Objective:To investigate the effect of bone marrow mesenchymal stem cells(BMSCs)on the proliferation and collagen expression levels of L929 cells,and to clarify its related mechanism.Methods:The BMSCs were extracted from the 4-week-old C57BL/6 mice.The phenotypes of BMSCs were identified by immunofluorescence staining.The L929 cells were divided into control group(L929 cells),co-culture group(L929 cells and BMSCs),inhibitor of Janus kinase(JAK)WP1066 group(WP1066-treated L929 cells and BMSCs),and dimethyl sulfoxide(DMSO)group(DMSO-treated L929 cells and BMSCs).Cell counting kit-8(CCK-8)assay was used to detect the proliferation activities of the L929 cells in various groups at different time points;Western blotting method was used to detect the expression levels of type Ⅰ collagen(Col Ⅰ)and type Ⅲ collagen(Col Ⅲ)in the L929 cells in various groups;immunofluorescence staining was used to detect the expressions of Col Ⅰ and Col Ⅲ proteins in the L929 cells in various groups.Results:The fluorescence assay results of surface antigen(SA)showed that the surface markers CD29+,CD45-,CD90+and CD105+were found in the BMSCs.The CCK-8 assay results showed that compared with control group,the proliferation activities of the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the proliferation activity of the L929 cells in WP1066 group was significantly decreased(P＜0.01).The Western blotting method results showed that compared with control group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in WP1066 group were significantly decreased(P＜0.01);compared with DMSO group,the expression levels of Col Ⅰ and Col Ⅲ proteins in the L929 cells in WP1066 group were significantly decreased(P＜0.01).The immunofluorescence staining results showed that compared with control group,the fluorescence intensities of Col Ⅰ and Col Ⅲ proteins in the L929 cells in co-culture group and DMSO group were significantly increased(P＜0.01);compared with co-culture group,the fluorescence intensities of Col Ⅰ and Col Ⅲ in the L929 cells in WP1066 group were significantly decreased(P＜0.01);compared with DMSO group,the fluorescence intensities of Col Ⅰ and Col Ⅲ in the L929 cells in WP1066 group were significantly decreased(P＜0.01).Conclusion:MSCs can promote the proliferation and collagen production of the L929 cells of the mice through the JAK2/signal transducer and activator of transcription 3(STAT3)signaling pathway.

Despite that sleep disturbance and poor neurocognitive performance are common complaints among coronavirus disease 2019 (COVID-19) survivors, few studies have focused on the effect of post-COVID-19 sleep disturbance (PCSD) on cognitive function. This study aimed to identify the impact of PCSD on neurocognitive function and explore the associated risk factors for the worsening of this condition. This cross-sectional study was conducted via the web-based assessment in Chinese mainland. Neurocognitive function was evaluated by the modified online Integrated Cognitive Assessment (ICA) and the Number Ordering Test (NOT). Propensity score matching (PSM) was utilized to match the confounding factors between individuals with and without PCSD. Univariate analyses were performed to evaluate the effect of PCSD on neurocognitive function. The risk factors associated with worsened neurocognitive performance in PCSD individuals were explored using binary logistic regression. A total of 8692 individuals with COVID-19 diagnosis were selected for this study. Nearly half (48.80%) of the COVID-19 survivors reported sleep disturbance. After matching by PSM, a total of 3977 pairs (7954 individuals in total) were obtained. Univariate analyses revealed that PCSD was related to worse ICA and NOT performance (P<0.05). Underlying disease, upper respiratory infection, loss of smell or taste, severe pneumonia, and self-reported cognitive complaints were associated with worsened neurocognitive performance among PCSD individuals (P<0.05). Furthermore, aging, ethnicity (minority), and lower education level were found to be independent risk factors for worsened neurocognitive performance in PCSD individuals (P<0.05). PCSD was related to impaired neurocognitive performance. Therefore, appropriate prevention and intervention measures should be taken to minimize or prevent PCSD and eliminate its potential adverse effect on neurocognitive function.
Humans ; COVID-19/epidemiology* ; Male ; Female ; Sleep Wake Disorders/epidemiology* ; Propensity Score ; Middle Aged ; Cross-Sectional Studies ; Adult ; SARS-CoV-2 ; Aged ; Risk Factors ; China/epidemiology* ; Cognition ; Cognitive Dysfunction/etiology* ; Neuropsychological Tests

