Predictive value of left ventricular ejection fraction reserve assessed by SPECT G-MPI for major adverse cardiovascular event in patients with coronary artery disease / 中华心血管病杂志

Objective: To evaluate the prognostic value of left ventricular ejection fraction (LVEF) reserve assessed by gated SPECT myocardial perfusion imaging (SPECT G-MPI) for major adverse cardiovascular event (MACE) in patients with coronary artery disease. Methods: This is a retrospective cohort study. From January 2017 to December 2019, patients with coronary artery disease and confirmed myocardial ischemia by stress and rest SPECT G-MPI, and underwent coronary angiography within 3 months were enrolled. The sum stress score (SSS) and sum resting score (SRS) were analyzed by the standard 17-segment model, and the sum difference score (SDS, SDS=SSS-SRS) was calculated. The LVEF at stress and rest were analyzed by 4DM software. The LVEF reserve (ΔLVEF) was calculated (ΔLVEF=stress LVEF-rest LVEF). The primary endpoint was MACE, which was obtained by reviewing the medical record system or by telephone follow-up once every twelve months. Patients were divided into MACE-free and MACE groups. Spearman correlation analysis was used to analyze the correlation between ΔLVEF and all MPI parameters. Cox regression analysis was used to analyze the independent factors of MACE, and the optimal SDS cutoff value for predicting MACE was determined by receiver operating characteristic curve (ROC). Kaplan-Meier survival curves were plotted to compare the difference in the incidence of MACE between different SDS groups and different ΔLVEF groups. Results: A total of 164 patients with coronary artery disease [120 male; age (58.6±10.7) years] were included. The average follow-up time was (26.5±10.4) months, and a total of 30 MACE were recorded during follow-up. Multivariate Cox regression analysis showed that SDS (HR=1.069, 95%CI: 1.005-1.137, P=0.035) and ΔLVEF (HR=0.935, 95%CI: 0.878-0.995, P=0.034) were independent predictors of MACE. According to ROC curve analysis, the optimal cut-off to predict MACE was a SDS of 5.5 with an area under the curve of 0.63 (P=0.022). Survival analysis showed that the incidence of MACE was significantly higher in the SDS≥5.5 group than in the SDS<5.5 group (27.6% vs. 13.2%, P=0.019), but the incidence of MACE was significantly lower in the ΔLVEF≥0 group than in theΔLVEF<0 group (11.0% vs. 25.6%, P=0.022). Conclusions: LVEF reserve (ΔLVEF) assessed by SPECT G-MPI serves as an independent protective factor for MACE, while SDS is an independent risk predictor in patients with coronary artery disease. SPECT G-MPI is valuable for risk stratification by assessing myocardial ischemia and LVEF.

Prevention， Treatment， and Recuperation of Infection with SARS-CoV-2 Variants by Traditional Chinese Medicine Based on Idea of Epidemic Prevention of Jiangnan Medical School / 中国实验方剂学杂志

Because of the frequent occurrence of epidemics in Jiangnan since ancient times， the local medical schools have accumulated rich experience in epidemic prevention， among which Yushan medical school， Wumen medical school， and Qiantang medical school are famous. The physicians have inherited the theory in Treatise on Cold Damage Diseases and developed the therapies for febrile diseases. Adhering to the idea of integrating cold and febrile diseases， the physicians in Jiangnan flexibly adapt ZHANG Zhongjing's theory by combining regional climate， patient physique and other factors to explain the pathogenesis， which is of great significance for the prevention and treatment of epidemics. Therefore， traditional Chinese medicine （TCM） has demonstrated good curative effect on coronavirus disease-2019 （COVID-19） in China. However， the SARS-CoV-2 variants （Delta and Omicron） characterized by strong infectivity， pathogenicity， and immune escape capacity keep emerging， which bring great challenges to the global prevention and control of this pandemic. To this end， we studied the ways of Jiangnan medical school for the prevention and treatment of epidemics， reviewed the evolution of TCM treatment protocols for COVID-19， and summarized China's experience in fighting against the emerging SARS-CoV-2 variants. Further， we explored the measures of TCM in treating SARS-CoV-2 variants from prevention， treatment， and rehabilitation according to the theory for epidemic prevention of Jiangnan medical school. This paper provides reference for the prevention and treatment of emerging SARS-CoV-2 variant and facilitates the development of TCM epidemiology.

