Differential cytotoxic effects of fenbendazole on mouse lymphoma EL-4 cells and spleen cells

Fenbendazole (FBZ) is a benzimidazole anthelmintic widely used to treat parasitic infections. The anticancer effect of FBZ has been recently highlighted leading to its consideration as a potential anticancer agent. Although previous studies have demonstrated the effect of FBZ on cancer cells, there is a paucity of studies on the effect of FBZ on lymphoma cells and normal immune cells. Herein, we investigated the effects of FBZ on a mouse lymphoma cell line, EL-4 cells, and spleen cells, using vincristine as a positive control. The cellular metabolic activity of EL-4 cells was decreased by FBZ, but that of the spleen cells was not decreased. Moreover, FBZ reduced the mitochondrial membrane potential and induced reactive oxygen species production in EL-4 cells, but not in spleen cells. FBZ induced G2/M phase arrest and increased the sub G0/G1 phase ratio, indicating apoptosis. Furthermore, compared to the control cells, the reactivity of spleen cells pretreated with FBZ to lipopolysaccharide was maintained. In summary, FBZ is cytotoxic to EL-4 cells, but not to spleen cells. This study provides experimental evidence that FBZ exerts an anticancer effect, and less cytotoxic effects and functional damage to normal spleen cells.

Anticancer effect of metformin alone and in combination with 2-deoxy-D-glucose on mouse T cell lymphoma EL4 cells

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T-cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

Hsa_circ_0000670 promoted the progression of gastric cancer through the miR-515-5p/SIX1 molecular axis / 中华肿瘤杂志

Objective: To explore whether hsa_circ_0000670 promotes the progression of gastric cancer by regulating the miR-515-5p/SIX1 molecular axis. Methods: The gastric cancer and adjacent normal tissues of 35 gastric cancer patients admitted to Rugao Hospital Affiliated to Nantong University from 2014 to 2015 were collected. The expression levels of circ_0000670, miR-515-5p and Sine oculis homeobox 1 (SIX1) in gastric cancer tissues and cells were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The correlations between circ_0000670 and miR-515-5p, miR-515-5p and SIX1, circ_0000670 and SIX1 were analyzed by the Pearson method. Patients were divided into low circ_0000670 expression group (17 cases) and high circ_0000670 expression group (18 cases) based on the median of circ_0000670 expression level, and Kaplan-Meier was used to analyze the 5-year survival of patients. Cell proliferation was assessed via clone formation assay. Cell cycle and apoptosis were detected by flow cytometry. Wound healing and Transwell assays were used to detect cell migration and invasion ability. The targeting relationship between miR-515-5p and circ_0000670 or SIX1 was confirmed by the dual luciferase reporter assay. Nude mice were injected into HGC-27 cells transfected with sh-NC or sh-circ_0000670, and the volume and weight of the transplanted tumor were measured, also, the levels of circ_0000670, miR-515-5p and SIX1 in the transplanted tumor tissue were detected. Results: The expression levels of circ_0000670 and SIX1 in gastric cancer tissues and cell lines were significantly increased (P<0.05), while the expression levels of miR-515-5p were significantly decreased (P<0.05). The survival rate of patients in the low circ_0000670 expression group (82.4%) was significantly higher than that in the high circ_0000670 expression group (28.7%, P=0.034). Circ_0000670 was negatively correlated with miR-515-5p (r=-0.846, P<0.001), and miR-515-5p was negatively correlated with SIX1 (r=-0.615, P<0.001), but circ_0000670 was positively correlated with SIX1 (r=0.814, P<0.001). Transfection of si-circ_0000670 or miR-515-5p mimic could significantly reduce the number of clone-forming cells, migration distance, migration and invasion cells (P<0.05), and increase the ratio of G(0)/G(1) phase cells, apoptosis rate and the protein level of E-cadherin (P<0.05), decreased the proportion of S-phase cells and the protein level of Vimentin (P<0.05). The dual luciferase report assay confirmed that circ_0000670 could target miR-515-5p, and miR-515-5p could bind to SIX1. Co-transfection of si-circ_0000670 and miR-515-5p inhibitor could significantly attenuate the effects of si-circ_0000670 on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Co-transfection of miR-515-5p mimic and pcDNA-SIX1 could significantly reduce the effects of miR-515-5p mimic on cell proliferation, migration, invasion, cell cycle and apoptosis (P<0.05). Compared with the sh-NC group [volume=(596.20±125.46) mm(3) and weight=(538.00±114.39) g], the volume and weight of transplanted tumors in the sh-circ_0000670 group [volume=(299.20±47.58) mm 3 and weight=(289.80±48.73 g)] were significantly reduced (P<0.05), the expression levels of circ_0000670 and SIX1 were significantly reduced (P<0.05), and the expression level of miR-515-5p was significantly increased (P<0.05). Conclusion: Knockdown of circ_0000670 could inhibit cell proliferation, migration, invasion of gastric cancer cells, induce cell cycle arrest in G(0)/G(1) phase and promote cell apoptosis by regulating the miR-515-5p/SIX1 axis.

