Clinical application and pharmacokinetic study of nanocarriers in drug delivery system / 药学学报

Nanotechnology has shown obvious advantages in the field of medical treatment and diagnosis. Through the encapsulation of nano carriers, drugs not only enhance the therapeutic effect and reduce toxic and side effects, but also become intelligent responsive targeted drug systems through the modification on the surface of nano carriers. However, due to the obstacles in relevant basic research, production conditions, cost, clinical trials, and the lack of pharmacokinetic research on various drug loading systems, few nano systems have been used in therapy. In order to solve the above problems, this paper reviewed and analyzed the research progress of nano carriers in drug delivery, including their auxiliary role and characteristics, types and functions, pharmacokinetics, application prospects and challenges.

Research strategies and applications of functional metabolomics in anti-depressive mechanisms of traditional Chinese medicine / 药学学报

Depression is a common emotional disorder that seriously affects people's life and health all over the world. The pathogenesis of depression is complex, and traditional Chinese medicine (TCM) for antidepressants has a good therapeutic effect because of its multi-component, multi-pathway, and multi-target action mode. At present, the anti-depressive mechanism of TCM has not been fully clarified, but it is clear that depression is closely related to metabolic health. Therefore, in order to further explore the anti-depressive mechanism of TCM, this paper proposes research strategies on the anti-depressive mechanism of TCM based on functional metabolomics from the perspective of metabolism, the potential biomarkers of depression are analyzed with the help of multi-omics combined analysis technology, and the functional molecules of TCM for antidepressant are studied. Molecular biology techniques are used to accurately capture the molecular interactions between biomarkers of depression and functional compounds, which identify effective drug targets and further elucidate the biochemical functions and related mechanisms involved in depression metabolic disorders. This paper systematically reviews the research strategies and applications of functional metabolomics in the anti-depressive mechanisms of TCM, expounds on the core value of functional metabolomics, and summarizes the current research status and hot issues of TCM for antidepressants in recent years, providing new methods and new ideas for the study of mechanisms of TCM with the help of functional metabolomics.

Restructuring Trade: Circulation of Medicinal Materials in East Asia in the 18th Century / 의사학

In the 18th century, the trade of medicinal materials in East Asia showed a trend of rapid development, and by the second half of the 18th century, it became the largest commodity category in East Asia's international trade. The growth of medicinal material trade during this period was not a simple trade issue, but was closely related to a series of changes in economic fields, such as the market network, trade balance and production. The changes in the international trade environment from the 17th to the 19th centuries greatly increased the demand for medicinal materials. It also affected the production of medicinal materials. The medicinal material industries in East Asian countries were characterised by specialisation and marketisation, and provided the market with abundant and high-quality medicinal materials. In turn, the development of the medicinal material industry promoted international trade, making medicinal materials the largest traded commodity in East Asia. In the 18th century, the development of medicinal material trade promoted the recalibration of international trade, and changed the commodity structure of East Asian trade. It is a result of the transformation of international trade and economic relations, and an important participant in the development of East Asian economy. Trade of medicinal materials in the 18th century expanded the market network and formed a positive interaction between trade and production, and reshaped the international trade structure of East Asia.

Evaluation and management of neonatal anemia and blood transfusion / 中国小儿急救医学

Anemia and blood transfusion are common clinical problems in newborns, especially premature infants.What are the definition and influencing factors of neonatal anemia? What is the difference between anemia in preterm infants and full-term infants? What are the changes of pathophysiology and their effects on tissues and cells during neonatal anemia? What are the prevention strategies and treatment methods of neonatal anemia? Is there a uniform hemoglobin threshold for neonatal transfusion of red blood cells? What are the risks of blood transfusion? In view of the above problems, this review proposed that the definition of anemia should consider the effects of gestational age, day age, intrauterine or postnatal development status(such as growth retardation), nutrition and so on. "Physiological anemia of infancy" can occur in healthy term infants; "anemia of prematurity" can not be considered as a physiologic and benign event, which is related to the low level of endogenous erythropoietin and iatrogenic blood loss.It is emphasized that neonatal anemia(especially premature infants) is preventable and can be prevented, and prevention is more important than treatment.Neonates lack a uniform hemoglobin threshold and are at risk of blood transfusion during red blood cell transfusion.

