OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To investigate the effects and mechanism of modified Xiaoqinglong decoction combined with bone marrow mesenchymal stem cells （BMSCs） on nasal-pulmonary-intestinal mucosal immunity in rats with cold asthma. METHODS SD rats were randomly divided into blank group， model group， BMSCs group， BMSCs+modified Xiaoqinglong decoction （6.39 g/kg） group， and BMSCs+dexamethasone （0.125 mg/kg） group， with 10 rats in each group. The cold asthma rat model was established by sensitization and atomization challenge with ovalbumin combined with aluminum hydroxide， together with cold air stimulation from air conditioners. One hour before the initial atomization challenge， rats in all groups except the blank group and model group were injected with BMSCs suspension via the tail vein. Starting from the 15th day of the experiment， rats in each group were intragastrically administered corresponding liquid medicine or normal saline once a day for 7 consecutive days. After the last administration， the asthmatic behavioral changes and pathological morphological changes of lung tissues in rats were evaluated. The levels of interleukin-6 （IL-6） and IL-10 in nasopharyngeal lavage fluid， bronchoalveolar lavage fluid （BALF） and intestinal mucus were detected. The expression levels of proteins related to the phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in nasal， lung and intestinal tissues were determined. RESULTS Compared with the blank group， the asthmatic behavioral score， lung tissue injury score， IL-6 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus， PI3K protein expression and Akt phosphorylation levels in nasal， lung and intestinal tissues of rats in the model group were significantly increased （ P ＜0.05）； the IL-10 levels in nasopharyngeal lavage fluid， BALF and intestinal mucus were significantly decreased （ P ＜0.05）. Alveolar atrophy， collapse and even fusion， abnormal hyperplasia and hypertrophy of bronchial smooth muscle， and massive inflammatory cell infiltration were observed. Compared with the model group， most of the above quantitative indicators in the BMSCs group， BMSCs+modified Xiaoqinglong decoction group and BMSCs+dexamethasone group were significantly reversed （ P ＜0.05）， and pathological injuries of lung tissues were markedly alleviated. Compared with the BMSCs group， most of the above quantitative indicators were further improved in the BMSCs+modified Xiaoqinglong decoction group （ P ＜0.05）. CONCLUSIONS Modified Xiaoqinglong decoction combined with BMSCs can effectively improve nasal-pulmonary-intestinal mucosal immunity and relieve asthmatic symptoms in cold asthma rats， and its mechanism may be related to inhibiting the activation of the PI3K/Akt signaling pathway.

Objective To explore the correlation between the characteristics of the endometrial microbiome in patients with recurrent implantation failure(RIF)and the subsequent transplantation outcomes.Methods A total of 438 RIF patients underwent embryo transfer again in our hospital were retrospective selection.According to the pregnancy status of the patients 8 weeks after embryo transfer,patients were divided into the pregnancy group(n=85)and the non-pregnancy group(n=353).The clinical data,characteristics and composition diversity of the endometrial microbiome were compared between the two groups.Binary Logistic regression was used to analyze the influencing factors,and the receiver operating characteristic(ROC)was employed to predict the efficacy of the influencing factors.The interaction between the above-mentioned risk factors and Shannon index in the subsequent transplantation outcomes of RIF patients was further analyzed.Results The levels of basal estradiol(E2),fasting insulin(Fins),total cholesterol(TC)and triglycerides(TG)were significantly higher in the non-pregnant group than those in the pregnant group(P＜0.05).Meanwhile,there were significant differences in the composition of endometrial microorganisms between the two groups(P＜0.05).Among them,the abundance of Fusobacterium phylum,the abundance of Bacillus genus and the α-diversity(Chao1,Shannon,Simpson)index all showed significant differences(all P＜0.05).Binary Logistic regression multivariate analysis showed that the abundance of Fusobacterium phylum increased(OR=1.628,95%CI:1.416-1.841),the abundance of Bacillus genus decreased(OR=0.725,95%CI:0.557-0.934)and E2 increased(OR=1.654,95%CI:1.343-1.965).The elevated insulin(OR=1.691,95%CI:1.393-1.980)and decreased Shannon index(OR=0.388,95%CI:0.075-0.697)were independent risk factors for failure after subsequent transplantation.ROC curve analysis showed that the area under the curve(AUC)of the Shannon index was 0.836(95%CI:0.782-0.890),with the highest predictive efficacy.There was significant interaction among the subgroups of Fusobacteria,Bacillus genus,E2 and insulin in Shannon index on the subsequent transplantation outcomes of patients with RIF.Conclusion The independent risk factors for subsequent transplantation failure in RIF patients can be used as sensitive indicators to predict the subsequent transplantation outcomes of RIF patients,and Shannon index has a higher clinical predictive value.

