Effects of gastrodin on the expression of BDNF and IL-6 in the striatum of rats with cerebral ischemia / 中国临床药理学与治疗学

AIM: To investigate the effect of gastrodin on the expression of brain-derived neurotrophic factor (BDNF) and interleukin-6 (IL-6) in the striatum of cerebral ischemia rats, and to explore the potential mechanism of gastrodin in treating cerebral ischemia. METHODS: The rats were randomly divided into four groups: normal, sham, model, and gastrodin groups, each consisting of 10 rats. After successful modeling using middle cerebral artery occlusion (MCAO), the gastrodin group received intraperitoneal injection of gastrodin injection at a dose of 10 mg/kg once a day for 14 consecutive days. Pathological changes in striatal neurons were observed using Nissl staining. Immunohistochemistry was utilized to detect positive expression of BDNF and IL-6 proteins in the striatum. Additionally, immunoblot analysis was performed to determine the expression levels of BDNF and IL-6 proteins in the striatum. RESULTS: Nissl staining revealed clear and intact structures of striatal neurons in the normal and sham groups, with tightly arranged cells. In the model group, the number of cells was significantly reduced compared to the sham group (P0.05). Compared to the sham group, the model group showed a decrease in the protein expression level of BDNF in the striatum on the ischemic side (P<0.01) and an increase in the protein expression level of IL-6 (P<0.05, P<0.01). In contrast, the gastrodin group showed an increase in the protein expression level of BDNF in the striatum on the ischemic side (P<0.05, P<0.01) and a decrease in the protein expression level of IL-6 (P< 0.05, P<0.01) compared to the model group. CONCLUSION: Gastrodin has a significant protective effect on striatal injury caused by cerebral ischemia, and its mechanism may be related to the up-regulation of the anti-inflammatory factor BDNF and the down-regulation of the pro-inflammatory factor IL-6.

Ligustilide delays senescence of auditory cortex in mice by inhibiting ferritinophagy / 中国药理学通报

Aim To investigate the mechanism of ligu aged 2 months of the same strain were used as the constilide (LIG) in delaying the senescence of auditory trol (Ctrl) group. Auditory brainstem response test was cortex and treating central presbycusis. Methods used to detect the auditory threshold of mice before and Forty C57BL/6J mice aged 13 months were randomly di after treatment. Levels of serum MDA and activity of vided into ligustilide low-dose(L-LIG) group, ligustil serum SOD were detected to display the level of oxidative ide medium-dose (M-LIG) group, ligustilide high-dose stress. The pathological changes of auditory cortex were (H-LIG) group and aging (Age) group, and 10 mice observed by HE staining. Ferroptosis was observed by

Xinjia Congrong Tusizi Decoction Regulates Ferroptosis of Granulosa Cells in Rat Model of Premature Ovarian Insufficiency via p53/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Xinjia Congrong Tusizi decoction （XJCTD） on ovarian functions in the rat model of premature ovarian insufficiency （POI） and decipher the mechanism of regulating the tumor suppressor protein （p53）/nuclear factor E2-related factor 2 （Nrf2） pathway to attenuate granulosa cell ferroptosis. MethodForty-eight SPF-grade female SD rats were randomized into control， model， low-， medium-， and high-dose （1.1， 2.2， 4.4 g·kg-1） XJCTD， and Western medicine （coenzyme Q10， 0.002 7 g·kg-1） groups， with eight rats in each group. The rat model of POI was established by gavage of triptolide （TP）， and after successful modeling， each group was administrated with the corresponding drugs by gavage for 14 d. The body weight and ovarian weight of each rat were weighed and the ovarian index was calculated. The morphology of the ovarian tissue was observed by hematoxylin-eosin staining， and the proportions of growing follicles and atretic follicles were calculated. The serum levels of anti-Müllerian hormone （AMM）， estradiol （E2）， and follicle-stimulating hormone （FSH） were measured by enzyme-linked immunosorbent assay （ELISA）. The DCFH-DA fluorescent probe was used to measure the reactive oxygen species （ROS） content in granulosa cells. The content of cellular Ferrous ion （Fe2+）， lipid peroxide （LPO）， malondialdehyde （MDA）， glutathione （GSH）， and superoxide dismutase （SOD） was detected by colorimetry. The expression of the tumor suppressor protein p53，Nrf2， solute carrier family 7 member 11 （SLC7A11）， and glutathione peroxidase 4 （GPX4） was determined by immunohistochemistry and Western blot. ResultCompared with the control group， the model group showed decreased ovarian weight， body weight， and ovarian index （P<0.01）， reduced ovarian tissue volume and proportion of growing follicles （P<0.01）， increased proportion of atretic follicles （P<0.01）， lowered AMH and E2 levels and elevated FSH level in the serum （P<0.01）， and elevated levels of Fe2+， ROS， LPO， and MDA （P<0.01） and lowered levels of GSH and SOD in granulosa cells （P<0.01）. Moreover， the modeling up-regulated the expression of p53 （P<0.01） and down-regulated the expression of Nrf2， SLC7A11， and GPX4 （P<0.05， P<0.01） in the ovarian tissue. Compared with the model group， XJCTD increased the body weight， ovarian weight， and ovarian index （P<0.01）， alleviated the pathological changes in the ovarian tissue， increased the proportion of growing follicles （P<0.01）， decreased the proportion of atretic follicles （P<0.01）， and reduced the content of ROS in granulosa cells （P<0.05， P<0.01）. In addition， medium- and high-dose XJCTD lowered the FSH level （P<0.01） and raised E2 and AMH levels （P<0.01） in the serum， reduced the Fe2+ content （P<0.05， P<0.01）， and increased the SOD content （P<0.01） in granulosa cells. High-dose XJCTD reduced the LPO and MDA content （P<0.01） and increased the SOD content （P<0.01） in the granulosa cells， down-regulated the expression of p53 （P<0.05）， and up-regulated the expression of Nrf2， SLC7A11， and GPX4 in the ovarian tissue （P<0.05， P<0.01）. ConclusionXJCTD may protect the ovarian function in the rat model of POI by regulating the p53/Nrf2 signaling pathway to attenuate the ferroptosis of ovarian granulosa cells.

