OBJECTIVE To investigate the intervention effect and its potential mechanism of Yifei xuanfei jiangzhuo formula by inhibiting mitochondrial fission in a vascular dementia （VaD） model rats. METHODS VaD rat model was established by bilateral common carotid artery ligation. The experimental animals were randomly divided into sham operation group （SHAM）， model group （MOD），Yifei xuanfei jiangzhuo formula low-dose group （YFXF-L）， Yifei xuanfei jiangzhuo formula high-dose group （YFXF-H）， and Donepezil hydrochloride group （positive control）， with 9 animals in each group. After 30 days of intervention， the spatial learning memory ability was assessed by Morris water maze experiment； HE staining was used to observe histopathological changes in CA1 area of hippocampus； ELISA was used to detect the levels of serum inflammatory factors [interleukin-1β （IL-1β） and IL-4]； Western blot was used to detect the expressions of heat shock protein 90 （HSP90）/mixed lineage kinase domain-like protein （MLKL）/dynamin-related protein 1 （Drp1） pathway-related proteins， mitochondrial fusion proteins （MFN1， MFN2）， and adenosine triphosphate synthase 5A （ATP5A） in hippocampal tissues. The immunohistochemistry was used to detect the level of phosphorylated MLKL （p-MLKL）； real-time fluorescence quantitative PCR was adopted to detect mRNA expressions ofHSP90， MFN1， MFN2 and ATP5A. RESULTS Compared with SHAM group， the escape latency of rats in the MOD group was significantly prolonged， the number of crossing the platform was significantly reduced， and the hippocampal tissues showed typical neuronal damage characteristics， the positive expression level of p-MLKL and the serum level of IL-1β significantly increased， while the serum level of IL-4 significantly decreased， the protein and mRNA expression of HSP90， as well as the protein expressions of p-MLKL/MLKL and p-Drp1（Ser616）/Drp1 were all significantly increased in hippocampal tissue， the protein and mRNA expressions of MFN1， MFN2 and ATP5A， and protein expression of p-Drp1（Ser637）/Drp1 were all significantly decreased （P＜0.05）. After the intervention of Yifei xuanfei jiangzhuo formula， above indicators in each treatment group were all significantly reversed （P＜0.05）. CONCLUSIONS Yifei xuanfei jiangzhuo formula may alleviate neuronal damage and neuroinflammatory responses in VaD rats by regulating the HSP90/MLKL/Drp1 signaling pathway， inhibiting mitochondrial fission， thereby maintaining mitochondrial dynamic balance and improving mitochondrial function.

N6-methyladenosine(m6A)denotes the addition of a methyl group to the sixth nitrogen atom of ade-nosine,a common occurrence in eukaryotic RNA.The m6A modifications govern RNA splicing,translocation,stability,and translation into proteins.The RNA methyltransferases,like methyltransferase-like protein 3(METTL3),METTL14,and Wilms'tumor 1-associated protein(WTAP),are responsible for these modifications,while the removal process in-volves demethylases,specifically fat mass and obesity-associated protein(FTO)and ALKB homolog 5(ALKBH5).Recog-nition of these modifications is facilitated by m6A-binding proteins,such as YTH family proteins and insulin-like growth factor 2 mRNA-binding proteins(IGF2BPs).The m6A modification regulators are involved in the onset and progression of non-small-cell lung cancer through multiple mechanisms.This review concentrates on the biological functions and molecu-lar mechanisms of m6A modification-related regulatory factors in the malignant progression of non-small-cell lung cancer.

