Advances on effects and mechanisms of PM2.5 on occurrence and development of kidney diseases / 环境与职业医学

Air pollution is a serious global public health problem. Air pollutants, especially fine particulate matter (PM2.5), are associated with increased risks of various diseases. In recent years, studies have confirmed that PM2.5 is closely related to chronic kidney disease, secondary kidney disease, and end-stage renal disease. This review summarized the effects of PM2.5 and its components on kidney diseases, and the potential mechanism of kidney injury induced by PM2.5 exposure from the aspects of inflammatory injury and oxidative stress, renal hemodynamic changes, and DNA damage and methylation, aiming to provide an insight for further mechanism research and the prevention and control of air pollution-induced kidney damage.

Investigation and analysis of Chinese public 's cognition for clinical research / 中南大学学报(医学版)

OBJECTIVES@#Clinical research plays a vital role in disease research and population health. The public is the main source of clinical research volunteers. Understanding the public's cognition of clinical research plays a decisive role in the development of clinical research. This study aims to understand the Chinese public's cognition for clinical research and the influencing factors.@*METHODS@#The questionnaire based on Chinese-translated Public Awareness of Research for Therapeutic Advancements through Knowledge and Empowerment (PARTAKE) was used to investigate the public's cognition for clinical research.@*RESULTS@#Of the 2 513 valid respondents, 91.84% had heard of "clinical research", 91.76% of the respondents believed that clinical research was beneficial to society, 65.90% were willing to participate in clinical research, 87.50% believed that confidentiality was a very important thing, 73.70% believed that their personal information had been protected when participating in clinical research, and, 46.40% did not know whether volunteers participating in clinical research could receive adequate compensation. Educational levels, employment status, and annual income impacted in public perceptions of willingness to participate in clinical research, especially in privacy protection, informed consent, whether clinical research is intended for society, compensation for clinical research, and safety of clinical research (all P<0.01).@*CONCLUSIONS@#The Chinese public's cognition level for clinical research is acceptable, but there is still a lot of room for improvement in privacy protection, informed consent, and compensation. By designing a reasonable knowledge training program for clinical research and using the multimedia, improving access to the relevant knowledge, more public will know about clinical research recruitment information, which is of great significance for the development of clinical research in China.

Knockout of farnesoid X receptor gene aggravates cisplatin-induced kidney injury / 中南大学学报(医学版)