Mechanism of Linggui Zhugantang in Repairing Blood-brain Barrier Injury of Alzheimer's Disease / 中国实验方剂学杂志

ObjectiveTo observe the effect of Linggui Zhugantang （LG） on the blood-brain barrier （BBB） model of Alzheimer's disease （AD） in vitro and to explore the mechanism of LG in repairing the BBB injury in AD. MethodA total of 50 male SPF rats were randomized into five groups： high-dose （4.8 g·kg-1）， medium-dose （2.4 g·kg-1）， and low-dose （1.2 g·kg-1） LG groups， western medicine （0.5 g·kg-1 donepezil hydrochloride） group， and normal group （normal saline of equivalent volume）. They received （ig） corresponding drugs twice a day for 7 d. Drug-containing serum was respectively collected from the abdominal aorta 1 h after the last administration. The BBB injury of AD in vitro was induced with the cell co-culture method， and 6 groups were designed： normal group， model group， high-， medium-， and low-dose LG groups， and western medicine group. The model group was added with 100 μL amyloid β1-42 （Aβ1-42， final concentration： 5 μmol·L-1）， and high-dose， medium-dose， and low-dose LG groups and the western medicine group were added with corresponding 10% drug-containing serum in addition to the 100 μL Aβ1-42 （final concentration： 5 μmol·L-1）. Cell survival rate was detected by methyl thiazolyl tetrazolium （MTT） assay， expression of BBB-related skeleton proteins （claudin-5， ZO-1， occludin）， matrix metalloproteinase-2 （MMP-2）， and matrix metalloproteinase-9 （MMP-9） by Western blot， and content of inflammatory factors interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） by enzyme-linked immunosorbent assay （ELISA）. BBB Aβ transporter low-density lipoprotein receptor-related protein 1 （LRP-1） and advanced glycation end product receptor （RAGE） at different time points in high-dose， medium-dose， and low-dose LG groups were determined by Real-time PCR and Western blot. ResultCell survival rate of the model group was lower than that of the normal group （P<0.05） and the survival rates of the western medicine group and high-dose LG group was higher than that in the model group （P<0.05）. The skeleton proteins were down-regulated and MMP-2 and MMP-9 were up-regulated in the model group compared with those in the normal group （P<0.05）. The expression of skeleton proteins was higher （P<0.05） and that of MMP-2 and MMP-9 was lower （P<0.05） in the western medicine group and high-dose LG group than in the model group. Compared with the model group， only the medium-dose LG group showed the up-regulation （P<0.05） of claudin-5 （P<0.05） and the decrease （P<0.05） of MMP-2. IL-1β， IL-6， and TNF-α in the model group were up-regulated （P<0.05） compared with those in the normal group， and those inflammatory factors in the western medicine group and high-dose and medium-dose LG groups were lower （P<0.05） than those in the model group. LRP-1 expression was up-regulated and RAGE expression was down-regulated at 3 h compared with those at 0 h （P<0.05）， while the expression of the two became stable at 6， 12， 24， 36 h. At 3 h， LRP-1 expression was down-regulated and RAGE expression was up-regulated in model group compared with those in the normal group at 3 h （P<0.05）. Moreover， the LRP-1 content was higher and RAGE content was lower in the western medicine group and high-dose LG group than in the model group. ConclusionLG can repair the BBB injury in vitro by inhibiting the expression of inflammatory factors and MMP-2， MMP-9， promoting the expression of skeletal proteins， and regulating the balance of transporters.

Streptococcus thermophilus Inhibits Colorectal Tumorigenesis Through Secreting ß-Galactosidase.

