Synthesis and biological activities of chlorin e6-based conjugate of fluorouracil as dual-mode antitumor photosensitizer / 药学实践杂志

Objective To design and synthesize the conjugate (compound 1) of chlorin e6 (compound 3) with fluorouracil (5-Fu) as novel pH-responsive dual-mode antitumor photosensitizer by acyl hydrazone bond coupling, based on literature reports that combination of 5-Fu and photosensitizer possess synergistic anti-tumor effect, and investigate its photodynamic antitumor activity and mechanism. Methods Lead compound 3 was obtained by alkali degradation with 25% KOH-CH3OH on pheophorbide a (compound 4) which was prepared through acid hydrolysis of chlorophyll a in crude chlorophyll extracts from silkworm excrement. Reflux reaction of 5-Fu with P2S5 in pyridine formed crude 4-thio-5-fluorouracil which was followed to react with hydrazine hydrate (N2H4·H2O) in CH3OH to give 5-fluorouracil-4-hydrazone (compound 2). Then, treatment of compound 3 i.e. acid alkali degradation product of chlorophyll a in silkworm excrement with EDC·HCl generated its 171- and 152 cyclic anhydride which was followed to directly react with intermediate compound 2 to successfully get title compound 1. In addition, its pH-responsive 5-Fu release and photodynamic antitumor activity and their mechanisms in vitro were investigated. Results Compound 1 could responsively release 5-Fu at pH 5.0, with a cumulative release rate of 60.3% within 24 h. It exhibited much higher phototoxicity against melanoma B16-F10 and liver cancer HepG2 cells than talaporfin and its precursor compound 3, with IC50 value being 0.73 μmol/L for B16-F10 cells and 0.90 μmol/L for HepG2 cells, respectively. Upon light irradiation, it also could significantly induce cell apoptosis and intracellular ROS level and block cell cycle in S phase. Its structure was confirmed by UV, 1H-NMR, ESI-MS and elemental analysis data. Conclusion The conjugate compound 1 of compound 3 and 5-Fu has the advantages of strong PDT anticancer activity, high therapeutic index (i.e. dark toxicity/phototoxicity ratio) and responsively release 5-Fu at pH 5.0 etc. which shows “unimolecular” dual antitumor effects of PDT and chemotherapy and is worthy of further research and development.

Epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China / 中华流行病学杂志

Objective: This study aimed to investigate the epidemiological characteristics of cardio-metabolic risk factors among children and adolescents aged 7-17 years in (Hebei, Zhejiang, Shaanxi, Hunan) 4 provinces of China and the influence of demographic and economic characteristics on them. Methods: A total of 1 747 children and adolescents aged 7-17 from a Community-based Cohort Study on Nervous System Disease in 2018 were selected. High waist circumference, central obesity, elevated TG, elevated TC, elevated LDL-C, decreased HDL-C, elevated blood pressure, elevated blood glucose, and clustering of risk factors was analyzed. χ2 test was used for univariate analysis, multivariate logistic regression was used to analyze the correlation between demographic and economic factors and risk factors, and the Cochran-Armitage trend test was used for trend analysis. Results: The detection rates of high waist circumference, decreased HDL-C, elevated blood pressure, elevated TG, elevated blood glucose, central obesity, elevated TC, and elevated LDL-C were 29.08%, 15.28%, 13.17%, 13.05%, 11.79%, 7.33%, 6.53%, and 5.15%, respectively. The rate of clustering of risk factors was 18.37%. Multivariate logistic regression analysis showed that the risk of high waist circumference in girls was higher than that in boys (OR=1.67, 95%CI: 1.26-2.22), and the risk of elevated blood glucose and clustering of risk factors was lower than that in boys (OR=0.69, 95%CI: 0.49-0.99; OR=0.72, 95%CI: 0.53-0.99). The risk of high waist circumference, decreased HDL-C, and clustering of risk factors in 13-17 years old group was higher than that in the 7-year-olds group (OR=2.24, 95%CI: 1.65-3.04; OR=1.59, 95%CI: 1.20-2.11; OR=1.75, 95%CI: 1.26-2.44), but the risk of central obesity was lower (OR=0.54, 95%CI: 0.37-0.78). The risk of elevated TC, elevated TG, and decreased HDL-C in children and adolescents in southern was higher than that in northern parts of China (OR=1.88, 95%CI: 1.25-2.83; OR=1.61, 95%CI: 1.17-2.22; OR=1.55, 95%CI: 1.19-2.04), but the risk of high waist circumference and central obesity was lower than that in northern China (OR=0.57, 95%CI: 0.43-0.75; OR=0.62, 95%CI: 0.42-0.90). The risk of decreased HDL-C in rural children and adolescents was higher than in urban children and adolescents (OR=1.36, 95%CI: 1.02-1.83). The risk of multiple risk factors increased with the increase in average monthly household income per capita and BMI level. Conclusions: High waist circumference, decreased HDL-C and elevated blood pressure were prominent cardio-metabolic risk factors among children and adolescents aged 7-17 years in 4 provinces of China in 2018. The region, average monthly household income per capita, and BMI were the main influencing factors of cardio-metabolic risk factors.

