ObjectiveTo investigate the effect of Liuwei Dihuangwan drug-containing serum （LDP） on epithelial-mesenchymal transition （EMT） and the expression of cancer stem cell （CSC） properties in 4T1 cells from triple-negative breast cancer by intervening myeloid-derived suppressor cells （MDSCs）. MethodsSPF-grade female SD rats were randomly divided into three groups， which were given 0.39， 1.94， 3.89 g·kg^-1·d^-1 suspension of Liuwei Dihuangwan for 7 days， respectively， to prepare low-， medium-， and high-dose LDPs. 4T1 cells were inoculated subcutaneously into the mammary glands of SPF-grade female Balb/c mice to construct a transplantation tumor model. Bone marrow cells were extracted from the tibia and femur and induced into MDSCs in vitro. The cell counting kit-8 （CCK-8） assay was used to detect the viability of 4T1 cells and MDSCs. The number of MDSCs and the expressions of CSC surface markers CD44 and CD24 in 4T1 cells were detected by flow cytometry （FC）. The migration， invasion， and proliferation of 4T1 cells were detected by cell scratch assay， Transwell invasion assay， and plate colony-forming assay， respectively. Western blot （WB） was used to detect the protein expression of transforming growth factor-β （TGF-β）， nuclear factor-κB （NF-κB）， C-X-C motif chemokine ligand 2 （CXCL2）， E-cadherin， and N-cadherin. The expression of EMT-related proteins E-cadherin and N-cadherin were detected by immunofluorescence （IF）. ResultsCompared with the normal group， LDP showed no significant inhibitory effect on the cell viability of 4T1 cells， but it significantly reduced the viability and number of MDSCs and reduced the number of MDSCs， as well as the expression of TGF-β （P<0.05， P<0.01）. The migration， invasion， and proliferation of 4T1 cells were increased after co-culture with MDSCs （P<0.05， P<0.01）. The expressions of NF-κB， CXCL2， and N-cadherin and the proportion of CSC （CD44⁺CD24^-） were elevated （P<0.05， P<0.01）， while the expression of E-cadherin was decreased （P<0.05）. After the intervention of MDSCs with LDP， followed by co-culture with 4T1 cells， the migration， invasion， and proliferation of 4T1 cells were obviously reduced （P<0.01）. The expressions of NF-κB， CXCL2， and N-cadherin were decreased （P<0.05， P<0.01）， and the expression of E-cadherin was increased （P<0.05， P<0.01）. There was no statistical difference in the proportion of CSC （CD44⁺CD24^-） in 4T1 cells. However， the proportion of CSC （CD44⁺CD24^-） was decreased in the co-culture system of 4T1 cells and MDSCs with LDP intervention （P<0.05， P<0.01）. ConclusionLDP can reduce the viability and number of MDSCs and the expression of TGF-β， NF-κB， and CXCL2， reverse EMT， and reduce the characteristic expression of CSC to inhibit the migration， invasion， and proliferation of 4T1 cells.

ObjectiveTo investigate the effect of Liuwei Dihuangwan drug-containing serum （LDP） on epithelial-mesenchymal transition （EMT） and the expression of cancer stem cell （CSC） properties in 4T1 cells from triple-negative breast cancer by intervening myeloid-derived suppressor cells （MDSCs）. MethodsSPF-grade female SD rats were randomly divided into three groups， which were given 0.39， 1.94， 3.89 g·kg^-1·d^-1 suspension of Liuwei Dihuangwan for 7 days， respectively， to prepare low-， medium-， and high-dose LDPs. 4T1 cells were inoculated subcutaneously into the mammary glands of SPF-grade female Balb/c mice to construct a transplantation tumor model. Bone marrow cells were extracted from the tibia and femur and induced into MDSCs in vitro. The cell counting kit-8 （CCK-8） assay was used to detect the viability of 4T1 cells and MDSCs. The number of MDSCs and the expressions of CSC surface markers CD44 and CD24 in 4T1 cells were detected by flow cytometry （FC）. The migration， invasion， and proliferation of 4T1 cells were detected by cell scratch assay， Transwell invasion assay， and plate colony-forming assay， respectively. Western blot （WB） was used to detect the protein expression of transforming growth factor-β （TGF-β）， nuclear factor-κB （NF-κB）， C-X-C motif chemokine ligand 2 （CXCL2）， E-cadherin， and N-cadherin. The expression of EMT-related proteins E-cadherin and N-cadherin were detected by immunofluorescence （IF）. ResultsCompared with the normal group， LDP showed no significant inhibitory effect on the cell viability of 4T1 cells， but it significantly reduced the viability and number of MDSCs and reduced the number of MDSCs， as well as the expression of TGF-β （P<0.05， P<0.01）. The migration， invasion， and proliferation of 4T1 cells were increased after co-culture with MDSCs （P<0.05， P<0.01）. The expressions of NF-κB， CXCL2， and N-cadherin and the proportion of CSC （CD44⁺CD24^-） were elevated （P<0.05， P<0.01）， while the expression of E-cadherin was decreased （P<0.05）. After the intervention of MDSCs with LDP， followed by co-culture with 4T1 cells， the migration， invasion， and proliferation of 4T1 cells were obviously reduced （P<0.01）. The expressions of NF-κB， CXCL2， and N-cadherin were decreased （P<0.05， P<0.01）， and the expression of E-cadherin was increased （P<0.05， P<0.01）. There was no statistical difference in the proportion of CSC （CD44⁺CD24^-） in 4T1 cells. However， the proportion of CSC （CD44⁺CD24^-） was decreased in the co-culture system of 4T1 cells and MDSCs with LDP intervention （P<0.05， P<0.01）. ConclusionLDP can reduce the viability and number of MDSCs and the expression of TGF-β， NF-κB， and CXCL2， reverse EMT， and reduce the characteristic expression of CSC to inhibit the migration， invasion， and proliferation of 4T1 cells.