OBJECTIVE To investigate the mechanism of Yifei xuanfei jiangzhuo formula （YFXF） against vascular dementia （VD）. METHODS The differentially expressed genes of YFXF （YDEGs） were obtained by network pharmacology. High-risk genes were screened from YDEGs by using the nomogram model. The optimal machine learning models in generalized linear， support vector machine， extreme gradient boosting and random forest models were screened based on high-risk genes. VD model rats were established by bilateral common carotid artery occlusion， and were randomly divided into model group and YFXF group （12.18 g/kg， by the total amount of crude drugs）， and sham operation group was established additionally， with 6 rats in each group. The effects of YFXF on behavior （using escape latency and times of crossing platform as indexes）， histopathologic changes of cerebral cortex， and the expression of proteins related to the secreted phosphoprotein 1 （SPP1）/phosphoinositide 3-kinase （PI3K）/protein kinase B （aka Akt） signaling pathway and the mRNA expression of SPP1 in cerebral cortex of VD rats were evaluated. RESULTS A total of 6 YDEGs were obtained， among which SPP1， CCL2， HMOX1 and HSPB1 may be high-risk genes of VD. The generalized linear model based on high-risk genes had the highest prediction accuracy （area under the curve of 0.954）. Compared with the model group， YFXF could significantly shorten the escape latency of VD rats， significantly increase the times of crossing platform （P＜0.05）； improve the pathological damage of cerebral cortex， such as neuronal shrinkage and neuronal necrosis； significantly reduce the expressions of SPP1 protein and mRNA （P＜0.05）， while significantly increase the phosphorylation levels of PI3K and Akt （P＜0.05）. CONCLUSIONS VD high-risk genes SPP1， CCL2， HMOX1 and HSPB1 may be the important targets of YFXF. YFXF may play an anti-VD role by down-regulating the protein and mRNA expressions of SPP1 and activating PI3K/Akt signaling pathway.

The tea beverages will be endowed with distinct aroma and taste, as well as various biologically active compounds including probiotic factors, when fermented with lactic acid bacteria (LAB). However, at present, few studies on the dynamics of flavors in tea soup at different fermentation stages were conducted. In this study, the composition of monosaccharides, aromatic components, free amino acids, and organic acids were measured, when the black tea beverages were fermented with Lactobacillus coryniformis FZU63 which was isolated from Chinese traditional kimchi. The results indicated that monosaccharides including glucose, fructose, mannose and xylose in black tea beverages are the main carbon sources for fermentation. In addition, the abundance of aromatic compounds in black tea soup are increased significantly at different fermentation stages, which endow the fermented black tea soup with fruit aroma on the basis of flowery and nutty aroma. Moreover, some bitter amino acids are reduced, whereas the content of sweet and tasty amino acids is elevated. Furthermore, the levels of lactic acid, malic acid, citric acid and other organic acids are accumulated during the fermentation. Additionally, sensory evaluation displays that black tea beverage is acquired with comprehensive high-quality after being fermented for 48 h. This study provides a theoretical basis to steer and control the flavor formation and quality of the fermented tea beverages during LAB fermentation.
Tea/chemistry* ; Beverages/microbiology* ; Camellia sinensis ; Fermentation ; Acids ; Amino Acids ; Glucose

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

OBJECTIVE：To study the effects and potential mechani sm of deoxyschizandrin on the proliferation ，migration and invasion of nasopharyngeal carcinoma cell HONE- 1. METHODS ：HONE-1 cell was set as cell model ，while CCK- 8 test，wound healing assay and Transwell chamber test were used to detect the proliferation ，migration and invasion ability changes of HONE- 1 cells after treatment with different concentrations [ 0（blank control ），10，20，40 μmol/L] of deoxyschizandrin. Computer molecular docking was performed to analyze the binding ability between deoxyschizandrin and Met protein. Western blotting assay was used to detect the relative protein expressions of p-Met ，p-PI3K，p-Akt，Bcl-2 and N-cadherin in cells. RESULTS ：Compared with blank control ，the proliferation ，migration and invasion ability of cells after treated with 10，20，40 μmol/L deoxyschizandrin were all decreased significantly （P＜0.05）. Results of molecular docking revealed that deoxyschizandrin could stably bind with the activity pocket of Met protein. Results of Western blotting assay demonstrated that compared with blank control ，10，20，40 μmol/L deoxyschizandrin all decreased the relative protein expressions of p-Met ，p-PI3K，p-Akt，Bcl-2 and N-cadherin in cells significantly（P＜0.05）. CONCLUSIONS ：Deoxyschizandrin can inhibit the proliferation ，migration and invasion of HONE- 1 cell via inhibiting the activation of Met/PI 3K/Akt signaling pathway.

