ObjectiveTo observe the efficacy and safety of Tongguan Capsule（通冠胶囊）on ventricular remodeling in patients after acute myocardial infarction （AMI）， and to explore the possible mechanism. MethodsA total of 53 ST-segment elevation myocardial infarction （STEMI） patients were collected and randomly divided into 26 cases in the treatment group and 27 cases in the control group. The control group was given conventional therapy after percutaneous coronary intervention （PCI） for AMI， and the treatment group was given Tongguan Capsules （4.5 g each time， 3 times a day） on the basis of the control group. The course of treatment was 12 weeks. Echocardiographic data and stool samples were collected from subjects before and after the intervention， and left ventricular ejection fraction （LVEF）， left ventricular end-diastolic volume index （LVEDVi）， left ventricular end-systolic volume index （LVESVi）， left ventricular mass index （LVMi） were measured and calculated， so as to compare the number of cases of left ventricular remodeling in the two groups. At the same time， 16S rDNA sequencing was performed on the stool samples to analyze the diversity of gut microbiota （GM）， the composition of the GM， the GM difference between the groups； recording the incidence of major adverse cardiovascular events （MACEs） and adverse reactions of patients in the two groups during the study period； and performing Spearman's correlation analyses of the post-treatment flora data with LVEF， LVEDVi， LVESVi， LVM， and LVMi in the two groups. ResultsOne case fail to follow up in the treatment group and 2 cases fail to follow up in the control group， and 25 cases in each of the two groups were finally included in the analysis. LVEDVi， LVESVi， and LVMi of the control group after treatment were higher than those before treatment （P＜0.05）； after treatment， LVEDVi， LVESVi and LVMi in the treatment group were lower than those in the control group （P＜0.05）. Left ventricular remodeling occurred in 5 cases （20.00%） in the treatment group and 13 cases （52.00%） in the control group， and the incidence of left ventricular remodeling in the treatment group was lower than that in the control group （P=0.03）. After treatment， the ACE estimation and Chao estimation of bacterial abundance in the treatment group were higher than that before treatment and that in the control group （P＜0.05）. The treatment group showed an increase in Mycobacterium anisopliae phylum and a decrease in Mycobacterium thickum， Mycobacterium anisopliae phylum， and Mycobacterium patella phylum after treatment （P＜0.05）. When comparing between groups after treatment， the relative abundance of Prevotella， Agathobacter， Dialister， Eubacterium coprostanoligenes group was up-reuglated and the relative abundance of Enterococcus was down-regulated in the treatment group（P＜0.05 or P＜0.01）. There was no statistically significant difference in the incidence of MACEs and the occurrence of adverse reactions between groups during treatment （P＞0.05）. The results of correlation analysis showed that Prevotella were positively correlated with LVEF and negatively correlated with LVEDVi， LVESVi， LVM， and LVMi （P＜0.01）. Agathobacter group were negatively correlated with LVEDVi， LVESVi （P＜0.01）； Enterococcus group were positively correlated with LVESVi （P＜0.05）. ConclusionTongguan Capsules can improve ventricular remodeling in patients with acute ST-segment elevation myocardial infarction with better safety； its mechanism may be related to adjusting the enrichment of related bacteria such as Prevotella， Dialister and Enterococcus and other related bacterial genera， increasing the colonization and diversity of beneficial bacteria， and adjusting the structure of GM.

