Coronary restenosis is an important cause of poor long-term prognosis in patients with coronary heart disease. Here, we show that lysine methyltransferase SMYD2 expression in the nucleus is significantly elevated in serum- and PDGF-BB-induced vascular smooth muscle cells (VSMCs), and in tissues of carotid artery injury-induced neointimal hyperplasia. Smyd2 overexpression in VSMCs (Smyd2-vTg) facilitates, but treatment with its specific inhibitor LLY-507 or SMYD2 knockdown significantly inhibits VSMC phenotypic switching and carotid artery injury-induced neointima formation in mice. Transcriptome sequencing revealed that SMYD2 knockdown represses the expression of serum response factor (SRF) target genes and that SRF overexpression largely reverses the inhibitory effect of SMYD2 knockdown on VSMC proliferation. HDAC3 directly interacts with and deacetylates SRF, which enhances SRF transcriptional activity in VSMCs. Moreover, SMYD2 promotes HDAC3 expression via tri-methylation of H3K36 at its promoter. RGFP966, a specific inhibitor of HDAC3, not only counteracts the pro-proliferation effect of SMYD2 overexpression on VSMCs, but also inhibits carotid artery injury-induced neointima formation in mice. HDAC3 partially abolishes the inhibitory effect of SMYD2 knockdown on VSMC proliferation in a deacetylase activity-dependent manner. Our results reveal that the SMYD2-HDAC3-SRF axis constitutes a novel and critical epigenetic mechanism that regulates VSMC phenotypic switching and neointimal hyperplasia.

Objective To observe the improvement of motor dysfunction and serum levels of C-reactive protein(CRP),blood glucose and blood lipid in post-stroke patients treated with scalp acupuncture at different needle retention time.Methods A total of 120 patients with motor dysfunction after stroke were randomly divided into control group,observation group 1 and observation group 2,with 40 cases in each group.The patients in the 3 groups were treated with scalp acupuncture,body acupuncture and routine rehabilitation exercise,once a day and 6 times a week,lasting for 2 weeks.The control group was given scalp acupuncture with retaining of needles for 30 minutes,the observation group 1 was given scalp acupuncture with retaining of needles for one hour,and the observation group 2 was given scalp acupuncture with retaining of needles for 2 hours.Before and after treatment,the 3 groups were observed in the changes of the scale scores of National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FM A),Berg Balance Scale(BBS)and modified Barthel Index(MBI),and the levels of laboratory indicators of peripheral blood CRP,fasting plasma glucose(FPG),total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDL-C)and low-density lipoprotein cholesterol(LDL-C).After treatment,the clinical safety of the three groups was evaluated.Results(1)After treatment,the scale scores of NIHSS in the three groups were lower(P＜0.01)and the scale scores FMA,BBS and MBI were higher than those before treatment(P＜0.05 or P＜0.01).The comparison of post-treatment scale scores showed that the differences among the three groups were statistically significant(P＜0.01).The intergroup comparison showed that the decrease of NIHSS score and the increase of FMA,BBS and MBI scores in the observation group 2 were significantly superior to those in the control group and the observation group 1(P＜0.01);the improvement of FMA score in the observation group 1 was significantly superior to that in the control group(P＜0.01),while the improvement of NIHSS,BBS and MBI scores tended to be superior to that in the control group without statistically significant differences(P＞0.05).The results indicated that the curative effect of scalp acupuncture plus exercise regimen was positively correlated with the duration of needle retention for scalp acupuncture.(2)After treatment,the laboratory indicator levels of CRP and FPG in the peripheral blood of the three groups,the levels of TG and LDL-C in the two observation groups and the level of HDL-C in the observation group 2 were improved compared with those before treatment(P＜0.05 or P＜0.01).Statistically significant differences were presented in the post-treatment levels of CRP and TG in peripheral blood among the three groups(P＜0.05 or P＜0.01).The intergroup comparison showed that the improvement of CRP and TG levels in the observation group 2 was significantly superior to that in the control group,and the improvement of CRP level in the observation group 2 was significantly superior to that in the observation group 1,the differences being statistically significant(P＜0.05 or P＜0.01).The TC level in the three groups after treatment did not differ from that before treatment,and there was no significant difference in TC level after treatment among the three groups either(P＞0.05).(3)During the treatment,no adverse reactions such as fainting,needle breaking and hematoma occurred in the three groups,the vital signs of the patients were stable,and there were no obvious abnormal changes in pulse,blood pressure and respiratory rate.Conclusion Scalp acupuncture can effectively improve the motor function of post-stroke patients in a pasitive time-effect relationship with the needle retention,and better the curative effect can be achieved by retaining of the needle for 2 h.