Research on the influence of meteorological factors on the incidence of foodborne diseases / 公共卫生与预防医学

Objective To explore the correlation between the incidence of foodborne diseases and meteorological factors in Jinan, and to provide targeted measures for the prevention and control of foodborne diseases. Methods Data from the reporting systems of two sentinel hospitals for active surveillance of foodborne diseases from 2013 to 2021 in Jinan were collected. The meteorological data in the same period in Jinan were also collected. The generalized additive model was used to explore the nonlinear relationship between meteorological factors and the incidence of foodborne diseases, and threshold function analysis was use to perform subsection regression. Results The incidence of foodborne diseases was positively correlated with daily average temperature (rs=0.23), relative humidity (rs=0.05), and daily average wind speed (rs=0.01), and negatively correlated with daily average air pressure (rs=-0.19). Based on the GAM results and segmented regression analysis of meteorological factors, it was found that when the daily average temperature was below or above the threshold of 24.63°C, for every 1°C increase in daily average temperature, the incidence of foodborne diseases correspondingly increased by 0.04% and 0.18%. When the daily average wind speed was above the threshold of 2.26 m/s, the incidence of foodborne diseases decreased by 0.36% for every 1 m/s increase in the daily average wind speed. Conclusion Nine years of observation and data analysis have shown that meteorological factors such as daily average temperature, relative humidity, air pressure, and wind speed are related to the incidence of foodborne diseases. These findings suggest that meteorological factors may be important factors leading to foodborne diseases, which provides an important scientific basis for formulating effective prevention and control measures.

Molecular mechanism of resveratrol combined with irinotecan in treatment of colorectal cancer / 中国中药杂志

This study aimed to investigate the mechanism of resveratrol(RES) combined with irinotecan(IRI) in the treatment of colorectal cancer(CRC). The targets of RES, IRI, and CRC were obtained from databases, and the targets of RES combined with IRI in the treatment of CRC were acquired by Venn diagram. The protein functional cluster analysis, GO and KEGG enrichment analyses were performed. In addition, the protein-protein interaction(PPI) network was constructed. The core target genes were screened out and the target-signaling pathway network was set up. IGEMDOCK was used to dock the core target gene molecules. Besides, the relationship between the expression level of key target genes and the prognosis and immune infiltration of CRC was analyzed. Based on the in vitro cell experiment, the molecular mechanism of RES combined with IRI in the treatment of CRC was explored and analyzed. According to the results, 63 potential targets of RES combined with IRI were obtained for CRC treatment. Furthermore, cluster analysis revealed that protein functions included 23% transmembrane signal receptors, 22% protein modifying enzymes, and 14% metabolite converting enzymes. GO analysis indicated that BPs were mainly concentrated in protein autophosphorylation, CCs in receptor complex and plasma membrane, and MFs in transmembrane receptor protein tyrosine kinase activity. Moreover, KEGG signaling pathways were mainly enriched in central carbon metabolism in cancer. The key targets of RES combined with IRI in the treatment of CRC were PIK3CA, EGFR, and IGF1R, all of which were significantly positively correlated with the immune infiltration of CRC. As shown by the molecular docking results, PIK3CA had the most stable binding with RES and IRI. Compared with the results in the control group, the proliferation ability and EGFR protein expression of CRC cells in the RES-treated group, the IRI-treated group, and the RES+IRI treated group significantly decreased. Moreover, the cell proliferation ability and EGFR protein expression level of CRC cells in the RES+IRI treated group were remarkably lower than those in the IRI-treated group. In conclusion, PIK3CA, EGFR, and IGF1R are the key targets of RES combined with IRI in CRC treatment. In addition, RES can inhibit the proliferation of CRC cells and improve IRI chemoresistance by downregulating the EGFR signaling pathway.