Objective:To study the subacute oral toxic effect of p-chloro-m-xylphenol on rats and provide a basis for its safety evaluation.Methods:SPF-grade Wistar rats were randomly divided into 4 groups according to body weight stratification randomization, with 20 rats in each group, half male and half female. The set concentrations of the p-chloro-m-xylphenol dose groups were 11.25, 22.50, and 45.00 mg/kg·BW respectively, with an intragastric volume of 10 ml/kg·BW. The blank control group was given the same amount of distilled water. The rats were treated with intragastric administration for 30 days. After intraperitoneal injection of 50 mg/kg·BW pentobarbital sodium for anesthesia, bloodletting and death, the organs were separated and weighed. Blood was collected from the abdominal aorta to determine the hematological and serum biochemical indicators of the whole blood of rats. Multiple groups comparison was performed by one-way analysis of variance, and pairwise comparison between groups was performed by the least significant difference test or Dunnett-t3 test.Results:The kidney weight in the 45.00 mg/kg·BW dose group of female rats [ (1.59±0.11) g] was lower than that in the blank control group [ (1.71±0.12) g], and the difference was statistically significant ( P<0.05) . The percentage of monocytes in the 11.25 mg/kg·BW dose group of male rats [ (4.81±0.74) %] was lower than that in the blank control group [ (5.86±0.58) %], the red blood cell count [ (6.93±0.26) ×10 12/L] and hemoglobin [ (134.30±4.95) g/L] in the 22.50 mg/kg·BW dose group of female rats were both lower than those in the blank control group[ (7.48±0.26) ×10 12/L, (146.20±4.42) g/L], the percentage of eosinophils in the 11.25 mg/kg·BW dose group of female rats [ (2.46±0.86) %] was higher than that in the blank control group [ (1.66±0.41) %], and the differences were statistically significant ( P<0.05) . Conclusion:P-chloro-m-xylphenol may have toxic effects on the blood system of rats, and the kidneys may be the potential target organs for its toxicity.

Objective:To study the subacute oral toxic effect of p-chloro-m-xylphenol on rats and provide a basis for its safety evaluation.Methods:SPF-grade Wistar rats were randomly divided into 4 groups according to body weight stratification randomization, with 20 rats in each group, half male and half female. The set concentrations of the p-chloro-m-xylphenol dose groups were 11.25, 22.50, and 45.00 mg/kg·BW respectively, with an intragastric volume of 10 ml/kg·BW. The blank control group was given the same amount of distilled water. The rats were treated with intragastric administration for 30 days. After intraperitoneal injection of 50 mg/kg·BW pentobarbital sodium for anesthesia, bloodletting and death, the organs were separated and weighed. Blood was collected from the abdominal aorta to determine the hematological and serum biochemical indicators of the whole blood of rats. Multiple groups comparison was performed by one-way analysis of variance, and pairwise comparison between groups was performed by the least significant difference test or Dunnett-t3 test.Results:The kidney weight in the 45.00 mg/kg·BW dose group of female rats [ (1.59±0.11) g] was lower than that in the blank control group [ (1.71±0.12) g], and the difference was statistically significant ( P<0.05) . The percentage of monocytes in the 11.25 mg/kg·BW dose group of male rats [ (4.81±0.74) %] was lower than that in the blank control group [ (5.86±0.58) %], the red blood cell count [ (6.93±0.26) ×10 12/L] and hemoglobin [ (134.30±4.95) g/L] in the 22.50 mg/kg·BW dose group of female rats were both lower than those in the blank control group[ (7.48±0.26) ×10 12/L, (146.20±4.42) g/L], the percentage of eosinophils in the 11.25 mg/kg·BW dose group of female rats [ (2.46±0.86) %] was higher than that in the blank control group [ (1.66±0.41) %], and the differences were statistically significant ( P<0.05) . Conclusion:P-chloro-m-xylphenol may have toxic effects on the blood system of rats, and the kidneys may be the potential target organs for its toxicity.