The molecular epidemiological characteristics of 1,4,[5],12:i:-Salmonella in Jiangsu Province were analyzed through whole genome sequencing(WGS).The distribution characteristics of related genes were obtained on the basis of anno-tated drug-resistant genes and plasmid types in the whole genome.Analysis of the molecular epidemiological characteristics of strains with cgMLST revealed possible modes of transmission of quinolone resistance in 1,4,[5],12:i:-Salmonella.Eleven cat-egories of antibiotic resistance genes(ARGs)were annotated among the fluoroquinolone-resistant strains.The detection rate of aminoglycoside ARGs was highest(100％).Twelve quinolone-resistant strains(92.3％)carried the IncHI2/IncHI2A plasmid type.PMQR gene analysis of various strains indicated that the strains from the United States and Europe carried six types of PMQR genes,and the detection rate of qnrB19 was highest.The Jiangsu strains carried three PMQR gene types,and the de-tection rate of aac(6')-Ib-cr was highest(11.84％).Analysis of cgMLST loci from different countries/regions revealed three main epidemic clusters.Some isolates from Jiangsu province might have the same evolutionary origin as some isolates from Eu-rope and the United States,and national/regional differences were observed in the PMQR gene carriage level.

OBJECTIVE: To evaluate the expression level of melatonin and its effects on immune function in aplastic anemia (AA) patients. METHODS: The enzyme-linked immunosorbent assay (ELISA) was used to detect the plasma levels of melatonin in AA patients, and the correlation between melatonin levels and laboratory indexs was analyzed. The activation, proliferation, and apoptosis of T cells from AA patients were analyzed by flow cytometry with or without melatonin in vitro. RESULTS: The plasma levels of melatonin in AA patients were significantly lower compared with healthy controls (HC) (12.23 pg/ml vs 20.04 pg/ml, P < 0.01), while the plasma melatonin levels of AA patients in remission group after immunosuppressive therapy (IST) were significantly higher than those in non-remission group (29.16 pg/ml vs 11.73 pg/ml, P =0.04). Moreover, the melatonin levels were positively correlated with platelets (r =0.49), the absolute reticulocyte count (r =0.45), and the percentage of neutrophils (r =0.43). Meanwhile, there was a negative correlation between melatonin levels and the percentages of lymphocytes (r =-0.45). The expressions of CD25 and CD69 in both CD4⁺ and CD8⁺ T cells from AA patients were remarkably inhibited by melatonin in vitro (all P < 0.05). When cultured with melatonin, the proliferation rates of both CD4⁺ and CD8⁺ T cells from AA patients were markedly suppressed (P =0.01 andP < 0.01). CONCLUSION The plasma levels of melatonin were decreased in AA patients, which might play an important role in the mechanism of immunological abnormalities. The hyperimmune status of AA patients could be partially ameliorated by melatonin in vitro.
Humans ; Anemia, Aplastic ; CD8-Positive T-Lymphocytes ; Melatonin ; Blood Cell Count