Immediate analgesic effect of electroacupuncture combined with diclofenac sodium on acute gouty arthritis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the immediate analgesic effect of electroacupuncture (EA) combined with diclofenac sodium on acute gouty arthritis (AGA).@*METHODS@#A total of 90 patients with AGA were randomly divided into a low-dose medication (LM) group (30 cases, 1 case was eliminated, 1 case dropped off), a conventional medication (CM) group (30 cases, 1 case dropped off) and a combination of acupuncture and medication (AM) group (30 cases ). The LM group was given oral administration of 50 mg diclofenac sodium sustained-release capsule; the CM group was given oral administration of 100 mg diclofenac sodium sustained-release capsule; on the basis of the treatment of LM group, the AM group was treated with electroacupuncture at ashi points, Dadu (SP 2), Taichong (LR 3), Taibai (SP 3), Neiting (ST 44), Sanyinjiao (SP 6), Zusanli (ST 36) and Yinlingquan (SP 9) on the affected side, and Taichong (LR 3) and Zusanli (ST 36), Sanyinjiao (SP 6) and Yinlingquan (SP 9) were connected to electroacupuncture respectively, continuous wave, 2 Hz in frequency. The visual analogue scale (VAS) scores of pain before treatment and after 10 min, 2 h, 4 h and 6 h of treatment completion, joint tenderness and swelling scores before treatment and after 10 min and 6 h of treatment completion were compared, and the rate of diclofenac sodium addition within 24 h after treatment completion was recorded among the three groups.@*RESULTS@#After 10 min of treatment completion, the scores of VAS, joint tenderness and joint swelling in the AM group were lower than those before treatment (P<0.05), and the VAS score in the AM group was lower than that in the other two groups (P<0.05). After 2, 4 and 6 h of treatment completion, the VAS scores of the three groups were lower than those before treatment (P<0.05), and the scores in the AM group were lower than those in the LM group (P<0.05). After 6 h of treatment completion, the joint tenderness scores of the three groups and the joint swelling scores of the AM group and the CM group were lower than those before treatment (P<0.05), and the joint tenderness and swelling scores of the AM group were lower than those of the LM group (P<0.05). The rate of diclofenac sodium addition was 3.3 % (1/30) and 3.4 % (1/29) in the AM group and the CM group, respectively, which were lower than 17.9% (5/28) in the LM group (P<0.05).@*CONCLUSION@#Electroacupuncture combined with diclofenac sodium have a good immediate analgesic effect in the treatment of AGA, and have the advantages of small dosage of analgesic drugs and less adverse reactions.

mRNA Expression of Aquaporins in Human Luteinized Granulosa Cells from Different Diameter Follicles / 中山大学学报(医学科学版)

ObjectiveTo investigate the mRNA expression levels of various aquaporins （AQPs） in luteinized granulosa cells from follicles of different diameters. MethodsFrom March 25， 2022 to September 23， 2022 in our reproductive medicine center， 48 women undergoing in-vitro fertilization （IVF） were enrolled and divided into the antagonist group and the agonist group according to the ovarian stimulation protocol. Follicular fluid samples were collected on the day of oocyte pick-up and granulosa cells were extracted from follicles of different diameters： small （<13 mm）， medium （13~18 mm） and large （≥18 mm）. After RNA quantification， 22 cases （66 samples） were included for analysis and mRNA expression levels of AQPs were compared among the three follicle groups. ResultsThe mRNA expression of aquaporin 2 （AQP2） in luteinized granulosa cells increased with the increase of follicle diameter （linear trend P = 0.004） and the difference was statistically significant between two groups of large and small follicles （P = 0.017）. Statistical difference was found in the antagonist group （P = 0.049 6）， but not in the agonist group （P = 0.108）. ConclusionThe mRNA level of AQP2 in luteinized granulosa cells increases with the increase of follicle diameter and its expression is related to the ovarian stimulation protocol， suggesting that AQP2 may play a role in follicle growth and follicular fluid formation， and its mRNA expression level may be regulated by follicle stimulating hormone （FSH） and luteinizing hormone （LH）.