Objective To explore the correlation between the characteristics of the endometrial microbiome in patients with recurrent implantation failure(RIF)and the subsequent transplantation outcomes.Methods A total of 438 RIF patients underwent embryo transfer again in our hospital were retrospective selection.According to the pregnancy status of the patients 8 weeks after embryo transfer,patients were divided into the pregnancy group(n=85)and the non-pregnancy group(n=353).The clinical data,characteristics and composition diversity of the endometrial microbiome were compared between the two groups.Binary Logistic regression was used to analyze the influencing factors,and the receiver operating characteristic(ROC)was employed to predict the efficacy of the influencing factors.The interaction between the above-mentioned risk factors and Shannon index in the subsequent transplantation outcomes of RIF patients was further analyzed.Results The levels of basal estradiol(E2),fasting insulin(Fins),total cholesterol(TC)and triglycerides(TG)were significantly higher in the non-pregnant group than those in the pregnant group(P＜0.05).Meanwhile,there were significant differences in the composition of endometrial microorganisms between the two groups(P＜0.05).Among them,the abundance of Fusobacterium phylum,the abundance of Bacillus genus and the α-diversity(Chao1,Shannon,Simpson)index all showed significant differences(all P＜0.05).Binary Logistic regression multivariate analysis showed that the abundance of Fusobacterium phylum increased(OR=1.628,95%CI:1.416-1.841),the abundance of Bacillus genus decreased(OR=0.725,95%CI:0.557-0.934)and E2 increased(OR=1.654,95%CI:1.343-1.965).The elevated insulin(OR=1.691,95%CI:1.393-1.980)and decreased Shannon index(OR=0.388,95%CI:0.075-0.697)were independent risk factors for failure after subsequent transplantation.ROC curve analysis showed that the area under the curve(AUC)of the Shannon index was 0.836(95%CI:0.782-0.890),with the highest predictive efficacy.There was significant interaction among the subgroups of Fusobacteria,Bacillus genus,E2 and insulin in Shannon index on the subsequent transplantation outcomes of patients with RIF.Conclusion The independent risk factors for subsequent transplantation failure in RIF patients can be used as sensitive indicators to predict the subsequent transplantation outcomes of RIF patients,and Shannon index has a higher clinical predictive value.

Objective: To investigate the effect of aloperine (Alo) on the proliferation , migration and invasion of gastric cancer cells. Methods: Human gastric cancer cell lines HGC⁃27 and AGS were treated with 0 , 100 , and tion. Flow cytometry was used to detect apoptosis. Scratch and Transwell migration assays were used to detect cell migration. Transwell invasion assay was used to detect cell invasion. Western blot was used to detect the expression of proteins related to proliferation , apoptosis , migration , invasion and Hippo pathway. Results: Compared with the control group , the cell viability , number of colony formation , cell migration and invasion were significantly reduced after 100 and 200 μmol/L Alo treatment , and the apoptosis rate significantly increased (P < 0. 05) . Additionally , the expressions of proliferating cell nuclear antigen (PCNA) , B -cell lymphoma/leukemia⁃2 protein (Bcl⁃2) , neural cadherin ( N⁃cadherin) , Vimentin , and transcriptional co⁃activator with PDZ⁃binding motif ( TAZ)were significantly reduced , whereas the expressions of Bcl⁃2 ⁃associated X protein (Bax) , phosphorylated yes⁃asso⁃ciated protein (p⁃YAP) , and large tumor suppressor 1/2 (LATS1/2) significantly increased (P < 0. 05) . Conclusion Alo inhibits the proliferation , migration and invasion of gastric cancer cells HGC⁃27 and AGS by regulating the Hippo signaling pathway.