Objective:To explore the difference of lymphocyte subsets in peripheral blood(PB)between aplastic anemia(AA)and hypoplastic myelodysplastic syndrome(hypo-MDS)patients,meanwhile to compare the clinical parameters obtained from PB and bone marrow(BM).Methods:The lymphocyte subsets in hypo-MDS(n=25)and AA(n=33)patients were investigated by flow cytometry.Meanwhile,the differences in PB cell counts,biochemical indicators,BM cell counts and abnormal chromosomes between the two groups were analyzed.Results:The percentage of CD8+T cells in A A group was significantly higher than that in hypo-MDS group(P=0.001),while the percentage of CD4+T cells and the CD4+/CD8+ratio in AA group were obviously lower than those in hypo-MDS group(P=0.015 and0.001,respectively).Furthermore,the proportion of CD4+andCD8+activated T(TA)cells,and memory Tregs in AA group was distinctly lower than those in hypo-MDS group(P=0.043,0.015 and 0.024,respectively).Nevertheless,the percentage of CD8+naive T(TN)cells in AA patients was remarkably higher(P=0.044).And hypo-MDS patients had declined lymphocyte counts(P=0.025),increased levels of total bilirubin(TBil),lactate dehydrogenase(LDH),vitamin B12 and proportion of BM blasts than AA patients(P=0.019,0.023,0.027 and 0.045,respectively).Conclusion:In this study it was confirmed that the percentages of CD4+and CD8+TA cells,memory Tregs and CD8+TN cells were significantly different between AA and hypo-MDS patients,which provide an essential basis for the identification of these two diseases.

Objective To investigate the infection status and epidemiological characteristics of Campylobacter jejuni in diarrhea cases in Jiangsu. Methods Stool specimens of diarrhea cases in Jiangsu Campylobacter jejuni surveillance program were collected in 2020. Campylobacter jejuni was isolated and cultured by the double-well filtration membrane method, and the isolated strains were identified using a fully automated biochemical identification system. Results The positive rate of Campylobacter jejuni in diarrhea cases was 8.38%, with the highest positive rate of Campylobacter jejuni in the diarrhea group of 4-17 years old (27.59%), and the lowest positive rate in the group of 0-3 years old (4.05%). In terms of seasonal distribution, the highest positive rate of Campylobacter jejuni was found in summer (June-August) (9.81%). The positive rate of Campylobacter jejuni in blood stool was the highest (7.39%). Vegetables and their products had the highest positive rate among different categories of suspected foods (33.33%). In terms of processing or packaging methods, catering service food had the highest positive rate (17.46%). In addition, school/institutional collective canteens had the highest positive rate (28.57%) among various eating places. The differences in the positive rates of Campylobacter jejuni among different age groups and different categories of suspected food were statistically significant. Conclusion The monitoring of Campylobacter jejuni in adolescent population should be strengthened, and at the same time, the surveillance and management of vegetables and their products, food service foods and school/institutional collective canteens should be further strengthened.

