Hepatic sinusoidal obstruction syndrome (HSOS) is a type of secondary vascular disease of the liver that is mainly associated with the ingestion of pyrrole alkaloids (PAs) and hematopoietic stem cell transplantation (HSCT) treatment, resulting in severe liver dysfunction, multiple organ failure, and even death. Hepatic sinusoidal dilatation and obstruction, hepatocyte coagulative necrosis, and hepatic lobular inflammation are the main pathological manifestations of HSOS. The key initiating process for the pathogenesis of HSOS is damage to liver sinusoidal endothelial cells (LSECs). Currently, it is believed that LSECs are damaged by the involvement of multiple etiologies and mechanisms, and secondary coagulation and fibrinolysis disorders, oxidative stress, and inflammatory responses are the occurrence contributors to HSOS; however, the mechanism has not been fully elucidated. Therefore, the role of immune-inflammatory mechanisms has received increasing attention in LSEC damage. This article provides an overview of the epidemiology, etiology, and pathological changes of HSOS and reviews the physiological functions, common etiological damage mechanisms, and the key role of LSEC damage in the pathogenesis of HSOS, with a special focus on the role and research progress of immune-inflammatory mechanisms for LSEC damage in recent years. Furthermore, we believe that in-depth study and elucidation of the role of immune-inflammatory mechanisms in LSEC damage and the pathogenesis of HSOS and diagnosis will provide feasible research and development ideas for the screening and identification of new markers and drug treatment targets for HSOS.

Objective:To investigate the risk factors for concomitant cardiac autonomic neuropathy in diabetic patients and to develop a Nomogram prediction model.Methods:One hundred and fifty-eight diabetic patients admitted to in Southern Hospital Zengcheng Branch from March 2019 to March 2021 were selected. Patients with normal heart rate variability were the diabetic group, and patients with abnormal heart rate variability were the group with diabetes mellitus complicated by cardiac autonomic neuropathy. Logistic regression analysis was used to analyze the risk factors of cardiac autonomic neuropathy. Nomogram models were developed and model performance was evaluated. Decision curve analysis (DCA) was used to assess the net clinical benefit of the Nomogram model.Results:Comparison of general data showed that fasting blood glucose, tumour necrosis factor-α (TNF-α), glomerular filtration rate (eGER), uric acid, C-reactive protein (CRP), interleukin-6 (IL-6), free fatty acids (FFA), standard deviation of sinus heart beat RR interval (SDNN), and duration of diabetes compared to the diabetic group had statistically significant ( P<0.05); the results of the subject work characteristics (ROC) curve analysis showed that the best cut-off values for fasting glucose, TNF-α, eGFR, uric acid, CRP, IL-6, FFA, SDNN and duration of diabetes were >7.53 mmol/L, >98.45 ng/L, ≤94.79 ml/(min·1.73 m 2), > 87.3 μmol/L, >6.22 μmol/L, >37.84 ng/L, >839.19 μmol/L, ≤ 95.88 ms, >9 years; multi-factorial Logistic regression analysis showed that fasting glucose (>7.53 mmol/L), TNF-α (>98.45 ng/L), CRP (>6.22 μmol/L), IL-6 (>37.84 ng/L), FFA (>839.19 μmol/L), SDNN (≤95.88 ms), and duration of diabetes (>9 years) were risk factors for the development of cardiac autonomic neuropathy in diabetic patients; internal validation showed that the Nomogram model predicted a C-index of 0.706 (95% CI 0.668 - 0.751) for the risk of cardiac autonomic neuropathy. The DCA results showed that the Nomogram model predicted a risk threshold of >0.25 for the development of cardiac autonomic neuropathy and that the Nomogram model provided a net clinical benefit. Conclusions:There are many risk factors for cardiac autonomic neuropathy, and the nomogram model based on risk factors in this study has good predictive power and may provide a reference for clinical screening of high-risk patients and further improvement of treatment planning.

