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.

BACKGROUND:Current research has shown that human umbilical cord mesenchymal stem cells and melatonin can both improve ovarian function.However,the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency have not been reported.OBJECTIVE:To investigate the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency.METHODS:Forty Wistar rats with normal estrous cycle were randomly divided into control group,model group,human umbilical cord mesenchymal stem cell group,melatonin group,and human umbilical cord mesenchymal stem cell+melatonin group,with 8 rats in each group.In addition to the control group,the rat model of premature ovarian insufficiency was constructed by intraperitoneal injection of cisplatin solution.The rats in the human umbilical cord mesenchymal stem cell group and the human umbilical cord mesenchymal stem cell+melatonin group were injected with 1×106 human umbilical cord mesenchymal stem cells in the tail vein at 1,6,and 11 days after modeling,respectively.The rats in the melatonin group and human umbilical cord mesenchymal stem cell+melatonin group were injected intraperitoneally with 10 mg/kg melatonin daily.The changes in body mass and estrous cycle of rats were monitored during treatment.After 14 days of treatment,ELISA was used to detect serum levels of estradiol,follicle stimulating hormone,luteinizing hormone,and anti Mullerian hormone.Ovarian index was calculated.Hematoxylin-eosin staining was performed to observe ovarian histological morphology.Ultrastructure of ovarian granulosa cells was observed by transmission electron microscopy.Western blot assay was conducted to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and LC3 and P62 autophagy proteins in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of rats in the model group decreased gradually,the estrous cycle was disturbed,and the ovarian index decreased significantly(P＜0.01).The levels of estradiol and anti-Mullerian hormone were decreased(P＜0.01),while the levels of follicle stimulating hormone and luteinizing hormone were increased(P＜0.01).The histological morphology and granulosa cell ultrastructure of ovary were seriously damaged.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly decreased(P＜0.01),while the protein expressions of LC3Ⅱ/Ⅰ were significantly increased(P＜0.001).(2)Compared with the model group,the body mass of rats in all treatment groups recovered gradually,the estrous cycle of some rats returned to normal,and the ovarian index was significantly increased(P＜0.01);the levels of estradiol and anti-Mullerian hormone were increased(P＜0.05),while the levels of follicle stimulating hormone and luteinizing hormone were decreased(P＜0.05).The histological morphology and ultrastructure of ovary were significantly improved.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly increased(P＜0.001),while the protein expression of LC3Ⅱ/Ⅰ was significantly decreased(P＜0.01).Human umbilical cord mesenchymal stem cell+melatonin group showed more significant improvement in the above indexes.The results suggest that human umbilical cord mesenchymal stem cells combined with melatonin may inhibit ovarian granulosa cell autophagy by upregulating PI3K/AKT/mTOR signaling pathway to treat premature ovarian insufficiency.

Objective To analyze the MRI imaging characteristics of brain metastases in non-small cell lung cancer(NSCLC)with different epidermal growth factor receptor(EGFR)mutation types and programmed cell death-ligand 1(PD-L1)expression,and to provide imaging diagnostic support for patients who can't undergo genetic and immunohistochemical testing.Methods A retrospec-tive selection was performed in 88 patients diagnosed with brain metastases of NSCLC,all patients were divided into EGFR mutation group and wild group according to the results of genetic testing,and patients with EGFR mutation group were divided into EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expression negative group according to whether the expression of PD-L1 was≥1％.The clinical data and MR image characteristics of brain metastases were compared in EGFR mutation group and wild group,as well as in EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expres-sion negative group.Results There were statistically significant differences in smoking history and intracranial symptoms between EGFR mutation group and wild group(P＜0.05).The edema diameter,edema index and enhancement ratio of EGFR mutation group and wild group were(0.67±1.10)cm,0.39±0.54,0.32±0.17 and(1.57±2.04)cm,1.05±1.21,0.53±0.27,respectively,and the differences were statistically significant(P＜0.05).There were 43 cases and 23 cases in EGFR mutation group and wild group with ≥2 metastases,respectively,and the difference was statistically significant(P＜0.05).Compared with＞60 years old,there were 15 patients(75％)of EGFR mutation with PD-L1 expres-sion positive in≤60 years old(P＜0.05).Conclusion Compared with EGFR wild patients,patients with EGFR mutation have more brain metastases(≥2),milder enhancement,less peritumoral edema,and fewer intracranial symptoms at initial diagnosis,and patients with EGFR mutation aged≤60 years are more likely to have PD-L1 expression positive.