OBJECTIVES@#Farnesoid X receptor (FXR) is a member of the nuclear receptor superfamily of ligand activated transcription factors and belongs to bile acid receptor. Studies have shown that the expression of FXR in renal tissue can reduce renal injury via regulation of glucose and lipid metabolism, inhibition of inflammatory response, reduction of oxidative stress and renal fibrosis. However, it is unclear whether FXR is involved in autophagy in renal diseases. This study aims to investigate the role of FXR in cisplatin-induced acute renal injury and whether its mechanism is related to autophagy regulation.@*METHODS@#Twelve male WT or FXR-KO mice at 12 weeks were randomly divided into a WT group, a WT+cisplatin group, a FXR-KO group, and a FXR-KO+cisplatin group, with 6 mice in each group. The WT+cisplatin group and the FXR-KO+cisplatin group were intraperitoneally injected with cisplatin (20 mg/kg), and the WT group and the FXR-KO group were intraperitoneally injected with equal volume of cisplatin solvent. Seventy-two hours later, the mice were killed and blood and renal tissue samples were collected. The levels of SCr and BUN were detected by immunoturbidimetry. After the staining, the pathological changes of renal tissue were observed under optical microscope. The protein levels of LC3 and p62 were detected by Western blotting and immunohistochemistry. The clearance of damaged mitochondria and the accumulation of lysosomal substrate were observed under electron microscope. The apoptosis of renal tubular epithelial cells was detected by TUNEL.@*RESULTS@#Compared with the WT group or the FXR-KO group, both SCr and BUN levels in the WT+cisplatin group or the FXR-KO+cisplatin group were significantly increased (P<0.01 or P<0.001), and SCr and BUN levels in the FXR-KO+cisplatin group were significantly higher than those in the WT+cisplatin group (both P<0.05). Under the light microscope, there were no obvious pathological changes in the renal tissue of mice in the WT group and the FXR-KO group. Both the WT+cisplatin group and the FXR-KO+cisplatin group had vacuolar or granular degeneration of renal tubular epithelial cells, flat cells, lumen expansion, brush edge falling off, and even exposed basement membrane and tubular formation. The scores of renal tubular injury in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the score in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05). Under the transmission electron microscope, the mitochondria of mouse tubular epithelial cell in the WT+cisplatin group and the FXR-KO+cisplatin group was swollen, round, vacuolated, cristae broken or disappeared; the lysosome was uneven and high-density clumps, and the change was more obvious in the FXR-KO+cisplatin group. Western blotting showed that the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased in the WT+cisplatin group compared with the WT group and the FXR-KO+cisplatin group compared with FXR-KO group (P<0.05 or P<0.01); compared with the FXR-KO group, the ratio of LC3-II to LC3-I was decreased and the expression of p62 was increased significantly in the FXR-KO+cisplatin group (both P<0.05). Immunohistochemistry results showed that the expression of total LC3 and p62 in renal cortex of the WT+cisplatin group and the FXR-KO+cisplatin group was increased significantly, especially in the FXR-KO+cisplatin group. TUNEL results showed that the mice in the WT group and the FXR-KO group had negative staining or only a few apoptotic tubular epithelial cells, and the number of apoptotic cells in the WT+cisplatin group and the FXR-KO+cisplatin group were increased. The apoptosis rates of renal tubular epithelial cells in the WT+cisplatin group and the FXR-KO+cisplatin group were significantly higher than those in the WT group and the FXR-KO group, respectively (both P<0.001), and the apoptosis rate in the FXR-KO+cisplatin group was significantly higher than that in the WT+cisplatin group (P<0.05).@*CONCLUSIONS@#Knockout of FXR gene aggravates cisplatin induced acute renal injury, and its mechanism may be related to inhibiting autophagy and promoting apoptosis.

Drinking behavior among government employees in Changsha and its influencing factors / 中南大学学报(医学版)

OBJECTIVES@#To analyze the prevalence and influencing factors for drinking behavior and heavy drinking among government employees in Changsha and provide a basis for carrying out interventions for drinking behaviors and formulating public health promotion plans for government employees.@*METHODS@#Government employees were recruited consecutively from the Health Management Center of a general hospital in Changsha between December 2017 and December 2018. Information on sociodemograpic characteristics, drinking behaviors, life events, and psychosocial characteristics was collected using a standard set of questionnaire. Drinking behavior was defined as drinking once or more per week for the past 12 months. The differences in drinking rates and excessive drinking rates among groups with different characteristics were compared. Multivariate analysis was performed to analyze the associated factors of drinking behaviors and heavy drinking for government employees.@*RESULTS@#A total of 6 190 people completed this investigation. The overall drinking rate of government employees in Changsha was 21.9%, and the rate of drinking was higher in males than that in females (44.7% vs 4.0%, @*CONCLUSIONS@#The drinking and heavy drinking rates of government employees are high in Changsha. Marital status, physical exercise, and frequency of social intercourse are the common influencing factors of male drinking behavior and female drinking behavior. The life events stimulation is the influencing factor of heavy drinking.

Progress in the study on innate immunity and non-alcohol fatty liver disease / 中南大学学报(医学版)

The incidence of non-alcohol fatty liver disease (NAFLD) is increasing year by year, and the relevant cardiovascular events have become a major problem in chronic diseases management. The activation of innate immunity is closely related to the development of NAFLD. The immune cells include Kupffer cells, neutrophils, dendritic cells, and natural killer T cells, which acts through the activation of innate immunity-related signals mediated by pattern recognition receptors.