Yinlai Decoction Protects Microstructure of Colon and Regulates Serum Level of D-Lactic Acid in Pneumonia Mice Fed with High-Calorie and High-Protein Diet / 中国结合医学杂志

OBJECTIVE@#To investigate the effect of Yinlai Decoction (YD) on the microstructure of colon, and activity of D-lactic acid (DLA) and diamine oxidase (DAO) in serum of pneumonia mice model fed with high-calorie and high-protein diet (HCD).@*METHODS@#Sixty male Kunming mice were randomly divided into 6 groups by the random number table method: normal control, pneumonia, HCD, HCD with pneumonia (HCD-P), YD (229.2 mg/mL), and dexamethasone (15.63 mg/mL) groups, with 10 in each group. HCD mice were fed with 52% milk solution by gavage. Pneumonia mice was modeled with lipopolysaccharide inhalation and was fed by gavage with either the corresponding therapeutic drugs or saline water, twice daily, for 3 days. After hematoxylin-eosin staining, the changes in the colon structure were observed under light microscopy and transmission electron microscope, respectively. Enzyme-linked immunosorbent assay was used to detect the protein levels of DLA and DAO in the serum of mice.@*RESULTS@#The colonic mucosal structure and ultrastructure of mice in the normal control group were clear and intact. The colonic mucosal goblet cells in the pneumonia group tended to increase, and the size of the microvilli varied. In the HCD-P group, the mucosal goblet cells showed a marked increase in size with increased secretory activity. Loose mucosal epithelial connections were also observed, as shown by widened intercellular gaps with short sparse microvilli. These pathological changes of intestinal mucosa were significantly reduced in mouse models with YD treatment, while there was no significant improvement after dexamethasone treatment. The serum DLA level was significantly higher in the pneumonia, HCD, and HCD-P groups as compared with the normal control group (P<0.05). Serum DLA was significantly lower in the YD group than HCD-P group (P<0.05). Moreover, serum DLA level significantly increased in the dexamethasone group as compared with the YD group (P<0.01). There was no statistical significance in the serum level of DAO among groups (P>0.05).@*CONCLUSIONS@#YD can protect function of intestinal mucosa by improving the tissue morphology of intestinal mucosa and maintaining integrity of cell connections and microvilli structure, thereby reducing permeability of intestinal mucosa to regulate the serum levels of DLA in mice.

Relationship of bone mineral density and bone metabolism indicators with osteoporosis in elderly patients with post-stroke hemiplegia / 中华老年心脑血管病杂志

Objective To explore the relationship of changes in bone mineral density and bone me-tabolism indicators with osteoporosis in elderly patients with hemiplegia after cerebral infarction.Methods A total of 197 elderly patients suffering post-stroke hemiplegia admitted to our hospital were enrolled between February 2018 and February 2021.Their bone mineral density and bone metabolism indicators were analyzed based on gender,disease course and hemiplegia severity.According to disease severity,they were divided into mild group(112 cases),moderate group(62 cases)and severe group(32 cases).Results Among the 197 elderly patients,83(42.13％)had osteoporosis.The males had significantly higher bone mineral density of proximal femur and levels of bone alkaline phosphatase(BALP)and osteocalcin,and lower levels of serum type Ⅰ collagen(CICP)and C-terminal telopeptides of type Ⅰ collagen(CTXI)than the females(P＜0.01,P＜0.05).Compared with the patients with hemiplegia course for 3-6 months,bone mineral density values of greater trochanter and total hip,and levels of BALP and osteocalcin were obviously de-creased,while levels of CICP and CTXI were notably increased in those with the course of 7-12 months and 13-24 months(P＜0.05).Compared with the mild group,bone mineral density val-ues of greater trochanter and total hip,and levels of BALP and osteocalcin were significantly de-creased,while levels of CICP and CTXI were significantly increased in moderate group and severe group(P＜0.05).Compared with the moderate group,bone mineral density values of greater tro-chanter,intertrochanteric site and total hip were significantly decreased in the severe group(P＜0.05).The bone mineral density of above parts was negatively correlated with CICP levels(r=-0.458,r=-0.403,r=-0.355,r=-0.482,P＜0.01)and CTXI levels(r=-0.305,r=-0.291,r=-0.273,r=-0.384,P＜0.05,P＜0.01),while positively correlated with BGP level(r=0.476,r=0.428,r=0.386,r=0.518,P＜0.01).Conclusion The incidence of osteoporosis is quite higher in the elderly patients with post-stroke hemiplegia.There exist bone mineral density decline and abnormal bone metabolism,and their changes are related to gender,course and severi-ty of hemiplegia.

