Objective:To analyze the clinical characteristics of intracranial infection caused by Mycobacterium lentiflavum. Methods:The clinical data of a patient with intracranial infection caused by Mycobacterium lentiflavum admitted to Tianjin Haihe Hospital in May 2023 were collected. Meanwhile relevant literatures in databases were searched. Only 1 English literature (1 patient) was obtained. The clinical characteristics of this patient and the case reported in the literature were analyzed and summarized. Results:Totally 2 patients, including this case, and the patient with meningoencephalitis caused by Mycobacterium lentiflavum reported in the literature, both are females, 42 and 55 years old respectively, both manifested a chronic course, without fever, and presented progressive headache and cognitive impairment. Clinical manifestations also included abnormal mental behavior, limb weakness, and seizure. At the early stage, only intracranial pressure increased, and cerebrospinal fluid tests were negative. As the disease aggravated, there was an elevation of cerebrospinal fluid cells and protein, with normal levels of glucose and chloride. Using brain tissue obtained by biopsy for polymerase chain reaction or next-generation sequencing examination, the pathogenic microorganism was confirmed, which made accurate diagnosis possible. Antibiotic treatment had good efficacy, with a long treatment course and a good prognosis. Conclusions:Central nervous system infection caused by Mycobacterium lentiflavum is very rare, and a chronic disease course makes diagnosis very difficult. The treatment effect is significant, and the prognosis is excellent.

Meningoencephalitis caused by the human herpes virus 6 is common in acquired immune deficiency syndrome patients or in patients after organ transplantation, rarely in immunocompetent adults. The clinical manifestations include headache, drowsinesss, coma, epileptic attack, psychiatric symptom and focal neurological signs. Antiviral therapy is effective, however the prognosis should be poor if the treatment is not timely. The clinical data of one case of meningoencephalitis caused by the human herpes virus 6 in Tianjin Haihe Hospital in October 2019 were analyzed. Meningoencephalitis caused by the human herpes virus 6 can be recurrent. The clinical manifestations are nonspecific and the diagnosis is difficult. The next generation sequencing of cerebrospinal fluid is a powerful method to identify pathogens.

High-mobility group box-1 (HMGB1) is a member of the high-mobility group proteins and is present in eukaryotic cells. HMGB1 is not only a nuclear protein but also a pro-inflammatory factor, and the increase in HMGB1 level in the body indicates cell destruction and inflammatory response. Hepatitis B virus (HBV) infection is a major cause of chronic hepatitis B, liver cirrhosis, and hepatocellular carcinoma in the world. In recent years, the role of HMGB1 in HBV-related liver diseases has attracted more and more attention, especially the important role of HMGB1 in the progression of liver inflammation and liver cancer. This article reviews the recent research advances in the role of HMGB1 in the development, progression, and treatment of HBV-related liver diseases.

Objective: To estimate the levels of free carnitine and acylcarnitine in neonates, and summarize the incidence and clinical characteristics of carnitine absorption deficiency in Xuzhou. Methods: Between November 2015 and December 2017, 216 903 newborns were recruited with carnitine absorption deficiency screened via tandem mass spectrometry in Xuzhou.They were divided into different groups according to gestational age, birth body weight, blood collecting time and season, in which the group with gestational age <37 weeks was selected as the premature delivery group, and the group with gestational age 37-41^{+ 6} weeks as the normal gestational age group for gestational age analysis, while the group with the birth body mass <2 500 g was selected as low birth body mass group and the group with the birth body mass of 2 500-3 999 g as normal birth body mass group for body mass analysis.SPSS 16.0 software was used for data analysis to clarify the influence of the above factors on the detection of carnitine indexes by tandem mass spectrometry.DNA sequencing was performed to confirm the diagnosis and analyze the relevant pathogenic genotypes in children with positive screening, and these confirmed individuals were followed up. Results: There was no statistical difference in the levels of C3, C8 and C102 between preterm infants and normal body mass infants in the gestational age group(all P>0.05), but other carnitine levels had statistically significant differences(all P<0.05). The difference of C102 level between the different birth weight groups was not statistically significant(P>0.05), but that of other carnitine levels were statistically significant(all P<0.05). There was no significant difference in the level of C182 between different blood collection time(P>0.05). The levels of free carnitine and acylcarnitine between the different season groups had statistically significant differences(all P<0.05). Primary carnitine deficiency was diagnosed in 10 cases, including 7 cases of maternal carnitine absorption deficiency.The incidence in Xuzhou was approximately 121 690.The pathogenic genotype showed a specific regional distribution characteristic in Xuzhou, in which pathogenic mutation type c. 1400C >G was the most common one. Conclusions Some factors play a role in neonatal screening for carnitine absorption deficiency by tandem mass spectrometry including gestational age, birth body weight, blood collecting time and season.Pathogenic genes present a regional characteristic in Xuzhou and maternal carnitine absorption deficiency with a higher rate, the clinical attention should be paid to screening for maternal carnitine absorption deficiency.

