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.

By organizing and studying on the original works of LI Wenrong， this paper aimed to explore his theories and methods for treating liver diseases. LI Wenrong believes that the liver is easily prone to physiological disturbances， difficult to pacify， and can be compared to a “chariot” that moves horizontally and vertically， acting as a “general” for both civil and military affairs. Pathologically， liver diseases tend to spread to other organs， resulting in ever-changing pathological changes， often affecting emotional health. In terms of therapeutic methods， LI Wenrong proposes ten methods including draining fire to calm the liver， nourishing water to moisten wood， clearing metal to calm the liver， calming gallbladder and harmonizing liver， subduing yang with shell-drug， treating liver diseases by supplementing spleen， soothing the liver with sweetness， astringing the liver with sourness， relieving the liver with spiciness， and draining the liver with excess-fire. These methods have great guidance and reference value for contemporary clinical practice in traditional Chinese medicine.

OBJECTIVE To evaluate the comprehensive value of four first-line combination immunotherapy for unresectable hepatocellular carcinoma， and provide a reference for determining the optimal clinical treatment decision for unresectable hepatocellular carcinoma. METHODS R4.2 software was used for network meta-analysis to obtain the effect values of the efficacy and safety indicators of four combination therapies [atezolizumab combined with bevacizumab （AB）， sintilimab combined with bevacizumab biosimilars （SB）， camrelizumab combined with apatinib （CA）， durvalumab combined with tremelimumab （DT）]. Combined with the efficacy， safety and economic indicators， the categorical based evaluation technique （M-MACBETH） was used to establish the value tree. At the same time， the comprehensive value scores of four therapies were calculated， and sensitivity analysis was performed to evaluate the robustness. RESULTS In terms of prolonging median overall survival， the advantage order of the four therapies was ranked as SB， CA， AB and DT. In terms of extending median progression-free survival， the advantage order of the four therapies was CA， SB， AB and DT. In terms of safety， the order of advantages was DT， AB， SB and CA. In terms of economy， the order of advantages was CA， SB， AB and DT. The comprehensive scores of SB， CA， AB and DT were 67.11， 57.77， 52.53 and 42.59 points， respectively. The results of the sensitivity analysis showed that the ranking results of comprehensive value for four regimens were robust. CONCLUSIONS Among the four first-line immune combination therapies for unresectable hepatocellular carcinoma， SB is the optimal treatment regimen， followed by CA， AB and DT.

The amount of data generated by the human experience in medical cases of classic formulas is large and the research value is high， but how to extract valuable information from these massive data is an important problem of researches on classical formulas. It is concluded that there are many problems in the current study of human experience in classical formulas， such as large amount of data， uneven quality， weak extrapolation and clinical application， which seriously affected the evidence strength of human experience in classical formulas and the contribution to experience accumulation and theoretical support. Therefore， from the structural perspective of the research questions， this paper proposed the research ideas of human experience in medical cases of classic formulas： firstly， according to the characteristics of traditional Chinese medicine （TCM） cases， based on the PICO model， which refers parti-cipants （P）， intervention （I）， comparisons （C）， and outcomes （O）， a TCM medical record evaluation tool in line with the evidence-based concept was constructed to evaluate the quality of medical cases； secondly， constructing a standardized database of human experience in classical formulas and using data mining algorithms to explore the deep relationship hidden in human experience； finally， the clinical value evaluation is carried out to verify the effectiveness of the diagnosis and treatment rules of classical formulas to achieve clinical transformation.