BACKGROUND: Asthma is a common chronic inflammatory airway disease and intermittent hypoxia is increasingly recognized as a factor that may impact disease progression. The present study investigated whether intermittent hypoxia (IH) could aggravate asthma by promoting hypoxia-inducible factor-1α (HIF-1α)/nucleotide-binding oligomerization domain (NOD)-like receptor pyrin domain-containing protein 3 (NLRP3)/interleukin (IL)-1β-dependent pyroptosis and the inflammatory response and further elucidated the underlying molecular mechanisms involved. METHODS: A total of 49 patients diagnosed with severe bronchial asthma and diagnosed by polysomnography were enrolled at Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, between January 2022 and December 2022, and their general data and induced sputum were collected. BEAS-2B cells were treated with IL-13 and subjected to IH. An ovalbumin (OVA)-treated mouse model was also used to assess the effects of chronic intermittent hypoxia (CIH) on asthma. Pyroptosis, the inflammatory response, and related signalling pathways were assessed in vivo and in vitro . RESULTS: In this study, as the apnoea and hypopnea index (AHI) increased, the proportion of patients with uncontrolled asthma increased. The proportions of neutrophils and the levels of IL-6, IL-8, HIF-1α and NLRP3 in induced sputum were related to the AHI. NLRP3-mediated pyroptosis, which could be mediated by the HIF-1α signalling pathway, was activated in IL-13 plus IH-treated BEAS-2B cells and in the lungs of OVA/CIH mice. HIF-1α downregulation significantly reduced lung pyroptosis and ameliorated neutrophil inflammation by modulating the NLRP3/IL-1β pathway both in vitro and in vivo . Similarly, pretreatment with LW6, an inhibitor of HIF-1α, effectively blocked the generation of inflammatory cytokines in neutrophils. In addition, administration of the NLRP3 activator nigericin obviously increased lung neutrophil inflammation. CONCLUSIONS Obstructive sleep apnoea-hypopnea syndrome (OSAHS) is a risk factor for asthma exacerbation. IH aggravates neutrophil inflammation in asthma via NLRP3/IL-1β-dependent pyroptosis mediated by the HIF-1α signalling pathway, which should be considered a potential therapeutic target for the treatment of asthma with OSAHS.
NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Humans ; Asthma/metabolism* ; Animals ; Pyroptosis/physiology* ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism* ; Mice ; Signal Transduction/physiology* ; Male ; Hypoxia/metabolism* ; Female ; Interleukin-1beta/metabolism* ; Adult ; Inflammation/metabolism* ; Middle Aged ; Mice, Inbred C57BL