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Objective:To investigate the relationship between number of daily steps and insomnia in patients with chronic insomnia using "WeChat Sports" program.Methods:A total of 190 patients with insomnia who received treatment in Department of Neurology, Zhejiang University of Traditional Chinese Medicine Affiliated Wenzhou Hospital between October 2017 and October 2019. General data (age, sex, body mass index, history of smoking and alcohol use) and the number of daily steps recorded by "WeChat Sports" program were collected. Patients whose average number of daily steps was greater than 7500 were assigned to the sufficient exercise group ( n = 68), and the remaining patients were assigned to the insufficient exercise group ( n = 122). Patient symptoms were assessed using the Pittsburgh Sleep Quality Index (PSQI), The Patient Health Questionnaire-9, and generalized Anxiety Disorder scale-7. Scale evaluation and data collection were performed by two trained investigators. Data were compared between the two groups. The correlation between average number of daily steps and each scale score was analyzed. Results:Total PSQI score in the sufficient exercise group was significantly lower than that in the insufficient exercise group [(12.94 ± 3.14) points vs. (14.93 ± 2.99) points, t = 4.31, P < 0.001]. Scores of subjective sleep quality, sleep latency, habitual sleep efficiency, use of sleep medication, and daytime dysfunction were significantly lower in the sufficient exercise group than those in the insufficient exercise group ( P = 0.011, 0.008, 0.025, 0.039, 0.006). The Patient Health Questionnaire-9 and Generalized Anxiety Disorder Scale-7 scores in the sufficient exercise group were significantly lower than those in the insufficient exercise group ( P = 0.011, P = 0.002). The average number of daily steps was significantly negatively correlated with total PSQI score, Patient Health Questionnaire-9 score, Generalized Anxiety Disorder Scale-7 score, and score of each PSQI component (subjective sleep quality, sleep latency, habitual sleep efficiency, and daytime dysfunction) ( r = -0.29, -0.16, -0.19, -0.24, -0.15, -0.18, -0.23). Conclusion:Insomnia patients with insufficient daily exercise have more serious insomnia and emotional symptoms than those with sufficient daily exercise. Daily average exercise is correlated with the severity of insomnia and emotional symptom.

Objective:To study the correlation between transcutaneous bilirubin (TcB) level measured from shielded skin and total serum bilirubin (TSB) level after phototherapy in premature infants.Methods:From July 2019 to July 2021,preterm infants with jaundice admitted to the Department of Neonatology of our hospital and received phototherapy were prospectively enrolled in the study. The infants were assigned into 26~31w group, 32~34w group and 35~36w group according to their gestational ages. During phototherapy, the forehead, the chest and the perineum were shielded. TcBs were measured at the above mentioned areas three times each before and after phototherapy and TSB was measured from venous blood samples.Results:A total of 306 premature infants were included, with 51 cases in 26~31w group, 126 cases in 32~34w group and 129 cases in 35~36w group. Before phototherapy, TcBs of the forehead, the chest and the perineum of all infants were correlated with TSB ( r=0.699, 0.913, 0.734, P<0.001) with TcB of the chest showed the best correlation. A linear regression equation was established using the TSB before phototherapy and the TcB of the chest: TSB=0.634+0.912TcB. After phototherapy, TcBs of the forehead, the chest and the perineum of all infants were also correlated with TSB ( r=0.586, 0.879, 0.690, P<0.001) with TcB of the chest showed the best correlation and the linear regression equation was TSB=1.910+0.736TcB. Conclusions:For preterm infants with gestational age of 26~36w, TcB of the shielded chest skin after phototherapy is correlated with TSB and a linear regression model can be established.

Background: Maedi/Visna virus (MVV) is a contagious viral pathogen that causes considerable economic losses to the sheep industry worldwide. Objectives: In China, MVV has been detected in several regions, but its molecular characteristics and genetic variations were not thoroughly investigated. Methods: Therefore, in this study, we conducted next-generation sequencing on an MVV strain obtained from northwest China to reveal its genetic evolution via phylogenetic analysis. Results: A MVV strain obtained from Inner Mongolia (NM) of China was identified. Sequence analysis indicated that its whole-genome length is 9193 bp. Homology comparison of nucleotides between the NM strain and reference strains showed that the sequence homology of gag and env were 77.1%–86.8% and 67.7%–75.5%, respectively. Phylogenetic analysis revealed that the NM strain was closely related to the reference strains isolated from America, which belong to the A2 type. Notably, there were 5 amino acid insertions in variable region 4 and a highly variable motif at the C-terminal of the surface glycoprotein (SU5). Conclusions The present study is the first to show the whole-genome sequence of an MVV obtained from China. The detailed analyses provide essential information for understanding the genetic characteristics of MVV, and the results enrich the MVV library.

Objective: Evaluation of improving the occupational protective effect of nurses in cytotoxic drugs. Methods: The occupational hazards of cytotoxic drugs in Qingdao Central hospital were taken as samples. Compare the occupational hazards of cytotoxic drugs before and after improvement. Results: From Sept.2017 to Aug.2018, the number of occupational hazards of cytotoxic drugs decreased by 90.38%; Sharp injuries, drug spillovers, distribution errors and excessive air diffusivity were decreased by 70%~100%. Conclusion Targeted occupational protection can significantly reduce the hazards of cytotoxic drugs and ensure the health of the medicinal staff.