Objective:To study the distribution and antibiotics resistance of the main pathogens of neonatal purulent meningitis in different regions of China.Methods:A retrospective descriptive clinical epidemiological study was conducted in children with neonatal purulent meningitis which admitted to 18 tertiary hospitals in different regions of China between January 2015 to December 2019. The test results of blood and cerebrospinal fluid, and drug sensitivity test results of the main pathogens were collected. The distributions of pathogenic bacteria in children with neonatal purulent meningitis in preterm and term infants, early and late onset infants, in Zhejiang Province and other regions outside Zhejiang Province, and in Wenzhou region and other regions of Zhejiang Province were analyzed. The chi-square test was used for statistical analysis.Results:A total of 210 neonatal purulent meningitis cases were collected. The common pathogens were Escherichia coli ( E. coli)(41.4%(87/210)) and Streptococcus agalactiae ( S. agalactiae)(27.1%(57/210)). The proportion of Gram-negative bacteria in preterm infants (77.6%(45/58)) with neonatal purulent meningitis was higher than that in term infants (47.4%(72/152)), and the difference was statistically significant ( χ2=15.54, P=0.001). There were no significant differences in the constituent ratios of E. coli (36.5%(31/85) vs 44.8%(56/125)) and S. agalactiae (24.7%(21/85) vs 28.8%(36/125)) between early onset and late onset cases (both P>0.05). The most common pathogen was E. coli in different regions, with 46.7%(64/137) in Zhejiang Province and 31.5%(23/73) in other regions outside Zhejiang Province. In Zhejiang Province, S. agalactiae was detected in 49 out of 137 cases (35.8%), which was significantly higher than other regions outside Zhejiang Province (11.0%(8/73)). The proportions of Klebsiella pneumoniae, and coagulase-negative Staphylococcus in other regions outside Zhejiang Province (17.8%(13/73) and 16.4%(12/73)) were both higher than those in Zhejiang Province (2.9%(4/137) and 5.1%(7/137)). The differences were all statistically significant ( χ2=14.82, 12.26 and 7.43, respectively, all P<0.05). The proportion of Gram-positive bacteria in Wenzhou City (60.8%(31/51)) was higher than that in other regions in Zhejiang Province (38.4%(33/86)), and the difference was statistically significant ( χ2=6.46, P=0.011). E. coli was sensitive to meropenem (0/45), and 74.4%(32/43) of them were resistant to ampicillin. E. coli had different degrees of resistance to other common cephalosporins, among which, cefotaxime had the highest resistance rate of 41.8%(23/55), followed by ceftriaxone (32.4%(23/71)). S. agalactiae was sensitive to penicillin, vancomycin and linezolid. Conclusions:The composition ratios of pathogenic bacteria of neonatal purulent meningitis are different in different regions of China. The most common pathogen is E. coli, which is sensitive to meropenem, while it has different degrees of resistance to other common cephalosporins, especially to cefotaxime.

Objectives:To verify the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of its clinical application.Methods:A convenience sampling method was used to collect 129 geriatric patients who underwent inguinal hernia surgery from January 2018 to January 2023 in nine hospitals in Liaoning Province. There were 120 males and 9 females, of whom 89 patients were 60 to <75 years old, 33 patients were 75 to <85 years old and 7 patients were ≥85 years old. The 129 patients included 11 elderly patients with inguinal hernia who had recovered from preoperative infection with COVID-19. Statistical methods such as Cronbach′s coefficient, Kaiser-Meyer-Olkin test, Bartlett′s test, Pearson′s correlation analysis, etc. were calculated to verify the reliability indexes such as feasibility, content validity, structural validity, criterion-related validity, internal consistency reliability, and re-test reliability. Taking the 5-item modified frailty index (5-mFI) as the gold standard, the area under the curve was used to analyze the ability of the two scales to predict the occurrence of postoperative acute urinary retention, postoperative delirium, poor incision healing, operative hematoma seroma, and postoperative complications.Results:The frailty assessment scale for elderly patients with inguinal hernia showed good reliability and validity (valid completion rate of 99.2%; item content validity index of 1.000, and the scale content validity index of 1.000; exploratory factor analysis extracted a total of 1 principal component, and factor loadings of each item of 0.565 to 0.873; the AUC for frailty diagnosis using 5-mFI as the gold standard of 0.795 ( P<0.01) Cronbach′s coefficient of 0.916, retest reliability coefficient of 0.926), it could effectively predict postoperative acute urinary retention, delirium, hematoma seroma in the operative area and total complications (AUC of 0.746, 0.870, 0.806, and 0.738, respectively; all P<0.05), and prediction efficiency was higher than that of 5-mFI (AUC of 0.694, 0.838, 0.626 and 0.641, P<0.05 for delirium only), but both scales were inaccurate in predicting poor incision healing (AUC of 0.519, P=0.913 for the frailty assessment scale and 0.455, P=0.791 for the 5-mFI). Conclusions:The frailty assessment scale for elderly patients with inguinal hernia is reliable and significantly predicts the occurrence of postoperative adverse events in elderly inguinal hernia patients. The scale can also be used for preoperative frailty assessment in elderly patients with inguinal hernia after rehabilitation from COVID-19 infection.

