ObjectiveTo investigate the regulatory effect of circular RNA circ_0120051 on the fibrotic phenotype of cardiac fibroblasts and the potential mechanism involved. MethodsThe expression of circ_0120051 and its host gene of solute carrier family 8 member A1（SLC8A1） mRNA in the myocardium of healthy organ donors （n=24） and heart failure （HF） patients （n=21） were assessed by real-time quantitative polymerase chain reaction （RT-qPCR） assay. RNA stability of circ_0120051 was identified by RNase R exonuclease digestion assay. The cytoplasmic and nuclear distribution of circ_0120051 in human cardiomyocyte AC16 was detected by RT-qPCR assay. The expression of fibrosis-related genes in mouse cardiac fibroblasts （mCFs） with adenovirus-mediated overexpression of circ_0120051 was detected by RT-qPCR and Western blot assay， respectively. The effect of overexpression of circ_0120051 on the migration activity of mCFs was evaluated by wound-healing assay. RNA co-immunoprecipitation （RIP） was conducted to detect the interaction between circ_0120051 and miR-144-3p. The binding site of miR-144-3p in the 3'-UTR of isocitrate dehydrogenase 2 （Idh2） mRNA was identified by the dual luciferase reporter gene assay. ResultsCirc_0120051 was significantly up-regulated in the myocardium of HF patients， while the mRNA expression of its host gene SLC8A1 was not changed. Circ_0120051 was mainly located in the cytoplasm of human AC16 cells. Results of RNase R exonuclease digestion revealed that circ_0120051 possesses the characteristic stability of circular RNA compared to the linear SLC8A1 mRNA. Overexpression of circ_0120051 could inhibit the expression of fibrosis-related gene in mCFs and mCFs migration. RIP assay confirmed the specific interaction between circ_0120051 and miR-144-3p. Transfection of miR-144-3p mimic could efficiently promote the expression of fibrosis-related genes in mCFs and reverse the inhibitory effect of circ_0120051 on the fibrotic phenotype of mCFs. Results of the dual luciferase reporter gene assay confirmed the interaction between miR-144-3p and the 3'-UTR of Idh2. Transfection of miR-144-3p transcriptionally inhibited Idh2 expression， and overexpression of circ_0120051 enhanced IDH2 expression in mCFs. MiR-144-3p mimic and Idh2 small interfering RNA （siRNA） could consistently reverse the inhibitory effects of circ_0120051 on fibrosis-related genes expression in mCFs and mCFs migration. ConclusionsCirc_0120051 inhibits the fibrotic phenotype of cardiac fibroblasts via sponging miR-144-3p to enhance the target gene of IDH2 expression.

ObjectiveThe potential suitable area for ecological planting， key ecological factors， and suitable range of Polygonatum odoratum in China were analyzed to provide theoretical and scientific guidance for the artificial planting of P. odoratum. MethodA total of 454 geographical distribution records of P. odoratum in China and 118 ecological factors were used in this study. The maximum entropy model （MaxEnt） was adopted to predict the suitable areas of P. odoratum. The key ecological factors and their suitable ranges were analyzed by the jackknife method， contribution rates of ecological factors， and response curves. ResultThe suitable areas of P. odoratum were mainly located in the northwest， north， and northeast of China， the highly suitable areas of which were concentrated in Shaanxi， Shanxi， Gansu， etc. Solar radiation in November （Srad11）， precipitation in July （Prec7）， percentage of evergreen/deciduous needleleaf trees （Class1）， silt content （2-50 μm） mass fraction （SLTPPT）， and annual average temperature （Bio1） were found to be the key ecological factors affecting the suitable distribution of P. odoratum in China. The cumulative contribution rate of solar radiation factors （31.29%）>vegetation factors （25.61%）>soil factors （19.52%）>precipitation factors （11.38%）>temperature factors （8.57%）>topography factors （3.63%）. ConclusionIt is suggested to carry out ecological planting of P. odoratum mainly in Shaanxi （such as Baoji and Ankang Cities and Ningshan， Liuba， and Hua Counties）， Gansu （such as Tianshui City， Gannan Tibetan Autonomous Prefecture， and Liangdang and Huating Counties）， and Shanxi （such as Yangquan， Taiyuan， Fenyang， and Jinzhong Cities， as well as Xingxian County） of China. Solar radiation factors should be given priority in the planting process， followed by vegetation， soil， precipitation， temperature， and topography factors. The range of key ecological factors， namely Srad11， Prec7， Class1， SLTPPT， and Bio1 should be controlled within 8 095.21-10 334.98 （optimum 8 787.50） kJ·m^-2·d^-1， 109.99-223.60 （146.91） mm， 1.00%-9.45% （6.76%-10.68%）， 41.73%-50.35% （46.53%）， and 3.29-16.33 （13.57） °C， respectively.