Management of neonatal hyperbilirubinemia: interpretation of the clinical management guidelines drafted by the American Academy of Pediatrics and other countries / 中华实用儿科临床杂志

Neonatal hyperbilirubinaemia, clinically presenting as jaundice, is a ubiquitous and commonly a benign metabolic condition in newborn infants.It is a leading cause of hospitalization of neonates in the first week of life.Serum bilirubin has been considered as the most potent superoxide with the peroxyl radical scavenger activity.However, uncontrolled hyperbilirubinaemia or rapidly rising bilirubin can reach a neurotoxic concentration, potentially leading to central nervous system sequelae.Thus, the health status of jaundiced newborn infants is dependent on striking an appropriate balance between the protective effects of serum bilirubin and the risk of bilirubin neurotoxicity.In order to standardize the management of neonatal hyperbilirubinemia (jaundice), many countries have developed clinical practice management guidelines.This review sorted out and briefly interpreted the main contents of clinical management guidelines for neonatal hyperbilirubinemia drafted by the American Academy of Pediatrics and other countries, aiming to provide references of clinical diagnosis and treatment practice to domestic pediatrician.

Association between sedentary behavior and force expiratory volume in 1 second reduction in middle-aged and elderly adults in communities / 中华流行病学杂志

Objective: To analyze the relationship between sedentary behavior and the force expiratory volume in 1 second (FEV1) reduction in middle-aged and elderly people in communities. Methods: The participants aged ≥40 years were randomly selected from a natural population cohort in Songjiang District, Shanghai, for pulmonary function tests and survey by using international physical activity questionnaire, a generalized additive model was used to analyze the association between sedentary behavior and FEV1 reduction in the study population and different sex-age subgroups. Results: A total of 3 121 study subjects aged ≥40 years were included. The prevalence of FEV1 reduction was 14.8%, which was higher in men than in women. There were 24.8% participants were completely sedentary. The prevalence of FEV1 reduction in women aged <60 years in complete sedentary group was 2.04 (95%CI: 1.11-3.72) times higher than that in non-complete sedentary group. In men aged <60 years, the prevalence of FEV1 reduction increased with daily sedentary time (OR=1.16, 95%CI: 1.04-1.29), and the prevalence of FEV1 reduction was also higher in those with sedentary time >5 hours/day than those with sedentary time ≤5 hours/day (OR=3.02, 95%CI: 1.28-7.16). The sensitivity analysis also found such associations. Conclusions: FEV1 reduction rate in age group <60 years was associated with sedentary behavior. Complete sedentary behavior or absence of moderate to vigorous physical activity played important roles in FEV1 reduction in women, while men were more likely to be affected by increased sedentary time, which had no association with physical activity. Reducing sedentary time to avoid complete sedentary behavior, along with increased physical activity, should be encouraged in middle-aged and elderly adults in communities to improve their pulmonary function.

Exposure level of neonicotinoid pesticides and their metabolites in pregnant women in the suburb of Shanghai / 中华预防医学杂志

In 2021, a total of 151 pregnant women were selected from the suburb of Shanghai. A questionnaire survey was conducted to obtain data about maternal age, gestational week, total annual household income, education level and passive smoking among pregnant women and one spot urine was collected. The concentrations of eight neonicotinoid pesticides and four metabolites in urine were measured by ultra-high performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry. The differences in detection frequencies and concentrations of neonicotinoid pesticides and their metabolites among pregnant women with different characteristics were compared, and the influencing factors of the detection of neonicotinoid pesticides in urine were analyzed. The results showed that at least one neonicotinoid pesticide was detected in 93.4% (141 samples) of urine samples. The detection frequencies of N-desmethyl-acetamiprid, clothianidin, thiamethoxam, and N-desmethyl-clothianidin were high, about 78.1% (118 samples), 75.5% (114 samples), 68.9% (104 samples), and 44.4% (67 samples), respectively. The median concentration of the sum of all neonicotinoid pesticides was 2.66 μg/g. N-desmethyl-acetamiprid had the highest detection concentration with a median concentration of 1.04 μg/g. A lower urinary detection frequency of imidacloprid and its metabolites was seen in pregnant women aged 30-44 years [OR (95%CI): 0.23 (0.07-0.77)]. A higher detection frequency of clothianidin and its metabolites was seen in pregnant women with per capita annual household income≥100 000 yuan [OR (95%CI): 6.15 (1.56-24.28)]. There was widespread exposure to neonicotinoid pesticides and their metabolites in pregnant women from the suburb of Shanghai, which might pose potential health risks to pregnant women, and maternal age and household income were potential influencing factors of the exposure to neonicotinoid pesticides.

Empirical analysis on lumbar disc herniation treated with "sinew-bone three needling technique" of Chinese medicine / 中国针灸

The paper presents professor WU Han-qing's experience in treatment of lumbar disc herniation (LDH) with "sinew-bone three needling technique" of Chinese medicine. Based on the theory of meridian sinew, the points are located by "three-pass method" in terms of the distribution of meridian sinew and syndrome/pattern differentiation. The cord-like muscles and adhesion are relieved by relaxing technique to work directly on the affected sites and alleviate the local compression to the nerve root. The needle technique is operated flexibly according to the affected regions involved, due to which, the needling sensation is increased while the safety ensured. As a result, the meridian qi is enhanced, the mind and qi circulation is regulated; and the clinical effect is improved.