Monitoring and analysis of radioactivity levels in drinking water sources in five cities of Sichuan province from 2016 to 2020 / 中华放射医学与防护杂志

Objective:To understand the radioactivity levels of water source in five key cities of Chengdu, Yibin, Mianyang, Guangyuan, Leshan in Sichuan province, and evaluate the radiation safety of these water sources.Methods:From 2016 to 2020, the measuring site selection, sampling and analysis were made for measuring the radioactivity levels of total alpha, total beta, 90Sr, 137Cs, 226Ra, U, Th in drinking water sources in these five cities. Reference was made, respectively, to the national standards Determination of total α radioactivity concentration in water thick source method (EJ/T 1075-1998), Determination of total β radioactivity in water evaporation method (EJ/T 900-1994), Radiochemical analysis method of strontium-90 in water and biological samples ash (HJ 815-2016), radiochemical analysis of cesium-137 in the ash of water and biological samples (HJ 816-2016), Analysis and determination of radium-226 in water (GB 11214-1989), Analysis of trace uranium in environmental samples -3 laser fluorescence law (HJ 840-2017), and Food safety in the test of radioactive substances in food determination of natural thorium and uranium (GB 14883.7-2016). Results:The activity concentration ranges from 0.011 to 0.076 Bq/L for total alpha, 0.027 to 0.098 Bq/L for total beta, 0.21 to 0.45 mBq/L for 137Cs, 1.0 to 2.4 mBq/L for 90Sr, 6.1 to 16.0 mBq/L for 226Ra, 0.06 to 0.21 μg/L for Th, and 0.73 to 3.30 μg/L for U. There were no significant differences in the concentrations of total alpha, total beta, 90Sr, 137Cs, 226Ra, U and Th in different water sources and different years ( P>0.05). There were no significant differences in the concentrations of total alpha, total beta, 90Sr, 137Cs and 226Ra during different water periods ( P>0.05). There were statistical differences in U activity concentration in different water periods ( H=16.53, P<0.05), and statistical differences in Th activity concentration in different water periods ( H=15.61, P<0.05). Conclusions:The survey showed that the total alpha, total beta, 90Sr, 137Cs, 226Ra, U and Th radioactivity levels in drinking water sources in Chengdu, Yibin, Mianyang, Guangyuan and Leshan of Sichuan province were at the same level as the relevant data in the Natural environmental radioactivity level in China published by the State Environmental Protection Bureau in 1995. All of there values were within the data range released by the 2013-2021 National Radiation Environment Monitoring Quality Report issued by the Radiation Environment Monitoring Technology Center of the Ministry of Ecology and Environment. The radioactivity level in water sources in the five key cities was at a safe level.

Evaluation of the effects of disulfiram, an alcohol-aversive agent with anti-cancer activity, on mouse bone marrow cells

Disulfiram (DSF) is an aldehyde dehydrogenase inhibitor. DSF has potent anti-cancer activity for solid and hematological malignancies. Although the effects on cancer cells have been proven, there have been few studies on DSF toxicity in bone marrow cells (BMs). DSF reduces the metabolic activity and the mitochondrial membrane potential of BMs. In subset analyses, we confirmed that DSF does not affect the proportion of BMs. In addition, DSF significantly impaired the metabolic activity and differentiation of BMs treated with granulocyte macrophage-colony stimulating factor, an essential growth and differentiation factor for BMs. To measure DSF toxicity in BMs in vivo, mice were injected with 50 mg/kg, a dose used for anti-cancer effects. DSF did not significantly induce BM toxicity in mice and may be tolerated by antioxidant defense mechanisms. This is the first study on the effects of DSF on BMs in vitro and in vivo. DSF has been widely studied as an anti-cancer drug candidate, and many anti-cancer drugs lead to myelosuppression. In this regard, this study can provide useful information to basic science and clinical researchers.