Objective To study the relationship between uridine diphosphate glucuronic acid (UGT1A1) gene polymorphism and unexplained neonatal unconjugated hyperbilirubinemia in Jinhua.Method Full-term infants with unidentified non-binding hyperbilirubinemia were selected as hyperbilirubinemia group from January 2016 to December 2017 in the obstetrics or neonatal intensive care unit of Jinhua Central Hospital,healthy full-term neonates and those with physiological jaundice admitted during the same period were selected as control group.Whole blood DNA was extracted and UGT1A1 was sequenced and then annotated with human gene mutation database.The distribution and frequency of UGT1A1 genotype were analyzed.The correlation between different genotypes and unexplained unconjugated hyperbilirubinemia in neonates was also studied.Result Two hundred and forty cases were enrolled in the hyperbilirubinemia group,and 216 cases were enrolled in the control group.Four single nucleotide variation (SNV) sites associated with the disease were found on UGT1A1,which were c.211G＞A (Gly71Arg),c.686C＞A (Pro229Gln),c.1091C＞T (Pro364Leu) and c.1456T＞G (Tyr486Asp),accounting for 83.9％(141/168),1.8％(3/168),8.9％(15/168) and 5.4％(9/168) in the experimental group respectively.The genotype frequency and allele frequency analysis showed that the distribution of the two SNV sites of c.211G＞A and c.1456T＞G were statistically different between the experimental group and the control group (P＜0.05),whereas there was no statistical difference of the other two SNV sites of c.686C＞A and c.1091C＞T between the two groups.Binary Logistic regression analysis showed that c.211G＞A and c.1456T＞G were related to the occurrence of unexplained hyperbilirubinemia,The OR values (95％CI) were 5.412 (3.567～ 8.212) and 8.377 (1.052～66.670) respectively,but no correlation was found of the other two polymorphic loci.At the different genotypes of c.211G＞A locus,the levels of total bilirubin and non-binding bilirubin in infants with homozygous mutant (AA) were higher than those in infants with heterozygous mutant (GA) and wild type (GG),which was statistically significant (P＜0.05).Conclusion The most common mutation site of the UGT1A1 gene in Jinhua is c.211G＞A.The mutations of c.211G＞A and c.1456T＞G are risk factors forunconjugated hyperbilirubinemia in neonates.Of the different genotypes of c.211G＞A locus,the serum bilirubin level of homozygous mutant group was significantly higher than heterozygous mutant group and wild type group.

BACKGROUND/AIMS: The integration of multiple profiling data and the construction of a transcriptional regulatory network may provide additional insights into the molecular mechanisms of hepatocellular carcinoma (HCC). The present study was conducted to investigate the deregulation of genes and the transcriptional regulatory network in HCC. METHODS: An integrated analysis of HCC gene expression datasets was performed in Gene Expression Omnibus. Functional annotation of the differentially expression genes (DEGs) was conducted. Furthermore, transcription factors (TFs) were identified, and a global transcriptional regulatory network was constructed. RESULTS: An integrated analysis of eight eligible gene expression profiles of HCC led to 1,835 DEGs. Consistent with the fact that the cell cycle is closely related to various tumors, the functional annotation revealed that genes involved in the cell cycle were significantly enriched. A transcriptional regulatory network was constructed using the 62 TFs, which consisted of 872 TF-target interactions between 56 TFs and 672 DEGs in the context of HCC. The top 10 TFs covering the most downstream DEGs were ZNF354C, NFATC2, ARID3A, BRCA1, ZNF263, FOXD1, GATA3, FOXO3, FOXL1, and NR4A2. This network will appeal to future investigators focusing on the development of HCC. CONCLUSIONS: The transcriptional regulatory network can provide additional information that is valuable in understanding the underlying molecular mechanism in hepatic tumorigenesis.
Carcinogenesis ; Carcinoma, Hepatocellular* ; Cell Cycle ; Dataset ; Gene Expression ; Humans ; Research Personnel ; Transcription Factors ; Transcriptome