Objective:To explore changes of acid-base metabolism in the brain tissue of patients with chronic ischemic cerebrovascular disease (CICVD) using MRI amide proton transfer-weighted (APTw) imaging.Methods:This was a cross-sectional study. From January 2021 to July 2022, thirty-nine patients with CICVD at West China Hospital, Sichuan University were retrospectively included. All patients received CT perfusion (CTP) and APTw imaging. NeuBrainCARE brain perfusion software was used to analyze the impaired perfusion sites and measure the mean transit time (MTT) and time to peak (TTP). Standard spatial matching between CTP and APTw images was performed to measure the APTw values of the same sites. For comparison with normal tissue, APTw values were measured for normal-appearing white matter (NAWM) in the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere in areas of impaired perfusion. ANOVA was used to compare the APTw values of impaired perfusion brain tissue, ipsilateral cerebral NAWM, contralateral cerebral NAWM, and ipsilateral cerebellar NAWM. The Bonferroni method was used to correct for multiple comparisons. Pearson correlation coefficient was used to analyze the correlation between APTw values and MTT and TTP in the cerebral tissue with impaired perfusion.Results:In 39 patients with CICVD, both the mean and minimum APTw values of cerebral tissue with impaired perfusion were significantly lower than those in the NAWM of the ipsilateral cerebral hemisphere, the contralateral cerebral hemisphere, and the ipsilateral cerebellar hemisphere ( P<0.001). In the NAWM of the cerebellar hemispheres with unimpaired perfusion, both the mean and minimum APTw values were significantly higher than those in the ipsilateral cerebral hemispheres and the contralateral cerebral hemisphere ( P<0.001). Correlation analysis showed that MTT was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.90 and -0.82, P<0.001). TTP was significantly negatively correlated with both the mean APTw and the minimum APTw ( r values were -0.86 and -0.78, P<0.001). Conclusion:APTw value can reflect acidosis in cerebral tissue with impaired perfusion in patients with CICVD.

Objective:To explore the risk factors for death within 1 year after hip fracture surgery in the elderly.Methods:A case control study was made on the clinical data of 551 elderly patients with hip fracture treated in Second Affiliated Hospital of Soochow University from January 2019 to December 2020, including 182 males and 369 females; aged 65-100 years [80(73,86)years]. Joint replacement, cannulated screw fixation or proximal femoral nail fixation were performed. The patients were divided into survival group ( n=494) and death group ( n=57) based on the death within 1 year after surgery recorded at postoperative telephone follow-up. The gender, age, hypertension, diabetes, cardiovascular diseases, chronic respiratory diseases, neurological diseases, chronic renal failure, anemia on admission, fracture types, American anesthesiologist Association (ASA) classification, operative methods, preoperative waiting time, duration of operation and perioperative blood transfusion were recorded in two groups. Univariate Cox regression was used to analyze the correlation between the above indexes and death within 1 year after surgery. All indexes with P<0.2 in the univariate analysis were included in multivariate Cox regression analysis to clarify the independent risk factors for death within 1 year after surgery. Results:Univariate Cox regression analysis showed that death within 1 year after surgery correlated with gender, age chronic respiratory diseases, chronic renal failure and anemia on admission (all P<0.01), but not with hypertension, diabetes, cardiovascular diseases, neurological diseases, fracture types, ASA classification, operative methods, preoperative waiting time, duration of operation or perioperative blood transfusion (all P>0.05). Multivariate Cox regression analysis showed that male ( HR=2.08, 95% CI 1.20, 3.61, P<0.01), age ≥ 80 years ( HR=2.22, 95% CI 1.15, 4.28, P<0.05), chronic respiratory diseases ( HR=2.54, 95% CI 1.19, 5.40, P<0.05), chronic renal failure ( HR=4.57, 95% CI 1.27, 16.44, P<0.05), anemia on admission ( HR=2.82, 95% CI 1.38, 5.76, P<0.01) were significantly associated with death within 1 year after surgery. Conclusion:Male age≥ 80 years, chronic respiratory disease, chronic renal failure and anemia on admission are independent risk factors for death within 1 year after hip fracture surgery in the elderly.

