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

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.

Objective To study the dynamic changes of cytochrome P4502E1 (CYP2E1) in alcohol-induced liver injury in mice and its sig nificance.Methods Fifty male mice were randomly divided into modelgroup (n =40) and control group (n =10).The model of alcoholic liver injury was established by continuous infusion of 56 ° Erguotou at 10 mL · kg-1 for 4 weeks.At the time of 1,2,3,4 weeks,to take 10 mice,eye blood for serum aspartate aminotransferase (AST) activity determina tion.Followed by cervical dislocation of mice,the number of CYP2E1positive cells in mice liver were detected by immunohistochemical SP method.Results The activity of hepatic AST enzyme in model group were (126 ±24),(967 ±30),(1010 ±35) and (206 ±23) U · L-1 in 1st,2nd,3rd and 4th weeks,respectively.Compared with the control group (112 ±22) U · L-1,the activity of hepatic AST enzyme in the model group increased continuouslyfrom 1st to 3rd weeks and reached the peak at 3rd week with significantly (P ＜ 0.01),which was decreased at the 4th week,but still higher than the control group with significantly (P ＜0.05).The number of CYP2E1 positive cells per square millimeter were (3.2 ±0.8),(8.4 ± 1.1),(13.2 ± 1.3),and (4.6±0.8) cell · mm-2 in 1st,2nd,3rd and 4th weeks.Compared with the control group (2.8 ±0.5) cell ·mm-2,the number were obviously increased in 1st,2nd and 3rd weeks and represented statistically significant (P ＜0.01)while the number of the 4th week decreased but still with statistically significant(P ＜0.05).Conclusion The expression of CYP2E1 was increased first and then decreased in alcohol-induced liver injury model,which was consistent with the trend of serum AST enzyme activity.The dynamic changes in expression may be associated with damage and repair of the hver.

BACKGROUNDThymosin beta-4 (TB-4) is considered key roles in tissue development, maintenance and pathological processes. The study aimed to prove TB-4 positive biological function on nucleus pulposus (NP) cell apoptosis and slowing the process of cell aging while increasing the cell proliferation.

METHODSTB-4 recombinant adeno-associated virus (AAV) was constructed and induced to human NP cells. Cell of same group were cultured without gene modification as controlled group. Proliferation capacity and cell apoptosis were observed during 6 passages of the cells. Morphology and expression of the TB-4 gene were documented as parameter of cell activity during cell passage.

RESULTSNP cells with TB-4 transfection has normal TB-4 expression and exocytosis. NP cells with TB-4 transfection performed significantly higher cell activity than that at the control group in each generation. TB-4 recombinant AAV-transfected human NP cells also show slower cell aging, lower cell apoptosis and higher cell proliferation than control group.

CONCLUSIONSTB-4 can prevent NP cell apoptosis, slow NP cell aging and promote NP cell proliferation. AAV transfection technique was able to highly and stably express TB-4 in human NP cells, which may provide a new pathway for innovation in the treatment of intervertebral disc degenerative diseases.

Apoptosis ; genetics ; physiology ; Cell Line ; Cell Proliferation ; genetics ; physiology ; Cells, Cultured ; Cellular Senescence ; genetics ; physiology ; Dependovirus ; genetics ; Humans ; Immunohistochemistry ; Intervertebral Disc ; metabolism ; pathology ; Male ; Thymosin ; genetics ; metabolism

The aim of this study was to assess the clinical efficacy and safety of chelation treatment with penicillamine (PCA) in cross combination with sodium 2, 3-dimercapto-1-propane sulfonate (DMPS) repeatedly in patients with Wilson's disease (WD). Thirty-five patients with WD were enrolled. They were administrated intravenous DMPS in cross combination with oral PCA alternately which was practiced repeatedly, all with Zinc in the meantime. During the treatment, clinical observations and 24-h urine copper excretion as well as adverse effects of medicines were recorded and analyzed. Although the incidence of adverse effects was not significantly different after either intravenous DMPS or oral PCA treatment, levels of 24-h urine copper tended to be higher after short-term intravenous DMPS than that of oral PCA. Adverse effects in the course of intravenous DMPS were mainly neutropenia, thrombocytopenia, allergic reaction and bleeding tendency. As compared with oral PCA alone or intravenous DMPS alone, such repeated cross combination treatment could as much as possible avoid continued drug adverse effects or poor curative effect and had less chance to stop treatment in WD patients. Improved or recovered liver function in 71% of the patients, alleviated neurologic symptoms in 50% of the patients, and disappeared hematuria in 70% of the patients could be observed during the follow-up period of 6 months to 5 years after such combined chelation regimen. Chelation treatment repeatedly with oral penicillamine in cross combination with intravenous DMPS alternately could be more beneficial for WD patients to relieve symptoms, avoid continued drug adverse effects and maintain lifelong therapy.
Administration, Oral ; Adolescent ; Chelating Agents ; administration & dosage ; adverse effects ; therapeutic use ; Chelation Therapy ; adverse effects ; methods ; Child ; Copper ; urine ; Drug Administration Schedule ; Drug Hypersensitivity ; etiology ; Drug Therapy, Combination ; Hepatolenticular Degeneration ; drug therapy ; Humans ; Injections, Intravenous ; Male ; Neutropenia ; chemically induced ; Partial Thromboplastin Time ; Penicillamine ; administration & dosage ; adverse effects ; therapeutic use ; Prothrombin Time ; Thrombocytopenia ; chemically induced ; Time Factors ; Treatment Outcome ; Unithiol ; administration & dosage ; adverse effects ; therapeutic use