Clinical trials during post-COVID pandemic: An interim review / 中国临床药理学与治疗学

China has experienced an unprecedented pandemic of corona virus disease 2019 (COVID-19) in 2020. In the background of serious public health events, clinical trials in most Chinese regions have experienced a series of tough periods such as suspension of admission and protocol violation. With resumption of work and production around the country, China has entered the post-COVID pandemic period. This article analyzes how clinical trial institutions resume professional work, and advocates to continue to strengthen the countermeasures and experience during the outbreak, such as the design of subject-centered clinical trial, comprehensively promotion of information technology, construction of professional clinical research centers and clinical research support teams, respecting evidence-based evidence and real-world evidence, optimal ethical committee review modes, and standardization of agency disaster recovery plan. These experiences should be applied to future clinical researches.

Caroli syndrome in full brothers caused by new mutation of PKHD1 gene / 中华普通外科杂志

Objective To explore the new gene mutation and clinical manifestations of Caroli syndrome in 2 blood brother cases.Methods The clinical data of the 2 brothers with clinical diagnosis of Caroli syndrome were analyzed,and the related genes were detected by second-generation sequencing technology.Results The PKHD1 gene of both brothers had the mutation of c.5059A ＞ T (exon32).c.4358 (exon 32)delC shift mutation,neither of which has been reported in OMIM database.Conclusion After analysis,c.4358 (exon32) delC and c.5059A ＞ T(exon32) may be the new pathogenic mutation of this disease,with the same mutant genotype but completely different phenotype.

Caroli syndrome in full brothers caused by new mutation of PKHD1 gene / 中华普通外科杂志

Objective@#To explore the new gene mutation and clinical manifestations of Caroli syndrome in 2 blood brother cases.@*Methods@#The clinical data of the 2 brothers with clinical diagnosis of Caroli syndrome were analyzed, and the related genes were detected by second-generation sequencing technology.@*Results@#The PKHD1 gene of both brothers had the mutation of c. 5059A>T(exon32). c. 4358(exon 32)delC shift mutation, neither of which has been reported in OMIM database.@*Conclusion@#After analysis, c. 4358(exon32) delC and c. 5059A>T(exon32) may be the new pathogenic mutation of this disease, with the same mutant genotype but completely different phenotype.

Experimental Study on the Anti-hyperuricemia Effect of Different Extracts of Tongkat Ali / 中国药师

Objective:To study the effects of various extracts of Tongkat Ali on uric acid excretion and renal function in rats with hyperuricemia. Methods:Totally 60 male Wistar rats were equally divided into the blank group,the model group,the positive control group,chloroform group,ethyl acetate group and n-butanol group. The rats were fed with yeast extract,adenine and potassium oxonate to make the model of hyperuricemia. After the animal model was made successfully,the other groups continued to give the modeling a-gent except for the blank group,and the other groups were given the corresponding medicine except for the model group after giving the modeling agent for one hour. After the model agent was given for 14 days,the levels of uric acid(UA),urea nitrogen(UN) and cre-atinine (Cr) in serum and urine and the activity of xanthine oxidase (XOD) in serum and liver were measured. Results: Compared with those in the model group,the levels of uric acid in chloroform group and n-butanol group were significantly lower than those in the model group (P<0.05),besides,the levels of uric acid and creatinine in urine in chloroform group and n-butanol group significantly increased (P<0.05). Compared with that in the model group,the XOD activity of chloroform group and n-butanol group significantly decreased (P<0.01). Compared with those in the positive control group,the levels of UA,Cr and UN in serum and urine and the ac-tivity of XOD in serum and liver in chloroform group, ethyl acetate group and n-butanol group had no significant differences (P >0.05). The levels of UA,Cr and UN in serum and urine and the activity of XOD in serum and liver in chloroform group,ethyl acetate group and n-butanol group had no significant differences (P>0.05). Conclusion: The chloroform extract and n-butanol extract in Tongkat Ali can reduce the serum level of uric acid in rats with hyperuricemia induced by adenine, yeast extract and potassium ox-onate,and the function may be related with the activity inhibition of xanthine oxidase.

210Po distribution after high temperature processes in coal-fired power plants.