Objective:To establish a reference interval for serum iodine of pregnant women with normal thyroid function and to analyze the relationship between serum iodine and thyroid disease risk.Methods:From July 2022 to October 2023, using cross-sectional survey method, pregnant women aged 18 to 48 years old who had lived in iodine-deficient areas in the six provinces of China (Shanxi Province, Fujian Province, Yunnan Province, Xinjiang Uygur Autonomous Region, Zhejiang Province, and Anhui Province) for more than six months were selected as the survey subjects. Blood samples were collected, serum iodine was tested, and the percentile method was used to establish a reference interval for serum iodine of pregnant women with normal thyroid function. Meanwhile, serum levels of free thyroxine, thyroid stimulating hormone, thyroglobulin antibody (TgAb), and thyroid peroxidase antibody (TPOAb) were tested, and logistic regression was used to analyze the relationship between serum iodine and thyroid disease risk.Results:A total of 1 409 pregnant women from 6 provinces were investigated, including 1 087 with normal thyroid function and 322 with abnormal thyroid function. The median serum iodine level of pregnant women with normal thyroid function was 79.74 μg/L, and the preliminary reference interval for serum iodine was 47.57 - 128.96 μg/L. When serum iodine levels were lower (< 47.57 μg/L), pregnant women had a significantly increased risk of developing TgAb positivity, TPOAb positivity, hypothyroxinemia, hypothyroidism, and autoimmune thyroiditis ( OR = 4.44, 2.91, 3.41, 41.67, 23.43, P < 0.05). When serum iodine levels were high (> 128.96 μg/L), pregnant women had a significantly increased risk of developing hyperthyroidism ( OR = 9.91, P = 0.001). Conclusions:The reference interval for serum iodine of pregnant women with normal thyroid function is successfully established. Low serum iodine levels are associated with an increased risk of TgAb positivity, TPOAb positivity, hypothyroxinemia, hypothyroidism, and autoimmune thyroiditis, while high serum iodine levels are associated with an increased risk of hyperthyroidism.

Objective:To establish a reference interval for serum iodine of pregnant women with normal thyroid function and to analyze the relationship between serum iodine and thyroid disease risk.Methods:From July 2022 to October 2023, using cross-sectional survey method, pregnant women aged 18 to 48 years old who had lived in iodine-deficient areas in the six provinces of China (Shanxi Province, Fujian Province, Yunnan Province, Xinjiang Uygur Autonomous Region, Zhejiang Province, and Anhui Province) for more than six months were selected as the survey subjects. Blood samples were collected, serum iodine was tested, and the percentile method was used to establish a reference interval for serum iodine of pregnant women with normal thyroid function. Meanwhile, serum levels of free thyroxine, thyroid stimulating hormone, thyroglobulin antibody (TgAb), and thyroid peroxidase antibody (TPOAb) were tested, and logistic regression was used to analyze the relationship between serum iodine and thyroid disease risk.Results:A total of 1 409 pregnant women from 6 provinces were investigated, including 1 087 with normal thyroid function and 322 with abnormal thyroid function. The median serum iodine level of pregnant women with normal thyroid function was 79.74 μg/L, and the preliminary reference interval for serum iodine was 47.57 - 128.96 μg/L. When serum iodine levels were lower (< 47.57 μg/L), pregnant women had a significantly increased risk of developing TgAb positivity, TPOAb positivity, hypothyroxinemia, hypothyroidism, and autoimmune thyroiditis ( OR = 4.44, 2.91, 3.41, 41.67, 23.43, P < 0.05). When serum iodine levels were high (> 128.96 μg/L), pregnant women had a significantly increased risk of developing hyperthyroidism ( OR = 9.91, P = 0.001). Conclusions:The reference interval for serum iodine of pregnant women with normal thyroid function is successfully established. Low serum iodine levels are associated with an increased risk of TgAb positivity, TPOAb positivity, hypothyroxinemia, hypothyroidism, and autoimmune thyroiditis, while high serum iodine levels are associated with an increased risk of hyperthyroidism.

Objective To investigate the clinical application value of MRI Radiomics score(Radscore)combined with clinicopatho-logical features in predicting postoperative progression-free survival(PFS)of patients with endometrial cancer(EC).Methods A total of 127 patients with EC were selected.The radiomic features of the lesions were extracted from T2 WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images.The features were screened by random forest model and Radscore was calcu-lated.Simultaneously,clinical and pathological characteristics of patients were collected and incorporated,and multivariate Cox regression analysis was used to screen the risk factors related to PFS.The MRI Radscore and clinicopathological features were mapped to the nomogram,and the performance of nomogram was evaluated by receiver operating characteristic(ROC)curve and calibration curve.Results Multivariate Cox regression analysis showed that progesterone receptor(PR),human epididymis protein 4(HE4)and MRI Radscore were independent risk factors for predicting PFS in patients with EC(P＜0.05).The area under the curve(AUC)of the predicted PFS at 1,3 and 5 years after surgery were 0.91,0.804 and 0.776,respectively.Calibration curves showed that nomogram had a good fit in predicting PFS in patients with EC 1,3 and 5 years after surgery.Conclusion The nomogram con-structed based on multi-sequence MRI Radscore and clinicopathological features has favorable accuracy and stability in predicting postoperative PFS in individuals diagnosed with EC.