Association of folic acid with the development and progression of liver cancer / 临床肝胆病杂志

So far, liver cancer is still a highly malignant tumor with a high incidence rate in China, and it seriously affects the life and health of Chinese people. Previous studies have shown that the development of liver cancer is associated with various factors such as virus, smoking, drinking, and nonalcoholic fatty liver disease. With continuous exploration, more and more studies have pointed out that nutritional factors and living environment are associated with the development and progression of liver cancer. Folic acid is a necessary nutrient for cell growth and reproduction, and its level in human body has an impact on the growth of tumor cells and is closely associated with liver cancer. This article reviews the research advances in the association between folic acid and liver cancer in recent years, so as to provide new reference and basis for the prevention and treatment of liver cancer.

PRMT6 promotes tumorigenicity and cisplatin response of lung cancer through triggering 6PGD/ENO1 mediated cell metabolism

Metabolic reprogramming is a hallmark of cancer, including lung cancer. However, the exact underlying mechanism and therapeutic potential are largely unknown. Here we report that protein arginine methyltransferase 6 (PRMT6) is highly expressed in lung cancer and is required for cell metabolism, tumorigenicity, and cisplatin response of lung cancer. PRMT6 regulated the oxidative pentose phosphate pathway (PPP) flux and glycolysis pathway in human lung cancer by increasing the activity of 6-phospho-gluconate dehydrogenase (6PGD) and α-enolase (ENO1). Furthermore, PRMT6 methylated R324 of 6PGD to enhancing its activity; while methylation at R9 and R372 of ENO1 promotes formation of active ENO1 dimers and 2-phosphoglycerate (2-PG) binding to ENO1, respectively. Lastly, targeting PRMT6 blocked the oxidative PPP flux, glycolysis pathway, and tumor growth, as well as enhanced the anti-tumor effects of cisplatin in lung cancer. Together, this study demonstrates that PRMT6 acts as a post-translational modification (PTM) regulator of glucose metabolism, which leads to the pathogenesis of lung cancer. It was proven that the PRMT6-6PGD/ENO1 regulatory axis is an important determinant of carcinogenesis and may become a promising cancer therapeutic strategy.

Effects of Total Saponins from Dioscorea Nipponica Makino on Monosodium Urate-Induced M1-Polarized Macrophages through Arachidonic Acid Signaling Pathway: An in vitro Study / 中国结合医学杂志

OBJECTIVE@#To investigate and reveal the underlying mechanism of the effect of total saponins from Dioscoreae nipponica Makino (TSDN) on the arachidonic acid pathway in monosodium urate (MSU) crystal-induced M1-polarized macrophages.@*METHODS@#M1 polarization of RAW264.7 cells were induced by 1 µ g/mL lipopolysaccharide (LPS). The methylthiazolyldiphenyl-tetrazolium bromide method was then used to screen the concentration of TSDN. MSU (500 µ g/mL) was used to induce the gouty arthritis model. Afterwards, 10 µ g/L TSDN and 8 µ mol/L celecoxib, which was used as a positive control, were added to the above LPS and MSU-induced cells for 24 h. The mRNA and protein expressions of cyclooxygenase (COX) 2, 5-lipoxygenase (5-LOX), microsomal prostaglandin E synthase derived eicosanoids (mPGES)-1, leukotriene B (LTB)4, cytochrome P450 (CYP) 4A, and prostaglandin E2 (PGE2) were tested by real-time polymerase chain reaction and Western blotting, respectively. The enzyme-linked immunosorbent assay was used to test the contents of M1 markers, including inducible nitric oxid synthase (NOS) 2, CD80, and CD86.@*RESULTS@#TSDN inhibited the proliferation of M1 macrophages and decreased both the mRNA and protein expressions of COX2, 5-LOX, CYP4A, LTB4, and PGE2 (P<0.01) while increased the mRNA and protein expression of mPGES-1 (P<0.05 or P<0.01). TSDN could also significantly decrease the contents of NOS2, CD80, and CD86 (P<0.01).@*CONCLUSION@#TSDN has an anti-inflammation effect on gouty arthritis in an in vitro model by regulating arachidonic acid signaling pathway.

Analysis of the effect of midazolam on pain in a rat model of lumbar disc herniation based on the p38 MAPK signaling pathway / 中国骨伤