Fibroblast growth factors (FGF) are a group of structurally related polypeptides which constitute an elaborate signaling system with their receptors. Evidence accumulated in the years suggests that the FGF family plays a key role in the repair of central nervous system injury. The main protective mechanisms include activating the expression of PI3K-Akt, peroxisome proliferator-activated receptor (PPARγ) and other signals; inhibiting NF-κB-mediated inflammatory response, oxidative stress and apoptosis; regulating neuronal differentiation and neuronal excitability as well as participating in protection of neurovascular units and nerve function repair. This paper comprehensively summarizes the latest research progress in FGF signaling related to diseases of the central nervous system such as cerebral infarction, cerebral hemorrhage, traumatic brain injury, Alzheimer's disease, Parkinson's disease, epilepsy and depression, aiming to provide scientific basis and reference for the development of innovative FGF drugs for the prevention and treatment of neurological diseases.
Humans ; Fibroblast Growth Factors ; Phosphatidylinositol 3-Kinases/metabolism* ; Central Nervous System/metabolism* ; Signal Transduction/physiology* ; Alzheimer Disease

ABSTRACT OBJECTIVE To explore the pharmacological mechanism of trace elements in preterm low birth weight infants through network pharmacology. METHODS Targets associated with trace elements were obtained from Drugbank database and TTD database. Genes related to preterm low birth weight infants were collected from GeneCards database and DisGeNET database. Two groups of data were intersected to get mapping targets. Protein-protein interaction network of mapping targets were constructed by STRING database. Candidate targets were screened by Cytoscape 3.6.1 and ranked to obtain key targets. The major trace elements were defined by establishing network of “trace elements-candidate targets”. Kyoto Encyclopedia of Genes and Genomes(KEGG) and Gene Ontology(GO) term enrichment analysis was performed via g:Profiler software to predict the molecular mechanisms and related pathways of trace elements on preterm low birth weight infants. RESULTS A sum of 211 targets of trace elements in preterm low birth weight infants were screened, including 26 candidate targets and three key targets: albumin(ALB), glyceraldehyde-3-phosphate dehydrogenase(GAPDH) and fibronectin 1(FN1). The major trace elements were copper(Cu) and zinc(Zn), regulating 22 and 19 targets respectively. KEGG pathway enrichment analysis predicted that three major pathways were complement and coagulation cascades, cholesterol metabolism as well as lipid and atherosclerosis. CONCLUSION The major trace elements Cu and Zn may cause neuronal damage and reduce the risk of oxidative stress-related diseases in premature infants through the regulation of GAPDH, ceruloplasmin(CP), superoxide dismutase 1(SOD1), etc. The appropriate levels of Cu and Zn for preterm infants may regulate cholesterol metabolism and other signaling pathways and therefore reduce the risk of cardiovascular diseases in premature infants and adult. Further investigation of the pharmacological mechanism of trace elements in preterm infants is necessary to provide a more sufficient theoretical basis for the good growth and development of preterm infants.

Objective To investigate the current situation of animal injury among children in Chongqing, and to provide a scientific basis for relevant departments to formulate and implement strategies and measures to prevent and control animal injury to children. Methods According to the method of multi-stage stratified cluster sampling, 14,056 children in grades 4-12 in four districts of Chongqing were selected as the investigation subjects, and the occurrence of animal injuries in the past 6 months was investigated. Results The incidence of animal injury among school children in Chongqing was 0.35% and the incidence of person-time was 0.36%. The incidence rate in males (0.48%) was higher than that in females (0.31%). The incidence rate in urban children (0.43%) was higher than that in rural children (0.30%). The incidence of animal injury was the lowest in nuclear families (0.25%), and the highest in single-parent families (0.82%). There were statistically significant differences in the incidence of animal injuries in children among different fathers' occupational types, family types and parents' parenting styles (P<0.05).  The main place of child animal injury was home (57.14%). Recreational activities were the main cause of animal injury (51.02%). The main injuries were lower limbs (42.86%), upper limbs (24.49%) and head (10.20%). Conclusion The prevention and control of children's animal injury in Chongqing should focus on boys and families. It is suggested to take targeted and comprehensive interventions to prevent animal injuries in children.