Changes in Notified Incidence of Pulmonary Tuberculosis in China, 2005-2020 / 生物医学与环境科学（英文）

OBJECTIVE@#To evaluate the trend of notified incidence of pulmonary tuberculosis (PTB) in China at different periods by population and region and to explore the effect of TB prevention and control in recent years.@*METHODS@#Using pooled data on TB cases reported by the TB Information Management Reporting System (TBIMS) from 2005 to 2020, we calculated the annual percentage change (APC) using the Joinpoint regression model.@*RESULTS@#From 2005 to 2020, a total of 16.2 million cases of PTB were reported in China, with an average notified incidence of 75.5 per 100,000 population. The age standardization rate (ASR) continued to decline from 116.9 (/100,000) in 2005 to 47.6 (/100,000) in 2020, with an average annual decrease of 5.6% [APC = -5.6, 95% confidence interval ( CI): -7.0 to -4.2]. The smallest decline occurred in 2011-2018 (APC = -3.4, 95% CI: -4.6 to -2.3) and the largest decrease in 2018-2020 (APC = -9.2, 95% CI: -16.4 to -1.3). From 2005 to 2020, the ASR in males (159.8 per 100,000 in 2005, 72.0 per 100,000 in 2020) was higher than that in females (62.2 per 100,000 in 2005, 32.3 per 100,000 in 2020), with an average annual decline of 6.0% for male and 4.9% for female. The average notified incidence was the highest among older adults (65 years and over) (182.3/100,000), with an average annual decline of 6.4%; children (0-14 years) were the lowest (4.8/100,000), with an average annual decline of 7.3%, but a significant increase of 3.3% between 2014 and 2020 (APC = 3.3, 95% CI: 1.4 to 5.2); middle-aged (35-64 years) decreased by 5.8%; and youth (15-34 years) decreased by an average annual rate of 4.2%. The average ASR in rural areas (81.3/100,000) is higher than that in urban areas (76.1/100,000). The average annual decline in rural areas was 4.5% and 6.3% in urban areas. South China had the highest average ASR (103.2/100,000), with an average annual decline of 5.9%, while North China had the lowest (56.5/100,000), with an average annual decline of 5.9%. The average ASR in the southwest was 95.3 (/100,000), with the smallest annual decline (APC = -4.5, 95% CI: -5.5 to -3.5); the average ASR in the Northwest China was 100.1 (/100,000), with the largest annual decline (APC = -6.4, 95% CI: -10.0 to -2.7); Central, Northeastern, and Eastern China declined by an average of 5.2%, 6.2%, and 6.1% per year, respectively.@*CONCLUSIONS@#From 2005 to 2020, the notified incidence of PTB in China continued to decline, falling by 55%. For high-risk groups such as males, older adults, high-burden areas in South, Southwest, and Northwest China, and rural regions, proactive screening should be strengthened to provide timely and effective anti-TB treatment and patient management services for confirmed cases. There is also a necessity to be vigilant about the upward trend of children in recent years, the specific reasons for which need to be further studied.

Clinical significance of loss of chromosome Y in patients with multiple myeloma / 中华检验医学杂志

Objective:To explore the risk stratification and prognostic significance of loss of chromosome Y (LOY) in patients with multiple myeloma (MM).Methods:The clinical data of 193 male patients with newly diagnosed MM admitted to Zhongshan Hospital of Fudan University from January 2018 to January 2020 were analyzed retrospectively and divided into a normal karyotype group(178) and a LOY karyotype group (15) according to the results of their primary conventional cytogenetics. Rank sum test, 2×2 chi-square test and independent sample t-test were used to compare laboratory findings, such as liver and kidney function, immunohistochemistry and cytogenetics, treatment efficacy and survival prognosis, between the two groups. The clinical prognostic significance of LOY was summarized through survival analysis and Cox regression. Results:Among the newly diagnosed male MM patients, 8%(15/178) were confirmed with LOY cases. The proportion of patients with Revised International Staging System(R-ISS) stage Ⅲ was significantly higher in the LOY group (8/15) than that in the normal karyotype group (40/178)(χ 2=7.052, P<0.01). A higher proportion of 1q21 amplification also occurred in the LOY group (10/13 vs 77/162)(χ 2=4.159, P<0.05). The proportion of complete response(CR)/stringent complete response(sCR) in the normal karyotype group after the fourth chemotherapy (63/171) was significantly higher than that in the LOY group (1/15)(χ 2=5.564, P<0.05). The proportion of progressive disease (PD) was lower in the normal karyotype group (16/171 vs 4/15) (χ 2=4.306, P<0.05). The 2-year progression-free survival (PFS) of MM patients for the LOY group was significantly shorter compared to that for the normal karyotype group ( Z=?3.201, P<0.01). Univariate survival analysis showed that PFS was significantly shorter in newly diagnosed MM patients with Creatinine(Cr)≥93 μmol/L, β 2-microglobulin (β 2-MG)≥4.0 mg/L, serum free light chain(sFLC)<0.06, bone marrow plasma cells (BMPC)≥30%, R-ISS stage Ⅲ, failure to achieve CR/sCR after the fourth chemotherapy, with LOY, 1q21 amplification, P53 deletion and t(4;14) ( P<0.05). Cox regression analysis showed that Cr≥93 μmol/L( HR=4.460, 95% CI 1.615-12.314, P=0.004), sFLC<0.06( HR=2.873, 95% CI 1.206-6.849, P=0.017), failure to achieve CR/sCR after the fourth chemotherapy( HR=3.522, 95% CI 1.437-8.634, P=0.006)and with LOY( HR=3.485, 95% CI 1.473-8.249, P=0.006)were independent risk factors for PFS in newly diagnosed MM patients. Conclusions:LOY is an independent risk factor for poor prognosis. It is important for the clinical outcome and prognosis of patients with newly diagnosed MM, and may become a novel clinical assessment indicator.