In this paper, the distribution of 210Po after high temperature processes in six units of coal-fired power plants (CFPs) were evaluated. The coal, bottom ashes, fly ashes from electrostatic precipitators (ESP), and flue gases from stacks were sampled from four CFPs and analyzed for 210Po contents. The results showed that 210Po was mainly captured by the ESP, with little left in the bottom ash, and a small fraction of 210Po was directly discharged into the environment through the stacks, accounting for 0.06%-0.6%, which was consistent with the reported data. It was also found that part of the 210Po could not be accounted for in the mass balance analysis for the whole combustion process in CFPs, which was also in line with the reported data. The results obtained in this study provided essential basic data for environmental radiological risk analysis for CFPs.

Study on the Toxicity of Jianpi Shengxue Granule on Perinatal Rats / 中国药房

OBJECTIVE:To investigate the toxicity effect of Jianpi shengxue granule on perinatal rats. METHODS:Based on body mass,pregnant rats were randomly divided into negative control group and Jianpi shengxue granule low-dose,medium-dose, high-dose groups(0.77,2.31,6.93 g/kg),21 in each group,and intragastrically given relevant medicines from the 15th d of preg-nancy until 21st d after delivery,once a day. Effects of Jianpi shengxue granule on general toxicity and fertility of maternal rats were observed,as well as the effects on athletic ability,learning and memory ability,fertility of F1 offspring and early viability of F2 offspring. RESULTS:In terms of toxicity effect on maternal rats,compared with control group,the days of pregnancy in Jianpi shengxue granule high-dose group was significantly prolonged(P0.05);there was no obvious effect on the indexes of offspring in Jianpi shengxue granule medium-dose,low-dose groups. CONCLUSIONS:The no toxic dose of Jianpi shengxue granule in maternal and offspring rats is 2.31 g/kg.

Pre-clinical characterization of 4SC-202, a novel class I HDAC inhibitor, against colorectal cancer cells.

Histone deacetylase (HDAC) overactivity in colorectal cancer (CRC) promotes cancer progression. In the current study, we showed that 4SC-202, a novel class I HDAC inhibitor (HDACi), potently inhibited survival and proliferation of primary human colon cancer cells and established CRC lines (HT-29, HCT-116, HT-15, and DLD-1). Yet, the same 4SC-202 treatment was non-cytotoxic to colon epithelial cells where HDAC-1/-2 expressions were extremely low. 4SC-202 provoked apoptosis activation in CRC cells, while caspase inhibitors (z-VAD-CHO and z-DVED-CHO) significantly alleviated 4SC-202-exerted cytotoxicity in CRC cells. Meanwhile, 4SC-202 induced dramatic G2-M arrest in CRC cells. Further studies showed that AKT activation might be an important resistance factor of 4SC-202. 4SC-202-induced cytotoxicity was dramatically potentiated with serum starvation, AKT inhibition (by perifosine or MK-2206), or AKT1-shRNA knockdown in CRC cells. On the other hand, exogenous expression of constitutively active AKT1 (CA-AKT1) decreased the sensitivity by 4SC-202 in HT-29 cells. Notably, 4SC-202, at a low concentration, enhanced oxaliplatin-induced in vitro anti-CRC activity. In vivo, we showed that oral gavage of 4SC-202 inhibited HT-29 xenograft growth in nude mice, and when combined with oxaliplatin, its activity was further strengthened. Together, these pre-clinical results indicate that 4SC-202 may be further investigated as a valuable anti-CRC agent/chemo-adjuvant.

Research progress in environmental pharmacology / 中国药理学与毒理学杂志

In recent years,researches on drugs concentrated in the ecosystem have become a hot topic. Environmental pharmacology is a new subject studying the source and fate of drugs in the environment. It is found that a lot of pharmaceuticals and pharmaceutically active compounds are released into the environment by the pharmaceutical industry,hospitals and agricultured activities. Drugs in the environment not only affect the ecosystem,which leads to bacterial resistance,but also affect the balance of flora in the biofilm. Furthermore,such drugs may induce epigenetic changes, which may leave to the body vulnerable to diseases. The enrichment of endocrine disruptors can inter?fere with the growth and function of the human reproductive system. China is becoming concerned about environmental drugs. The development of environmental pharmacology can help clarify the interac?tions between drugs and the environment while contributing to public health and food safety in China.