OBJECTIVE@#To investigate the effect of midazolam on pain in lumbar disc herniation model rats based on p38 MAPK signaling pathway.@*METHODS@#Fifty SPF-grade Sprague-Dawley healthy rats, half male and half female, were selected and randomly divided into normal group, model group, and low-dose, medium-dose, high-dose groups. Model group and low-dose, medium-dose, high-dose groups were initially modeled for lumbar disc herniation. Intraperitoneal injection of saline was performed in rats of normal and model groups; and in the low-dose, medium-dose, and high-dose groups, intraperitoneal injection of midazolam was performed with doses of 30, 60, and 90 mg/kg, respectively. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), 5-hydroxytryptamine (5-HT), β-endorphin (β-EP), substance P (SP), neuropeptide Y (NPY) were detected in the serum of rats by enzyme-linked immunoassay. The expression of p38 MAPK and matrix metalloproteinase-3(MMP-3) protein were detected by Western blot in the tissues of rats of each group.@*RESULTS@#The levels of TNF-α, IL-1β and β-EP were higher and the level of 5-HT was lower in the model group than in the normal group(P<0.05);the levels of TNF-α, IL-1β and β-EP were lower and the level of 5-HT was higher in the low-dose, medium-dose and high-dose groups than in the model group(P<0.05). The levels of SP and NPY increased in the model group compared with the normal group (P<0.05) and the levels of SP and NPY decreased in the low-dose, medium-dose and high-dose groups compared with the model group (P<0.05). The expression of p38 MAPK and MMP-3 increased in the model group compared with the normal group (P<0.05); the expression of p38 MAPK and MMP-3 decreased in the low-dose, medium-dose and high-dose compared with the model group(P<0.05).@*CONCLUSION@#Midazolam may ameliorate the immune inflammatory response in rats with a model of lumbar disc herniation, possibly regulated through the p38MAPK signaling pathway.

The risk prediction value of paraquat poisoning dose, urine protein and myocardial enzymes / 中华劳动卫生职业病杂志

Objective: To explore the value of paraquat (PQ) intake, urine protein and myocardial enzyme indexes in judging the prognosis of patients with acute PQ poisoning. Methods: From September to December 2021, all 201 patients with acute PQ poisoning admitted to Guangzhou Twelfth People's Hospital from January 2010 to December 2019 were selected as the research objects. Based on follow-up results 60 days after poisoning, the research objects were divided into survival group (n=78) and death group (n=123) . The differences in information about poisoning, treatment plan, PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase between the two groups of patients were compared and analyzed. Logistic regression and Cox regression were used to analyze the correlation between poisoning outcome and PQ intake, urine protein and myocardial enzymes. ROC curve and principal component analysis were used to explore high-efficiency indicators for predicting the outcome of acute PQ poisoning. Results: The PQ intake[50 (20, 100) ml], urine protein (total rank 15570.50) , creatine kinase[ (336.36±261.96) U/L], creatine kinase isoenzyme[ (43.91±43.74) U/L], lactate dehydrogenase [ (346.01±196.50) U/L], α-hydroxybutyrate dehydrogenase content[ (271.23±11.92) U/L] of patients in the death group were all higher than the survival group[15 (10, 20) ml, 4730.50, (187.78±178.06) U/L, (18.88±15.50) U/L, (190.92±60.50) U/L, (152.60±48.34) U/L, respectively] (P<0.05) . The outcome of acute PQ poisoning was positively correlated with PQ intake, urine protein, creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase (P<0.05) . Multivariate logistic regression and multivariate Cox regression analysis showed that creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase and α-hydroxybutyrate dehydrogenase was positively correlated with the prognosis of patients with acute PQ poisoning (P<0.05) . ROC curve analysis and principal component analysis showed that the combined indexes of PQ intake, urine protein and myocardial enzymes had the highest efficacy and weight in judging the prognosis of patients (AUC=0.91, weight coefficient=0.19, sensitivity=0.76, specificity=0.89) . When the combined score was ≥4, the probability of accurately predicting the death of patients was as high as 91% (positive predictive value=0.91) . Conclusion: PQ intake, urine protein combined with creatine kinase, creatine kinase isoenzyme, lactate dehydrogenase, and α-hydroxybutyrate dehydrogenase has high value in predicting the prognosis of patients with acute PQ poisoning.

Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta / 中华妇产科杂志

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.

Forecasting the burden of disease from diabetes under the scenarios of specific risk factors control in China in 2030 / 中华流行病学杂志

Objective: To forecast mortality, age-standardized mortality, and probability of premature mortality from diabetes, and to simulate the impact of controlling risk factors by 2030 in China. Methods: We simulated the burden of disease from diabetes in six scenarios according to the development goals of risk factors control by the WHO and Chinese government. Based on the theory of comparative risk assessment and the estimates of the burden of disease for China from the Global Burden of Disease Study 2015, we used the proportional change model to project the number of deaths, age-standardized mortality, and probability of premature mortality from diabetes under different scenarios of risk factors control in 2030. Results: If the trends in exposures to risk factors from 1990 to 2015 continued. Mortality, age-standardized mortality, and probability of premature mortality from diabetes would increase to 32.57/100 000, 17.32/100 000, and 0.84% by 2030, respectively. During that time, mortality, age-standardized mortality and probability of premature mortality for males would all be higher than for females. If the goals of controlling risk factors were all achieved, the number of deaths from diabetes in 2030 would decrease by 62.10% compared to the predicted numbers based on the historical trends in exposure to risk factors, and the probability of premature mortality would drop to 0.29%. If only the exposure to a single risk factor were achieved by 2030, high fasting plasma glucose control would have the greatest impact on diabetes, resulting in a 56.00% reduction in deaths compared to the predicted numbers based on the historical trends, followed by high BMI (4.92%), smoking (0.65%), and low physical activity (0.53%). Conclusions: Risk factors control plays an important role in reducing the number of deaths, age-standardized mortality rate, and probability of premature mortality from diabetes. We suggest taking comprehensive measures to control relevant risk factors for certain populations and regions, to achieve the goal of reducing the burden of disease from diabetes as expected.