This study examined the effect of copper ions on the proliferation of hepatic stellate cells (HSCs) and the role of oxidative stress in this process in order to gain insight into the mechanism of hepatic fibrosis in Wilson's disease. LX-2 cells, a cell line of human HSCs, were cultured in vitro and treated with different agents including copper sulfate, N-acetyl cysteine (NAC) and buthionine sulfoximine (BSO) for different time. The proliferation of LX-2 cells was measured by non-radioactive cell proliferation assay. Real-time PCR and Western blotting were used to detect the mRNA and protein expression of platelet-derived growth factor receptor β subunit (PDGFβR), ELISA to determine the level of glutathione (GSH) and oxidized glutathione (GSSG), dichlorofluorescein assay to measure the level of reactive oxygen species (ROS), and lipid hydroperoxide assay to quantify the level of lipid peroxide (LPO). The results showed that copper sulfate over a certain concentration range could promote the proliferation of LX-2 cells in a time- and dose-dependent manner. The effect was most manifest when LX-2 cells were treated with copper sulfate at a concentration of 100 μmol/L for 24 h. Additionally, copper sulfate could dose-dependently increase the levels of ROS and LPO, and decrease the ratio of GSH/GSSG in LX-2 cells. The copper-induced increase in mRNA and protein expression of PDGFβR was significantly inhibited in LX-2 cells pre-treated with NAC, a precursor of GSH, and this phenomenon could be reversed by the intervention of BSO, an inhibitor of NAC. It was concluded that copper ions may directly stimulate the proliferation of HSCs via oxidative stress. Anti-oxidative stress therapies may help suppress the copper-induced activation and proliferation of HSCs.
Cell Line ; Cell Proliferation ; drug effects ; Copper ; administration & dosage ; Dose-Response Relationship, Drug ; Hepatic Stellate Cells ; cytology ; drug effects ; physiology ; Humans ; Ions ; Liver Cirrhosis ; metabolism ; Oxidative Stress ; drug effects ; physiology ; Oxygen ; metabolism

BACKGROUNDWe conducted a prospective, multicenter investigation of incidence, management and outcome of neonatal acute respiratory disorders (NARD), and evaluated related perinatal risk factors and efficacy of respiratory therapies in neonatal intensive care units (NICUs) in a Chinese neonatal network.

METHODSData were prospectively collected in 2004 - 2005 from infants with NARD defined as presence of respiratory distress and oxygen requirement during the first 3 days of life.

RESULTSA total of 2677 NARD was classified (20.5% of NICU admissions). There were 711 (5.44%) with respiratory distress syndrome (RDS), 589 (4.51%) pulmonary infection, 409 (3.13%) meconium aspiration syndrome, 658 (5.03%) aspiration of amniotic fluid and 239 (1.83%) transient tachypnoea. Meconium aspiration syndrome had the highest rate with fetal distress, transient tachypnoea from cesarean section, and RDS with maternal disorders. Assisted mechanical ventilation was applied in 53.4% of NARD, and in above five disorders with 84.7%, 52.3%, 39.8%, 24.5%, and 53.6%, respectively. Corresponding mortality in these disorders was 31.4%, 13.6%, 17.8%, 4.1% and 5.0%, respectively. Surfactant was provided to 33.9% of RDS. In all RDS infants, the survival rate was 78.8% if receiving surfactant, and 63.4% if not (P < 0.001).

CONCLUSIONSThis study provided NICU admission-based incidence and mortality of NARD, reflecting efficiency of advanced respiratory therapies, which should be a reference for current development of respiratory support in NICU at provincial and sub-provincial levels, justifying efforts in upgrading standard of care in emerging regions through a collaborative manner.