Risk factors of elbow stiffness after open reduction and internal fixation of intercondylar fracture of humerus / 中国骨伤

OBJECTIVE@#To investigate the risk factors of elbow stiffness after open reduction and internal fixation of intercondylar fracture of humerus.@*METHODS@#From March 2015 to February 2019, 120 patients with humeral intercondylar fractures were treated with open fixation including 59 males and 61 females, aged from 25 to 77 years with an average of(53.5±3.2) years. According to the occurrence of elbow stiffness after operation, 120 patients were divided into stiffness group(37 cases) and control group(83 cases). The related factors of elbow stiffness were analyzed by single factor analysis, and the risk of elbow stiffness after internal fixation of humeral intercondylar fracture was analyzed by logistic regression factor.@*RESULTS@#There were 37 cases of elbow stiffness(stiff group), and 83 cases had no elbow stiffness(control group). The incidence of joint stiffness was 30.83%. There were significant differences between the stiffness group and the control group in age, injury energy, fracture to operation time, AO classification of fracture, open injury and postoperative premature or hyperactivity. Multivariate logistic regression analysis showed that age>50 years old, high energy injury, AO classification of fracture, open fracture and postoperative premature or hyperactivity were risk factors for elbow stiffness after internal fixation of humeral intercondylar fracture. The postoperative mobility and Mayo elbow performance score(MEPS) scores of the postoperative stiffness group were lower than those of the non-stiffness group with statistical significance(P<0.05). There were no significant differences in postoperative mobility and MEPS scores between flexion stiffness and rotation stiffness after humeral intercondylar fracture(P>0.05).@*CONCLUSION@#In view of the risk factors of elbow stiffness after internal fixation of humeral intercondylar fracture, reasonable operation plan and rehabilitation strategy should be formulated before operation to minimize the incidence of elbow stiffness.

Potentiating effect and mechanism of extract of Jingfang Granules on activation of macrophages / 中国中药杂志

This study aimed to explore the potentiating effect and mechanism of the extract of Jingfang Granules(JFG) on the activation of macrophages. The RAW264.7 cells were treated with JFG extract and then stimulated by multiple agents. Subsequently, mRNA was extracted, and reverse transcription-polymerase chain reaction(RT-PCR) was used to measure the mRNA transcription of multiple cytokines in RAW264.7 cells. The levels of cytokines in the cell supernatant were detected by enzyme-linked immunosorbent assay(ELISA). In addition, the intracellular proteins were extracted and the activation of signaling pathways was determined by Western blot. The results showed that JFG extract alone could not promote or slightly promote the mRNA transcription of TNF-α, IL-6, IL-1β, MIP-1α, MCP-1, CCL5, IP-10, and IFN-β, and significantly enhance the mRNA transcription of these cytokines in RAW264.7 cells induced by R848 and CpG in a dose-dependent manner. Furthermore, JFG extract also potentiated the secretion of TNF-α, IL-6, MCP-1, and IFN-β by RAW264.7 cells stimulated with R848 and CpG. As revealed by mechanism analysis, JFG extract enhanced the phosphorylation of p38, ERK1/2, IRF3, STAT1, and STAT3 in RAW264.7 cells induced by CpG. The findings of this study indicate that JFG extract can selectively potentiate the activation of macrophages induced by R848 and CpG, which may be attributed to the promotion of the activation of MAPKs, IRF3, and STAT1/3 signaling pathways.