Objective:To investigate the effects of multiple trace elements in neonatal parenteral nutrition (PN) on the stability of fat emulsion, and to assess the changes of stability indexes after filtration.Methods:With the standard body weight of 1.5 kg, seven groups of neonatal PN solutions with different concentrations of multiple trace elements were designed, including blank group (without multiple trace elements), normal dose group (1 ml/kg, i.e., 0.75 ml per 100 ml PN) and five experimental groups (i.e., 1.5 ml, 3 ml, 4.5 ml, 6 ml, and 7.5 ml per 100 ml PN respectively). Macroscopic observation was performed 0 h and 24 h after preparation. The mean droplet diameter (MDD) of lipid emulsion was determined with dynamic light scattering before and after filtration. The percentage of fat residing in globules larger than 5 μm (PFAT5) and the globule size distribution before and after filtration were determined with light blockage method.Results:Macroscopic examination of the 7 groups of PN solutions identified neither changes in color nor stratification within 24 hours after solution preparation. Within 24 hours after solution preparation, the MDDs of all PN solutions before filtration were between (338.67±6.11) nm and (370.00±15.13) nm, and the PFAT5 values before filtration ranged from (32.00±1.00) ×10 -3% to (85.67±6.81) ×10 -3%. The MDDs of all PN solutions after filtration were between (310.67±8.62) nm and (362.33±19.86) nm, and the PFAT5 values after filtration ranged from (4.67±1.15) ×10 -3% to (17.33±0.58) ×10 -3%. The concentration of multiple trace elements was positively correlated with PFAT5 ( P<0.05). There was statistically significant difference in PFAT5 values at 0 h and 24 h after preparation ( P=0.004). The difference of PFAT5 values before and after filtration was also statistically significant ( P=0.000). Conclusions:Within 24 hours after solution preparation at room temperature, the appearance of neonatal PN solutions with different concentrations of trace elements supplementation was unchanged, and the MDDs of fat emulsions were all within the safe range. However, when the concentration of monovalent cations (Na +, K +) was 38.9 mmol/L, the concentration of divalent cation (Ca 2+) was 5 mmol/L, and the concentration of trace elements (Zn 2+, Cu 2+, Mn 2+, and Se 4+) was higher than 0.063 mmol/L, the PFAT5 value was higher than 0.05%. In this case, filtration with a 1.2 μm filter was necessary, which could significantly reduce the PFAT5 value and the globule size distribution, and improve the safety and standardization of the clinical application of PN solutions. It is suggested that the neonatal PN solutions supplemented with multiple trace elements injection (I) may be administered through a terminal filter.

In recent years, with the changes in living standards and dietary structure, the incidence of non-alcoholic fatty liver disease has been increasing year by year in China, and the incidence rate in the general population is as high as 29.81%. An increasingly epidemiological evidence suggests that non-alcoholic fatty liver disease has become one of the causes of increasing liver cirrhosis and liver cancer. However, its etiology and pathogenesis are complex and have not yet been fully elucidated. Therefore, establishing an appropriate non-alcoholic fatty liver disease animal models for pre-clinical research is essential to elucidate its pathogenesis. This article summarizes the latest research progress of non-alcoholic fatty liver disease animal models, which are common at home and abroad in recent years.