Episodic ataxia (EA) is a group of disorders characterized by recurrent spells of vertigo, truncal ataxia, and dysarthria. Episodic ataxia type 2 (EA2), the most common subtype of EA, is an autosomal dominant disease caused by mutation of the CACNA1A gene. EA2 has been rarely reported in the Chinese population. Here we present an EA2 family admitted to Xiangya Hospital in October 2018. The proband was a 22-year-old male who complained of recurrent spells of vertigo, slurred speech, and incoordination for 4 years. Brain magnetic resonance imaging (MRI) showed cerebellar atrophy. He had neuropsychological development disorder in childhood, and cognitive assessment in adulthood showed cognitive impairment. The proband's mother and grandmother had a similar history. Peripheral blood samples from the proband and family members were collected, and genomic DNA was isolated. Whole exome sequencing of the proband detected a heterozygous frameshift mutation c.2042_2043del (p.Q681Rfs*100) of CACNA1A gene. This mutation was verified in the proband and 2 family members using Sanger sequencing. One family member carrying this mutation was free of symptoms and signs, suggesting an incomplete penetrance of the mutation. We reported a variant c.2042_2043del of CACNA1A gene as the pathogenic mutation in a Chinese EA2 family for the first time. This case enriched the clinical spectrum of CACNA1A related EA2, and contributed to the understanding of clinical and genetic characteristics of EA2 to reduce misdiagnosis.
Adult ; Ataxia ; Calcium Channels/genetics* ; Humans ; Male ; Mutation ; Nystagmus, Pathologic ; Pedigree ; Vertigo ; Young Adult

Fusidane-type antibiotics, represented by helvolic acid, fusidic acid and cephalosporin P

OBJECTIVES: Idiopathic intracranial hypertension (IIH) is a syndrome that excludes secondary causes such as intracranial space-occupying lesion, hydrocephalus, cerebrovascular disease, and hypoxic ischemic encephalopathy. If not be treated promptly and effectively, IIH can cause severe, permanent vision disability and intractable, disabling headache. This study aims to explore the clinical and image features for IIH, to help clinicians to understand this disease, increase the diagnose rate, and improve the outcomes of patients. METHODS: We retrospectively analyzed 15 cases of IIH that were admitted to Xiangya Hospital, Central South University, during January 2015 to September 2020. The diagnosis of IIH was based on the updated modified Dandy criteria. We analyzed clinical data of patients and did statistical analysis, including age, gender, height, weight, medical history, physical examination, auxiliary examination, treatment and outcome. RESULTS: There were 10 females and 5 males. Female patients were 22 to 42 years old with median age of 39.5. Male patients were 27 to 52 years old with the median age of 44.0. The BMI was 24.14-34.17 (28.71±2.97) kg/m CONCLUSIONS IIH primarily affects women of childbearing age who are overweight. The major hazard of IIH is the severe and permanent visual loss. Typical image signs have high specificity in IIH diagnosis. Prompt diagnosis and effective treatment are significantly important to improve the outcomes of patients.
Adult ; Anemia, Iron-Deficiency ; Female ; Humans ; Intracranial Hypertension ; Male ; Middle Aged ; Pseudotumor Cerebri/diagnostic imaging* ; Retrospective Studies ; Ventriculoperitoneal Shunt ; Young Adult

Fusidic acid is the only fusidane-type antibiotic that has been clinically used. However, biosynthesis of this important molecule in fungi is poorly understood. We have recently elucidated the biosynthesis of fusidane-type antibiotic helvolic acid, which provides us with clues to identify a possible gene cluster for fusidic acid ( cluster). This gene cluster consists of eight genes, among which six are conserved in the helvolic acid gene cluster except and . Introduction of the two genes into the NSAR1 expressing the conserved six genes led to the production of fusidic acid. A stepwise introduction of and revealed that the two genes worked independently without a strict reaction order. Notably, we identified two short-chain dehydrogenase/reductase genes and in the cluster, which showed converse stereoselectivity in 3-ketoreduction. This is the first report on the biosynthesis and heterologous expression of fusidic acid.