A multi-layer feature attention enhanced network is proposed to further improve the diagnostic accuracy of the severity of diabetic retinopathy.To address the inconsistent expression of global and local features when processing diabetic retinopathy images,a dual-branch parallel model combining ResNet-50 and DeiT-S is employed as the backbone architecture,and a feature fusion module is designed at the end of the network.Concurrently,a multi-scale location awareness enhancement module is developed to extract multi-scale information through dilated convolution with positional attention mechanism for enhancing the feature representation of lesions in fundus images,and a local feature enhancement module is constructed to strengthen the model's capability in extracting local information,thus improving model's capability to identify small lesions and minor changes.The experimental results show that the proposed multi-layer feature attention enhanced network achieves an accuracy of 87.61%,exhibiting excellent classification performance.This advancement provides a strong support for further development of diabetic retinopathy detection technology.

BACKGROUND:Current research has shown that human umbilical cord mesenchymal stem cells and melatonin can both improve ovarian function.However,the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency have not been reported.OBJECTIVE:To investigate the protective effect and mechanism of human umbilical cord mesenchymal stem cells combined with melatonin on chemotherapy-induced premature ovarian insufficiency.METHODS:Forty Wistar rats with normal estrous cycle were randomly divided into control group,model group,human umbilical cord mesenchymal stem cell group,melatonin group,and human umbilical cord mesenchymal stem cell+melatonin group,with 8 rats in each group.In addition to the control group,the rat model of premature ovarian insufficiency was constructed by intraperitoneal injection of cisplatin solution.The rats in the human umbilical cord mesenchymal stem cell group and the human umbilical cord mesenchymal stem cell+melatonin group were injected with 1×106 human umbilical cord mesenchymal stem cells in the tail vein at 1,6,and 11 days after modeling,respectively.The rats in the melatonin group and human umbilical cord mesenchymal stem cell+melatonin group were injected intraperitoneally with 10 mg/kg melatonin daily.The changes in body mass and estrous cycle of rats were monitored during treatment.After 14 days of treatment,ELISA was used to detect serum levels of estradiol,follicle stimulating hormone,luteinizing hormone,and anti Mullerian hormone.Ovarian index was calculated.Hematoxylin-eosin staining was performed to observe ovarian histological morphology.Ultrastructure of ovarian granulosa cells was observed by transmission electron microscopy.Western blot assay was conducted to detect the expression of PI3K/AKT/mTOR signaling pathway proteins and LC3 and P62 autophagy proteins in ovarian tissues.RESULTS AND CONCLUSION:(1)Compared with the control group,the body mass of rats in the model group decreased gradually,the estrous cycle was disturbed,and the ovarian index decreased significantly(P＜0.01).The levels of estradiol and anti-Mullerian hormone were decreased(P＜0.01),while the levels of follicle stimulating hormone and luteinizing hormone were increased(P＜0.01).The histological morphology and granulosa cell ultrastructure of ovary were seriously damaged.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly decreased(P＜0.01),while the protein expressions of LC3Ⅱ/Ⅰ were significantly increased(P＜0.001).(2)Compared with the model group,the body mass of rats in all treatment groups recovered gradually,the estrous cycle of some rats returned to normal,and the ovarian index was significantly increased(P＜0.01);the levels of estradiol and anti-Mullerian hormone were increased(P＜0.05),while the levels of follicle stimulating hormone and luteinizing hormone were decreased(P＜0.05).The histological morphology and ultrastructure of ovary were significantly improved.The protein expressions of p-PI3K/PI3K,p-AKT/AKT,p-mTOR/mTOR,and P62 were significantly increased(P＜0.001),while the protein expression of LC3Ⅱ/Ⅰ was significantly decreased(P＜0.01).Human umbilical cord mesenchymal stem cell+melatonin group showed more significant improvement in the above indexes.The results suggest that human umbilical cord mesenchymal stem cells combined with melatonin may inhibit ovarian granulosa cell autophagy by upregulating PI3K/AKT/mTOR signaling pathway to treat premature ovarian insufficiency.