Lambert-Eaton myasthenic syndrome(LEMS)is an immune-mediated disorder involving neuromuscular junctions,characterized by muscle weakness,autonomic dysfunction,and reduced tendon reflexes.We report a LEMS case presented initially with dizziness and ataxia,followed by eyelid ptosis.Repetitive nerve stimulation revealed low frequency decreasing and high frequency increasing.P/Q type Voltage-gated calcium channels(VGCC)antibody was positive.Chest CT showed pulmonary nodules and enlarged mediastinal lymph nodes which were pathologically confirmed as small cell lung cancer.Given that ataxia is also an important manifestation of LEMS,the case report intends to increase the awareness of LEMS-related ataxia among neurologists to avoid misdiagnosis.

Objective:To analyze the characteristics of accidental injury death among Chinese population from 2005 to 2021 and predict its trends from 2022 to 2031.Methods:Based on the China Death Surveillance Database, the accidental injury death data of Chinese population from 2005 to 2021 were collected. The overall accidental injury death of Chinese population during the period was calculated, such as crude mortality rate and standardized mortality rate. A Joinpoint regression model was applied to calculate the standardized mortality rate including the annual percentage change (APC) and average annual percentage change (AAPC) of accidental injury death among Chinese population of different genders, in urban and rural areas, age groups and eastern, central and western regions from 2005 to 2021. The standardized mortality rate of accidental injuries among Chinese population from 2022 to 2031 was predicted by using the exponential smoothing method. Results:From 2005 to 2021, the crude mortality rate of accidental injury among Chinese population decreased from 45.96/100 000 in 2005 to 39.97/100 000 in 2021, with the standardized mortality rate decreasing from 50.20/100 000 in 2005 to 30.74/100 000 in 2021, which showed a monotonous downward trend (APC=AAPC=-2.63, P<0.01). From 2005 to 2021, the standardized mortality rate of accidental injury in males was higher than that in females, showing a downward trend in both males and females (AAPC male=-2.85, AAPC female=-2.17, P<0.01) . From 2005 to 2021, the standardized mortality rate of accidental injury in rural population was higher than that in urban population, showing a downward trend in both urban and rural population (AAPC city=-2.39, P<0.01; AAPC rural=-2.58, P<0.05). From 2005 to 2021, the standardized mortality rate of accidental injury in Chinese population mainly fell in the age group of 15-44 years. From 2005 to 2021, the standardized mortality rate of accidental injury in the western region was higher than that in the eastern and central regions and there was an inflection point from up to down in the standardized mortality rate of accidental injury in the western and central regions in 2011. As the forecasting results showed, the standardized mortality rate of accidental injury among Chinese population would be reduced from 30.26/100, 000 to 20.93/100, 000 from 2022 to 2031. Conclusions:The standardized mortality rate of accidental injury among Chinese population from 2005 to 2021 shows a downward trend. Moreover, the male, rural, young and middle-aged population and population in the western region are still the key groups needing prevention of accidental injuries. There will also be a downward trend in the standardized mortality rate of accidental injuries in Chinese population from 2022 to 2031.