Objective To investigate the therapeutic outcomes of unilateral adrenalectomy for Cushing syndrome in patients with adrenocorticotropic hormone (ACTH) independent bilateral macronodular adrenal hyperplasia.Methods 22 patients diagnosed with Cushing syndrome caused by ACTH independent bilateral macronodular adrenal hyperplasia from January 2005 to December 2015 were retrospectively concluded.There are 17 male patients and 5 female patients with the median age of 46.5 years.All patients were presented with Cushing syndrome such as moon face, buffalo hump and other typical symptoms of Cushing syndrome.The laboratory tests showed disappearance of cortisol rhythm, elevated 24-hour urinary free cortisol, suppressed or normal ACTH and unsuppressed low dose dexamethasone suppressing test.CT scan showed bilateral macronodular adrenal hyperplasia in all patients.Results All the patients received unilateral adrenalectomy.Pathological results showed adrenal cortex nodular hyperplasia.16 patients had reexamination in the endocrine department.The median follow-up time was 26 (17-118)months for these 16 patients.In the follow-up between 3 to 9 months after surgery, laboratory test showed serum and urinary cortisol level returned to normal range and Cushing syndrome also disappeared in these 16 patients.CT scan showed no recurrence.And no adrenal insufficiency occurred.One patient had recurrence one year after surgery and two patients turned better after surgery but had recurrence at 3 years and 10 years after surgery.Two patients received contralateral adrenalectomy and cortisol hormone replacement therapy after surgery.Another patient with recurrence refused second surgery.No recurrence was observed in other patients.Four patients were followed up by telephone, and all recovered well after surgery.18 patients had hypertension before surgery and their blood pressure significantly decreased after surgery.Among them 13 cases blood pressure returned to normal range.5 patients had elevated blood glucose before surgery, and 3 patients' blood glucose returned to normal range.Conclusions Unilateral adrenalectomy for Cushing syndrome in patients with ACTH independent bilateral macronodular adrenal hyperplasia is safe and effective.

Objective To study radiographic classification of tarsometatarsal joint dislocation and postoperative imaging evaluation.Methods 74 patients with tarsometatarsal joint dislocation were included in this study.Tarsometatarsal joint dislocations were classified by the Myerson fracture displacements classification.All patients were evaluated according to the American Orthopedics Foot & Ankle Society (AOFAS)clinical rating systems.Results There were 19 patients with Myerson A,46 patients with Myerson B and 9 patients with Myerson C tarsometatarsal joint dislocation.39 distal tarsal bone fractures and 156 metatarsal fractures,with simultaneous scaphoid fractures in 10 patients were showed.All patients who were followed up and no infection.The AOFAS scale was categorized as excellent,good,fair or poor,and 22 patients were considered as excellent,29 patients as good,17 patients as fair and 6 patients as poor.Postoperative imaging evaluation required anatomical reduction of tarsometatarsal joint.On the anteroanterior radiogragh,the base medial edge of the second metatarsal bone and the medial edge of intermediate cuneiform were combined to form a straight line.The shortest distance between the base of the first metatarsal bone and the second metatarsal bone should be less than 2 mm.On the medial oblique radiogragh,a smooth line connecting the medial edge of the fourth metatarsal bone with the medial edge of cuboid bone always appeared.On the lateral radiogragh,the dorsal edge of the second metatarsal bone and intermediate cuneiform formed a smooth line.The height of metatarsus should not exceed the dorsal edge of corresponding cuneiform.The longitudinal arch angle was restored within normal limits.Conclusion The type-B tarsometatarsal joint dislocation is the most common type and frequently accompanies by multiple fractures.Intraoperative and postoperative multidirectional observation of anatomical reduction of tarsometatarsal joint dislocation can reduce incidence of posttraumatic arthritis.