Laboratory and clinical characteristics of patients with different SF3B1 genotypes in myelodysplastic syndromes / 中华检验医学杂志

Objective:To analyze the distribution of different SF3B1 genotypes in patients with myelodysplastic syndromes (MDS) and its prognostic value.Methods:Totally, 377MDS patients who were initially diagnosed in the First Affiliated Hospital of Nanjing Medical University from January 2014 to January 2022 were included in the retrospective analysis.The patients were divided into three different groups according to mutation stcote of SF3B1, including 317 patients with SF3B1 wild type (SF3B1 WT) (214 males and 103 females, 63(49, 71) years old),39 patients with SF3B1 K700E mutation(SF3B1 K700E(17 males and 22 females, 65(52, 73)years old)) and 21 patients with SF3B1 non-K700E mutation(SF3B1 non-K700E)(13 males and 8 females, 67(63, 73) years old). MDS-related 20 gene mutations were detected using targeted sequencing technology; Survival curves were constructed by the Kaplan-Meier method; Cox proportional hazards model was established to evaluate different factors at diagnosis on survival by univariate and multivariate analyses.. Results:Compared with SF3B1 non-K700E patients, SF3B1 K700E patients had a higher median absolute neutrophil count ( P=0.002) and were likely to be in the low/int-1 International Prognostic Scoring System (IPSS) categories ( P=0.023). A 20-gene targeted sequencing analysis showed that, compared with SF3B1 WT patients, SF3B1 K700E patients were associated with lower frequency of ASXL1 and U2AF1 mutations ( P=0.018 and P=0.003); while compared with SF3B1 non-K700E patients, the frequency of ASXL1 mutation was significantly lower in SF3B1 K700E cases ( P=0.029). Patients with SF3B1 K700E had better overall survival (OS) in comparison with SF3B1 WT and SF3B1 non-K700E in MDS patients ( P<0.001 and P=0.045, respectively). In comparison with SF3B1 WT patients, SF3B1 MUT patients had more favorable OS and progression-free survival (PFS) in MDS without excess blasts ( P<0.001 and P<0.001, respectively), but no significant difference was found in MDS with excess blasts ( P>0.05). Compared with SF3B1 WT patients, SF3B1 K700E patients had superior OS and PFS in the int-1 IPSS category ( P=0.010 and P=0.013, respectively). By multivariable analysis, the presence of SF3B1 K700Ewas an independent predictor of superior OS ( HR=0.461,95% CI 0.262-0.811, P=0.007). Conclusion:SF3B1 K700E and SF3B1 non-K700E patients had significantly improved OS in comparison with SF3B1 WT MDS patients. Furthermore, SF3B1 K700E patients were associated with a better OS compared with SF3B1 non-K700E MDS patients. SF3B1 mutation could not overcome the poor prognostic effect of excess blasts, which highlights the importance of the SF3B1 mutation subtype in risk assessment of MDS without excess blasts.