BACKGROUND & AIMS: Streptococcus thermophilus was identified to be depleted in patients with colorectal cancer (CRC) by shotgun metagenomic sequencing of 526 multicohort fecal samples. Here, we aim to investigate whether this bacterium could act as a prophylactic for CRC prevention. METHODS: The antitumor effects of S thermophilus were assessed in cultured colonic epithelial cells and in 2 murine models of intestinal tumorigenesis. The tumor-suppressive protein produced by S thermophilus was identified by mass spectrometry and followed by ß-galactosidase activity assay. The mutant strain of S thermophilus was constructed by homologous recombination. The effect of S thermophilus on the gut microbiota composition was assessed by shotgun metagenomic sequencing. RESULTS: Oral gavage of S thermophilus significantly reduced tumor formation in both Apcmin/+ and azoxymethane-injected mice. Coincubation with S thermophilus or its conditioned medium decreased the proliferation of cultured CRC cells. ß-Galactosidase was identified as the critical protein produced by S thermophilus by mass spectrometry screening and ß-galactosidase activity assay. ß-Galactosidase secreted by S thermophilus inhibited cell proliferation, lowered colony formation, induced cell cycle arrest, and promoted apoptosis of cultured CRC cells and retarded the growth of CRC xenograft. The mutant S thermophilus without functional ß-galactosidase lost its tumor-suppressive effect. Also, S thermophilus increased the gut abundance of known probiotics, including Bifidobacterium and Lactobacillus via ß-galactosidase. ß-Galactosidase-dependent production of galactose interfered with energy homeostasis to activate oxidative phosphorylation and downregulate the Hippo pathway kinases, which partially mediated the anticancer effects of S thermophilus. CONCLUSION: S thermophilus is a novel prophylactic for CRC prevention in mice. The tumor-suppressive effect of S thermophilus is mediated at least by the secretion of ß-galactosidase.

The Inhibiting Effect of Autophagy Inhibitor ROC-325 on Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of autophagy inhibitor ROC-325 and its combination with bortezomib on the proliferation, apoptosis and autophagy of multiple myeloma cell lines.@*METHODS@#Multiple myeloma cells were treated with ROC-325 at different concentration. The cell proliferation was detected by CCK-8. Apoptosis was determined by Caspase-3/7 and Caspase-9 activity assays. Autophagy was detected by monodansylcadaverine staining. The apoptosis-related proteins (PARP and Caspase-3) and autophagy-related proteins (P62, Beclin-1, and LC3A/B) were analyzed by Western blot. The combined effect with bortezomib on bortezomib-resistant cell line was detected by CCK-8.@*RESULTS@#ROC-325 inhibited the proliferation of RPMI 8226, RPMI 8226-BTZ100, U266 and IM9 cells in a dose-dependent manner (r=-0.8275, r=-0.9079, r=-0.9422, r=-0.9305), the 72 h IC@*CONCLUSION@#ROC-325 can inhibit the proliferation, induce the apoptosis of myeloma cells through the mitochondrial pathway, inhibit the autophagy of myeloma cells by affecting the fusion of autophagosomes and lysosomes, and overcome bortezomib resistance by the combination of ROC-325 with bortezomib.

Serine and one-carbon metabolism, a bridge that links mTOR signaling and DNA methylation in cancer.

Mammalian / mechanistic target of rapamycin (mTOR) is a critical sensor of environmental cues that regulates cellular macromolecule synthesis and metabolism in eukaryotes. DNA methylation is the most well-studied epigenetic modification that is capable of regulating gene transcription and affecting genome stability. Both dysregulation of mTOR signaling and DNA methylation patterns have been shown to be closely linked to tumor progression and serve as promising targets for cancer therapy. Although their respective roles in tumorigenesis have been extensively studied, whether molecular interplay exists between them is still largely unknown. In this review, we provide a brief overview of mTOR signaling, DNA methylation as well as related serine and one-carbon metabolism, one of the most critical aspects of metabolic reprogramming in cancer. Based on the latest understanding regarding the regulation of metabolic processes by mTOR signaling as well as interaction between metabolism and epigenetics, we further discuss how serine and one-carbon metabolism may serve as a bridge that links mTOR signaling and DNA methylation to promote tumor growth. Elucidating their relationship may provide novel insight for cancer therapy in the future.