Objective: To investigate the effects of hypoxia on the phenotype transformation of human dermal fibroblasts to myofibroblasts and the mechanism. Methods: The third passage of healthy adult human dermal fibroblasts in logarithmic phase were cultured in DMEM medium containing 10% fetal bovine serum for the following five experiments. (1) In experiments 1, 2, and 3, cells were divided into normoxia group and hypoxia group according to the random number table, with 10 dishes in each group. Cells of normoxia group were cultured in incubator containing 21% oxygen, while those of hypoxia group with 1% oxygen. At post culture hour (PCH) 0 and 48, 5 dishes of cells were collected from each group, respectively. mRNA expressions of markers of myofibroblasts including alpha smooth muscle actin (α-SMA), type Ⅰ collagen, and type Ⅲ collagen of cells were determined with real time fluorescent quantitative reverse transcription polymerase chain reaction in experiment 1. Protein expressions of α-SMA, type Ⅰ collagen, and type Ⅲ collagen of cells were determined with Western blotting in experiment 2. The protein expression of nuclear factor-kappa B (NF-κB) of cells was determined with Western blotting in experiment 3. (2) In experiment 4, cells were divided into normoxia group, hypoxia group, and hypoxia+ pyrrolidine dithiocarbamate (PDTC) group according to the random number table, with 5 dishes in each group. Cells in the former two groups were treated the same as those in experiment 1. Cells in hypoxia+ PDTC group were treated the same as those in hypoxia group plus adding 4 mL PDTC with a final molarity of 10 μmol/L in the culture medium. At PCH 48, the protein expression of NF-κB of cells was determined with Western blotting. (3) In experiment 5, cells were divided into normoxia group, hypoxia group, hypoxia+ PDTC group, and normoxia+ PDTC group according to the random number table, with 5 dishes in each group. Cells in the former three groups were treated the same as those in experiment 4. Cells in normoxia+ PDTC group were treated the same as those in normoxia group plus adding 4 mL PDTC with a final molarity of 10 μmol/L in the culture medium. At PCH 48, protein expressions of α-SMA, type Ⅰ collagen, and type Ⅲ collagen of cells were determined with Western blotting. Data were processed with analysis of variance of factorial design, one-way analysis of variance, and LSD-t test. Results: (1) Compared with those of normoxia group at corresponding time point, mRNA expressions and protein expressions of α-SMA, type Ⅰ collagen, and type Ⅲ collagen and the protein expression of NF-κB in fibroblasts of hypoxia group were not changed obviously at PCH 0 (with t values from -1.21 to 2.04, P values above 0.05), while mRNA expressions and protein expressions of α-SMA, type Ⅰ collagen, and type Ⅲ collagen and the protein expression of NF-κB significantly increased at PCH 48 (with t values from -12.57 to -3.44, P values below 0.01). (2) At PCH 48, the protein expression of NF-κB in fibroblasts of hypoxia group was 0.83±0.12, significantly higher than that of normoxia group (0.17±0.06, t=-16.96, P<0.001). The protein expression of NF-κB in fibroblasts of hypoxia+ PDTC group was 0.31±0.08, significantly lower than that of hypoxia group (t=12.73, P<0.001). (3) At PCH 48, protein expressions of α-SMA, type Ⅰ collagen, and type Ⅲ collagen in fibroblasts of hypoxia group were 0.73±0.09, 1.25±0.10, and 1.16±0.07, respectively, significantly higher than those of normoxia group (0.14±0.06, 0.87±0.08, and 0.77±0.13, respectively, with t values from 9.24 to 11.24, P values below 0.001). The protein expression of α-SMA in fibroblasts of normoxia+ PDTC group was 0.24±0.07, significantly higher than that of normoxia group (t=4.22, P<0.01). Protein expressions of type Ⅰ collagen and type Ⅲ collagen in fibroblasts of normoxia+ PDTC group were 0.25±0.06 and 0.32±0.11, respectively, significantly lower than those of normoxia group (with t values respectively -4.31 and -3.88, P values below 0.01). Protein expressions of α-SMA, type Ⅰ collagen, and type Ⅲ collagen in fibroblasts of hypoxia+ PDTC group were 0.09±0.08, 0.38±0.12, and 0.47±0.08, respectively, significantly lower than those of hypoxia group (with t values from 11.78 to 22.98, P values below 0.001). Conclusions Hypoxia can significantly up-regulate the expressions of α-SMA, type Ⅰ collagen, and type Ⅲ collagen in human dermal fibroblasts, which may promote the phenotype transformation of fibroblasts to myofibroblasts, and this is likely to be associated with the activation of NF-κB signal pathway.