Clinicopathological characteristics and prognosis of anorectal malignant melanoma / 中华普通外科杂志

Objective:To investigate the impact of the clinicopathological characteristics of anorectal malignant melanoma (ARMM) on the prognosis.Methods:The clinicopathological data of 40 ARMM patients undergoing surgery at the Department of Colorectal Surgery, Cancer Hospital, Chinese Academy of Medical Sciences from Apr 2012 to Apr 2022 were collected, and the impact of different clinicopathological factors and treatment modalities on the overall survival of ARMM patients was investigated using Kaplan-Meier survival analysis and multifactorial Cox proportional risk model analysis.Results:Among 40 ARMM patients , 16 were male and 24 were female. The median age of onset was 61 yr. The median follow-up period for all patients was 47 (25-69) months, with a median survival of 19 (15-23) months and 1-year and 3-year survival rates of 74.3% and 21.7%, respectively. There was no statistically significant difference in survival time between the two groups of patients receiving wide local excision and abdominoperineal resection( χ2=1.281, P=0.258). Univariate analysis showed that overall survival in patients with ARMM was related to tumour diameter, depth of infiltration, specimen margin and lymph node metastasis ( χ2=1.281, P=0.039; χ2=3.760, P=0.042; χ2=6.581, P=0.010; χ2=21.683, P<0.001), and multivariate analysis suggested that lymph node metastasis was an independent risk factor for overall survival in patients with ARMM. Conclusion:Tumour diameter, depth of infiltration, specimen margin and lymph node metastasis were important prognostic influences in ARMM, and lymph node metastasis was an independent risk factor for overall survival in ARMM patients.

Research progress on the ferroptosis role in liver injury induced by inorganic arsenic / 中华地方病学杂志

Inorganic arsenic (iAs) is a common carcinogen that exists in the environment. Liver, as the main target organ of arsenic metabolism, long-term exposure to iAs can ultimately lead to carcinogenesis through two stages: liver fibrosis and cirrhosis. Ferroptosis is a type of programmed cell death caused by the accumulation of iron dependent lipid peroxides that affects the normal function of mitochondria. It has been found that ferroptosis occurs during liver fibrosis. Liver fibrosis caused by iAs has been a global health problem for a long time, but so far there is no effective treatment. The discovery of ferroptosis provides a new way to solve this problem. Therefore, this article will review the research progress of the mechanism of liver injury caused by iAs and ferroptosis.

Screening of DNA methylation sites and construction of differential methylation profiles in human hepatic stellate cells fibrosis and autophagy induced by sodium arsenite / 中华地方病学杂志

Objective:To analyze DNA methylation sites related to fibrosis and autophagy in human hepatic stellate cells (LX-2 cells) induced by sodium arsenite (NaAsO 2), and to screen specific methylation genes related to fibrosis and autophagy. Methods:Genome-wide DNA detection was performed using Illumina Infinium Methylation EPIC BeadChips (850K methylation chip) to derive differential methylation sites in LX-2 cells (control group) and the fibrosis and autophagy models of LX-2 cells induced by NaAsO 2(low, medium and high dose groups: the final concentrations were 5, 10, 15 μmol/L NaAsO 2, respectively, after 48 h intervention). Gene ontology (GO) function enrichment analysis and Kyoto encyclopedia of genes and genomes (KEGG) signaling pathway enrichment analysis were used to explore gene function. Results:The model of cell fibrosis and autophagy was established successfully in high dose group. The results of 850K methylation chip detection showed that there were 25 817 significant different methylation sites between the high dose group and the control group, including 12 083 hypermethylation sites and 13 734 hypomethylation sites. GO function enrichment analysis showed that the molecular functions of differentially methylated genes mainly included protein binding, ion binding, catalytic activity, enzyme binding. KEGG signaling pathway enrichment analysis showed that the pathways involved in differentially methylated genes mainly included metabolic pathway, cancer pathway, phosphatidylinositol-3-kinase-protein kinase B (PI3K-Akt) signaling pathway, endocytosis, and mitogen activated protein kinase (MAPK) signaling pathway. In the promoter region, 11 and 29 differentially methylated genes related to fibrosis and autophagy were screened, respectively.Conclusions:A large number of differential methylation sites exist in the process of NaAsO 2 induced fibrosis and autophagy of LX-2 cells. Specific methylation genes related to fibrosis and autophagy are screened out.

Bear bile powder alleviates Parkinson's disease-like behavior in mice by inhibiting astrocyte-mediated neuroinflammation / 中国天然药物