Study on Tonifying Qi and Producing Blood Mechanism of Jianpi Shengxue Tablets / 中国药师

Objective:To study the tonifying Qi and producing blood mechanism of Jianpi Shengxue tablets. Methods: SD rats were randomly divided into the normal group,FeSO4group, and low, medium and high dosage groups(0.65,1.3,2.6 g·kg-1). All the groups except the normal group received low iron diet,to induce anemia. After the two-week intragastric administration, real-time PCR was carried out to identify the changes of Hepcidin mRNA expression, while western blot was applied to test the changes of DMT-1 protein expression. Results:The medium and high dosage groups could significantly increase the DMT-1 expression compared with the normal group,while FeSO4 could reduced the DMT-1 expression. The Hepcidin expression in liver was increased along with the in-crease of the dosage. Conclusion:The Chinese medicine ingredients in Jianpi Shengxue tablets is beneficial to the expression of DMT-1 protein and the expression of Hepcidin mRNA in liver, which can finally improve the iron supply in the body.

Study on the Differences of Pregnancy Informs between Chinese and Foreign Informed Consent Form in Drug Clinical Trial / 中国医学伦理学

Objective:To explore and discuss the differences of pregnancy contents and inform formats in in-formed consent form ( ICF) for the drug clinical trial between China and foreign countries. Methods:We collected Chinese and foreign ICFs for drug clinical trial that had been audited by the Ethics Committee of the third Xiangya Hospital for the past five years. Based on the relevant domestic and foreign law, we concluded the element stand-ards and inform formats about pregnancy inform. By analyzing the integrity of the whole elements, the inform rate of every element and the using rate of every inform format, we compared the differences of pregnancy contents and in-form formats between Chinese ICFs and foreign ICFs. Results:The total number of ICFs was 177 in this study, in-cluding 107 Chinese ICFs and 70 foreign ICFs. The integrity rate of pregnancy in Chinese ICFs was statistically lower than them in foreign ICFs (19% vs. 56%, P=0. 000). Compared with foreign ICFs, the low informed ele-ments were the study of the pregnancy risk (32% vs. 73%, P=0. 000), the pregnancy test during the following-up period (33% vs. 56%, P=0. 002) and the measurements for contraception (22% vs. 53%, P=0. 000). Conclusion:The integrity level of pregnancy content in Chinese ICFs was lower than that of the foreign ICFs. And the three elements including pregnancy risk study, pregnancy test during the following-up period and measure-ments for contraception was obviously defected. Pregnancy informing forms of informed consent in China was inferi-or to abroad.

Effects of Common Percutaneous Enhancers on Transdermal Permeability of Cetirizine Hydrochloride / 中国药房

OBJECTIVE:To study the effects of common percutaneous enhancers on transdermal permeability of cetirizine hy-drochloride(CET). METHODS:Using pH 7.4 phosphate buffer as receiving solution,accumulative permeation rate as index,mod-ified Franz diffusion cell was used to investigate the effects of common percutaneous enhancers on transdermal permeability of CET in skin of abdomen isolated from mice,such as azone (0.06%-2.5%),oleic acid (0.5%-10%),1,3-propanediol (0.5%-10%),propanetriol(0.5%-5%). RESULTS:1,3- propanediol had no improvement effect on the permeability of CET. 24 h accu-mulative permeation amount of CET in 0.06% azone,0.5% oleic acid and 1% propanetriol were the highest among same types, being 227.94,85.25 and 215.15 μg/cm2,respectively. CONCLUSIONS:Of four percutaneous enhancers,the transdermal enhanc-ing efficiencies from high to low are azone>glycerol>oleic acid>1,3-propanediol. Azone and glycerol have the conspicuous pene-tration enhancing effects.