Effect of Tongdu Tiaoshen electroacupuncture pretreatment on PPARγ-mediated pyroptosis of cerebral cortex in rats with cerebral ischemia reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effect of Tongdu Tiaoshen (promoting the circulation of the governor vessel and regulating the spirit) electroacupuncture (EA) pretreatment on pyroptosis mediated by peroxisome proliferators-activated receptor γ (PPARγ) of the cerebral cortex in rats with cerebral ischemia reperfusion injury (CIRI) and explore the potential mechanism of EA for the prevention and treatment of CIRI.@*METHODS@#A total of 110 clean-grade male SD rats were randomly divided into a sham-operation group, a model group, an EA group, an EA + inhibitor group and an agonist group, 22 rats in each group. In the EA group, before modeling, EA was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14), with disperse-dense wave, 2 Hz/5 Hz in frequency, 1 to 2 mA in intensity, lasting 20 min; once a day, consecutively for 7 days. On the base of the intervention as the EA group, on the day 7, the intraperitoneal injection with the PPARγ inhibitor, GW9662 (10 mg/kg) was delivered in the EA + inhibitor group. In the agonist group, on the day 7, the PPARγ agonist, pioglitazone hydrochloride (10 mg/kg) was injected intraperitoneally. At the end of intervention, except the sham-operation group, the modified thread embolization method was adopted to establish the right CIRI model in the rats of the other groups. Using the score of the modified neurological severity score (mNSS), the neurological defect condition of rats was evaluated. TTC staining was adopted to detect the relative cerebral infarction volume of rat, TUNEL staining was used to detect apoptosis of cerebral cortical nerve cells and the transmission electron microscope was used to observe pyroptosis of cerebral cortical neural cells. The positive expression of PPARγ and nucleotide-binding to oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex was detected with the immunofluorescence staining. The protein expression of PPARγ, NLRP3, cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D (GSDMD) and GSDMD-N terminal (GSDMD-N) in the cerebral cortex was detected with Western blot. Using the quantitative real-time fluorescence-PCR, the mRNA expression of PPARγ, NLRP3, caspase-1 and GSDMD of the cerebral cortex was detected. The contents of interleukin (IL)-1β and IL-18 in the cerebral cortex of rats were determined by ELISA.@*RESULTS@#Compared with the sham-operation group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.01), pyroptosis was severe, the protein and mRNA expression levels of PPARγ, NLRP3, caspase-1 and GSDMD were elevated (P<0.01); and the protein expression of GSDMD-N and contents of IL-1β and IL-18 were increased (P<0.01) in the model group. When compared with the model group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1β and IL-18 were lower (P<0.01) in the EA group and the agonist group; while, in the EA + inhibitor group, the protein expression of PPARγ was increased (P<0.01), the protein and mRNA expression levels of NLRP3 and GSDMD were decreased (P<0.01, P<0.05), the mRNA expression of caspase-1 was reduced (P<0.01); and the contents of IL-1β and IL-18 were lower (P<0.01). When compared with the EA + inhibitor group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.05, P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1β and IL-18 were declined (P<0.01) in the EA group. Compared with the agonist group, in the EA group, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.05, P<0.01), the mRNA expression of PPARγ was decreased (P<0.01) and the protein expression of GSDMD-N was elevated (P<0.05); and the contents of IL-1β and IL-18 were higher (P<0.01).@*CONCLUSION@#Tongdu Tiaoshen EA pretreatment can attenuate the neurological impairment in the rats with CIRI, and the underlying mechanism is related to the up-regulation of PPARγ inducing the inhibition of NLRP3 in the cerebral cortex of rats so that pyroptosis is affected.

Establishment and Evaluation of Intestinal Injury Model of Mouse Acute Graft Versus Host Disease Based on An Organoid Technology / 中国实验血液学杂志

OBJECTIVE@#To establish an intestinal organoid model that mimic acute graft versus host disease (aGVHD) caused intestinal injuries by using aGVHD murine model serum and organoid culture system, and explore the changes of aGVHD intestine in vitro by advantage of organoid technology.@*METHODS@#20-22 g female C57BL/6 mice and 20-22 g female BALB/c mice were used as donors and recipients for bone marrow transplantation, respectively. Within 4-6 h after receiving a lethal dose (8.0 Gy) of γ ray total body irradiation, a total of 0.25 ml of murine derived bone marrow cells (1×107/mice, n=20) and spleen nucleated cells (5×106/mice, n=20) was infused to establish a mouse model of aGVHD (n=20). The aGVHD mice were anesthetized at the 7th day after transplantation, and the veinal blood was harvested by removing the eyeballs, and the serum was collected by centrifugation. The small intestinal crypts of healthy C57BL/6 mice were harvested and cultivated in 3D culture system that maintaining the growth and proliferation of intestinal stem cells in vitro. In our experiment, 5%, 10%, 20% proportions of aGVHD serum were respectively added into the organoid culture system for 3 days. The formation of small intestinal organoids were observed under an inverted microscope and the morphological characteristics of intestinal organoids in each groups were analyzed. For further evaluation, the aGVHD intestinal organoids were harvested and their pathological changes were observed. Combined with HE staining, intestinal organ morphology evaluation was performed. Combined with Alcian Blue staining, the secretion function of aGVHD intestinal organoids was observed. The distribution and changes of Lgr5+ and Clu+ intestinal stem cells in intestinal organoids were analyzed under the conditions of 5%, 10% and 20% serum concentrations by immunohistochemical stainings.@*RESULTS@#The results of HE staining showed that the integrity of intestinal organoids in the 5% concentration serum group was better than that in the 10% and 20% groups. The 5% concentration serum group showed the highest number of organoids, the highest germination rate and the lowest pathological score among experimental groups, while the 20% group exhibited severe morphological destruction and almost no germination was observed, and the pathological score was the highest among all groups(t=3.668, 4.334,5.309,P<0.05). The results of Alican blue staining showed that the secretion function of intestinal organoids in serum culture of aGVHD in the 20% group was weaker than that of the 5% group and 10% of the organoids, and there was almost no goblet cells, and mucus was stainned in the 20% aGVHD serum group. The immunohistochemical results showed that the number of Lgr5+ cells of intestinal organoids in the 5% group was more than that of the intestinal organoids in the 10% aGVHD serum group and 20% aGVHD serum group. Almost no Clu+ cells were observed in the 5% group. The Lgr5+ cells in the 20% group were seriously injuried and can not be observed. The proportion of Clu+ cells in the 20% group significantly increased.@*CONCLUSION@#The concentration of aGVHD serum in the culture system can affect the number and secretion function of intestinal organoids as well as the number of intestinal stem cells in organoids. The higher the serum concentration, the greater the risk of organoid injury, which reveal the characteristics of the formation and functional change of aGVHD intestinal organoids, and provide a novel tool for the study of intestinal injury in aGVHD.