OBJECTIVE： To observe neuroprotective effects of low-molecular-weight chondroitin sulfate （CS） on dopaminergic neurons in Parkinson’s disease （PD） mice model induced by 1-methyl-4-phenyl-1，2，3，6-tetrahydropyridine （MPTP）. METHODS： C57BL/6 mice were randomly divided into control group， MPTP injury group， low-molecular-weight CS low-dose and high-dose groups （100， 400 mg/kg）. Control group and MPTP injury group were given constant volume of normal saline intragstrically， administration groups were given relevant medicine intragastrically， once a day， for consecutive 17 d. Since 11th day after medication， except for control group， other groups were given MPTP solution （20 mg/kg） intraperitoneally to induce PD model， once a day， consecutive 5 d. After last medication， behavioral changes of mice （10 mice in each group） were evaluated by rotary rod fatigue tester. The damage of dopamine neurons （the percentage of TH positive cell and the percentage of fluorescence intensity） in substantia nigra of mice （3 mice in each group） was detected by immunohistochemistry and immunofluorescence. The content of dopamine in striatum was determined by HPLC （6 mice in each group）. The changes of oxidant stress indexes （SOD， GSH-Px， MDA） in substantia nigra of mice were determined by chemical colorimetry （6 mice in each group）. RESULTS： Compared with control group， retention time of mice on rotating rods was shortened significantly in MPTP injury group； TH positive cells of substantia nigra were decreased significantly， fluorescence intensity was obviously weakened； the percentage of positive cells and fluorescence intensity， the content of dopamine in striatum， the activities of SOD and GSH-Px in substantia nigra were decreased significantly， while the content of MDA was increased significantly （P＜0.01）. Compared with MPTP injury group， retention time of mice on the rotating rods was prolonged significantly in low-molecular-weight CS groups， the number of TH positive cells was increased significantly in substantia nigra and fluorescence intensity was increased significantly； the percentage of positive cells， the percentage of fluorescence intensity and the content of dopamine in striatum were increased significantly， while above indexes of high-dose group were significantly longer or higher than those of low-dose group （P＜0.05 or P＜0.01）. The activities of SOD and GSH-Px in substantia nigra were increased significantly in low-molecular-weight CS groups， while the content of MDA in substantia nigra was decreased significantly in low-molecular-weight CS high-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Prophylactic administration of low-molecular-weight CS can relieve the damage of dopaminergic neurons in substantia nigra of PD model mice induced by MPTP in a dose-dependent manner， and increase the secretion of dopamine in striatum. The effect may be related to the inhibition of lipid peroxidation and the enhancement of antioxidant capacity of tissues.

Objective To investigate the prevalence,clinical classification,treatment and prognosis of neonatal hyperphenylalaninemia(HPA) in Xuzhou area,China.Methods Infants born between July 1,2003 and July 1,2015 in Xuzhou area were investigated.Heel blood samples of neonates were collected at 72 hours after birth,and the concentration of blood phenylalanine(Phe) was determined by fluorescent quantitative method in Xuzhou Maternity and Child Health Care Station Neonatal Disease Screening Center.Differential diagnosis was performed in all 265 cases diagnosed as HPA by urinary pterin analysis and dihydropteridine reductase activity determination.The blood Phe concentration and mental development were followed up regularly in infants with HPA.Mutations of phenylalanine hydroxylase (PAH) gene were analyzed by gene sequencing.The relationship between blood Phe concentration and mental development was analyzed by Bivariate correlation analysis.Results (1) The prevalence of HPA in neonates in Xuzhou was 1/4 635.Among the 265 confirmed HPA cases,260 cases(98.11％) had PAH deficiency,including 90(33.96％) classical phenylketonuria(PKU),84(31.70％) mild PKU and 86(32.45％) mild HPA.The other five patients(1.89％) diagnosed with tetrahydrobiopterin (BH4) deficiency all had 6-pyruvoyl tetrahydropteim synthase(PTPS) deficiency.(2) Among the 265 HPA cases,26 cases refused any treatment,including five cases of PTPS deficiency and 21 cases of PKU.Of the five patients with PTPS deficiency,two died and the other three had normal mental and physical development.Twenty-one PKU patients who refused treatment had mental retardation of various degrees.Among 153 PKU patients who received medical treatment,three died and 12 were lost to follow-up.(3) For 138 PKU patients who received dietary treatment and follow-up,the ages at the last visit were two months to 12 years,116 of them had normal mental development,the remaining 22 patients had mental retardation,and a negative correlation was observed between mental development and the average Phe concentration.(4) Thirty-five patients with PAH deficiency underwent gene sequencing,and 22 kinds of mutations of PAH gene were detected.Conclusions The prevalence of HPA in Xuzhou area is higher than the average national level.With early diagnosis and standard treatment,most of PKU neonates can have normal mental development.Phe level control is an important factor for mental development.