The prevention of deep venous thrombosis in pregnant women by a new nursing model / 中国基层医药

Objective To observe the preventive effect of the new nursing mode on the formation of deep venous thrombosis(DVT)in pregnant women with high risk factors.Methods 186 pregnant women who had high risk factors were selected,by using digital table method they were randomly divided into control group(93 cases)and observation group(93 cases).The control group was treated with routine nursing,the observation group was given the new nursing mode on the basis of routine nursing.The postpartum 2 weeks of lower limb swelling,pain,lower extremity deep vein thrombosis formation of incidence,and the nursing satisfaction were compared between the two groups. Results 2 weeks postpartum,the incidence rates of lower limb pain occurrence,lower extremity deep vein thrombosis in the observation group were 8.6%,2.1%,which in the control group were 20.4%,9.7%,there were statistically significant differences between the two groups(χ2 =4.56,4.82,all P <0.05).The satisfaction of the observation group was 95.6%,which of the control group was 81.7%,the difference between the two groups was statistically sig-nificant(χ2 =5.27,P <0.01).Conclusion The new nursing model used in pregnant women with high risk factors can effectively prevent the occurrence of DVT,reduce the incidence of DVT,improve the satisfaction of nursing.

Study on the Optimization of Matrix Formula of Lanlian Ertong Qingre Cataplasm / 中国药房

OBJECTIVE:To optimize the matrix formula of Lanlian ertong qingre cataplasm. METHODS:Taking adhesion force,peel strength and sensory description as index,the ratio of matrix framework material(sodium polyacrylate-gan hydroxyl alu-minum-tartaric acid-glycerin) was optimized with orthogonal test. The single factor test was adopted to select adhesive and filler;the amount of penetrating agent azone was screened using the in vitro penetration amount of phillyrin. RESULTS:The best matrix ratio of Lanlian ertong qingre cataplasm was sodium polyacrylate-gan hydroxyl aluminum-tartaric acid-glycerin(4.0:0.8:0.4:15);PVP K-90 was used as adhesive,and bolus alba as filler;penetration enhancers azone accounted for 2.0%. Validation test showed, prepared cataplasm had good appearance,could stick on the 5th or the 6th ball;it's peel strength was 7.5 N;all RSDs of score were lower than 4%(n=3). CONCLUSIONS:The optimized matrix formula of Lanlian ertong qingre cataplasm is simple,stable and good in molding.

Enhancement of phagocytosis and cytotoxicity in macrophages by tumor-derived IL-18 stimulation.

Inoculation of mice with the murine NFSA cell line caused the formation of large tumors with necrotic tumor cores. FACS analysis revealed accumulations of CD11b(+) cells in the tumors. Microarray analysis indicated that the NFSA cells expressed a high level of the pro-inflammatory factor interleukin-18 (il-18), which is known to play a critical role in macrophages. However, little is known about the physiological function of IL-18-stimulated macrophages. Here, we provide direct evidence that IL-18 enhances the phagocytosis of RAW264 cells and peritoneal macrophages, accompanied by the increased expression of tumor necrosis factor (tnf-α), interleukin-6 (il-6) and inducible nitric oxide synthase (Nos2). IL-18-stimulated RAW264 cells showed an enhanced cytotoxicity to endothelial F-2 cells via direct cell-to-cell interaction and the secretion of soluble mediators. Taken together, our results demonstrate that tumor-derived IL-18 plays an important role in the phagocytosis of macrophages and that IL-18-stimulated macrophages may damage tumor endothelial cells.

miR-370 is stage-specifically expressed during mouse embryonic development and regulates Dnmt3a.

MicroRNAs (miRNAs) are small non-coding RNAs that participate in a large variety of biological processes. In this paper, the spatiotemporal expression pattern of miR-370 was characterized during mouse embryonic development, and was found to be stage- and tissue-specifically expressed. In addition, through luciferase reporter assays and western blot analyses, DNA methyltransferase 3A (Dnmt3a) was identified as a directly regulated target of miR-370. Altogether, our results indicate that miR-370 may play important roles in the morphogenesis of diverse organs, especially brain and adrenal glands, by mediating Dnmt3a expression during mouse development.