OBJECTIVES: To investigate the incidence of extrauterine growth retardation (EUGR) and its risk factors in very preterm infants (VPIs) during hospitalization in China. METHODS: A prospective multicenter study was performed on the medical data of 2 514 VPIs who were hospitalized in the department of neonatology in 28 hospitals from 7 areas of China between September 2019 and December 2020. According to the presence or absence of EUGR based on the evaluation of body weight at the corrected gestational age of 36 weeks or at discharge, the VPIs were classified to two groups: EUGR group (n=1 189) and non-EUGR (n=1 325). The clinical features were compared between the two groups, and the incidence of EUGR and risk factors for EUGR were examined. RESULTS: The incidence of EUGR was 47.30% (1 189/2 514) evaluated by weight. The multivariate logistic regression analysis showed that higher weight growth velocity after regaining birth weight and higher cumulative calorie intake during the first week of hospitalization were protective factors against EUGR (P<0.05), while small-for-gestational-age birth, prolonged time to the initiation of total enteral feeding, prolonged cumulative fasting time, lower breast milk intake before starting human milk fortifiers, prolonged time to the initiation of full fortified feeding, and moderate-to-severe bronchopulmonary dysplasia were risk factors for EUGR (P<0.05). CONCLUSIONS It is crucial to reduce the incidence of EUGR by achieving total enteral feeding as early as possible, strengthening breastfeeding, increasing calorie intake in the first week after birth, improving the velocity of weight gain, and preventing moderate-severe bronchopulmonary dysplasia in VPIs.
Female ; Fetal Growth Retardation ; Gestational Age ; Hospitalization ; Humans ; Incidence ; Infant ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; Prospective Studies ; Risk Factors

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.
Caffeine/therapeutic use* ; Citrates ; Humans ; Infant ; Infant, Newborn ; Infant, Premature ; Respiration, Artificial ; Retrospective Studies

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Objective:To explore the effects of Huatan Tongluo Decoction （HTTLD） on the morphology and function of brain tissues and intestine in rats with cerebral ischemia/reperfusion based on the gut-brain axis. Method:Sixty SPF male rats were randomly divided into a sham operation group， a model group， high- （28.66 g·kg^-1）， medium- （14.33 g·kg^-1）， and low-dose （7.16 g·kg^-1） HTTLD groups， and an edaravone （4 g·kg^-1）+Clostridium butyricum （5.0×10⁸ cfu·mL^-1） group. The model was established by focal cerebral ischemia/reperfusion in rats. The drugs were administered by gavage. The brain tissue injury was determined by neurological deficit score and 2，3，5-triphenyl tetrazolium chloride （TTC） staining. The effect of cerebral ischemia/reperfusion on intestinal motility was assessed by the propulsion rate of small intestine. The intestinal mucosal cell damage was evaluated by the pathomorphological examination of the duodenal mucosa. Enzyme-linked immunosorbent assay （ELISA） was used to determine the content of D-lactate （D-LAC）， diamine oxidase （DAO）， and bacterial endotoxin （lipopolysaccharide， LPS） in serum. Western blot was used to detect the expression of Occludin， Claudin-5， and zonula occludens 1 （ZO-1） in the duodenum. Result:After cerebral ischemia/reperfusion， rats developed neurological deficit symptoms. The neurological deficit score in the model group was higher than that in the sham operation group （P<0.01）. Compared with the model group， the high- and medium-dose HTTLD groups could relieve the symptoms of neurological deficits and lower neurological deficit scores （P<0.01）. The results of TTC staining showed that the model group presented obvious infarcts in brain tissues compared with the sham operation group （P<0.01）. The cerebral infarction volumes of HTTLD groups were reduced compared with that in the model group （P<0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. Furthermore， the propulsion rate of small intestine in the model group was significantly reduced compared with that in the sham operation group （P<0.01）. Compared with the model group， HTTLD groups could increase propulsion rates of small intestine （P<0.01）， especially the high-dose HTTLD group， and the effect was dose-dependent. After cerebral ischemia/reperfusion， obvious duodenal mucosal damage could be observed， which was relieved after the administration of HTTLD. Western blot results showed that the protein expression of ZO-1， Occludin， and Claudin-5 in the model group was reduced compared with that in the sham operation group （P<0.01）. Compared with the model group， the HTTLD groups could up-regulate the expression of ZO-1， Occludin， and Claudin-5 to varying degrees （P<0.05， P<0.01）， especially the high-dose HTTLD group. ELISA showed that the serum D-LAC， DAO， and LPS of the model group were elevated compared with those in the sham operation group （P<0.01）. Compared with the model group， the HTTLD groups showed reduced D-LAC and DAO （P<0.05， P<0.01）， and the medium- and high-dose HTTLD groups showed reduced LPS （P<0.05， P<0.01）， especially the high-dose HTTLD group. Conclusion:After cerebral ischemia/reperfusion， the rats showed damaged brain tissues， neurological dysfunction， intestinal mucosal injury， weakened intestinal motility， and destroyed the intestinal mucosal barrier. HTTLD can protect against brain-gut axis injury after cerebral ischemia/reperfusion by reducing the damage on brain tissues and gastrointestinal mucosa， relieving the symptoms of neurological deficits， promoting gastrointestinal motility， improving intestinal barrier function， and reducing the release of intestinal bacterial metabolites or poisons.