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people. In particular, increasing evidence has showed that astrocyte-mediated neuroinflammation is involved in the pathogenesis of PD. As a precious traditional Chinese medicine, bear bile powder (BBP) has a long history of use in clinical practice. It has numerous activities, such as clearing heat, calming the liver wind and anti-inflammation, and also exhibits good therapeutic effect on convulsive epilepsy. However, whether BBP can prevent the development of PD has not been elucidated. Hence, this study was designed to explore the effect and mechanism of BBP on suppressing astrocyte-mediated neuroinflammation in a mouse model of PD. PD-like behavior was induced in the mice by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) (30 mg·kg-1) for five days, followed by BBP (50, 100, and 200 mg·kg-1) treatment daily for ten days. LPS stimulated rat C6 astrocytic cells were used as a cell model of neuroinflammation. THe results indicated that BBP treatment significantly ameliorated dyskinesia, increased the levels of tyrosine hydroxylase (TH) and inhibited astrocyte hyperactivation in the substantia nigra (SN) of PD mice. Furthermore, BBP decreased the protein levels of glial fibrillary acidic protein (GFAP), cyclooxygenase 2 (COX2) and inducible nitric oxide synthase (iNOS), and up-regulated the protein levels of takeda G protein-coupled receptor 5 (TGR5) in the SN. Moreover, BBP significantly activated TGR5 in a dose-dependent manner, and decreased the protein levels of GFAP, iNOS and COX2, as well as the mRNA levels of GFAP, iNOS, COX2, interleukin (IL) -1β, IL-6 and tumor necrosis factor-α (TNF-α) in LPS-stimulated C6 cells. Notably, BBP suppressed the phosphorylation of protein kinase B (AKT), inhibitor of NF-κB (IκBα) and nuclear factor-κB (NF-κB) proteins in vivo and in vitro. We also observed that TGR5 inhibitor triamterene attenuated the anti-neuroinflammatory effect of BBP on LPS-stimulated C6 cells. Taken together, BBP alleviates the progression of PD mice by suppressing astrocyte-mediated inflammation via TGR5.

Professor GAO Wei-bin's clinical experience of using electroacupuncture for dry eye / 中国针灸

The academic thoughts of professor GAO Wei-bin regarding the use of electroacupuncture in the treatment of dry eye are introduced. Professor GAO believes that the occurrence of dry eye is mainly related to the stagnation of qi and blood in the eye meridians, leading to inadequate nourishment of the eyes. The acupuncture treatment principle focuses on promoting blood circulation, clearing and benefiting the eye orifices. By integrating traditional acupuncture theory with modern neuroanatomy, the treatment approach centers on stimulating the lacrimal gland, emphasizing the importance of promoting, addressing symptoms as a priority, and considering both the root cause and symptoms.The precise acupoint selection is emphasized. Acupoints of periocular region, such as Taiyang (EX-HN 5) and Leixian point are selected along with Fengchi (GB 20) and Gongxue point to treat dry eye. Attention is also given to the use of electroacupuncture and the selection of its frequencies, emphasizing specific needling techniques based on the severity and classification of the disease.

Relationship between nutrient-related dietary pattern and mild cognitive impairment in middle-aged and elderly people in 15 provinces of China / 中华流行病学杂志

Objective: To explore the relationship between nutrient-related dietary pattern and mild cognitive impairment (MCI) in middle-aged and elderly people. Methods: A total of 6 444 middle-aged and elderly people aged ≥55 years were selected in 2018 China Health and Nutrition Survey. MCI was evaluated by Mini-Mental State Examination, and the intakes of various foods were obtained by consecutive 3-day 24-hour dietary survey and weighing method. The intakes of various nutrients and total dietary energy were calculated based on the food composition table. Demographic and social information, lifestyle and health status of the respondents were obtained through questionnaire survey and physical measurements. In this study, vitamin C, vitamin E, zinc, iron, copper and selenium were selected as dependent variables. Nutrient-related dietary patterns were extracted by reduced rank regression method, and the relationship between dietary patterns and MCI was analyzed by multivariate logistic regression model. Results: Six dietary patterns were extracted in this study, and dietary pattern 1 with the highest explanatory degree was selected for subsequent analysis. Dietary pattern 1 was characterized by higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products and plant oil. Multivariate logistic regression analysis showed that the risk of MCI was lower in Q4 dietary score group than in Q1 dietary score group (OR=0.69, 95%CI: 0.49-0.98) in the 55-64 age group. In people with sleep duration of 8 hours per day, the risk of MCI was reduced in Q2, Q3 and Q4 dietary score groups compared with the Q1 dietary score group, with OR values of 0.68 (95%CI: 0.51-0.92), 0.67 (95%CI: 0.49-0.92) and 0.65 (95%CI: 0.45-0.92), respectively. Interaction analysis showed that the risk for MCI increased in those aged 65-74 years and ≥75 years compared with those aged 55-64 years in Q1 dietary score group. However, the risk for MCI decreased in both age groups as dietary pattern scores increased. Compared with those with sleep duration less or more than 8 hours per day in Q1 dietary score group, those with sleep duration of 8 hours per day in Q2 and Q3 dietary score groups had a reduced risk for MCI. Conclusion: Dietary patterns with higher intakes of legume products, vegetables, fruits, nuts, pork, aquatic products, and plant oil are negatively associated with MCI in people aged 55-64 years and those who slept 8 hours per day, and may reduce the risk of MCI with aging.