Impact of composite clinical worsening events on outcome of patients with pulmonary arterial hypertension associated with congenital heart disease / 中华心血管病杂志

Objective: To explore the impact of composite clinical worsening (cCW) events and its components on the prognosis of patients with pulmonary arterial hypertension associated with congenital heart disease (CHD-PAH). Methods: This is a retrospective study. Patients who were diagnosed with CHD-PAH in Beijing Anzhen Hospital between January 2007 and July 2018, were included, and their baseline clinical data including demographic, clinical manifestations and New York Heart Association (NYHA) classification were collected retrospectively. All-cause deaths and clinical worsening events were recorded, which included syncope, PAH related hospitalization, NYHA classification deterioration and ≥ 2 PAH related clinical symptoms (dyspnea, hemoptysis, edema, chest pain, palpitations, cyanosis) appearance/progress. Three kinds of cCW events were defined: cCW1 (included PAH related hospitalization, NYHA classification deterioration), cCW2 (increased syncope on the basis of cCW1) and cCW3 (increased ≥ 2 PAH related clinical symptoms appearance/progress on the basis of cCW2). The Kaplan-Meier survival curve was used to analyze the long-term survival of the included patients. Univariate and multivariate Cox regression models were used to evaluate the impact of cCW events and their components on the risk of all-cause mortality. Results: A total of 525 patients with CHD-PAH were included in this study. The median age at diagnosis was 20.7 (11.2, 30.3) years. There were 43.8% children (<18 years), and 68.8% female patients. There were 431 patients (82.1%) with NYHA classification II. A total of 180 patients had PAH symptoms at diagnosis. The median follow-up time was 4.5 (2.6, 6.7) years. Forty-seven patients (9.0%) died during the follow-up period. Survival rates at 1, 5 and 10 years after diagnosis of PAH were 98.0%, 89.9% and 84.4%, respectively. Cox multivariate analysis showed that NYHA classification deterioration (HR=3.901, 95%CI 1.863-8.169, P<0.001), ≥2 PAH symptoms appearance/progress (HR=4.458, 95%CI 1.870-10.625, P<0.001), PAH-related hospitalization (HR=4.058, 95%CI 1.851-8.896, P<0.001) and syncope (HR=11.313, 95%CI 4.860-26.332, P<0.001) were independent predictors of increased risk of death. All 3 kinds of cCW events were significantly associated with the significantly increased risk of death, and cCW2 was highly predictive to increased risk of death (HR=15.476, 95%CI 4.346-37.576, P<0.001). Conclusions: The overall long-term prognosis of CHD-PAH patients in this study is relatively good. cCW events and its components (NYHA classification deterioration, ≥2 PAH symptoms occurrence/worsening, PAH-related hospitalization and syncope) have adverse influence on all-cause death in this patient cohort.

Baihutang Syndrome and Treatment： A New Interpretation Based on Six Dimensional Syndrome Differentiation Theory / 中国实验方剂学杂志