Objective To investigate the effect and molecular mechanism of safflower yellow(SY)on wound healing of diabetic foot ulcer(DFU)in mice.Methods Forty-five C57BL/6 mice were injected intraperitoneally with streptozotocin to establish diabetic models.The diabetic mice were randomly divided into the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with insulin-like growth factor-1(IGF-1)group,with 9 mice in each group.Before modelling,mice in the model group were not given any intervention,mice in the low-dose SY intervention group and high-dose SY intervention group were injected intraperitoneally with 5 and 20 mg·kg-1 SY,respectively,and mice in the high-dose SY combined with IGF-1 group were injected intraperitoneally with 20 mg·kg-1 SY and 0.03 mg·kg-1 IGF-1.Except for the sham operation group,the DFU model was established by incising the dorsal skin of the foot in the remaining four groups of mice.No wound on the dorsal skin of the foot was made in the sham operation group,and the remaining surgical steps were the same as those in the model group.The body mass of mice in each group was measured on day 14 after modelling using an electronic scale,tail vein blood was collected for fasting blood glucose measurement,and the wound width was measured using a small vernier caliper.Then,the mice were executed to collect the wound tissues.Hematoxylin-eosin staining was used to detect the histopathological changes in the wound tissues of mice in each group.Reverse transcription-quantitative real-time polymerase chain reaction was used to measure the relative expression levels of platelet-derived growth factor(PDGF),vascular endothelial growth factor(VEGF),alpha-smooth muscle actin(α-SMA),type Ⅰ collagen(collagen Ⅰ),protein tyrosine phosphatase 1B(PTP1B)and advanced glycation end products(AGEs)mRNA in the wound tissues of mice in each group.Western blot was used to detect the relative expression levels of proliferation marker Ki-67,proliferating cell nuclear antigen(PCNA),apoptosis-associated proteins(caspase-3,caspase-6,and caspase-7),p85 phosphatidylinositol-3-kinase(PI3K)and phosphorylated protein kinase B(p-AKT)protein in the wound tissues of mice in each group.Enzyme-linked immunosorbent assay(ELISA)was used to measure the levels of tumor necrosis factor-α(TNF-α),interleukin(IL)-1β,and IL-6 in the wound tissues of mice in each group.Results The differences in blood glucose and body mass of mice among the sham operation group,model group,low-dose SY intervention group,high-dose SY intervention group,and high-dose SY combined with IGF-1 group were not statistically significant(P＞0.05).The healing rate of wound tissues in the high-dose SY intervention group was significantly greater than that in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the healing rate of wound tissues among the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＞0.05).In the high-dose SY intervention group,a large number of collagen fibers were densely and orderly arranged in the wound tissues,accompanied by a large number of neovessels;in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group,the wound tissues were sparsely populated with collagen fibers,accompanied by a small number of neovessels.The relative expression levels of PDGF,VEGF,α-SMA and collagen Ⅰ mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expression levels of PTP1B and AGEs mRNA in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).The relative expression levels of PDGF,VEGF,α-SMA,collagen Ⅰ,PTP1B and AGEs mRNA showed no statistically significant difference among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The relative expression levels of Ki-67 and PCNA protein in the wound tissues of mice in the high-dose SY intervention group were significantly higher than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01);the relative expre-ssion levels of caspase-3,caspase-6,caspase-7,p85 PI3K,and p-AKT protein were significantly lower than those in the model group,low-dose SY intervention group,and high-dose SY combined with IGF-1 group(P＜0.01).There was no statistically significant difference in the relative expression levels of Ki-67,PCNA,caspase-3,caspase-6,caspase-7,p85 PI3K and p-AKT protein among the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＞0.05).The levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the high-dose SY intervention group were significantly lower than those in the model,low-dose SY intervention,and high-dose SY combined with IGF-1 groups(P＜0.01).There was no statistically significant difference in the levels of TNF-α,IL-1β and IL-6 in the wound tissues of mice in the model,low-dose SY intervention and high-dose SY combined with IGF-1 groups(P＞0.05).Conclusion High-dose SY intervention promotes DFU wound healing in mice by increasing angiogenesis,collagen formation and cell proliferation and reducing insulin resistance,inflammatory response and cell apoptosis,which may be related to the inhibition of the PI3K/AKT pathway.