Meta-Analysis of the Diagnostic Efficacy of the Luminex xTAG Respiratory Viral Panel FAST v2Assay for Respiratory Viral Infections

Purpose@#Acute respiratory viral infections pose significant morbidity and mortality, making it essential to diagnose respiratory viral infections rapidly. In this study, the diagnostic efficacy of the Luminex xTAG Respiratory Virus Panel (RVP) FAST v2 test was evaluated on respiratory viral infections. @*Materials and Methods@#Information was retrieved from electronic databases, including Embase, Web of Science, PubMed, and Cochrane Library, for systematic review. Studies that fulfilled predefined inclusion criteria were included. After the extraction of information, statistical software was utilized for quality evaluation, data analysis, and assessment of publication bias. @*Results@#Eighty groups in fourfold tables from nine articles were included to perform statistical analyses. Therein, the mean specificity and mean sensitivity of Luminex xTAG RVP FAST v2 test for the detection of respiratory viral infections were 0.99 (0.98–0.99) and 0.88 (0.87–0.90), respectively. Additionally, the negative and positive likelihood ratios were 0.14 (0.11–0.19) and 87.42 (61.88– 123.50), respectively. Moreover, the diagnostic odds ratio and area under the curve of summary receiver operating characteristic were 714.80 and 0.9886, respectively. @*Conclusion@#The Luminex xTAG RVP FAST v2 test could be a reliable and rapid diagnostic method for multiple respiratory viral infections.

Increasing the rate of timely completion of a rapid frozen-section pathological report using the PDCA cycle / 中国基层医药

Objective:To investigate the application value of the PDCA cycle in increasing the rate of timely completion of a rapid frozen-section pathological report.Methods:The basic data of 1 926 rapid frozen section pathological reports not managed by the PDCA cycle in the Department of Pathology, Zhoushan Hospital, during January to August 2019 were collected. The number of pathological reports completed within 30 minutes and the rate of timely completion of pathological reports were calculated and compared with those calculated based on 1 051 pathological reports managed by the PDCA cycle during September to December 2019.Results:After management by the PDCA cycle, the rate of timely completion of frozen-section pathological reports was significantly increased from (84.51 ± 3.61)% to (91.87 ± 1.37)% ( t = 3.86, P < 0.05). Conclusion:Application of the PDCA cycle to pathology management can help monitor the completion of pathological reports on frozen sections. This facilitates determination of reasonable intervention measures and thereby increases the rate of timely completion of pathological reports on frozen sections.

The Patatin-like Phospholipase Domain Containing Protein 7 (PNPLA7) Facilitates M2 Polarization of Macrophages Through a PPARγ-Dependent Mechanism / 中国生物化学与分子生物学报

Lysophosphatidylcholine (LPC) modulates the dynamic and integral process of macrophage polarization in immune responses, tissue inflammation and remodeling. Patatin-like phospholipase domain containing protein 7 (PNPLA7) was identified as an LPC-preferring lysophospholipase recently. However, the expression and role of PNPLA7 in macrophage polarization remained unknown. In the present study, PNPLA7 was found to be upregulated in the process of macrophage polarization toward an alternatively activated (M2) phenotype stimulated with interleukin 4 (IL-4) (P<0.05). We found that knockdown and overexpression of PNPLA1 decreased and increased the expression of M2 marker genes, including arginase 1 (Argl) and chitinase-like 3 (Ym\ ), respectively (P<0.05). Further studies showed that PNPLA7 regulated the expression of peroxisome proliferator activated receptor-γ (P P A R γ) at the mRNA and protein levels during M2 polarization (P < 0.05). However, the phosphorylation of signal transducer and activator of transcription 6 (STAT6) was not influenced by PNPLA7. These findings suggest that PNPLA7 favors macrophage anti-inflammatory M2 polarization through a PPAR

Study on anti-gastric cancer mechanism of Wisteria sinensis tumor based on network pharmacology, molecular docking technology and experimental verification / 中国药理学通报

To investigate the pharmacological mechanism of Wisteria sinensis tumor in the treatment of gastric cancer, using a network pharmacology and molecular docking approach, with verification of the results by experiments. Methods The main active components and corresponding targets of Wisteria sinensis tumor monocytogenes, as well as the disease targets of gastric cancer, were obtained through the network pharmacology database. The Venny 2.1.0 platform was used to take the intersection of drug and disease. The String database was used to construct target protein interaction(PPI)network for common targets, and Metascape database was used to analyze GO function enrichment KEGG pathway enrichment of related targets. The interactive network of "component-target-pathway" of Wisteria sinensis tumor on gastric cancer was constructed by Cytoscape3.7.2 software. The molecular docking of the key targets and active compunds was carried out by using Autodock Vina software. The effect of Wisteria sinensis tumor on gastric cancer was verified by in vitro cell tests. Results A total of 8 main active components, 290 drug targets and 251 gastric cancer-related targets were screened out. A total of 19 targets intersected between with drug and diseases. Seven pathways were involved in the treatment of gastric cancer by Wisteria sinensis tumor. The results of molecular docking showed that the main active components of Wisteria sinensis tumor had good binding ability with the key targets of gastric cancer. The results of in vitro experiments confirmed that, the formononetin from Wisteria sinensis tumor had certain activity on gastric cancer cells, and the formononetin could also induce apoptosis of gastric cancer SGC-7901 cells and increase the level of intracellular calcium ion. Conclusions This study preliminarily reveals the potential components and regulatory network of Wisteria sinensis tumor monocytogenes acting on gastric cancer clarified that Wisteria sinensis tumor monocytogenes has antitumor effect, and may be related to inducing apoptosis of gastric cancer SGC-7901 cells, and it provides references for the future research and clinical application.