Six dimensional syndrome differentiation theory， put forward by professor GU Xiao-hong at Beijing University of Chinese Medicine based on her theoretical teaching and clinical experience， emphasizes that the syndrome differentiation should be carried out from six dimensions including etiology， disease location， disease stage， disease condition， pathology， and disease nature， which is conducive to clinical thinking training and formation of traditional Chinese medicine （TCM）. The differentiation and treatment of Baihutang syndrome frequently seen in cold damage and warm disease still need to be explored. Guided by the six dimensional syndrome differentiation theory coupled with diverse viewpoints of cold damage and warm disease schools， this paper summarized and reinterpreted the understandings and thoughts of GU Xiao-hong and YU He， warm disease specialists of two generations. Considering the lung-stomach dysfunction caused by the internal invasion of exogenous pathogens， Baihutang syndrome was staged into Qi aspect. In this stage， exuberant pathogens and sufficient healthy Qi allowed the prevailing of internal heat and the consumption of body fluid， manifested as high fever， profuse sweating， thirst， and the pulse corresponding to interior excess and heat syndrome. This paper also pointed out that the Baihutang syndrome involved both lung and stomach， and the adoption of Baihutang contributed to preventing tu from restricting shui in the case of extreme excess of Yang brightness and protecting the kidney Yin. As revealed by the dynamic analysis of prognosis of Baihutang syndrome based on the six dimensional syndrome differentiation theory， even though the Baihutang syndrome could be present in both cold damage and warm disease， the specific disease stage， transmission and change， condition， prognosis， pathology， and medication differed. On this basis， a series of prescriptions have been modified from Baihutang， which has expanded the application scope of Baihutang and enriched its research value， thus better promoting its clinical application.

Epidemiological characteristics and influencing factors of delayed diagnosis of pulmonary tuberculosis in schools in Hefei during 2019-2020 / 中国学校卫生

Objective@#To explore epidemiological characteristics and diagnosis delay among tuberculosis patients, and to provide reference basis for pulmonary tuberculosis prevention and control in schools.@*Methods@#Retrospective data of school based tuberculosis patients information and cluster epidemiological information in Hefei during Jan. 2019 to Dec. 2020 was collected. Changes of the epidemiological characteristics and diagnosis delay of school tuberculosis epidemic and possible role were explored.@*Results@#The reported incidence of Hefei school pulmonary tuberculosis was 14.04/10 5 in 2020. Two peaks of cases occurred during May to Jun. and Oct. to Nov. Teacher account for 8.00% of pulmonary tuberculosis cases in school, a significant increase was observed compared with 2019 ( χ 2=4.30, P <0.05). In 2020, the median length of treatment for cases reported by local medical institutions was 5.14 days, and the median length of diagnosis was 18 days, both of which were shorter than those in 2019 ( Z =22.45, 4.52, P <0.05). In multiple cases sporadic of school pulmonary tuberculosis, strong positive rate of PPD test was 13.50% among close contacts, and new case detectable rate was 0.62%. The median duration from exposure to symptoms onset among close contacts was 132 days, which significant increased compared to 2019 ( Z =251.50, P <0.05). The diagnosis delay among tuberculosis patients diagnosed by chest CT was 12.10%, and was 16.15% through supervision by school or parents. Chest radiograph was associated with higher risk of delayed diagnosis ( OR=4.34, P <0.05) compared to chest CT as the first medical radiology option. Low delayed diagnosis rate was associated with supervision of tuberculosis by school or parents than control ( OR=0.26, P <0.05).@*Conclusion@#Factors such as the selection of diagnostic radiology and case supervision are associated with delay diagnosis. It s necessary to strengthen the management and monitoring of the pulmonary tuberculosis epidemic in school.

Effect of incentive spouse cooperative psychological intervention on the delivery outcome of primipara / 上海预防医学

ObjectiveTo explore the effect of incentive spouse collaborative psychological intervention on delivery outcomes of primipara. MethodsFrom July 2019 to July 2020， 300 primiparas with an uneventful pregnancy were recruited and divided into the control group and the intervention group， with 150 cases in each group. The control group was managed by routine nursing care， and the intervention group was managed by incentive spouse collaborative psychological intervention. The delivery outcomes in two groups， including delivery route， postpartum blood loss， and perineal laceration were compared. ResultsAfter intervention， the cesarean section rate， the 2-hour postpartum blood loss and perineal laceration in the intervention group were less common than those in the control group and the difference was statistically significant （P<0.05）. The first， second and total stages of labor duration in the intervention group were shorter than those in the control group and the difference was statistically significant （P<0.05）. There was no significant difference in the incidence of neonatal asphyxia between these two groups （P>0.05）. In terms of vaginal delivery experience scores of the two groups， the intervention group was better than the control group and the difference was statistically significant （P<0.05）. ConclusionThe mode of incentive spouse collaborative psychological intervention can reduce the rate of cesarean section， the amount of bleeding 2 hours after delivery， and perineum injury. It can shorten the labor process， and effectively improve the delivery outcome of primiparas.