Objective To investigate the reproductive and developmental effects of Clothianidin in rats. Methods Clothianidin was administrated by diet to both parental and first filial (F 1) generations of rats at the dosages of 0, 30.51, 110.84 and 304.26 mg/(kg·d) in females, and 0, 26.45, 92.69 and 279.42 mg/(kg·d) in males. Clothianidin was administered through diet to male and female rats for 8 weeks before mating. Clothianidin was administered to female rats in the parental and F1 generations during mating, gestation and lactation periods. During the test, toxicity performance was observed, reproduction index was calculated, and pathological examination was carried out. Results The body weights of rats in the parent and F1 generations in the high-dose group were lower than those in the control group during pre-mating exposure and at various time points during pregnancy and lactation (P<0.05). The pregnancy rates of parental and F1 generations in the high-dose group were lower than those of the control group (48.57% vs 71.43%, 45.71% vs 80.00%, P＜0. 05). Sperm concentration and sperm motility of the parental generation were lower than those of the control group [(42.55±12.87) vs (53.84±7.65) ×106/ml, (58.94±10.59) vs (65.59±6.03), （P＜0.05）]. Sperm concentration and sperm motility of the F1 generation were lower than those of the control group [(41.64±12.42) vs (53.09±9.48), (55.13±9.19) vs (64.53±6.31), (P＜0.05). Conclusion Exposure to clothianidin has reproductive toxicity to Wistar rats, and the no-observed adverse effect level (NOAEL) in the two-generation reproductive toxicity test is 92.69 mg/kg·BW for males and 110.84 mg/kg·BW for females in Wistar rats.

Objective: Nonalcoholic fatty liver disease (NAFLD) has become a common chronic liver disease that is harmful to human health. Moreover, there is currently no FDA-approved first-line drug for the treatment of nonalcoholic steatohepatitis (NASH) or NAFLD. Traditional Chinese medicine (TCM) is widely used to ameliorate liver diseases, such as the traditional ancient recipe called Three Flower Tea (TFT), which consists of double rose (Rosa rugosa), white chrysanthemum (Chrysanthemum morifolium), and Daidaihua (Citrus aurantium). However, the mechanisms of the action of TFT are not clear. Therefore, this study aimed to elucidate the mechanisms of TFT against NAFLD in high-fat diet (HFD)-induced rats. Methods: This study utilized bioinformatics and network pharmacology to establish the active and potential ingredient-target networks of TFT. Furthermore, a protein–protein interaction (PPI) network was constructed, and enrichment analysis was performed to determine the key targets of TFT against NAFLD. Furthermore, an animal experiment was conducted to evaluate the therapeutic effect and confirm the key targets of TFT against NAFLD. Results: A total of 576 NAFLD-related genes were searched in GeneCards, and under the screening criteria of oral bioavailability (OB) ≥30% and drug-likeness (DL) ≥0.18, a total of 19 active ingredients and 210 targets were identified in TFT. Network pharmacology analysis suggested that 55 matching targets in PPIs were closely associated with roles for NAFLD treatment. Through the evaluation of network topology parameters, four key central genes, PPARγ, SREBP, AKT, and RELA, were identified. Furthermore, animal experiments indicated that TFT could reduce plasma lipid profiles, hepatic lipid profiles and hepatic fat accumulation, improve liver function, suppress inflammatory factors, and reduce oxidative stress. Through immunoblotting and immunofluorescence analysis, PPARγ, SREBP, AKT, and RELA were confirmed as targets of TFT in HFD-induced rats. Conclusion: In summary, our results indicate that TFT can prevent and treat NAFLD via multiple targets, including lipid accumulation, antioxidation, insulin sensitivity, and inflammation.

Objective:To Investigate comprehensive predictive ability of first-trimester complete blood count combined with maternal characteristics for gestational diabetes mellitus (GDM).Methods:From May 2015 to July 2018, 1 412 pregnant women were retrospectively screened at the Fifth People′s Hospital of Shanghai, Fudan University. We recruited 258 women who developed GDM and 1 154 women who had normal glucose level during pregnancy. At the first visit, clinical data and complete blood count result were obtained. GDM prediction models were established through logistic regression analysis of GDM related risk factors and the prediction abilities of each model were compared.Results:Logistic regression analyses identified age, pre-pregnancy body mass index, previous GDM history, family history of diabetes mellitus, the neutrophil-to-lymphocyte ratio, leukocyte, neutrophil, and monocyte counts were significantly independent predictors of GDM. In the entire cohort, the predictive ability of neutrophil and monocyte counts together with maternal basal characteristics model for the development of GDM [areas under the receiver operating characteristic curve (AUC-ROC)=0.809, integrated discrimination improvement (IDI)=0.056, P=0.001] was the best among various models (basal characteristics model, AUC-ROC=0.753; Monocyte count+ basal characteristics model, AUC-ROC=0.764; neutrophil count + basal characteristics model, AUC-ROC=0.775). Similar results obtained by the same way in all pregnant women without previous GDM history. Conclusion:It could improve the prediction of GDM with model incorporated maternal characteristics and first-trimester neutrophil and monocyte counts.