A Case Series of Olfactory Dysfunction in Imported COVID-19 Patients: A 12-Month Follow-Up Study / 生物医学与环境科学（英文）

Objective@#The scientific community knows little about the long-term influence of coronavirus disease 2019 (COVID-19) on olfactory dysfunction (OD). With the COVID-19 pandemic ongoing worldwide, the risk of imported cases remains high. In China, it is necessary to understand OD in imported cases.@*Methods@#A prospective follow-up design was adopted. A total of 11 self-reported patients with COVID-19 and OD from Xi'an No. 8 Hospital were followed between August 19, 2021, and December 12, 2021. Demographics, clinical characteristics, laboratory and radiological findings, and treatment outcomes were analyzed at admission. We surveyed the patients via telephone for recurrence and sequelae at the 1-, 6-, and 12-month follow-up.@*Results@#Eleven patients with OD were enrolled; of these, 54.5% (6/11) had hyposmia and 45.5% (5/11) had anosmia. 63.6% (7/11) reported OD before or on the day of admission as their initial symptom; of these, 42.9% (3/7) described OD as the only symptom. All patients in the study received combined treatment with traditional Chinese medicine and Western medicine, and 72.7% (8/11) had partially or fully recovered at discharge. In terms of OD recovery at the 12-month follow-up, 45.5% (5/11) reported at least one sequela, 81.8% (9/11) had recovered completely, 18.2% (2/11) had recovered partially, and there were no recurrent cases.@*Conclusions@#Our data revealed that OD frequently presented as the initial or even the only symptom among imported cases. Most OD improvements occurred in the first 2 weeks after onset, and patients with COVID-19 and OD had favorable treatment outcomes during long-term follow-up. A better understanding of the pathogenesis and appropriate treatment of OD is needed to guide clinicians in the care of these patients.

The efficacy of eltrombopag plus cyclosporine A in patients with transfusion-dependent non-severe aplastic anemia: a retrospective study from single center / 中华内科杂志

The main purpose of our study was to evaluate the efficacy and safety of eltrombopag plus cyclosporine A (CsA) in transfusion-dependent non-severe aplastic anemia(TD-NSAA). The clinical characteristics of 13 TD-NSAA patients who received initial treatment of eltrombopag plus CsA from 2019 to 2021 were retrospectively analyzed. The 3-month overall hematological response (OR) rate was 12/13. Until the end of follow-up, 12 patients responded, among whom 2 patients reached complete response (CR) and 9 patients reached partial response (PR) and 1 with HR. Paroxysmal nocturnal hemoglobinuria (PNH) developed in one patient at 6 months after treatment. Five of thirteen patients reported mild adverse reactions, which were all manageable. Compared with historical data, the combination of eltrombopag with CsA is an effective regimen in patients with TD-NSAA.

Influence of road types on road traffic accidents in northern Guizhou Province, China / 中华创伤杂志(英文版)

PURPOSE@#The increasing number of deaths due to road traffic accidents (RTAs) has attracted global attention. However, the influence of road types is rarely considered in the study of RTAs. This study evaluates the influence of different road types in RTAs in northern Guizhou to provide a basis for the formulation of evidence-based policies and measures.@*METHODS@#We obtained the data from the Zunyi Traffic Management Data Platform for the years 2009-2018. The mortality rates of RTAs were calculated. Descriptive methods and Chi-square tests were used to analyze the characteristics of road traffic collisions on different road types. We also examined the associations between the mortality rate per 10,000 vehicles and the growth of per capital gross domestic product (GDP) with Spearman's rank correlation analysis. According to the passing volume and the infrastructure, we defined different types of roads, like administrative road, functional road, general urban road and urban expressway.@*RESULTS@#In 2012, the traffic mortality rate of administrative roads was 8.9 per 100,000 people, and the mortality rate of functional roads was 7.4 per 100,000 people, which decreased in 2018 to 6.1 deaths per 100,000 people and 5.2 deaths per 100,000 people, respectively. The mortality rate per 10,000 vehicles reached the highest level in 2011 (28.8 per 10,000 vehicles and 22.5 per 10,000 vehicles on administrative and functional roads, respectively). The death rate of county roads was the highest among administrative roads (χ@*CONCLUSION@#Although our research shows that RTAs in northern Guizhou have steadily declined in recent years, the range of decline is relatively small. Many measures and sustainable efforts are needed to control road traffic death and accelerate the progress in road traffic safety in northern Guizhou.