OBJECTIVE:To investigate the inhibitory effects mechanism of scallop skirt glycosaminoglycan(SS-GAG)on inju-ry in human umbilical vein endothelium cells (HUVEC). METHODS:In the test,there was a negative control group,a model group and the groups of SS-GAG at high,middle and low concentrations(mass concentrations of 200,100 and 50 mg/L respective-ly). The cells in latter 3 groups were cultured in SS-GAG at different mass concentrations for 12 h,and then in 50 μmol/L oxidized low-density lipoprotein(OX-LDL)for 24 h. MTT method was used to detect cell viability and the activity of lactic dehydrogenase (LDH),the flow cytometer to determine the level of reactive oxygen species (ROS),real-time fluorescence quantitative poly-merase chain reaction (RT-PCR) to detect mRNA expression of lectin-like oxidized low-density lipoprotein receptor 1 (LOX-1), and Western blot to detect NOX4 protein expression. RESULTS:Compared to the cells in the negative control group,those in the model group demonstrated lower viability,higher activity of LDH,higher level of ROS,and stronger expressions of LOX-1 mRNA and NOX4 protein. There was statistical significance (P<0.01). Compared to the cells in the model group,those in the groups of SS-GAG at high,middle and low concentrations showed higher viability,lower activity of LDH,lower level of ROS and weaker expressions of LOX-1 mRNA and NOX4 protein. There was statistical significance (P<0.01). CONCLUSIONS:SS-GAG can protect HUVEC to some degree by a mechanism which may be related to inhibiting ROS production via LOX-1/NOX4 pathway and relieving oxidative stress injury.

Objective Congestive heart failure (CHF) is the final common pathway of various heart diseases.Calcineurin,a calcium/calmodulindependent phosphatase consisting of a catalytic subanit A (CnA) and a regulatory calcium-binding subunit B (CnB),is activated in heart failure.This study aimed to investigate the relationship between mRNA level of calcineurin in circulating T-lymphocyte and that in myocardium in patients with CHF. MethodsA total of 38 patients with CHF (aged from 29 to 62 years) were included in this study.The mRNA levels of alpha-and beta-isoform of CnA in left ventricular anterior papillary muscle and peripheral lymphocytes were determined by semi-quantitative reverse transcription polymerase chain reaction.Pearson linear correlation analysis was performed,and difference was considered statistically significant at a P value <0.05. ResultsCalcineurin mRNA levels in lymphocytes were positively correlated with those in myocardium (for CnA-alpha mRNA,r=0.820;for CnA-beta mRNA,r=0.875;both P<0.01).CnA-beta mRNA levels in both circulating lymphocytes and myocardium increased significantly with increasing NYHA class (r=0.877 for peripheral blood and r=0.805 for cardiac muscle;both P<0.01). ConclusionsThe mRNA level of CnA-beta in circulating lymphocytes is positively correlated with that in myocardium and is a promising marker for the severity of cardiac dysfunction in patients with CHF.

Objective To construct the short hairpin RNA recombinant plasmids targeting mdr1 gene which expresses highly in ovarian cancer resistance strain SKOV3/TAXOL to silence endogenefic mdr1 gene expression and investigate the role of mdr1 gene in the development of resistant ovarian cancer. Methods The pGPU6/GFP/Neo-mdr1 were constructed by gene clone technology. The influence on proliferation and apoptosis were investigated by CCK-8 in SKOV3/TAXOL after transfected pGPU6/GFP/Neo-mdr1. Results The expression against mdr1 proteins were inhibited by pGPU6/GFP/Neo-mdr1. The cell proliferation were inhibited after transfected pGPU6/GFP/Neo-mdr1 by CCK-8. The apoptosis were observed in DAB experiments and the apoptosis rate increased. Conclusion mdr1 plays an important role in proliferation of resistant ovarian cancer and the short hairpin RNA of mdr1 can efficiently suppress mdr1 expression and enhance the apoptosis in SKOV3/ATAXOL.

Objective To understand the clinical features of infant pulmonary hemorrhage of enterovirus 71 infection without skin rash, and to improve the diagnosis and treatment of this disease.Methods Six infants infected with enterovirus 71 and presented pulmonary hemorrhage but no skin rash between November 2007 and October 2008 were retrospectively reviewed. The clinical manifestations, clinical outcomes, treatments, laboratory data and chest imaging changes of the cases were analyzed. Results The 6 cases were all younger than 2 years old. The cases distributed throughout the whole year without peak season. Enterovirus 71 gene was detected by reverse transcription-polymerase chain reaction (RT-PCR) and real time polymerase chain reaction from throat swabs and secretions of the respiratory tract. All the cases began with fever, and 4 of which were accompanied with vomit, and 2 accompanied with cough. After 1 to 3 days, they all got sudden deterioration, manifested with pale and cyanosis, and 1 had hyperspasmia. After intubation, they all had pink frothy fluid from the endotracheal tube. They all had obvious hyperglycaemia, 4 had tachycardia, and 2 had hypertension. All the 6 cases died, and 4 died within 6 h after deterioration. Conclusions Pulmonary hemorrhage of enterovirus 71 infection without skin rash is seen in infants. It is sporadic throughout the whole year. The disease is fulminant and the case often dies in short period of time.