Safety of delayed vaccination with the national immunization program vaccines in children aged 0-6 years from 2019 to 2021 in Xuhui District, Shanghai City in China / 中华预防医学杂志

Objective: To understand the incidence of delayed vaccination with the national immunization program vaccines among children aged 0-6 years in Xuhui District, Shanghai, and to evaluate the safety of delayed vaccination. Methods: A stratified random sampling was used to obtain six vaccination clinics in Xuhui District, Shanghai. The vaccination records of children 0-6 years from these six vaccination clinics were collected from the Shanghai Immunization Program Information Management System. Adverse events following immunization (AEFI) data were collected from the China Information System for Disease Control and Prevention. Descriptive epidemiology was used to analyze the data. Children were divided into the timely vaccination group and delayed vaccination group according whether they were delayed in vaccination (received one month or more after the recommended age among children aged ≤1 year; received three months or more after the recommended age among children aged >1 year). The safety of four vaccination methods-individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination-were further compared. Differences between groups were compared using chi-square test. Results: From 2019 to 2021, six vaccination clinics in Xuhui District administered 124 031 doses of the national immunization program vaccines among children aged 0-6 years, and delayed vaccinations accounted for 25.99% (32 234/124 031) of these doses. In 2020, the delayed vaccination rate during the first-level COVID-19 public health emergency response period in Shanghai was significantly higher than that in the same period in 2019 (34.70% vs. 24.19%, χ2=136.23, P<0.05). The delayed vaccination rate during the COVID-19 vaccination campaign in 2021 was significantly higher than that in the same period in 2019 (25.27% vs. 22.55%, χ2=82.80, P<0.05). From 2019 to 2021, a total of 475 cases of AEFI were reported in six vaccination clinics, with a reported incidence of 382.97 per 100 000 doses, including 421 cases of common adverse reaction (88.63%, 339.43 per 100 000 doses), 51 cases of rare adverse reaction (10.74%, 41.12 per 100 000 doses) and 3 cases of coincidences (0.63%, 2.42 per 100 000 doses). The reported incidence of AEFI among delayed vaccinations was significantly lower than that among timely vaccinations (291.62 per 100 000 doses vs. 415.05 per 100 000 doses). The incidence of AEFI for the four delayed vaccination methods (individual vaccination, simultaneous vaccination, routine vaccination and combined vaccination) was lower than that for timely vaccination. There were significant differences between the groups except for the routine vaccination group (χ2=9.82, P<0.05; χ2=5.46, P<0.05; χ2=2.97, P>0.05; χ2=11.89, P<0.05). Conclusions: In Xuhui District of Shanghai, 25.99% of doses of the national immunization program vaccines administered to children 0-6 years were delayed. Delayed vaccination does not increase the risk of AEFI compared with timely vaccination.

Feasibility study of using bridging temporary permanent pacemaker in patients with high-degree atrioventricular block after TAVR / 中华心血管病杂志

Objective: To determine the feasibility of using temporary permanent pacemaker (TPPM) in patients with high-degree atrioventricular block (AVB) after transcatheter aortic valve replacement (TAVR) as bridging strategy to reduce avoidable permanent pacemaker implantation. Methods: This is a prospective observational study. Consecutive patients undergoing TAVR at Beijing Anzhen Hospital and the First Affiliated Hospital of Zhengzhou University from August 2021 to February 2022 were screened. Patients with high-degree AVB and TPPM were included. Patients were followed up for 4 weeks with pacemaker interrogation at every week. The endpoint was the success rate of TPPM removal and free from permanent pacemaker at 1 month after TPPM. The criteria of removing TPPM was no indication of permanent pacing and no pacing signal in 12 lead electrocardiogram (EGG) and 24 hours dynamic EGG, meanwhile the last pacemaker interrogation indicated that ventricular pacing rate was 0. Routinely follow-up ECG was extended to 6 months after removal of TPPM. Results: Ten patients met the inclusion criteria for TPPM, aged (77.0±11.1) years, wirh 7 females. There were 7 patients with third-degree AVB, 1 patient with second-degree AVB, 2 patients with first degree AVB with PR interval>240 ms and LBBB with QRS duration>150 ms. TPPM were applied on the 10 patients for (35±7) days. Among 8 patients with high-degree AVB, 3 recovered to sinus rhythm, and 3 recovered to sinus rhythm with bundle branch block. The other 2 patients with persistent third-degree AVB received permanent pacemaker implantation. For the 2 patients with first-degree AVB and LBBB, PR interval shortened to within 200 ms. TPPM was successfully removed in 8 patients (8/10) at 1 month without permanent pacemaker implantation, of which 2 patients recovered within 24 hours after TAVR and 6 patients recovered 24 hours later after TAVR. No aggravation of conduction block or permanent pacemaker indication were observed in 8 patients during follow-up at 6 months. No procedure-related adverse events occurred in all patients. Conclusion: TPPM is reliable and safe to provide certain buffer time to distinguish whether a permanent pacemaker is necessary in patients with high-degree conduction block after TAVR.