Evaluation of different platform detection of cfDNA tumor mutation in patients with NSCLC / 中华检验医学杂志

Objective:To verify the performance of the next-generation sequencing (NGS) platform and evaluate the application of NGS, droplet digital PCR (ddPCR) and super amplification refractory mutation system (super-ARMS) in the detection of circulating free DNA (cfDNA) mutations in patients with non-small-cell lung cancer (NSCLC).Methods:A total of 75 patients with NSCLC in the respiratory department of Zhongshan Hospital Affiliated to Fudan University were enrolled. The standards, cfDNA from 25 patients with newly diagnosed and untreated NSCLC, and self-made mixed samples mixed with hemoglobin (1 000 mg /dl), bilirubin (500 mg/l), fat emulsion (2%), enterococcus gDNA and Escherichia coli gDNA were used to verify the blank limit, analytical sensitivity, precision, accuracy and specificity of NGS platform. The cfDNA mutations of 75 NSCLC patients were detected by ddPCR and NGS, and the mutation positive rates of the two platforms were compared. The linear relationship between the two platforms was compared by Pearson correlation test. 12 patients were selected by simple random sampling for the detection of plasma super-ARMS platform. The performance of three platforms in the detection of plasma cfDNA mutation in patients with NSCLC was compared.Results:The blank limit of NGS platform was set to 0.00%, the analytical sensitivity was 0.2%, the intra-assay precision and inter-assay precision were 100%. The test results were not affected by endogenous hemoglobin, bilirubin or fat emulsion in plasma or exogenous DNA interference, and the analysis specificity was good. The mutation positive rates of plasma cfDNA in 75 NSCLC patients detected by ddPCR and NGS were 61.33% and 60.00%, respectively. The complete coincidence rate was 89.33%, which suggests there was a positive correlation between the mutation abundance of NGS and ddPCR ( r=0.984, P=0.001). Among the plasma of 12 NSCLC patients, the results of NGS, ddPCR and super-ARMS were completely consistent in 7 cases, including 2 wild-types and 5 mutants. Conclusion:The NGS platform was verified to be useful for cfDNA mutation detection in patients with NSCLC. The ddPCR, NGS and super-ARMS have their own advantages in detecting cfDNA mutations in patients with NSCLC.

The level and significance of CD4 + CD25 + Foxp3 + Treg in peripheral blood of patients with type 2 diabetic peripheral neuropathy / 中国医师杂志

Objective:To investigate the level and significance of CD4 + CD25 + Foxp3 + Treg in peripheral blood of patients with type 2 diabetes mellitus (T2DM) peripheral neuropathy. Methods:160 patients with T2DM (T2DM group) treated in Yancheng First People's Hospital from January 2018 to March 2019 were selected, including 54 patients with peripheral neuropathy and 106 patients without peripheral neuropathy. At the same time, 160 healthy people were selected as the control group to detect the levels of CD4 + CD25 + Foxp3 + Treg and 25-(OH)D 3 in peripheral blood. Pearson correlation analysis was used to analyze the correlation between CD4 + CD25 + Foxp3 + Treg in peripheral blood and other indexes. The receiver operating characteristic (ROC) value curve was used to analyze the predictive value of CD4 + CD25 + Foxp3 + Treg in peripheral blood of type 2 diabetic peripheral neuropathy. Results:The ratio of CD4 + CD25 + Foxp3 + Treg in T2DM group was (7.82±1.03)%, which was significantly lower than that in control group [(15.53±3.82)%, P<0.05]; The duration of T2DM patients with peripheral neuropathy was (7.71±1.18)years, which was significantly longer than that without peripheral neuropathy ( P<0.05), while the proportions of 25-(OH)D 3 and CD4 + CD25 + Foxp3 + Treg were (49.88±12.27)mmol/L and (5.88±1.20)% respectively, which were significantly lower than that without peripheral neuropathy ( P<0.05); Patients with peripheral neuropathy in group T2DM had significantly higher Michigan Diabetic Neuropathy Scores (MDNS) than that in patients without peripheral neuropathy [(14.82±2.01) vs (4.41±0.43), P<0.05]. The CD4 + CD25 + Foxp3 + Treg was positively correlated with 25-(OH)D 3 ( r=0.367, P<0.05), and negatively correlated with MDNS ( r=-0.398, P<0.05); the CD4 + CD25 + Foxp3 + Treg predicted that the area under the ROC curve of T2DM patients with peripheral neuropathy was 0.822, the cut-off value was 6.50%, and the sensitivity and specificity were 80.00% and 72.00% respectively. Conclusions:The level of CD4 + CD25 + Foxp3 + Treg in peripheral blood of T2DM patients decreased, which may play a role in the occurrence and development of peripheral neuropathy.