Objective: To analyze the etiological and epidemiological characteristics of Vibrio cholerae in Beijing during 2015-2021 and provide evidence for the prevention and control of cholera. Methods: The V. cholerae strains isolated in Beijing during 2015-2021 were analyzed by serotyping and virulence genes detection. Pulsed field gel electrophoresis (PFGE) was performed for the molecular typing of the strains. Based on the collected epidemiological and clinical data of cholera cases,the epidemiological characteristics of cholera were analyzed by descriptive epidemiology method. Results: A total of 76 Vibrio cholerae O1 strains were isolated in Beijing during 2015-2021, including 61 strains from human, 10 strains from environment and 5 strains from seafood. The 76 strains consisted of 68 Ogawa strains and 8 Inaba strains. Six Ogawa strains isolated from sporadic cases carried ctxAB. After NotⅠ digestion, 76 strains were divided into 33 PFGE patterns. From 2015 to 2021, a total of 38 cholera epidemics were reported in Beijing, most of them were sporadic ones, accounting for 92.11% (35/38). A total of 45 cases were reported, and the cases occurred during June-September accounted for 97.78% (44/45). Cholera cases occurred in 9 districts of Beijing, and the cases reported in Chaoyang district accounted for 42.22% (19/45) and in Changping district accounted for 31.11% (14/45). The age of the cholera cases ranged from 19 to 63 years. Except for one case with unknown clinical symptoms, 44 cases had diarrhea symptoms with 84.09% (37/44) of the cases reporting diarrhea (3-9 times/day), followed by yellow watery stool (95.45%, 42/44), abdominal pain (68.18%, 30/44), nausea and vomiting (40.91%, 18/44) and fever (36.36%, 16/44). Conclusion: Vibrio cholerae strains isolated in Beijing during 2015-2021 were mainly O1 serotype Ogawa,most of which were non-toxigenic. The PFGE of the strains varied. Cholera epidemics occurred in 9 districts of Beijing, but most were sporadic ones with incidence peak during June-September.
Adult ; Beijing/epidemiology* ; Cholera/epidemiology* ; Diarrhea/epidemiology* ; Electrophoresis, Gel, Pulsed-Field ; Humans ; Middle Aged ; Vibrio cholerae O1/genetics* ; Young Adult

Mitochondria are dynamic organelles that continuously divide and fuse. In recent years, in addition to the studies related to mitochondrial metabolism, the unique dynamics of mitochondria have gradually attracted researchers' attention. A growing body of research has revealed that mitochondrial dynamics are related to the biological behavior of tumor cells. Mitochondrial fission proteins (mitochondrial fission protein 1, FIS1) mediate the assembly of mitochondrial fission complexes and participate in the execution of mitochondrial fission. They are important proteins in the process of mitochondrial fusion and fission. However, few studies have revealed the expression and role of FIS1 in human cervical cancer. In this study, the expression level of FIS1 in human cervical cancer tissues and paracancer tissues were compared. The results showed that the level of FIS1 mRNA in human cervical cancer tissues was significantly lower than that in paracancer tissues (P<0. 01). Further KEGG pathway and GO Term-BP pathway analysis showed that the differential genes are mainly related to mitochondrial biological functions. Subsequently, HeLa cells with overexpressed FIS1 were investigated for their proliferation, migration, mitochondrial fission and ROS levels. The experimental results showed that FIS1 overexpression decreased HeLa cell proliferation and migration ability, enhanced mitochondrial fission and higher ROS levels. In conclusion, the expression of FIS1 in human cervical cancer cells was attenuated, while overexpression of FIS1 resulted in a series of abnormal biological functions in human cervical cancer cells. Further studies can be carried out to investigate the role of FIS1 in the treatment of human cervical cancer.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

Higher alcohols that contain more than two carbon atoms have better fuel properties than ethanol, making them important supplements and alternatives to fossil fuels. Using microbes to produce higher alcohols from renewable biomass can alleviate the current energy and environmental crises, and has become a major future direction for green biomanufacturing. Since natural microbes can only produce a few higher alcohols in small amounts, it is necessary to reconstruct the synthetic pathways for higher alcohols in model industrial strains through metabolic engineering and synthetic biology to overcome the metabolic bottlenecks. A series of milestones have been accomplished in past decades. The authors of this review have witnessed the entire journey of this field from its first success to the leaping development. On the 30th anniversary of the founding of the discipline of metabolic engineering, this review dates back to the great milestones in achieving heterologous production of higher alcohols in non-native strains. The design and optimization of high alcohol biosynthetic pathways, the expansion of feedstock, the engineering of host strains and the industrialization process are summarized. This review aims to draw further attention to microbial synthesis of higher alcohols, inspire the development of novel techniques and strategies of metabolic engineering, and promote the innovation and upgrade of China's biofuel industry.
Alcohols ; Biofuels ; Biosynthetic Pathways ; Ethanol ; Metabolic Engineering ; Synthetic Biology