Study on the relationship among the extracurricular time management ability, self-efficacy and learning effect of medical undergraduates / 中华医学教育探索杂志

Objective:To understand the current situation of management ability and self-efficacy of medical undergraduates in Suzhou and their influence on the learning effect.Methods:General data questionnaire, present situation of college students' spare time management ability questionnaire and Chinese general self-efficacy scale were used to collect data from September 2018 to April 2019 in 5 colleges and 5 grades of medicine in a comprehensive university in Suzhou using cluster sampling method. A total of 450 full-time undergraduates completed the questionnaire. SPSS 22.0 was used for t-test, one-way ANOVA and Chi-square test. Multiple Logistics regression analysis was used to analyze the influence of extracurricular time management ability and self-efficacy on academic performance. Results:A total of 450 questionnaires were distributed, and 421 were recovered, with the effective recovery rate of 93.6%. The extracurricular time of full-time medical undergraduates was relatively low, and the management ability of extracurricular time was different in different grades, whether to be a student leader, professional interests, economic status and other aspects. Students of different grades had different levels of self-efficacy. Multivariate Logistics regression analysis was carried out with the dependent variables, with the model fitted χ2=220.488, P=0.002 and the determination coefficient = 0.660. The management ability and self-efficacy in spare time were independent influencing factors of academic performance. Conclusion:Schools should take specific measures to improve the learning effect and educational quality of medical students.

On standards of and approaches to "Golden Course" construction of medical English writing in the era of big data / 中华医学教育探索杂志

In order to cultivate talents who fuel and lead medical innovation, it is critical to implement medical English writing "Golden Course" in the substantial development of English teaching in medical universities. Based on the guidelines issued by the Ministry of Education, this paper proposes five principles in the construction of medical English writing "Golden Course", suggests the integration of big data technology, and explores approaches to construct "Golden Course" in terms of teaching objectives, curriculum design, models of instruction, curriculum evaluation and teaching staff.

Clinical treatment outcomes and their changes in extremely preterm twins: a multicenter retrospective study in Guangdong Province, China / 中国当代儿科杂志

OBJECTIVES@#To investigate the clinical treatment outcomes and the changes of the outcomes over time in extremely preterm twins in Guangdong Province, China.@*METHODS@#A retrospective analysis was performed for 269 pairs of extremely preterm twins with a gestational age of <28 weeks who were admitted to the department of neonatology in 26 grade A tertiary hospitals in Guangdong Province from January 2008 to December 2017. According to the admission time, they were divided into two groups: 2008-2012 and 2013-2017. Besides, each pair of twins was divided into the heavier infant and the lighter infant subgroups according to birth weight. The perinatal data of mothers and hospitalization data of neonates were collected. The survival rate of twins and the incidence rate of complications were compared between the 2008-2012 and 2013-2017 groups.@*RESULTS@#Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of severe asphyxia and smaller head circumference at birth (P<0.05). The mortality rates of both of the twins, the heavier infant of the twins, and the lighter infant of the twins were lower in the 2013-2017 group compared with the 2008-2012 group (P<0.05). Compared with the 2008-2012 group, the 2013-2017 group (both the heavier infant and lighter infant subgroups) had lower incidence rates of pulmonary hemorrhage, patent ductus arteriosus (PDA), periventricular-intraventricular hemorrhage (P-IVH), and neonatal respiratory distress syndrome (NRDS) and a higher incidence rate of bronchopulmonary dysplasia (P<0.05).@*CONCLUSIONS@#There is a significant increase in the survival rate over time in extremely preterm twins with a gestational age of <28 weeks in the 26 grade A tertiary hospitals in Guangdong Province. The incidences of severe asphyxia, pulmonary hemorrhage, PDA, P-IVH, and NRDS decrease in both the heavier and lighter infants of the twins, but the incidence of bronchopulmonary dysplasia increases. With the improvement of diagnosis and treatment, the multidisciplinary collaboration between different fields of fetal medicine including prenatal diagnosis, obstetrics, and neonatology is needed in the future to jointly develop management strategies for twin pregnancy.