Outcome of surgical repair for aortic coarctation with coexisting descending aortic aneurysm in adult patients / 中华心血管病杂志

Objective: To evaluate the efficacy of surgical treatment of aortic coarctation combined with descending aortic aneurysm in adult patients. Methods: This is a retrospective cohort study. Adult patients with aortic coarctation who were hospitalized in Beijing Anzhen Hospital from January 2015 to April 2019 were enrolled. The aortic coarctation was diagnosed by aortic CT angiography, and the included patients were divided into the combined descending aortic aneurysm group and the uncomplicated descending aortic aneurysm group based on descending aortic diameter. General clinical data and surgery-related data were collected from the included patients, and death and complications were recorded at 30 days after surgery, and upper limb systolic blood pressure was measured in all patients at discharge. Patients were followed up after discharge by outpatient visit or telephone call for their survival and the occurrence of repeat interventions and adverse events, which included death, cerebrovascular events, transient ischemic attack, myocardial infarction, hypertension, postoperative restenosis, and other cardiovascular-related interventions. Results: A total of 107 patients with aortic coarctation aged (34.1±15.2) years were included, and 68 (63.6%) were males. There were 16 cases in the combined descending aortic aneurysm group and 91 cases in the uncomplicated descending aortic aneurysm group. In the combined descending aortic aneurysm group, 6 cases (6/16) underwent artificial vessel bypass, 4 cases (4/16) underwent thoracic aortic artificial vessel replacement, 4 cases (4/16) underwent aortic arch replacement+elephant trunk procedure, and 2 cases (2/16) underwent thoracic endovascular aneurysm repair. There was no statistically significant difference between the two groups in the choice of surgical approach (all P>0.05). In the combined descending aortic aneurysm group at 30 days after surgery, one case underwent re-thoracotomy surgery, one case developed incomplete paraplegia of the lower extremity, and one case died; and the differences in the incidence of endpoint events at 30 days after surgery were similar between the two groups (P>0.05). Systolic blood pressure in the upper extremity at discharge was significantly lower in both groups compared with the preoperative period (in the combined descending aortic aneurysm group: (127.3±16.3) mmHg vs. (140.9±16.3) mmHg, P=0.030, 1 mmHg=0.133 kPa; in the uncomplicated descending aortic aneurysm group: (120.7±13.2) mmHg vs. (151.8±26.3) mmHg, P=0.001). The follow-up time was 3.5 (3.1, 4.4) years. There were no new deaths in the combined descending aortic aneurysm group, no transient ischemic attack, myocardial infarction or re-thoracotomy surgery, and one patient (1/15) suffered cerebral infarction and 10 patients (10/15) were diagnosed with hypertension. The differences in the occurrence of endpoint events during postoperative follow-up were similar between the two groups (P>0.05). Conclusion: In experienced centers, long-term prognosis of patients with aortic coarctation combined with descending aortic aneurysm is satisfactory post surgical intervention.

Anti-neutrophil cytoplasmic antibody-associated vasculitis with gastrointestinal bleeding as the main symptom: a case report and literature review / 中华危重病急救医学

Anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) has a wide range of symptoms, and it is difficult for clinicians to make a quick and correct diagnosis. On November 11, 2021, a 36-year-old male patient with AAV was admitted to the emergency and critical care department of Yichang Central People's Hospital. He was admitted to the emergency intensive care unit (EICU) with gastrointestinal symptoms (abdominal pain, black stool) as the main physical signs, and was initially diagnosed as AAV with gastrointestinal hemorrhage (GIH). No bleeding point was found after repeated gastroscopy and colonoscopy. Abdominal emission CT (ECT) showed diffuse hemorrhage in the ileum, ascending colon and transverse colon. Multi-disciplinary consultation in the whole hospital considered the diffuse hemorrhage caused by small vascular lesions in the digestive tract caused by AAV. Pulse therapy with methylprednisolone 1 000 mg/d and immunosuppressive therapy with cyclophosphamide (CTX) 0.2 g/d were administered. The patient's symptoms quickly relieved and transferred out of the EICU. After 17 days of treatment, the patient finally died of massive gastrointestinal bleeding. A systematic review of relevant literatures combined with the case diagnosis and treatment process found that only a minority of AAV patients present with gastrointestinal symptoms as their first symptoms, and patients with GIH were very rare. Such patients had a poor prognosis. This patient delayed the use of induced remission and immunosuppressive agents due to the treatment of gastrointestinal bleeding, which may be the main cause of life-threatening GIH secondary to AAV. Gastrointestinal bleeding is a rare and fatal complication of vasculitis. Timely and effective induction and remission treatment is the key to survival. Whether patients should receive maintenance therapy, the duration of maintenance therapy, and the search for markers of disease diagnosis and treatment response are directions and challenges for further research.