Effect of incentive spouse cooperative psychological intervention on the delivery outcome of primipara / 上海预防医学

ObjectiveTo explore the effect of incentive spouse collaborative psychological intervention on delivery outcomes of primipara. MethodsFrom July 2019 to July 2020， 300 primiparas with an uneventful pregnancy were recruited and divided into the control group and the intervention group， with 150 cases in each group. The control group was managed by routine nursing care， and the intervention group was managed by incentive spouse collaborative psychological intervention. The delivery outcomes in two groups， including delivery route， postpartum blood loss， and perineal laceration were compared. ResultsAfter intervention， the cesarean section rate， the 2-hour postpartum blood loss and perineal laceration in the intervention group were less common than those in the control group and the difference was statistically significant （P<0.05）. The first， second and total stages of labor duration in the intervention group were shorter than those in the control group and the difference was statistically significant （P<0.05）. There was no significant difference in the incidence of neonatal asphyxia between these two groups （P>0.05）. In terms of vaginal delivery experience scores of the two groups， the intervention group was better than the control group and the difference was statistically significant （P<0.05）. ConclusionThe mode of incentive spouse collaborative psychological intervention can reduce the rate of cesarean section， the amount of bleeding 2 hours after delivery， and perineum injury. It can shorten the labor process， and effectively improve the delivery outcome of primiparas.

Association between LIPC gene rs10468017 polymorphism and the susceptibility to age-related macular degeneration: a Meta-analysis / 中华实验眼科杂志

Objective:To systematically evaluate the association between the hepatic lipase ( LIPC) gene rs10468017 polymorphism and susceptibility to age-related macular degeneration (AMD). Methods:A systematic search was performed in both English databases (PubMed, Embase, EBSCO, Web of Knowledge and Cochrane library) and Chinese databases (CNKI, WanFang, VIP and CBM) from database establishment to December 31, 2019.Literature about LIPC rs10468017 polymorphism and AMD was searched.Odds ratios ( OR) and 95% confidence intervals ( CI) of allele mode (T and C), heterozygous model (TC and CC) and homozygous model (TT and CC) as well as the correlation between types of AMD and races were calculated using Stata 12.0 software. Results:Twenty-one studies were included in the Meta-analysis.There were 25 649 AMD patients and 26 294 normal controls.There was a significant correlation between LIPC rs10468017 polymorphism and risk of AMD in different genetic models (T vs. C: OR=0.83, 95% CI: 0.80-0.87; TC vs. CC: OR=0.82, 95% CI: 0.75-0.90; TT vs. CC: OR=0.65, 95% CI: 0.56-0.76). The subgroup analysis showed that the LIPC rs10468017 polymorphism was significantly associated with the risk of early AMD ( OR=0.87, 95% CI: 0.78-0.96), advanced AMD ( OR=0.83, 95% CI: 0.77-0.88), geographic atrophy ( OR=0.79, 95% CI: 0.72-0.87) and choroidal neovascularization ( OR=0.83, 95% CI: 0.78-0.89). Stratified analysis by ethnicity showed that there was a significant association between T allele and the decreased risk of AMD in the Caucasian population (early AMD: OR=0.77, 95% CI: 0.67-0.89; advanced AMD: OR=0.80, 95% CI: 0.75-0.87), but not in the Asian population (early AMD: OR=0.98, 95% CI: 0.85-1.13; advanced AMD: OR=0.93, 95% CI: 0.81-1.06). Conclusions:There is a significant association between T allele of LIPC rs10468017 polymorphism and the reduced risk of AMD, which exists in different subtypes of AMD with certain racial differences.

Intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain / 中国针灸

OBJECTIVE@#To observe the effect of intradermal needling combined with heat-sensitive moxibustion for moderate to severe cancer pain.@*METHODS@#A total of 60 patients with moderate to severe cancer pain were randomly divided into an observation group and a control group，30 cases in each one. In the control group，opioids were taken to relief pain according to the three-step analgesic method of World Health Organization. On the base of the treatment as the control group, intradermal needling combined with heat-sensitive moxibustion were applied at Neiguan (PC 6), Hegu (LI 4), Zusanli (ST 36), Taichong (LR 3), etc. in the observation group, 14 days of treatment were required. The equivalent morphine consumption at the first day and whole course, the scores of cancer quality of life questionnaire-C30 (QLQ-C30) and Hamilton anxiety scale before and after treatment, and the adverse reaction rate were compared in the two groups. The total analgesic effective rate was evaluated.@*RESULTS@#The total analgesic effective rate was 93.3% (28/30) in the observation group, higher than 73.3% (22/30) in the control group (@*CONCLUSION@#Intradermal needling combined with heat-sensitive moxibustion can reduce the dose of opioids, improve the quality of life, relief the anxiety in patients with moderate to severe cancer pain, and reduce the incidence of common adverse reaction of opioids.