Effects of subchronic fluoride exposure through drinking water on renal toxicity and the expressions of STIM1 and ORAI1 in renal tissues in mice / 环境与职业医学

Background It has been found that fluoride may cause cell damage by inducing intracellular calcium overload. Store-operated calcium entry (SOCE) plays an important role in maintaining intracellular calcium homeostasis, but the effect of fluoride on renal SOCE is unknown. Objective To explore the renal toxicity and the expression levels of the key proteins of SOCE, stromal interaction molecule 1 (STIM1) and calcium release-activated calcium modulator 1 (ORAI1) in the kidney tissues of mice exposed to fluoride subchronically. Methods Twenty male ICR mice were randomly divided into four groups with five mice in each group, including 0 (control group), 0.3, 3, and 30 mg·L−1 fluoride groups. The mice were given drinking water containing designed fluoride for 12 weeks. Body weight and liver and kidney organ coefficients of the mice were measured after the exposure; histopathological changes of the mouse kidney were observed; 24 h urine was collected at the end of 12 weeks of exposure to determine the levels of urine creatinine (UCr), urine calcium (UCa), albumin (ALB), and β2-microglobulin (β2-MG); the protein expression levels of STIM1 and ORAI1 in the kidney were detected by Western blotting; the fluorescence co-localization of STIM1 and ORAI1 was used to further verify the expression levels of STIM1 and ORAI1. Results After the exposure, there were no differences in body weight as well as liver and kidney organ coefficients among the groups (P > 0.05). Under optical microscope, the renal tubular cell showed degeneration, apical protrusion, shedding, and dilation in the 3 and 30 mg·L−1 fluoride groups. There was no statistical difference in UCr among the mice in each group (P > 0.05). Compared with the control group, the levels of UCa adjusted by UCr in the 3 and 30 mg·L−1 fluoride groups were (0.075±0.014) and (0.081±0.012) mol·mol−1 (represent by UCr per mol), which had a rising trend but showed no statistical difference. No difference was identified in the level of ALB among the groups (P > 0.05). The levels of β2-MG showed difference in different exposure groups, and the level of urine β2-MG in the 30 mg·L−1 fluoride group was (0.077±0.014) g·mol−1, higher than that in the control group (P<0.05). Based on the results of Western blotting, the protein expression levels of STIM1 and ORAI1 showed significant differences among the groups (F=18.411, 6.853; P=0.001, 0.013); compared with the control group, the expression levels of STIM1 protein increased in the 3 and 30 mg·L−1 fluoride groups (P < 0.05), and the protein expression level of ORAI1 in the 30 mg·L−1 fluoride group was increased (P < 0.05). The fluorescence co-localization results of STIM1 and ORAI1 showed that the expressions of STIM1 and ORAI1 were up-regulated in the 3 and 30 mg·L−1 fluoride groups. Conclusion Subchronic exposure to fluoride through drinking water can up-regulate the expression levels of STIM1 and ORAI1 in renal tissues and induce renal injury.

Comparison of the efficacy of stereotactic body radiotherapy and surgery for intrapulmonary recurrence patients after non-small cell lung cancer surgery / 中华放射医学与防护杂志

Objective:To compare the efficacy of stereotactic body radiotherapy(SBRT) and surgery in treating intrapulmonary recurrence of non-small cell lung cancer (NSCLC) after radical surgery.Methods:A retrospective analysis was conducted on NSCLC patients, who underwent radical surgery at the Cancer Hospital Affiliated to University of Chinese Academy of Sciences from November 2012 to December 2018 and then received SBRT or secondary surgery because of postoperative intrapulmonary recurrence. The survival rates of these patients were calculated using the Kaplan-Meier method. The comparison between the two groups was made using the Log-rank method, and the univariate and multivariate analysis was made using the Cox regression method.Results:Among 62 eligible patients, 33 received SBRT and 29 received secondary surgery, and they were divided into the SBRT group and the surgery group accordingly. For the SBRT and surgery groups, the median follow-up time was 45.8 months and 37.4 months, the 3-year locoregional control rate (LRCR) 79.8% and 90.2%, respectively ( P > 0.05), the progression-free-survival (PFS) 58.5% and 42.3%, respectively ( P >0.05), and the overall survival (OS) 78.0% and 85.5%, respectively ( P >0.05). The multivariate analysis suggested that treatment method, Charlson comorbidity index (CCI), and adjuvant drug therapy were independent prognostic factors for PFS ( P = 0.027, 0.013, 0.001). Conclusions:The efficacy of SBRT and surgery is comparable for patients with intrapulmonary recurrence of NSCLC after radical surgery.