Objective To analyze the MRI imaging characteristics of brain metastases in non-small cell lung cancer(NSCLC)with different epidermal growth factor receptor(EGFR)mutation types and programmed cell death-ligand 1(PD-L1)expression,and to provide imaging diagnostic support for patients who can't undergo genetic and immunohistochemical testing.Methods A retrospec-tive selection was performed in 88 patients diagnosed with brain metastases of NSCLC,all patients were divided into EGFR mutation group and wild group according to the results of genetic testing,and patients with EGFR mutation group were divided into EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expression negative group according to whether the expression of PD-L1 was≥1％.The clinical data and MR image characteristics of brain metastases were compared in EGFR mutation group and wild group,as well as in EGFR mutation with PD-L1 expression positive group and EGFR mutation with PD-L1 expres-sion negative group.Results There were statistically significant differences in smoking history and intracranial symptoms between EGFR mutation group and wild group(P＜0.05).The edema diameter,edema index and enhancement ratio of EGFR mutation group and wild group were(0.67±1.10)cm,0.39±0.54,0.32±0.17 and(1.57±2.04)cm,1.05±1.21,0.53±0.27,respectively,and the differences were statistically significant(P＜0.05).There were 43 cases and 23 cases in EGFR mutation group and wild group with ≥2 metastases,respectively,and the difference was statistically significant(P＜0.05).Compared with＞60 years old,there were 15 patients(75％)of EGFR mutation with PD-L1 expres-sion positive in≤60 years old(P＜0.05).Conclusion Compared with EGFR wild patients,patients with EGFR mutation have more brain metastases(≥2),milder enhancement,less peritumoral edema,and fewer intracranial symptoms at initial diagnosis,and patients with EGFR mutation aged≤60 years are more likely to have PD-L1 expression positive.

A multi-layer feature attention enhanced network is proposed to further improve the diagnostic accuracy of the severity of diabetic retinopathy.To address the inconsistent expression of global and local features when processing diabetic retinopathy images,a dual-branch parallel model combining ResNet-50 and DeiT-S is employed as the backbone architecture,and a feature fusion module is designed at the end of the network.Concurrently,a multi-scale location awareness enhancement module is developed to extract multi-scale information through dilated convolution with positional attention mechanism for enhancing the feature representation of lesions in fundus images,and a local feature enhancement module is constructed to strengthen the model's capability in extracting local information,thus improving model's capability to identify small lesions and minor changes.The experimental results show that the proposed multi-layer feature attention enhanced network achieves an accuracy of 87.61%,exhibiting excellent classification performance.This advancement provides a strong support for further development of diabetic retinopathy detection technology.

Objective To investigate the risk factors associated with prolonged hospitalization in patients diagnosed with diabetic foot ulcers(DFU),to develop a predictive model,and to conduct internal validation of the model.Methods The clinical data of DFU patients admitted to West China Hospital,Sichuan University between January 2012 and December 2022 were retrospectively collected.The subjects were randomly assigned to a training cohort and a validation cohort at a ratio of 7 to 3.Hospital stays longer than 75th percentile were defined as prolonged length-of-stay.A thorough analysis of the risk factors was conducted using the training cohort,which enabled the development of an accurate risk prediction model.To ensure robustness,the model was internally validated using the validation cohort.Results A total of 967 inpatients with DFU were included,among whom 245 patients were identified as having an extended length-of-stay.The training cohort consisted of 622 patients,while the validation cohort comprised 291 patients.Multivariate logistic regression analysis revealed that smoking history(odds ratio[OR]=1.67,95%confidence interval[CI],1.13 to 2.48,P=0.010),Wagner grade 3 or higher(OR=7.13,95%CI,3.68 to 13.83,P＜0.001),midfoot ulcers(OR=1.99,95%CI,1.07 to 3.72,P=0.030),posterior foot ulcers(OR=3.68,95%CI,1.83 to 7.41,P＜0.001),multisite ulcers(OR=2.91,95%CI,1.80 to 4.69,P＜0.001),wound size≥3 cm2(OR=2.00,95%CI,1.28-3.11,P=0.002),and white blood cell count(OR=1.11,95%CI,1.05 to 1.18,P＜0.001)were associated with an increased risk of prolonged length of stay.Additionally,a nomogram was constructed based on the identified risk factors.The areas under the receiver operating characteristic(ROC)curves for both the training cohort and the validation cohort were 0.782(95%CI,0.745 to 0.820)and 0.756(95%CI,0.694 to 0.818),respectively,indicating robust predictive performance.Furthermore,the calibration plot demonstrated optimal concordance between the predicted probabilities and the observed outcomes in both the training and the validation cohorts.Conclusion Smoking history,Wagner grade≥3,midfoot ulcers,posterior foot ulcers,multisite ulcers,ulcer area≥3 cm2,and elevated white blood cell count are identified as independent predictors of prolonged hospitalization.Therefore,it is imperative that clinicians conduct a comprehensive patient evaluation and implement appropriate diagnostic and therapeutic strategies to effectively shorten the length of stay for DFU patients.

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.