Objective To investigate the expression of PD-1 on CD4 +and CD8 + T cells in patients with HBeAg-positive chronic hepatitis B(CHB)treated with telbivudine.Methods Fifty-six HBeAg-positive CHB patients admitted in the First Affiliated Hospital of Zhengzhou University during January 201 3 and June 201 4 were enrolled in this study.The expression of PD-1 on CD4 +and CD8 + T cells was detected with flow cytometry at baseline,24,48 and 72 wks after telbivudine treatment.The relationship of PD-1 expression with alanine aminotransferase (ALT)level,HBeAg seroconversion and HBV DNA loads was analyzed.t test and completely random variance analysis were used to analyze the data.Results The PD-1 expression on CD4 + and CD8 + T cells at baseline was higher in patients with low ALT levels compared to those with high ALT levels(t =1 2.20 and 9.69,both P <0.01 ),while higher levels of PD-1 expression was also observed in patients with high HBV DNA load (≥5 lgIU /mL)compared to those with low HBV DNA load (t =4.39 and 4.85,both P <0.01 ).PD-1 levels on CD4 + and CD8 + T cells presented a declining trend after telbivudine treatment(F =6.98 and 8.97,both P <0.01 ),PD-1 expression in patients with HBeAg seroconversion showed lower levels compared with baseline values (t =1 8.45 and 1 8.01 ,both P <0.01 ). Conclusion In HBeAg-positive CHB patients,the expression of PD-1 on CD4 + and CD8 + T lymphocytes shows a decreasing trend during the treatment with telbivudine,indicating that antiviral therapy may alleviate the immunosuppression in these patients.

Objective To investigate the dynamic changes of regulatory T cells (Treg ) and the surface expression of programmed death (PD)‐1 and the level of transforming growth factor (TGF )‐βduring antiviral treatment in patients with chronic hepatitis C (CHC) .Methods Eighty‐six CHC patients referred to the First Affiliated Hospital of Zhengzhou University from October 2012 to October 2013 were included ,and all of them were administered with pegylated interferon α‐2a and ribavirin .Thirty healthy controls were enrolled .The percentage of Treg cells ,PD‐1 expression and TGF‐β level were analyzed by flow cytometry at baseline and at time of achieving rapid virological response (RVR ) , early viral virological (EVR ) , end‐of‐treatment virological response (ETVR ) and sustained virological response (SVR) ,or not achieving SVR .Comparison between two groups was analyzed by t test .Results Among 86 CHC patients ,the proportions of RVR ,EVR ,ETVR ,and SVR at week 24 of follow‐up were 29 cases ,67 cases ,79 cases and 67 cases ,respectively .Percentage of Treg cells in CHC patients was much higher than that in healthy controls (10 .31 ± 5 .61 vs 2 .18 ± 0 .65 ,t = 2 .28 , P< 0 .05) .During antiviral therapy ,percentages of Treg cells declined ,not only in CHC patients with HCV genotype 1b (at baseline , RVR ,EVR ,and ETVR :14 .44 ± 3 .78 ,11 .01 ± 1 .79 ,8 .24 ± 2 .98 ,and 5 .36 ± 1 .47 ,respectively ) ,but also in those infected with HCV genotype 2a (at baseline ,RVR ,EVR ,and ETVR :12 .34 ± 2 .82 ,8 .99 ± 1 .68 ,7 .53 ± 2 .96 ,and 4 .79 ± 1 .23 ,respectively ) .Expressions of PD‐1 and TGF‐β also decreased .At baseline ,the expressions of PD‐1 in patients with SVR and without SVR were 29 .11 ± 14 .65 and 37 .73 ± 11 .65 ,respectively (t = 2 .15 , P = 0 .04) ,and the levels of TGF‐β were 41 .20 ± 18 .96 and 56 .75 ± 14 .42 ,respectively (t= 2 .66 ,P< 0 .01) .At week 24 ,the expressions of PD‐1 in patients with SVR and without SVR were 10 .36 ± 4 .81 and 36 .46 ± 10 .52 ,respectively (t= 13 .95 ,P< 0 .01) ,and the levels of TGF‐β were 10 .06 ± 4 .64 and 45 .23 ± 17 .85 , respectively ( t = 11 .85 , P < 0 .01 ) . Conclusions Percentages of Treg cells and expressions of PD‐1 and TGF‐β decrease during antiviral treatment in CHC patients .Thus ,it could be of assist to predict the treatment response by monitoring these parameters .