Effects of Paclitaxel and Quizartinib Alone and in Combination on AML Cell Line MV4-11 and Its STAT5 Signal Pathway / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of paclitaxel, quizartinib and their combination on proliferation, apoptosis and FLT3/STAT5 pathway of human leukemia cell line MV4-11 (FLT3-ITD+).@*METHODS@#MV4-11 cells were treated with paclitaxel and quizartinib at different concentrations for 24 h, 48 h and 72 h, respectively, and then the two drugs were combined at 48 h to compare the inhibition of proliferation, the apoptosis rate was detected by flow cytometry, the expression of FLT3 and STAT5 mRNA was determined by fluorescence quantitative PCR, and the protein expression of FLT3, p-FLT3, STAT5 and p-STAT5 was determined by Western blot.@*RESULTS@#Different combination groups of paclitaxel and quizartinib had synergistic inhibitory effect. The cell survival rate in the combination group was significantly lower than that in the single drug group (P<0.05). The cell apoptosis rate in the combination group was significantly higher than that in the single drug group (P<0.001). The expression of FLT3 mRNA in combination group was significantly higher than that in two single drugs (P<0.01). The expression of STAT5 mRNA in combination group was significantly higher than that in quizartinib group (P<0.001); increased compared with paclitaxel group, but there was no statistical significance. The expression level of p-FLT3、p-STAT5 protein in the combination group was significantly lower than that in the single drug group (P<0.05, P<0.05).@*CONCLUSION@#Paclitaxel combined with quizartinib can synergistically inhibit the proliferation of MV4-11 cell line and promote the apoptosis of MV4-11 cell line by inhibiting the activity of FLT3/STAT5 pathway.

A comparative study of artificial intelligence nasal polyp classification based on whole-slide imaging and JESREC diagnostic criteria / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the types and clinical characteristics of chronic rhinosinusitis with nasal polyps (CRSwNP) based on artificial intelligence and whole-slide imaging (WSI), and to explore the consistency of the diagnostic criteria of the Japanese epidemiological survey of refractory eosinophilic chronic rhinosinusitis (JESREC) in Chinese CRSwNP patients. Methods: The data of 136 patients with CRSwNP (101 males and 35 females, aging 14 to 70 years) who underwent endoscopic sinus surgery from 2018 to 2019 in the Department of Otorhinolaryngology Head and Neck Surgery, the Third Affiliated Hospital of Sun Yat-sen University were analysed retrospectively. The preoperative clinical characteristics of patients were collected, such as visual analogue scale (VAS) of nasal symptoms, peripheral blood inflammatory cell count, total immunoglobulin E (IgE), Lund-Kennedy score and Lund-Mackay score. The proportion of inflammatory cells such as eosinophils, lymphocytes, plasma cells and neutrophils were calculated on the WSI of each patient through artificial intelligence chronic rhinosinusitis evaluation platform 2.0 (AICEP 2.0), and the specific type of nasal polyps was then obtained as eosinophilic CRSwNP (eCRSwNP) or non-eosinophilic CRSwNP (non-eCRSwNP). In addition, the JESREC diagnostic criteria was used to classify the nasal polyps, and the classification results were compared with the current gold standard for nasal polyps diagnosis (pathological diagnosis based on WSI). The accuracy, sensitivity and specificity of the diagnostic criteria of JESREC were evaluated. The data were expressed in M (Q1, Q3) and statistically analyzed by SPSS 17.0. Results: There was no significant difference between eCRSwNP and non-eCRSwNP in age distribution, gender, time of onset, total VAS score, Lund-Kennedy score or Lund-Mackay score. However, there was a significant difference in the ratio of nasal polyp inflammatory cells (eosinophils 40.5% (22.8%, 54.7%) vs 2.5% (1.0%, 5.3%), neutrophils 0.3% (0.1%, 0.7%) vs 1.3% (0.5%, 3.6%), lymphocytes 49.9% (39.3%, 65.9%) vs 82.0% (72.8%, 87.5%), plasma cells 5.1% (3.6%, 10.5%) vs 13.0% (7.4%, 16.3%), χ2 value was 9.91, 4.66, 8.28, 5.06, respectively, all P<0.05). In addition, eCRSwNP had a significantly higher level of proportion of allergic symptoms (nasal itching and sneezing), asthma, peripheral blood eosinophil and total IgE (all P<0.05). The overall accuracy, sensitivity and specificity of the JESREC diagnostic criteria was 74.3%, 81.3% and 64.3%, respectively. Conclusions: The eCRSwNP based on artificial intelligence and WSI has significant high level of allergic symptoms, asthma, peripheral blood eosinophils and total IgE, and the percentages of inflammatory cells in nasal polyps are different from that of non-eCRSwNP. The JESREC diagnostic criteria has good consistency in our research.