Professor
Acupuncture ; Acupuncture Therapy ; Angina, Stable ; Combined Modality Therapy ; Humans ; Moxibustion

OBJECTIVE: To study the PTEN gene expression level and its clinical significance in patients with acute T lymphoblastic leukemia. METHODS: One hundred and twenty-four patients with T-ALL treated in our hospital from January 2014 to May 2018 were selected, and 120 healthy people were selected as control group. The bone marrow of the patients were collected, and mononuclear cells were separated out. PTEN gene expression level was detected by RT-PCR, PTEN protein expression level was detected by Western blot, Kaplan-Meier was used to analyze the survival rate of patients with T-ALL, Cox multivariate regression analyzed was used to analyze the independent influencing factors of patients, and the correlation between PTEN level and clinical characteristics of patients with T-ALL and its prognostic value were analyzed. RESULTS: The relative level of PTEN gene in patients with T-ALL was 0.19±0.06, which was significantly lower than that in control groups (P<0.05). There was significantly positive correlation of the expression level of PTEN gene with white blood cell count （r=0.993）and peripheral blood immature cells （r=0.996） in patients with T-ALL. There was no correlation between PTEN gene expression level and sex, age, LDH level, Hb level, platelet count in patients with T-ALL. And it was found that expression levels PTEN protein in the middle-risk group, the standard-risk group and the high-risk group were significant lower than those in the control group (P<0.05), while those in the high-risk group were significantly lower than those in other groups (P<0.05). Kaplan-Meier survival analysis showed that OS and DFS in PTEN gene high expression group were higher than those in PTEN low expression group (P<0.05). Cox multivariate regression analysis showed that white blood cell count and PTEN gene were independent influencing factors of OS (P<0.05); platelet count and PTEN gene were independent influencing factors of DFS (P<0.05). CONCLUSION PTEN gene level relates to the prognosis of patients with T-ALL. Patients with better prognosis show a higher PTEN gene level, which provides reference for clinical treatment of patients with T-ALL.
Bone Marrow ; Humans ; Leukemia-Lymphoma, Adult T-Cell ; PTEN Phosphohydrolase ; Prognosis

Filamin A and 14-3-3-σ are closely associated with the development of breast cancer.However,the exact relationship between them is still unknown.The present study aimed to examine the interaction of filamin A with 14-3-3-σ in the invasion and migration of breast cancer.RNA interference technology was employed to silence filamin A in MDA-MB-231 cells.Real-time PCR and Western blotting were used to detect the expression of filamin A and 14-3-3-σ at mRNA and protein levels,respectively.Double immunofluorescence was applied to show their colocalization morphologically.Wound healing assay and Trans-well assay were used to testify the migration and invasion of MDA-MB-231 cells in filamin A-silenced cells.The results showed that silencing filamin A significantly increased the mRNA and protein levels of 14-3-3σ.In addition,double immunofluorescence displayed that filamin A and 14-3-3σ were predominantly colocalized in the cytoplasm of MDA-MB-231 cells.Silencing filamin A led to the enhanced fluorescence of 14-3-3σ.Furthermore,cell functional experiments showed that silencing filamin A inhibited the migration and invasion of MDA-MB-231 cells in vitro.In conclusion,silencing filamin A may inhibit the invasion and migration of breast cancer cells by upregulating 14-3-3σ.

Dendrobii Caulis (DC), named 'Shihu' in Chinese, is a precious herb in traditional Chinese medicine. It is widely used to nourish stomach, enhance body fluid production, tonify "Yin" and reduce heat. More than thirty Dendrobium species are used as folk medicine. Some compounds from DC exhibit inhibitory effects on macrophage inflammation. In the present study, we compared the anti-inflammatory effects among eight Dendrobium species. The results provided evidences to support Dendrobium as folk medicine, which exerted its medicinal function partially by its inhibitory effects on inflammation. To investigate the anti-inflammatory effect of Dendrobium species, mouse macrophage cell line RAW264.7 was activated by lipopolysaccharide. The nitric oxide (NO) level was measured using Griess reagent while the pro-inflammatory cytokines were tested by ELISA. The protein expressions of inducible NO synthase (iNOS), cyclooxygenase-2 (COX-2) and mitogen-activated protein kinases (MAPKs) phosphorylation were evaluated by Western blotting analysis. Among the eight Dendrobium species, both water extracts of D. thyrsiflorum B.S.Williams (DTW) and D. chrysotoxum Lindl (DCHW) showed most significant inhibitory effects on NO production in a concentration-dependent manner. DTW also significantly reduced TNF-α, MCP-1, and IL-6 production. Further investigations showed that DTW suppressed iNOS and COX-2 expression as well as ERK and JNK phosphorylation, suggesting that the inhibitory effects of DTW on LPS-induced macrophage inflammation was through the suppression of MAPK pathways. In conclusion, D. thyrsiflorum B.S.Williams was demonstrated to have potential to be used as alternative or adjuvant therapy for inflammation.
Animals ; Anti-Inflammatory Agents ; pharmacology ; Cyclooxygenase 2 ; genetics ; Cytokines ; metabolism ; Dendrobium ; chemistry ; Gene Expression Regulation, Enzymologic ; drug effects ; Inflammation ; chemically induced ; drug therapy ; Lipopolysaccharides ; Macrophages ; drug effects ; enzymology ; Mice ; Mitogen-Activated Protein Kinases ; antagonists & inhibitors ; genetics ; metabolism ; Nitric Oxide ; analysis ; Nitric Oxide Synthase Type II ; genetics ; Phosphorylation ; drug effects ; Plant Extracts ; pharmacology ; RAW 264.7 Cells ; Signal Transduction ; drug effects