MT1G is Silenced by DNA Methylation and Contributes to the Pathogenesis of Hepatocellular Carcinoma.

Using genome-wide screening and TCGA-based data analysis, we identified a DNA methylation-related gene named metallothionein-1G (MT1G), which may play an important role in hepatocellular carcinoma (HCC). In this study, we found that MT1G expression was silenced in 4/6 HCC cell lines and negatively related to aberrant promoter hypermethylation. Its mRNA level was restored with demethylation treatment. Moreover, MT1G downregulation at both the transcriptional and protein level was also detected in 8 pairs of clinical HCC samples compared with its expression in adjacent normal tissues. Ectopic expression of MT1G in silenced HCC cell lines inhibited colony formation, suppressed cell migration and invasion, and repressed xenograft tumor growth in nude mice. In contrast, knockdown of MT1G by short hairpin RNA showed the opposite effect on cell proliferation and the malignant phenotype. Moreover, our data showed that MT1G suppressed tumor invasion and metastasis mainly through regulating the expression of proteins in the matrix metalloproteinase family (MMP) and modulating the epithelial-mesenchymal transition (EMT) process. To our surprise, the data from TCGA showed that hypermethylation of MT1G is associated with good survival of HCC patients. In conclusion, our study demonstrated that MT1G acts as a tumor suppressor gene in HCC development, but its clinical potential in HCC requires further evaluation.

p53R2 overexpression in cervical cancer promotes AKT signaling and EMT, and is correlated with tumor progression, metastasis and poor prognosis.

p53R2 is a p53-inducible ribonucleotide reductase subunit involved in deoxyribonucleotide biosynthesis and DNA repair. Although p53R2 has been linked to human cancer, its role in cervical cancer remains unknown. In this study, we investigated the expression and clinical significance of p53R2 in early-stage cervical cancer. p53R2 expression is significantly upregulated at both mRNA and protein levels in cervical cancer cells and tissues, compared with that in matched normal cervical cells and tissues, respectively. p53R2 overexpression is associated with increased risk of pelvic lymph node metastasis (PLNM, p = 0.001) and cancer relapse (p = 0.009). Patients with high p53R2 expression have a shorter overall survival (OS) and disease-free survival (DFS). p53R2 is an independent factor for predicting OS and DFS of cervical cancer patients. We further show that p53R2 is important for oncogenic growth, migration and invasion in cervical cancer cells. Mechanistically, p53R2 promotes Akt signaling and epithelial-mesenchymal transition (EMT). In conclusion, our study demonstrates for the first time that p53R2 protein is overexpressed in early-stage cervical cancer and unravels some unconventional oncogenic functions of p53R2. p53R2 may be a useful prognostic biomarker and therapeutic target for cervical cancer.

Comparative study of the chitooligosaccharides effect on the proliferation inhibition and radiosensitization of three types of human gastric cancer cell line

Objective To observe the chitooligosaccharides (COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line. Mothods CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells, MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells. The clonogenic assay was used to detect the cell viability of 0, 1, 2, 4, 6 and 8 Gy (6 dose grades) in RAY group and RAY + COS group after X-ray, and the cell survival curve was used to analyze the sensitization enhancement ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY + COS group after 48 h treatment. Results COS inhibited the proliferation of three types of cells. The inhibition rate was positively correlated with the concentration of COS, and the susceptibility of MKN45 cells, SGC7901 cells and BGC823 cells to COS decreased in turn. The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY + COS group (P < 0.01). The cell viabilities of RAY + COS group were lower than those of RAY group at all the dose grades under X-ray exposure (P < 0.01), and the sensitization enhancement ratios of COS on BGC823 cells, MKN45 cells and SGC7901 cells were 1.06, 1.28 and 1.15, respectively. In controlled trials, apoptosis rate and percentage in the G