Delivery room resuscitation and short-term outcomes of extremely preterm and extremely low birth weight infants: a multicenter survey in North China / 中华医学杂志(英文版)

BACKGROUND@#Delivery room resuscitation assists preterm infants, especially extremely preterm infants (EPI) and extremely low birth weight infants (ELBWI), in breathing support, while it potentially exerts a negative impact on the lungs and outcomes of preterm infants. This study aimed to assess delivery room resuscitation and discharge outcomes of EPI and ELBWI in China.@*METHODS@#The clinical data of EPI (gestational age [GA] <28 weeks) and ELBWI (birth weight [BW] <1000 g), admitted within 72 h of birth in 33 neonatal intensive care units from five provinces and cities in North China between 2017 and 2018, were analyzed. The primary outcomes were delivery room resuscitation and risk factors for delivery room intubation (DRI). The secondary outcomes were survival rates, incidence of bronchopulmonary dysplasia (BPD), and risk factors for BPD.@*RESULTS@#A cohort of 952 preterm infants were enrolled. The incidence of DRI, chest compressions, and administration of epinephrine was 55.9% (532/952), 12.5% (119/952), and 7.0% (67/952), respectively. Multivariate analysis revealed that the risk factors for DRI were GA <28 weeks (odds ratio [OR], 3.147; 95% confidence interval [CI], 2.082-4.755), BW <1000 g (OR, 2.240; 95% CI, 1.606-3.125), and antepartum infection (OR, 1.429; 95% CI, 1.044-1.956). The survival rate was 65.9% (627/952) and was dependent on GA. The rate of BPD was 29.3% (181/627). Multivariate analysis showed that the risk factors for BPD were male (OR, 1.603; 95% CI, 1.061-2.424), DRI (OR, 2.094; 95% CI, 1.328-3.303), respiratory distress syndrome exposed to ≥2 doses of pulmonary surfactants (PS; OR, 2.700; 95% CI, 1.679-4.343), and mechanical ventilation ≥7 days (OR, 4.358; 95% CI, 2.777-6.837). However, a larger BW (OR, 0.998; 95% CI, 0.996-0.999), antenatal steroid (OR, 0.577; 95% CI, 0.379-0.880), and PS use in the delivery room (OR, 0.273; 95% CI, 0.160-0.467) were preventive factors for BPD (all P < 0.05).@*CONCLUSION@#Improving delivery room resuscitation and management of respiratory complications are imperative during early management of the health of EPI and ELBWI.

ER71/ETV2 Promotes Hair Regeneration from Chemotherapeutic Drug-Induced Hair Loss by Enhancing Angiogenesis

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

Biphasic immunomodulatory effects of ionized biosilica water on the antigen-presenting capability of mouse dendritic cells

Biosilica is a silica-based substance derived from the cell walls (frustules) of diatoms and has various biological activities. Recently, research into biosilica’s biological functions are underway, but little has been reported on the effects of biosilica on immune cells. In this study, we investigated the effect of ionized biosilica water (iBW) on dendritic cells (DCs), which play crucial roles as antigen (Ag)-presenting cells. Treatment with iBW increased the expression of immune response-related markers, closely connected to the maturation of DCs, and the production of tumor necrosis factor-alpha. In addition, iBW-treated DCs (iBW-DCs) had a lower uptake of fluorescein isothiocyanate-dextran than that of control DCs. Mixed leukocyte response analysis, used for measuring the Ag-presenting capability of DCs, showed iBW-DCs had a higher capability than that of control DCs. Interestingly, DCs treated with lipopolysaccharide (LPS) and iBW had a lower level of Ag-presenting capability than that of LPS-treated DCs. Taken together, the results indicate that iBW alone can mature DCs, but it decreases the Ag-presenting capability of DCs in the presence of LPS, a representative agent of inflammation. This study may provide valuable information regarding the effect of iBW on immune cells. Further research is needed to investigate how iBW induces the observed biphasic immunomodulatory activity.