Effects of environmental factors on the death of cardiovascular and cerebrovascular diseases during the high temperature process in Wuhan in 2014-2019 / 公共卫生与预防医学

Objective To explore the impact of temperature and environmental factors on the risk of deaths from cardiovascular and cerebrovascular diseases (CVD) in Wuhan during the course of high temperature. Methods The daily CVD death data and meteorological and atmospheric pollutant concentration data during the high temperature process in Wuhan from 2014 to 2019 were collected. The generalized additive models (GAM) were used to obtain the characteristics of meteorological factors, atmospheric pollutant concentrations, high impact factors and thresholds affecting the relative risk of CVD death. Results The analysis results showed that: (1) When the maximum temperature reached 36.7°C and the lowest temperature reached 25.3°C, the relative risk of CVD death increased significantly; (2) The risk of CVD death during the first high temperature process was the largest, and the average CVD excess mortality rate during the first high temperature process from 2014 to 2019 reached 21.7%; and (3) The average temperature, maximum temperature and PM10 during the course of high temperature were important environmental factors that increased the risk of CVD deaths, and the relative risks were 1.14 (95% confidence interval (95% CI): 1.11-1.17), 1.11 (95% confidence interval (95% CI): 1.08-1.15, and 1.06 (95% confidence interval (95% CI): 1.02-1.09), respectively. Conclusion Temperature and PM10 are important environmental factors that increase the risk of death from CVD during the high temperature process in Wuhan from 2014 to 2019, with the first annual high temperature process having the greatest impact on the risk of CVD death.

Predictive value of single high-sensitivity cardiac troponin Ⅰ level on the 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome / 中华检验医学杂志

Objective:To explore the predictive value of single high-sensitivity cardiac troponin I (hs-cTnI) concentration of 30-day cardiovascular adverse events in patients with suspected acute coronary syndrome (ACS).Methods:This is a multicenter, prospective and observational clinical study. Patients with suspected ACS who were admitted into the emergency department of Fuwai Hospital, the First Affiliated Hospital of Sun Yat-sen University and Nanjing First Hospital from January 2017 to September 2020 were enrolled. hs-cTnI result at the time of visit was obtained from patients with suspected ACS. Patients were followed up for 30 days and patients were divided into no events group and events group according to the presence or absence of 30-day cardiovascular adverse events (acute myocardial infarction (including index), unplanned revascularization and cardiovascular death). The predictive value of single Hs-cTnI at different concentration thresholds on the adverse event was evaluated in terms of sensitivity, negative predictive value (NPV) and 95% confidence interval ( CI). The best threshold was defined as: missed diagnosis rate <2% and NPV >99%. Patients were sub-grouped according to the confounders of hs-cTnI (sex, age, chest pain duration, estimated glomerular filtration rate), and Chi-square test was used to compare sensitivity and NPV among various subgroups. Results:A total of 1 461 patients were included. Among them, 387 patients (26.5%) had 30-day adverse cardiovascular events and 1 074 patients (73.5%) had no adverse cardiovascular events. Mean age was (62±12) years old and 905 were males (61.9%). When the concentration of hs-cTnI was less than 2 ng/L (limit of detection), the missed diagnosis rate of 30-day cardiovascular adverse events was 0.8% (3/387), the sensitivity was 99.2% (95% CI 97.6%-99.8%), and NPV was 98.7% (95% CI 96.0%-99.7%). When hs-cTnI concentration was less than 6 ng/L, the missed diagnosis rate was 1.8%, the sensitivity was 98.2% (95% CI 96.1%-99.2%), and NPV was 99.0% (95% CI 97.9%-99.6%). Subgroup analysis showed that the sensitivity and NPV of single hs-cTnI concentration <6 ng/L for 30-day cardiovascular adverse events were lower in patients with chest pain less than 3 h than those with chest pain time>3 hours ( P<0.05). Conclusions:Single hs-cTnI concentration less than 6 ng/L can predict the risk of 30-day cardiovascular adverse events in suspected ACS patients, but continuous monitoring is recommended for patients with chest pain onset≤3 hours.