Objective:To investigate the characteristics of urinary microflora in women with type 2 diabetic peripheral neuropathy without lower urinary tract symptoms.Methods:By completing nerve conduction function and the American Urological Association Symptom Index questionnaire (AUA-SI), a total of 30 cases of women hospitalized with type 2 diabetes and no symptoms of lower urinary tract from May 2017 to August 2018 were included. 17 patients with diabetic peripheral neuropathy were assigned to the DPN group, and 13 patients without diabetic peripheral neuropathy were assigned to the nDPN group. Urine specimens were collected from clean catch midstream urine and processed for extracting DNA. Microbial diversity and composition were analyzed using the Illumina sequencing platform targeting to 16S rDNA gene. Sequencing reads were processed by QIIME. LEfSe algorithm was used to analyze the flora with significant differences between the two groups.Results:The duration of diabetes in the DPN group was lower than that in the nDPN group [(4.12 ± 3.28)years vs.(8.03 ± 6.11)years, P = 0.03], and the retinopathy cases were more in the DPN group than those in the nDPN group (6 vs. 0, P=0.03). Except for above two indicators, there was no significant difference in demographic characteristics between DPN group and nDPN group( P>0.05). The urinary microenvironment of DPN was characterized by increased bacterial richness(sobs index, chao index and aec index, 67.24±40.25 vs.108.69±57.18; 81.36±47.99 vs.122.55±55.70; 88.58±55.03 vs.125.78±53.03, all P<0.05) and by the enrichment of Mycoplasmataceae(Metastats value: 0.52±0.01vs.0.01±0.00001, P=0.02). Beta diversity showed that no significant difference of bacterial composition was found between these two group( P>0.05). LEfSe analysis showed that at the genus level, the relative abundance of eight genera(e.g., Bacillus, Duganella, Leptotrichia, Proteus, Propionibacterium, Pseudoxanthomonas, Bdellovibrio and uncultured_soil_bacterium) in DPN group decreased at the level of genus( P<0.05). Conclusions:Female patients with type 2 diabetes without lower urinary tract symptoms of peripheral neuropathy exhibit a different microbial community compared to nDPN controls. Mycoplasmataceae may be a potential biomarker for patients with DPN.

Objective:To summarize the clinical manifestations of four patients with 46, XY disorders of sex development(46, XY DSD)due to doublesex and mab-3 related transcription factor 1(DMRT1)gene variant/haploinsufficiency, and to improve the understanding of clinicians for this disease.Methods:The medical history, physical examination, endocrine function assessment, gonadal pathology, and genetic data of 4 patients with 46, XY DSD were retrospectively collected.Results:A heterozygous new missense mutation in DMRT1 was found in one child. The chief complain was primary amenorrhoea at the age of 15 years, with the external masculinisation score(EMS)0. The DMRT1 haploinsufficiency was found in 3 cases, 1.2 Mb, 5.1 Mb, and 6.0 Mb fragments were deleted at the 9p, and one of 3 cases had 33.3 Mb repeats in the 5p. All patients visited doctor under 1 year. Two patients were raised as females, and one was raised as male. All chief complains were external genital abnormalities, EMS of them were 1, 0, and 5 respectively. Endocrine evaluation of 2 out of 4 children showed varying degrees of primary hypogonadism, and presented with complete gonadal dysgenesis. One patient showed a well function of Leydig cells and poorly function of Sertoil cells, and presented with mixed gonadal dysgenesis. One of 3 cases was diagnosed with gonadoblastoma at the age of 18 months. Patient No.4 didn′t agree with the gonadal biopsy. The chromosome karyotypes of 4 children were 46, XY.Conclusions:The visiting ages of 46, XY DSD patients caused by DMRT1 variation were older than those of patients caused by DMRT1 haploinsufficiency. The clinical manifestations are complex, and gonadal function can vary from normal to complete gonadal dysgenesis. Such patients are at high risk of gonadoblastoma and young onset. Gonadal biopsy should be performed as early as possible.

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease in children and adults, and is closely related to obesity and metabolic factors. In recent years, with the changes in living standards and dietary structure, the incidence of NAFLD has been increasing year by year. Pediatric NAFLD has many similarities with adult NAFLD in terms of epidemiology, etiology, pathogenesis, and diagnosis and treatment strategies; however it has its own unique characteristics. This paper reviews the latest research progress of pediatric NAFLD in recent years at home and abroad.