathogenic factors.

Effect of erythropoietin combined with hypothermia on serum tau protein levels and neurodevelopmental outcome in neonates with hypoxic-ischemic encephalopathy.

Although hypothermia therapy is effective to treat neonatal hypoxic-ischemic encephalopathy, many neonatal patients die or suffer from severe neurological dysfunction. Erythropoietin is considered one of the most promising neuroprotective agents. We hypothesized that erythropoietin combined with hypothermia will improve efficacy of neonatal hypoxic-ischemic encephalopathy treatment. In this study, 41 neonates with moderate/severe hypoxic-ischemic encephalopathy were randomly divided into a control group (hypothermia alone for 72 hours, n = 20) and erythropoietin group (hypothermia + erythropoietin 200 IU/kg for 10 days, n = 21). Our results show that compared with the control group, serum tau protein levels were lower and neonatal behavioral neurological assessment scores higher in the erythropoietin group at 8 and 12 days. However, neurodevelopmental outcome was similar between the two groups at 9 months of age. These findings suggest that erythropoietin combined with hypothermia reduces serum tau protein levels and improves neonatal behavioral neurology outcome but does not affect long-term neurodevelopmental outcome.

Predictive Value of Neurodevelopmental Outcome and Serum Tau Protein Level in Neonates with Hypoxic Ischemic Encephalopathy.

BACKGROUND: Tau protein is s specific protein expressed by neurons in the central nervous system. Elevated serum Tau protein is associated with many diseases of the central nervous system. The serum Tau protein level in neonates with hypoxic ischemic encephalopathy (HIE) is still poorly understood. METHODS: Forty-one human neonates with HIE and thirty-five healthy neonates (control group) within 24 hours after birth were studied. Tau protein in serum was detected by enzyme-linked immunosorbent assay. Neurological outcome was assessed at 9 months of age according to the Gesell developmental scale. RESULTS: Tau protein in serum was significantly higher in the HIE group than in the control group (p < 0.01), in neonates with severe HIE than neonates with moderate HIE (p < 0.01), and in infants with neurodevelopmental retardation compared with those with normal neurodevelopment (p < 0.01). The result of this study showed an obvious negative correlation between the serum Tau protein level and development quotients of neonates with HIE (rs = -0.6172, p < 0.01). Receiver operator characteristic curve analysis showed that Tau protein (cutoff value 933.04 pg/mL) was a predictor of neurodevelopmental retardation outcome (AUC value = 0.860 (95% CI: 0.736 - 0.983, p < 0.01), sensitivity 100%, specificity 70.8%). CONCLUSIONS: Serum Tau protein level within 24 hours after birth can be used as a marker for the early diagnosis of neonatal HIE and predicting neurodevelopmental outcomes.

Protective effects of a green tea polyphenol, epigallocatechin-3-gallate, against sevoflurane-induced neuronal apoptosis involve regulation of CREB/BDNF/TrkB and PI3K/Akt/mTOR signalling pathways in neonatal mice.

Epigallocatechin-3-gallate (EGCG), a polyphenol in green tea, is an effective antioxidant and possesses neuroprotective effects. Brain-derived neurotrophic factor (BDNF) and cyclic AMP response element-binding protein (CREB) are crucial for neurogenesis and synaptic plasticity. In this study, we aimed to assess the protective effects of EGCG against sevoflurane-induced neurotoxicity in neonatal mice. Distinct groups of C57BL/6 mice were given EGCG (25, 50, or 75 mg/kg body weight) from postnatal day 3 (P3) to P21 and were subjected to sevoflurane (3%; 6 h) exposure on P7. EGCG significantly inhibited sevoflurane-induced neuroapoptosis as determined by Fluoro-Jade B staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL). Increased levels of cleaved caspase-3, downregulated Bad and Bax, and significantly enhanced Bcl-2, Bcl-xL, xIAP, c-IAP-1, and survivin expression were observed. EGCG induced activation of the PI3K/Akt pathway as evidenced by increased Akt, phospho-Akt, GSK-3ß, phospho-GSK-3ß, and mTORc1 levels. Sevoflurane-mediated downregulation of cAMP/CREB and BDNF/TrkB signalling was inhibited by EGCG. Reverse transcription PCR analysis revealed enhanced BDNF and TrkB mRNA levels upon EGCG administration. Improved performance of mice in Morris water maze tests suggested enhanced learning and memory. The study indicates that EGCG was able to effectively inhibit sevoflurane-induced neurodegeneration and improve learning and memory retention of mice via activation of CREB/BDNF/TrkB-PI3K/Akt signalling.

[Impact of premature rupture of membranes on neonatal complications in preterm infants with gestational age <37 weeks].

OBJECTIVE: To investigate the effect of premature rupture of the membrane (PROM) on neonatal complications in premature infants. METHODS: The registration information of 7684 preterm infants with gestational age <37 weeks were collected from the cooperative units in the task group between January 1, 2014 to December 31, 2014. Specially trained personnel from each cooperative units filled in the unified form in a standardized format to record the gender, gestational age, birth weight, PROM, placental abruption, antenatal corticosteroid, Apgar score, amniotic fluid pollution, and complications of the infants. The data were analyzed comparatively between the cases with PROM and those without (control). RESULTS: The preterm mortality rate was significantly lower but the incidences of ICH, NEC, ROP and BPD were significantly higher in PROM group than in the control group (P<0.05). The 95% confidence interval of the OR value was <1 for mortality, and was >1 for ICH, NEC, ROP and BPD. After adjustment for gestational age, birth weight, gender, mode of delivery, placental abruption, placenta previa, prenatal hormones, gestational diabetes mellitus (GDM), gestational period hypertension and 5-min Apgar score <7, the incidences of NEC, ROP and BPD were significantly different between the two groups (P<0.05) with 95% confidence interval of OR value >1, but the mortality rate and incidence of ICH were not significantly different between the two groups (P>0.05). CONCLUSION: PROM is a risk factor for NEC, ROP and BPD in preterm infants, and adequate intervention of PROM can reduce the incidences of such complications as NEC, ROP and BPD in the infants.

Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage.

The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P<0.01) and the SOD activities were lower while the MDA levels were higher (P<0.01) in the HIBD group. No significant differences in ultrastructure, the latency of F-VEPs or SOD/MDA levels were identified between the HBO-treated HIBD group and the normal control group (P>0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.

[Expression of nesfatin-1/NUCB2 and ghrelin in gastric mucosa of rats with intrauterine growth retardation].

OBJECTIVE: To investigate the expression of nesfatin-1/NUCB2 and ghrelin in the gastric mucosa of rats with intrauterine growth retardation (IUGR) and its significance. METHODS: The IUGR animal model was established by feeding rats low-protein diets during their pregnancy. Newborn rats were divided into catch-up growth, non-catch-up growth and control groups. Protein and mRNA levels of nesfatin-1/NUCB2 and ghrelin in the gastric mucosa of rats were determined by RT-PCR and Western blot, respectively. RESULTS: Nesfatin-1/NUCB2 mRNA and protein were expressed in the gastric mucosa of rats immediately after birth, and their expression increased in an age-dependent manner in all three groups. Furthermore, the level of nesfatin-1/NUCB2 in the catch-up growth group was higher than that in the control group before weaning, whereas there was no significant difference in nesfatin-1/NUCB2 expression between the two groups after weaning. The level of nesfatin-1/NUCB2 in the non-catch-up growth group was lower than that in the catch-up growth group during the whole observation period. The level of ghrelin in the catch-up growth group was higher than that in the control group starting from day 12 after birth, whereas there was no significant difference in ghrelin expression between the two groups after weaning. The level of ghrelin in the non-catch-up growth group was lower compared with those in the catch-up growth and control groups from days 12 to 28 after birth. CONCLUSIONS: Nesfatin-1 and ghrelin are co-expressed in the gastric mucosa of rats with IUGR after birth and interact with each other to produce long-term nutritional regulation.

Expression levels of IL-27 and IL-17 in multiple myeloma patients: a higher ratio of IL-27:IL-17 in bone marrow was associated with a superior progression-free survival.

The goal of the study was to investigate the levels of interleukin-27 (IL-27) and IL-17 in bone marrow (BM) and peripheral blood (PB) of multiple myeloma (MM). The levels of IL-27 and IL-17 were determined in MM patients and controls using ELISA. The results showed a decreased IL-27 and elevated IL-17 level in MM patients and a negative association of IL-27 with IL-17. The ratio of IL-27:IL-17 in BM of newly diagnosed MM was significantly decreased and correlated with the progression of disease. Multivariate analysis showed that a higher ratio of IL-27:IL-17 in BM was associated with a superior progression-free survival (HR=0.160; 95% CI: 0.058-0.443; p<0.001). Our results suggest that there might be a possible competitive role of IL-27 and IL-17 in MM.

Norcantharidin enhances bortezomib-antimyeloma activity in multiple myeloma cells in vitro and in nude mouse xenografts.

Norcantharidin (NCTD), the demethylated analog of the Chinese medicine cantharidin, exhibits anti-myeloma activity by inactivating nuclear factor-κB (NF-κB), which is implicated in multiple myeloma (MM) cell survival and resistance to bortezomib (BTZ). We investigated whether NCTD could potentiate the anti-tumor activity of BTZ in MM. NCTD inhibited the proliferation of MM cells and potentiated the anti-myeloma effects of BTZ by down-regulating IKKα and p-IκBα, which induced the accumulation of IκBα and inhibited the constitutive activation of NF-κB. This effect was correlated with the suppression of NF-κB-regulated gene products. Furthermore, a chemotherapy-potentiating effect of NCTD on BTZ was also observed in vivo. Our study demonstrated that NCTD and BTZ exhibit significant therapeutic effects on MM through the NF-κB signal pathway in vitro and in vivo. Future studies will investigate the combined effects of NCTD and BTZ in patients with MM.

Anti-proliferative and pro-apoptotic effect of CPT13, a novel camptothecin analog, on human colon cancer HCT8 cell line.

10-(2-pyrazolyl-ethoxy)-(20S)-camptothecin (CPT13) is a novel semi-synthetic analogue of camptothecin, our previous report had shown that it possessed higher in vitro cytoxicity activity towards human colon cancer HCT8 cell line than topotecan. In this study, the anti-proliferative effect of CPT13 on HCT8 cell line in vitro was analyzed. In order to further explore the underlying mechanism of cell growth inhibition of CPT13 towards HCT8 cell line, the cell cycle distribution, apoptosis proportion, the nuclei morphological changes and caspase-8 and caspase-3 activities were measured. Additionally the changes of mitochondrial morphology and membrane potential (DeltaPsim) were analyzed by atomic force microscopy (AFM) and flow cytometry, respectively. The results showed that CPT13 inhibited HCT8 cell growth by causing cell cycle arrest at G2/M transition and induced apoptosis, as evidenced by the typical apoptotic morphology such as condensation and fragmentation of nuclei and formation of apoptotic bodies. The changes of mitochondrial morphology, dose-dependently decrease in DeltaPsim and the enhancement of caspase-8 and caspase-3 activities were observed in different concentrations of drug treatment group. Our results suggest that CPT13 induces apoptosis by alternations of mitochondrial transmembrane depolarization, activation of caspase-8 and caspase-3. Therefore, CPT13 appears to be a potent drug against human colon cancer via induction of apoptosis and may be used as an alternative drug to therapy cancer.