Objective:To analyze the mortality of accidental falls among the elderly in China from 2004 to 2019 and predict the standardized mortality from 2020 to 2024, so as to provide scientific evidence for formulating strategies to prevent accidental falls among the elderly.Methods:The death data of accidental falls of the elderly in China from 2004 to 2019 were collected from the China Death Cause Monitoring Data Set, and the total number of deaths, mortality rate and standardized mortality rate in the elderly from 2004 to 2019 and those data among them of different genders, residences and age groups were calculated. Joinpoint 4.8.0.1 statistical software was used to calculate the annual percent change (APC) and average annual percent change (AAPC) of standardized mortality. The Autoregressive Integrated Moving Average Model (ARIMA) was used to predict the standardized mortality rate of accidental falls among the elderly in China from 2020 to 2024. Results:The number of deaths related to accidental falls among the elderly in China was increased from 2 908 in 2004 to 23 709 in 2019. The mortality rate was increased from 51.89/100 000 in 2004 to 67.74/100 000 in 2019. The standardized mortality rate of accidental falls showed an overall upward trend from 2004 to 2019 (AAPC=1.65, P>0.05), including an upward trend from 2004 to 2010 (APC=1.66, P>0.05), a downward trend from 2010 to 2013 (APC=-9.67, P>0.05), and another upward trend from 2013 to 2019 (APC=7.83, P<0.01). The number of death and mortality rate related to accidental falls in Chinese elderly males and females both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed upward trends from 2004 to 2019 (AAPC males=2.19, AAPC females=0.29, all P>0.05). The standardized mortality rate in males was generally higher than that in females, with that of males showing an upward trend from 2013 to 2019 (APC=7.36, P<0.05) and that of female showing an upward trend from 2014 to2019 (APC=6.92, P>0.05). The number of deaths and mortality rate among the elderly living in rural and urban areas both showed upward trends from 2004 to 2019, and the standardized mortality rate also showed an upward trend from 2004 to 2019 (AAPC rural = 1.71, AAPC urban =1.00, all P>0.05). The standardized mortality rate among the elderly living in rural areas was generally higher than that in urban areas. The rural and urban elderly both showed upward trends from 2013 to 2019 (APC rural = 8.24, APC urban =6.11, all P<0.05). The number of death and mortality rate of different age groups all showed upward trends from 2004 to 2019. The standardized mortality rates of the elderly aged 65-74 years and ≥85 years also showed upward trends from 2004 to 2019 (AAPC 65-74 years=0.38, AAPC ≥ 85 years=4.09, all P>0.05). The standardized mortality rate of the elderly aged 75-84 years showed a downward trend from 2004 to 2019 (AAPC=-0.10, P>0.05), and that of the elderly aged 65-74 years showed an upward trend from 2010 to 2019 (APC=5.35, P<0.05). The standardized mortality rate of the elderly aged 75-84 years and ≥85 years showed upward trends from 2013 to 2019 (APC 75-84 years=6.49, APC ≥ 85 years=10.47, all P<0.05). The ARIMA prediction results showed that the overall standardized mortality rates of accidental falls in the elderly in China from 2020 to 2024 were 69.11/100 000, 72.33/100 000, 74.41/100 000, 76.34/100 000, and 76.48/100 000, respectively, showing a slow upward trend. Conclusions:The accidental fall-related mortality among the elderly in China showed an overall upward trend from 2004 to 2019, and the standardized mortality rate from 2020 to 2024 also shows an upward trend. The elderly who are male in gender, live in rural areas, or at age of ≥85 years are the key population for prevention and control of accidental fall. Active and effective measures should be taken to reduce accidental falls in the elderly so as to contribute to active and healthy aging.

Background::Urticaria is a common skin disease characterized by episodes of wheals, and it has a negative effect on patients’ quality of life. Large-scale population-based epidemiological studies of urticaria are scarce in China. The aim of this survey was to determine the prevalence, clinical forms, and risk factors of urticaria in the Chinese population.Methods::This survey was conducted in 35 cities from 31 provinces, autonomous regions, and municipalities of China. Two to three communities in each city were selected in this investigation. Participants completed questionnaires and received dermatological examinations. We analyzed the prevalence, clinical forms, and risk factors of urticaria.Results::In total, 44,875 questionnaires were distributed and 41,041 valid questionnaires were collected (17,563 male and 23,478 female participants). The lifetime prevalence of urticaria was 7.30%, with 8.26% in female and 6.34% in male individuals ( P < 0.05). The point prevalence of urticaria was 0.75%, with 0.79% in female and 0.71% in male individuals ( P < 0.05). Concomitant angioedema was found in 6.16% of patients. Adults had a higher prevalence of urticaria than adolescents and children. Living in urban areas, exposure to pollutants, an anxious or depressed psychological status, a personal and family history of allergy, thyroid diseases, and Helicobacter pylori infection were associated with a higher prevalence of urticaria. Smoking was correlated with a reduced risk of urticaria. Conclusion::This study demonstrated that the lifetime prevalence of urticaria was 7.30% and the point prevalence was 0.75% in the Chinese population; women had a higher prevalence of urticaria than men. Various factors were correlated with urticaria.