OBJECTIVETo investigate the effect of docosahexaenoic acid (DHA) on apoptosis, migration and invasion of cervical cancer cell lines.

METHODScervical cancer cell lines Hela and Siha in logarithmic phase were treated different concentrations of DHA. The morphological changes of the cells were observed microscopically and cell apoptosis was observed using Hoechst 33258 fluorescent staining. MTT assay was used to evaluate the effect of DHA in suppressing cell growth, and flow cytometry was employed to analyze the changes of cell apoptotic rate following DHA stimulations. Wound healing assay and Transwell migration assay were used to evaluate the migration of the cell lines. The expression levels of Bax, Bcl-2 cleaved caspase3, MMP-9 and VEGF proteins were detected by Western blotting.

RESULTSDHA exposure of the cells caused obvious morphological changes and dose-dependently increased the number of apoptotic bodies in the cells. MTT assay showed that DHA inhibited the growth of the cancer cells in a time- and concentration-dependent manner. DHA also effectively suppressed migration and invasion of the cancer cells. The cells exposed to DHA showed significantly down-regulation of Bcl-2, MMP-9 and VEGF proteins and up-regulation of cleaved-caspase 3 and Bax.

CONCLUSIONDHA can promote cervical carcinoma cell apoptosis by down-regulating the anti-apoptotic proteins Bax, Bcl-2 and cleaved-caspase3 and suppress cell invasion by decreasing MMP-9 and VEGF expressions.

Apoptosis ; Caspase 3 ; metabolism ; Cell Cycle ; Cell Line, Tumor ; drug effects ; Cell Movement ; Cell Proliferation ; Docosahexaenoic Acids ; pharmacology ; Down-Regulation ; Female ; HeLa Cells ; drug effects ; Humans ; Matrix Metalloproteinase 9 ; metabolism ; Neoplasm Invasiveness ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Up-Regulation ; Uterine Cervical Neoplasms ; pathology ; Vascular Endothelial Growth Factor A ; metabolism ; bcl-2-Associated X Protein ; metabolism

BACKGROUND:Denis B thoracolumbar burst fractures are common spinal injury and may be involved in the upper end plate injury. Fracture reduction and pedicle screw fixation are used to repair above injury. This scheme can effectively achieve the aim of correcting deformity, but the trabecular bone after crushing cannot be fuly recovered. OBJECTIVE:To observe the repair effect of fracture reduction and pedicle screw fixation + artificial bone graft in vertebral body on Denis B thoracolumbar burst fracture, and compare with fracture reduction and pedicle screw fixation alone. METHODS:Clinical data of 70 cases of Denis B thoracolumbar burst fractures, who were treated in the Department of Orthopedics, Zhangjiagang Aoyang Hospital from January 2012 to December 2014, were retrospectively analyzed. According to repair scheme, they were equaly divided into two groups. Patients in the control group received fracture reduction and pedicle screw fixation. Patients in the observation group received fracture reduction and pedicle screw fixation + artificial bone graft in vertebral body. Oswsetry Disability Index, height of anterior border of injured vertebral body, lower back pain visual analogue scale and vertebral kyphosis Cobb’s angle were compared and observed between the two groups before repair, 1 week, 3 and 6 months after repair. RESULTS AND CONCLUSION:No significant difference in Visual Analogue Scale was detected at 1 week, 3 and 6 months after repair between the observation and control groups (P > 0.05). Oswsetry Disability Index was significantly lower in the observation group than in the control group (P < 0.05). No significant difference in the height of anterior border of injured vertebral body was detected between the observation and control groups (P > 0.05). Cobb’s angle was significantly lower in the observation group than in the control group (P < 0.05). These findings suggest that fracture reduction and pedicle screw fixation + artificial bone graft in vertebral body obtained good repair effects on Denis B thoracolumbar burst fracture, not only effectively corrected Cobb’s angle and the height of anterior border of injured vertebral body, but also helped to restore normal spinal loads by filing bone in the injured vertebral body.