ObjectiveTo establish the mathematical model of transcutaneous bilirubin (TcB) and total serum bilirubin (TSB) after phototherapy in neonates.MethodsNeonates with pathological jaundice were enrolled from October 2013 to June 2014. The neonates were divided into three groups by gestational age: full-term neonates (gestation age of 37-42 weeks), late preterm neonates (gestation age of 34-36+6 weeks), early and mid-preterm neonates (gestation age of 28-33+6 weeks). The neonates received single or double sided phototherapy. During the phototherapy, the forehead and chest were covered by opaque material. The TcB was measured at forehead, mid sternum, perineum area three times each before and after phototherapy. Mean-while the TSB was tested.Results Two hundred and sixty-one neonates with hyperbilirubinemia were enrolled, among whom there were 169 full-term neonates, 63 late preterm neonates and 29 early and mid-preterm neonates. Before phototherapy, there were signiifcantly correlation of TSB with TcB on forehead, mid sternum and perineum (r=0.813, 0.827, 0.754;P<0.001) and the best correlation was with TcB on mid sternum. The linear regression equation was TSB=1.35TcB-5.50. After phototherapy, there were signiifcantly correlateion of TSB with TcB on forehead, mid sternum, and perineum (r=0.751, 0.807, 0.683;P<0.001) and the best correlation was with TcB on mid sternum. The linear regression equation was TSB=1.01×TcB-0.62. Among three groups, the full-term neonates had the best correlation.ConclusionsAfter phototherapy, the TcB measured on mid sternum which was covered by opaque material is well correlated with TSB. The linear regression model can be established.

Objective To investigate the dynamic characteristics of the pacemaker current of canine sino-atrial node cells and compare them with the wild type mHCN2 pacemaker current overexpressed in neonatal rat myocardial cells.Methods Fresh canine sino-atrial node cells were enzymatically isolated in a calcium-free solution containing collagenase and elastase,and the funny current was recorded and compared with the mHCN2 current overexpressed in cultured neonatal rat myocardial cells under the same experimental conditions.Results The canine sinus node cells were elongated,spindle-shaped or polygonal,with well-defined boundaries,and showed spontaneous beating.The elicited pacemaker current was an inward current and its rise in amplitude quickened as the hyperpolarization potential increased.At V ＝-75 mV,the canine sinus atrial node pacemaker current was (-2.1±0.3) pA/pF and had the same activation kinetics as those of the mHCN2 channel current overexpressed in neonatal rat myocardial cells [τact:(728±137) ms vs.(530±65) ms,P＞0.05].Conclusions Within the physiological range,the pacemaker current in canine sino-atrial node cells and the wild type mHCN2 pacemaker current over expressed in neonatal rat myocardial cells have similar activation kinetics.

This study is to report the establishment of an UPLC-MS/MS method for the determination of plasma concentration of UA carried in self-microemulsifying drug delivery system (SMEDDS) and its pharmacokinetics in rats. It was used for determination and analysis when serum with internal standard was extracted from C18 solid-phase column. Acquity UPLC BEH C18 column (100 mm x 2.1 mm, 1.7 microm) was used for separation. The mobile phase was acetonitrile -0.1% ammonia with gradient elution at the flow rate of 0.2 mL x min(-1). The column temperature was 40 degrees C and the detection wave length was 210 nm. It was detected by negative ion using electrospray ionization source (ESI) and scanned by multiple reaction ion monitoring (MRM) mode. The liner relationship of UA was very good in the range of 1.19-3 815.00 ng x mL(-1) (r = 0.999 0). Recovery rate of different concentrations were 87.42%-89.95%. The precision of inter-day and intra-day were less than 11%. The method developed in our study was proved to be sensitive, rapid and simple. It is suitable for the pharmacokinetic study of UA-SMEDDS in rats.