Acute Disease ; Cost of Illness ; Female ; Humans ; Incidence ; Infant, Low Birth Weight ; Infant, Newborn ; Intensive Care Units, Neonatal ; Male ; Prospective Studies ; Respiration, Artificial ; Respiratory Tract Diseases ; complications ; epidemiology ; mortality ; therapy

OBJECTIVETo study the rotary angle and image features, so as to help early diagnosis.

METHODSFour adult cervical spine (C1-T1) specimens were used, including 2 males and 2 females,ranging in age from 28 to 40 years old. X-ray and CT examination were performed before the experiment. C2-C4 and C5-T1 were fixed respectively using self-made clamp. Unilateral locked facet of cervical spine was simulated under the violence of inflection and rotation, in which the muscle contraction was partially simulated, and at last the plain radiographs and CT of unilateral locked facet of cervical spine were analyzed.

RESULTSIn unilateral locked facet of cervical spine, the average rotary angle was 19.75 degrees, and average forward shift of vertebral was 3.68 mm. The intervertebral foramina below the injury plane were showed at 0 degrees,10 degrees, 180 degrees,190 degrees; the intervertebral foramina above the injury plane were showed at 150 degrees,160 degrees, 00 degrees, -10 degrees, and the facet was locked or in disorder at the injury plane. The intervertebral foramina at the anterior oblique position was bigger in interlocking side, but it was smaller in the opposite side. CT scan showed rotary spine, the naked facet sign; coronal plane reconstruction showed bilateral asymmetry; sagittal plane reconstruction obviously showed unilateral locked facet.

CONCLUSIONX-ray and CT both can independently diagnose unilateral locked facet of cervical spine. CT and three-dimensional reconstruction are more better than X-ray to diagnosing it.

Adult ; Cervical Vertebrae ; diagnostic imaging ; injuries ; pathology ; Female ; Humans ; Joint Dislocations ; diagnostic imaging ; Male ; Rotation ; Tomography, X-Ray Computed ; methods

OBJECTIVETo review a group of clinical data of pedicle screw implantation in the treatment of middle-upper thoracic fracture and dislocation and explore these clinical effect.

METHODSThrough the retrospective analysis of 23 patients (31 vertebraes) of middle-upper thoracic fracture and dislocation included 21 male and 2 female,aged from 20 to 47 years in average of 33.5 years. The location and type of fractures were as follows: 2 in T2, 2 in T3, 5 in T4, 6 in T5, 10 in T6, 4 in T7, 2 in T8. Three cases were compression fractures, 7 burst fractures, 9 fracture-dislocations, 4 burst-dislocations.

RESULTSAfter a followed-up from 3 to 48 months, average 25.5 months, all cases had no serious complications. Anterior height of affected vertebral bodies had been restored from 40.4% to 90.3% after operation. Patients with incomplete spinal cord injuries improved one to two grades according to ASIA grade of spinal cord injury. Patients with complete spinal cord injuries improved 21.7 scores on average according to Sensory and Motion Scores.

CONCLUSIONMulti-segmental pedicle screw implantation for the injuries of vertebral body may get satisfactory reduction and fixation effects, and prevent the long-term loss of the vertebral body height and implanting failure.

Adult ; Bone Screws ; Female ; Fracture Fixation, Internal ; methods ; Humans ; Joint Dislocations ; surgery ; Male ; Middle Aged ; Retrospective Studies ; Spinal Fractures ; surgery ; Thoracic Vertebrae ; injuries ; surgery

OBJECTIVETo investigate the long-term complications after liver transplantation.

METHODSTotally 85 living patients who received liver transplantation from December 30th 1998 to May 28th 2002 in Tianjin First Central Hospital were followed up till October 2007. Liver and kidney functions, blood drug levels, blood pressure, blood sugar, and blood fat were recorded and ultrasound imaging was performed during follow-up.

RESULTSAt the end of the study, most patients had experienced one or more complications of prolonged immunosuppressant treatment, including posttransplantation diabetes mellitus (21.18%, 18/85), hypertension (10.59%, 9/85), renal impairment (8.24%, 7/85), hyperlipemia (7.06%, 6/85), hyperuricaemia (7.06%, 6/85), denovo malignancy (2.35%, 2/85), new-onset hepatitis C (7.06%, 6/ 85), recurrent hepatitis B (5.56%, 4/72).

CONCLUSIONRecipients of liver transportation often suffers long-term complications, which should be carefully managed to improve their quality of life.

Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Kidney ; physiopathology ; Liver ; physiopathology ; Liver Transplantation ; adverse effects ; immunology ; Male ; Middle Aged ; Postoperative Complications ; etiology ; immunology ; physiopathology ; Young Adult