Safety evaluation of hyperthermic intraperitoneal chemotherapy in patients with local advanced gastric cancer after radical resection for prevention of peritoneal metastasis / 中华胃肠外科杂志

Objective: Patients with advanced gastric cancer have a poor prognosis and a possibility of peritoneal metastasis even if receiving gastrectomy. Hyperthermic intraperitoneal chemotherapy (HIPEC) can effectively kill free cancer cells or small lesions in the abdominal cavity. At present, preventive HIPEC still lacks safety evaluation in patients with locally advanced gastric cancer. This study aims to explore the safety of radical resection combined with HIPEC in patients with locally advanced gastric cancer. Methods: A descriptive case series study was carried out. Clinicopathological data of 130 patients with locally advanced gastric cancer who underwent radical resection + HIPEC at the Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2020 to February 2021 were retrospectively analyzed. Inclusion criteria: (1) locally advanced gastric adenocarcinoma confirmed by postoperative pathology; (2) no distant metastasis was found before surgery; (3) radical resection; (4) at least one HIPEC treatment was performed. Exclusion criteria: (1) incomplete clinicopathological data; (2) tumor metastasis was found during operation; (3) concomitant with other tumors. HIPEC method: all the patients received the first HIPEC immediately after D2 radical resection, and returned to the ward after waking up from anesthesia; the second and the third HIPEC were carried out according to the patient's postoperative recovery and tolerance; interval between two HIPEC treatments was 48 h. Observation indicators: (1) basic information, including gender, age, body mass index, etc.; (2) treatment status; (3) perioperative adverse events: based on the standard of common adverse events published by the US Department of Health and Public Health (CTCAE 5.0), the adverse events of grade 2 and above during the treatment period were recorded, including hypoalbuminemia, bone marrow cell reduction, wound complications, abdominal infection, lung infection, gastroparesis, anemia, postoperative bleeding, anastomotic leakage, intestinal obstruction, pleural effusion, abdominal distension, impaired liver function, and finally a senior professional title chief physician reviewed the above adverse events and made a safety evaluation of the patient; (4) association between times of HIPEC treatment and adverse events in perioperative period; (5) analysis of risk factors for adverse events in perioperative period. Results: Among the 130 patients, 79 were males and 51 were females with a median age of 59 (54, 66) years and an average body mass index of (23.9±7.4) kg/m(2). The tumor size was (5.4±3.0) cm and 100 patients (76.9%) had nerve invasion. All the 130 patients received radical resection + HIPEC and 125 (96.2%) patients underwent laparoscopic surgery. The mean operative time was (345.6±52.3) min and intraoperative blood loss was (82.0±36.5) ml. One HIPEC treatment was performed in 54 patients (41.5%), 2 HIPEC treatments were in 57 (43.8%), and 3 HIPEC treatments were in 19 (14.6%). The average postoperative hospital stay was (13.1±7.5) d. A total of 57 patients (43.8%) had 71 cases of postoperative complications of different degrees. Among them, the incidence of hypoalbuminemia was 22.3% (29/130), and the grade 2 and above anemia was 15.4% (20/130), lung infection was 3.8% (5/130), bone marrow cell suppression was 3.7% (4/130), abdominal cavity infection was 2.3% (3/130), and liver damage was 2.3% (3/130), wound complications was 1.5% (2/130), abdominal distension was 1.5% (2/130), anastomotic leakage was 0.8% (1/130), gastroparesis was 0.8% (1/130) and intestinal obstruction was 0.8% (1/130), etc. These adverse events were all improved by conservative treatments. There were no statistically significant differences in the incidence of adverse events during the perioperative period among patients undergoing 1, 2, and 3 times of HIPEC treatments (all P>0.05). Univariate and multivariate logistic analyses showed that age > 60 years (OR: 2.346, 95%CI: 1.069-5.150, P=0.034) and neurological invasion (OR: 2.992, 95%CI: 1.050-8.523, P=0.040) were independent risk factors for adverse events in locally advanced gastric cancer patients undergoing radical resection+HIPEC (both P<0.05). Conclusions: Radical surgery + HIPEC does not significantly increase the incidence of perioperative complications in patients with advanced gastric cancer. The age >60 years and nerve invasion are independent risk factors for adverse events in these patients.