Objectives:To verify the reliability and validity of the frailty assessment scale for elderly patients with inguinal hernia and to evaluate the value of its clinical application.Methods:A convenience sampling method was used to collect 129 geriatric patients who underwent inguinal hernia surgery from January 2018 to January 2023 in nine hospitals in Liaoning Province. There were 120 males and 9 females, of whom 89 patients were 60 to <75 years old, 33 patients were 75 to <85 years old and 7 patients were ≥85 years old. The 129 patients included 11 elderly patients with inguinal hernia who had recovered from preoperative infection with COVID-19. Statistical methods such as Cronbach′s coefficient, Kaiser-Meyer-Olkin test, Bartlett′s test, Pearson′s correlation analysis, etc. were calculated to verify the reliability indexes such as feasibility, content validity, structural validity, criterion-related validity, internal consistency reliability, and re-test reliability. Taking the 5-item modified frailty index (5-mFI) as the gold standard, the area under the curve was used to analyze the ability of the two scales to predict the occurrence of postoperative acute urinary retention, postoperative delirium, poor incision healing, operative hematoma seroma, and postoperative complications.Results:The frailty assessment scale for elderly patients with inguinal hernia showed good reliability and validity (valid completion rate of 99.2%; item content validity index of 1.000, and the scale content validity index of 1.000; exploratory factor analysis extracted a total of 1 principal component, and factor loadings of each item of 0.565 to 0.873; the AUC for frailty diagnosis using 5-mFI as the gold standard of 0.795 ( P<0.01) Cronbach′s coefficient of 0.916, retest reliability coefficient of 0.926), it could effectively predict postoperative acute urinary retention, delirium, hematoma seroma in the operative area and total complications (AUC of 0.746, 0.870, 0.806, and 0.738, respectively; all P<0.05), and prediction efficiency was higher than that of 5-mFI (AUC of 0.694, 0.838, 0.626 and 0.641, P<0.05 for delirium only), but both scales were inaccurate in predicting poor incision healing (AUC of 0.519, P=0.913 for the frailty assessment scale and 0.455, P=0.791 for the 5-mFI). Conclusions:The frailty assessment scale for elderly patients with inguinal hernia is reliable and significantly predicts the occurrence of postoperative adverse events in elderly inguinal hernia patients. The scale can also be used for preoperative frailty assessment in elderly patients with inguinal hernia after rehabilitation from COVID-19 infection.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

Objective: To monitor and analyze the epidemiological characteristics of influenza in schools and understand the disease burden of students, and to provide a scientific reference for instructing the prevention of influenza in schools. Methods: A school influenza surveillance sentinel to conduct influenza like case (ILI) surveillance and outbreak surveillance. Through network, we understood the burden of flu disease among students. Descriptive epidemiology was used to analyze influenza like case surveillance and questionnaire survey data. Results: Surveillance confirmed that from the 42th week of 2019 to the 1st week of 2020, the cumulative reported ILI of 3 school influenza surveillance sites in Jinan accounted for 7.91% (ILI%) of the total number of surveillance personnel during the same period, with the highest ILI% (24.19%) of kindergarten children, ILI% gradually decreased with the increase of grade, and teachers were the lowest. The reporting of ILI was concentrated in the 49th to 52nd week of 2019, during which the reported influenza like cases accounted for 84.81% of the total number of ILI reported during the surveillance period. Two influenza outbreaks were monitored. The pathogens were H3N2 and B (Victoria). The epidemics mainly occurred in the lower grades of elementary school. A survey of 2 297 students found that 577 people had fever and respiratory symptoms since October 2019. Among them, 85.26% of them went to the hospital, 32.75% of those who used anti influenza drugs such as oseltamivir, and 64.81% of those who used antibiotics. 42.63% received infusion therapy, 3.99% were hospitalized, and the average cost of inpatients was 6 686 yuan. The sick students were absent from school for an average of 3.77 days, and the parents of the sick children missed work for an average of 4.26 days. Conclusion Surveillance of influenza like cases in schools is an important way to proactively discover influenza epidemic trends and outbreaks, and to accurately grasp the characteristics of influenza epidemics in schools. The key populations affected by influenza are kindergarten children and lower grades of primary school students. Suffering from influenza has caused a heavy disease burden on students and children in kindergartens, and is also an important factor that causes student absenteeism and parents to miss work.

Objective:To investigate the role and possible molecular mechanisms of m6A methyltransferase METTL3 and demethylase FTO in H7N9 virus infection.Methods:Western blot(WB) was used to detect the expression of METTL3 and FTO after H7N9 virus infected A549 cells. After knocking down and over-expressing METTL3 and FTO, H7N9 virus infection was tested by WB and TCID 50 for its effect on virus replication. Transcriptome sequencing method were used to analyze differentially expressed genes at the transcriptome level in METTL3 or FTO knockdown and wild-type control cells, and preliminary analysis of potential targets was performed. Results:After 24 h of H7N9 virus infection in A549 cells, METTL3 expression was up-regulated, and FTO did not significantly change. After knocking down METTL3 and FTO, the virus nucleoprotein (NP) expression level and virus titer decreased significantly. Consistent with the result of the knockdown experiments, we found that the viral titer was increased by METTL3 and FTO overexpression. Transcriptome sequencing result showed that 314 and 555 differentially expressed genes were found between the METTL3 or FTO knockdown group and the control group, respectively. GO functional enrichment analysis and KEGG pathway enrichment analysis showed that these genes were related to the host immune response.Conclusions:METTL3 and FTO may play a key role in H7N9 virus infection by regulating host-virus interactions.