Objective:To compare the setup errors between deep inspiration breath hold (DIBH) and free breathing (FB) for breast cancer patients who were treated with whole breast irradiation (WBI) after breast conserving surgery (BCS).Methods:In this retrospective analysis, 30 breast cancer patients receiving WBI following BCS using DIBH in National Cancer Center/ Chinese Academy of Medical Sciences, an 30 patients treated with WBI using FB were enrolled as comparator.The kilovoltage cone-beam computed tomography (CBCT) was performed to evaluate and reduce setup errors. The optimal margins from clinical target volume (CTV) to planning target volume (PTV) for DIBH were estimated. The differences of setup errors between two techniques were compared using independent two-sample t-test. Results:A total of 318 sets of CBCT images were acquired, with (5.1±1.1) sets per patient on average. The setup errors along the three translational directions (laternal, longitudinal and vertical) were (2.1±1.6) mm, (2.6±1.7) mm and (2.5±2.1) mm for DIBH, and (2.2±1.7) mm, (3.1±2.5) mm and (3.3±2.3) mm for FB, respectively. Compared with FB, DIBH significantly reduced setup errors in the longitudinal ( P=0.015) and vertical ( P=0.004) directions, whereas the setup errors in the lateral direction did not significantly differ ( P=0.294). The optimal margins from CTV to PTV using DIBH were 6.2 mm, 7.3 mm and 7.8 mm, respectively. In the DIBH group, treatment fractions at the beginning and higher body mass index (BMI) did not associate with larger set-up deviation. Conclusions:DIBH technique yields less setup errors than FB for breast cancer patients treated with WBI after BCS. The CTV-PTV margins of 6-8 mm are recommended for DIBH.

It's important that the university teachers apply proper linguistic strategies in the Traditional Chinese medicine courses for foreign students,which can reduce the non-native language ability limitation to teaching effect to a certain extent,which can let students better understand and grasp the contents.This paper summarize the influence of linguistic strategies on teaching effect,such as signposting,signalling importance,back channeling,repetition,questioning,commenting,which is the important foundation and powerful guarantee of ideal teaching effects of EMI.

Objective To investigate the setup errors and influencing factors of the whole breast intensity-modulated radiotherapy (IMRT) after breast-conserving surgery,and to identify the margins from clinical target volume (CTV) to planning target volume (PTV).Methods Thirty patients with left-sided (n=15) or right-sided breast cancer (n=15) receiving whole breast hypofractionated IMRT with breast board immobilization after breast-conserving surgery in Cancer Hospital from 2016 to 2017 were enrolled.The kilo-voltage cone-beam computed tomography (CBCT) was used to compare the errors of planning CT and treatment unit and determine the setup errors.The margins from CTV to PTV were calculated.The setup errors under different conditions were statistically compared by t-test.Results A total of 151 sets of CBCT images were taken in the whole cohort,(5.0± 1.3) sets per patient on average.The setup errors in the x-axis (left-right direction),y-axis (cranial-caudal direction) and z-axis (anterior-posterior direction) were (2.2± 1.7) mm,(3.1±2.5) mm and (3.3±2.3) mm,respectively.The margins from CTV to PTV were 6.39 mm,10.00 mm and 8.57 mm,respectively.The setup error in anterior-posterior direction in the first week was (3.7±2.5) mm,significantly larger than (2.6±1.6) mm in the following week (P=0.002).The setup error of the patients with overweight or obesity was (3.9±2.6) mm,significantly higher than (2.9±2.0) mm in those with normal weight in the z-axis direction (P=0.033).Conclusion The margins from CTV to PTV are recommended to be ranged from 6 to 10 mm during hypofractionated whole breast IMRT with breast board immobilization after breast-conserving surgery.More frequent imaging verification should be applied in the first week of IMRT.