ER71/ETV2 Promotes Hair Regeneration from Chemotherapeutic Drug-Induced Hair Loss by Enhancing Angiogenesis

Chemotherapy-induced alopecia and hair loss can be stressful in patients with cancer. The hair grows back, but sometimes the hair tends to stay thin. Therefore, understanding mechanisms regulating hair regeneration may improve the management of chemotherapy-induced alopecia. Previous studies have revealed that chemotherapeutic agents induce a hair follicle vascular injury. As hair growth is associated with micro-vessel regeneration, we postulated that the stimulation of angiogenesis might enhance hair regeneration. In particular, mice treated with 5-fluorouracil (5-FU) showed delayed anagen initiation and reduced capillary density when compared with untreated controls, suggesting that the retardation of anagen initiation by 5-FU treatment may be attributed to the loss of perifollicular micro-vessels. We investigated whether the ETS transcription factor ETV2 (aka ER71), critical for vascular development and regeneration, can promote angiogenesis and hair regrowth in a 5-FU-induced alopecia mouse model. Tie2-Cre; Etv2 conditional knockout (CKO) mice, which lack Etv2 in endothelial cells, presented similar hair regrowth rates as the control mice after depilation. Following 5-FU treatment, Tie2-Cre; Etv2 CKO mice revealed a significant reduction in capillary density, anagen induction, and hair restoration when compared with controls. Mice receiving lentiviral Etv2 injection after 5-FU treatment showed significantly improved anagen induction and hair regrowth. Two-photon laser scanning microscopy revealed that enforced Etv2 expression restored normal vessel morphology after 5-FU mediated vessel injury. Our data suggest that vessel regeneration strategies may improve hair regrowth after chemotherapeutic treatment.

Inhibitory effects of fenbendazole, an anthelmintics, on lipopolysaccharide-activated mouse bone marrow cells

Fenbendazole (FBZ) is a commonly used anthelmintic in veterinary medicine that has recently been found to have anticancer effects in humans. On the other hand, few studies have examined the anti-inflammatory effects of FBZ, and its mechanism is unknown. In this study, mouse bone marrow cells (BMs) were treated with lipopolysaccharide (LPS), a representative inflammation-inducing substance, to generate a situation similar to osteomyelitis in vitro. The effect of FBZ on inflammatory BMs was examined by measuring the metabolic activity, surface marker expression, cell nuclear morphology, and mitochondrial membrane potential (MMP) of BMs. FBZ decreased the metabolic activity and MMP of LPS-treated BMs. Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide staining and Hoechst 33342 staining showed that FBZ reduced the number of viable cells and induced the cell death of inflammatory BMs. In addition, FBZ reduced the proportion of granulocytes more than B lymphocytes in LPS-treated BMs. Overall, FBZ induces cell death by destabilizing the MMP of LPS-induced inflammatory BMs. FBZ can play a role as an anthelmintic and anticancer agent and an anti-inflammatory agent.

Biphasic immunomodulatory effects of ionized biosilica water on the antigen-presenting capability of mouse dendritic cells

Biosilica is a silica-based substance derived from the cell walls (frustules) of diatoms and has various biological activities. Recently, research into biosilica’s biological functions are underway, but little has been reported on the effects of biosilica on immune cells. In this study, we investigated the effect of ionized biosilica water (iBW) on dendritic cells (DCs), which play crucial roles as antigen (Ag)-presenting cells. Treatment with iBW increased the expression of immune response-related markers, closely connected to the maturation of DCs, and the production of tumor necrosis factor-alpha. In addition, iBW-treated DCs (iBW-DCs) had a lower uptake of fluorescein isothiocyanate-dextran than that of control DCs. Mixed leukocyte response analysis, used for measuring the Ag-presenting capability of DCs, showed iBW-DCs had a higher capability than that of control DCs. Interestingly, DCs treated with lipopolysaccharide (LPS) and iBW had a lower level of Ag-presenting capability than that of LPS-treated DCs. Taken together, the results indicate that iBW alone can mature DCs, but it decreases the Ag-presenting capability of DCs in the presence of LPS, a representative agent of inflammation. This study may provide valuable information regarding the effect of iBW on immune cells. Further research is needed to investigate how iBW induces the observed biphasic immunomodulatory activity.