Comparative study of the chitooligosaccharides effect on the proliferation inhibition and radiosensitization of three types of human gastric cancer cell line

OBJECTIVE@#To observe the chitooligosaccharides (COS) effect on the proliferation inhibition and radiosensitivity of three types of human gastric cancer cell line.@*MOTHODS@#CCK-8 assay was employed to obtain the inhibition ratio of COS on BGC823 cells, MKN45 cells and SGC7901 cells at 48 h after treatment and the proliferation-inhibition curve was drawn with the inhibition ratio of COS on three types of cells. The clonogenic assay was used to detect the cell viability of 0, 1, 2, 4, 6 and 8 Gy (6 dose grades) in RAY group and RAY + COS group after X-ray, and the cell survival curve was used to analyze the sensitization enhancement ratio of COS. Flow cytometry was employed to detect cell cycle and apoptosis rate in control group, RAY group and RAY + COS group after 48 h treatment.@*RESULTS@#COS inhibited the proliferation of three types of cells. The inhibition rate was positively correlated with the concentration of COS, and the susceptibility of MKN45 cells, SGC7901 cells and BGC823 cells to COS decreased in turn. The cell viability decreased gradually with the increasing radiation dose in RAY group and RAY + COS group (P < 0.01). The cell viabilities of RAY + COS group were lower than those of RAY group at all the dose grades under X-ray exposure (P < 0.01), and the sensitization enhancement ratios of COS on BGC823 cells, MKN45 cells and SGC7901 cells were 1.06, 1.28 and 1.15, respectively. In controlled trials, apoptosis rate and percentage in the G2/M phase of three types of cells in RAY + COS group were higher than those in control group and RAY group, and percentage in the S phase and the G0/G1 phase in RAY + COS group were lower than those in the other two groups (P < 0.01).@*CONCLUSIONS@#COS can inhibit the proliferation of three types of human gastric cancer cells and enhance the radiosensitivity by inducing apoptosis and G2/M phase arrest.

Drug resistance of methicillin resistant Staphylococcus strains in burn ward and relative analysis / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the distribution and drug resistance of methicillin resistant Staphylococcus strains in various specimens of inpatients in burn wards, and to provide reference for clinical treatment.</p><p><b>METHODS</b>Bacteria were isolated from specimens of wound exudate, blood, sputum, and bronchoalveolar lavage fluid etc., which were collected from patients hospitalized in our burn wards from January 2008 to December 2010. The bacteria were routinely cultured and identified. Drug resistance of the Staphylococci to 15 antibiotics commonly used in clinic was identified by K-B disk diffusion method. Data were processed with statistical software WHONET 5.5. The homology of 40 strains of methicillin resistant Staphylococcus aureus (MRSA) was analyzed by pulsed-field gel electrophoresis (PFGE).</p><p><b>RESULTS</b>Altogether 386 strains of Staphylococcus were isolated, including 196 strains of Staphylococcus aureus and 190 strains of coagulase negative Staphylococcus. The mean annual isolation rates of MRSA and methicillin resistant coagulase negative Staphylococcus (MRCoNS) were respectively 73.00% (143/196) and 74.20% (141/190). The resistance rates of MRSA and MRCoNS to β-lactams drugs, such as penicillin, oxacillin, cefazolin, and cefuroxime were 100.00% in every year. No Staphylococcus strains resistant to vancomycin, teicoplanin, or linezolid were found. Three different PFGE patterns A, B, and C were identified among 40 MRSA strains, including 33 strains of type A (30 strains in sub-type A1 and 3 strains in sub-type A2), 6 strains of type B (respectively 3 strains in sub-types B1 and B2), and 1 strain of type C.</p><p><b>CONCLUSIONS</b>The isolation rates of MRSA and MRCoNS were high in our burn wards from January 2008 to December 2010. All of them showed strong drug resistance property, and they were multidrug resistant. The most prevalent strain was PFGE type A.</p>

Investigation of 728 strains of infectious bacteria in burn ward and analysis of their antibiotic resistance / 中华烧伤杂志

<p><b>OBJECTIVE</b>To study the infectious strains of bacteria in our burn ward in recent 5 years, and analyze their antibiotic resistance.</p><p><b>METHODS</b>Bacteria were isolated from the wound excretions of 306 burn patients hospitalized during 2001 to 2006 for analyzing their strains and their antibiotic resistance.</p><p><b>RESULTS</b>378 strains were Grams positive bacteria, among them Staphylococcus aureus was the predominant strain. Further analysis showed that methicillin resistant staphylococcus aureus (MRSA) ranked the first in occurrence, followed by methicillin-resistance Staphylococcus epidermidis (MRSE) and Enterococcus fecalis, 338 strains were Gram negative bacteria, and among them Acinetobacter baumannii was predominant, and Enterobacter cloacae and Pseudomonas aeruginosa ranked the 2nd and 3rd. Twelve strains were fungi.</p><p><b>CONCLUSION</b>Drug resistance to antibiotics in our burn ward may be related to the beta-lactamases from acinetobacter baumannii and multiple-drug-resistance of MRSA.</p>

Study on factors causing the delay of access to tuberculosis diagnosis and its influencing factors in migrating tuberculosis patients in Putuo district, Shanghai / 中华流行病学杂志

<p><b>OBJECTIVE</b>To describe factors causing the delay of diagnosis among non-resident tuberculosis (TB) patients and to study its implications from demographic, socio-economic aspects in order to provide information to policy makers for TB control programs in Shanghai.</p><p><b>METHODS</b>A historical cohort study through questionnaire interview was conducted in 146 newly diagnosed TB patients. The questionnaire covered the general information of subjects and information on patients' health care seeking experiences from the first symptom to the TB diagnosis in health facilities. Index adopted to reflect the access to TB diagnosis would include the days due to delayed diagnosis consisting the days from both patient's and doctor's responsibilities.</p><p><b>RESULTS</b>The median days due to patients' delay was 19 (7-33.5) days, which was 3.8 times longer than 5 (2.5-10) days caused by doctor's. The median of total diagnostic delay was 31 (11-59) days. Female TB patients, patients with lower than annual 5000 Yuan income had an increased risk of a longer diagnostic delay with an OR of 3.226 and 11.958 relatively. Smear positive patients had a shorter delay (OR = 0.280, P < 0.05).</p><p><b>CONCLUSION</b>Delayed diagnosis was mostly caused by the patients, suggesting that TB control strategy for non-residents should aim at improving the access to TB diagnosis among patients with lower income and female non-residents.</p>

Comparison between Cognitive-behavior Therapy and Medication on Chronic Insomnia / 中国心理卫生杂志

Objective: to compare clinical effect of cognitive-behavior therapy and pharmacological treatment on chronic insomnia Method:48 patients with chronic insomnia were divided into 4 groups, receiving treatments of cognitive-behavior therapy, medication, placebo,and cognitive-behavior plus medication separately All of the subjects were assessed with polysomnogram over night and sleep diary Result:the three active treatments were more effective than placebo at post-treatment assessment On the eighth day of treatments, medication group and combined group showed improvement, sleep latencies were 20 min and 27 min, sleep efficacy were 80% and 82%, total sleep time were 381 min and 356 min, which were better than the results before treatments At the end of 8 weeks, cognitive-behavior group showed improvement in the above three indexes At the end of 8 months' follow-up, cognitive-behavior group still showed better effect in sleep latency 26 min, sleep efficacy 80%, total sleep time 378 min than those of 8 weeks While the indexes of the medication group and combined group could not maintain the effect of treatment Conclusion:medication shows a short-term effect on chronic insomnia, cognitive-behavior therapy shows long-term effect