Microbial ecosystem comprises a complex community in which bacteria interact with each other. The potential roles of the intestinal microbiome play in human health have gained considerable attention. The imbalance of gut microbial community has been looked to multiple chronic diseases. Cardiovascular diseases (CVDs) are leading causes of morbidity worldwide and are influenced by genetic and environmental factors. Recent advances have provided scientific evidence that CVD may also be attributed to gut microbiome. In this review, we highlight the complex interplay between microbes, their metabolites, and the potential influence on the generation and development of CVDs. The therapeutic potential of using intestinal microbiomes to treat CVD is also discussed. It is quite possible that gut microbes may be used for clinical treatments of CVD in the near future.

Objective:To investigate the incidence, clinical characteristics and risk factors for hip fractures in patients within two years after stroke onset.Methods:A total of 332 persons with first-onset stroke from the neurology department of our hospital between 1 June 2013 and 31 December 2014 were recruited and were divided into the hip fracture group and the non-hip fracture group.Clinical characteristics were recorded.Vision was tested as normal or impaired.Patients were accessed by the National Institutes of Health Stroke Scale(NIHSS), Behavioral Inattention Test, Baking Tray Task, Mini-Mental State Examination(MMSE), Birgitta Lindmark(BL)motor assessment scale, Berg Balance Scale(BBS), Timed Up & Go(TUG)Scale, and Stops Walking When Talking(SWWT)Scale.The clinic characteristics and risk factors for hip fractures were compared between the two groups after a 2-year follow-up.The accuracy of risk factors for fracture prediction was assessed by the sensitivity, specificity, and positive and negative predictive values.Results:Of 332 patients with stroke, 16 cases fractured their hips within two years after stroke onset, which corresponded to an incidence of 33‰/year(95% CI: 15‰/year-50‰/year). The 2-year mortality rate was 44%(95% CI: 25%-60%)and 48%(95% CI: 42%-54%)in patients with and without hip fractures respectively( χ2=0.036, P=0.724). The mean survival time for patients with and without hip fracture was 2.72 years(95% CI: 1.45-2.79)and 2.21 years(95% CI: 1.48-2.34)respectively.The proportions of patients with previous fractures history( χ2=16.780, P=0.041)and impaired vision( χ2=11.210, P=0.027), MMSE scale score( U=14.220, P=0.031), TUG ≥ 15 s( χ2=18.560, P=0.000)were higher, and SWWT( χ2=20.340, P=0.000)was lower in the hip fracture group than in the non-hip fracture group.The negative predictive values of previous fractures history, impaired vision, TUG and SWWT were higher than their positive predictive value.The specificities of previous fractures history, impaired vision, and SWWT were higher than their sensitivities.And the sensitivity of TUG was higher than its specificity. Conclusions:Hip fractures after stroke are common in elderly patients.Fractures often occur during daytime at home in daily activities.The previous fractures history, visual and cognitive dysfunction and impaired functional mobility are risk factors for hip fractures.We should take measures to prevent falls according to the relevant factors.Among the test scales, the timed up & go(TUG)scale could much more accurately identify patients at high risk for hip fractures.

Objective To examine the incidence ,clinical characteristics ,and risk factors for falls within two years after stroke in elderly patients. Methods A total of 365 elderly stroke patients from the Department of Neurology at the 8th Nanning People's Hospital were recruited from June 1 , 2013 to December 31 ,2014. They were divided into a fall group and a non-fall group and were followed up for two years. The incidence and clinic characteristics of falls were analyzed. The risk factors for falls were analyzed by multiple Logistic regression analysis. Results Of the 365 stroke patients included in this study ,falls were observed in 146(40.2％ )patients. The interval between the stroke and the first fall :72(49.3％ )patients had the first fall within 3 months;22(15.1％ )occurred between 4 and 6 months;20 (13.7％ )between 7 and 12 months ;17 (11.6％ )between 13 and 18 months ;and 15 (10.3％ )between 19 and 24 months.A hundred and five(71.9％ )patients fell during daytime and 41 (28.1％ )patients during night.Eighteen(12.3％ )patients had one fall ;65(44.5％ )patients fell 2 to 4 times ;60(41.1％ )patients fell 5 to 10 times ;and 3(2.1％ )patients fell over 10 times.A total of 709 falls were observed.Places of falls :102(69.9％ )falls happened indoors and 44(30.1％ )falls occurred outdoors.Circumstances of falls :27 (18.5％ )patients fell when turning over ;23 (15.8％ )fell when rising from a seating position ;4(2.7％ )patients fell when showering ;15(10.3％ )patients fell while standing ;9(6.8％ )fell when turning around ;56(38.3％ )fell while walking ;and 12(8.2％ )fell while climbing the stairs or running.The severity of falls :52(35.6％ )patients had no injury ;78(53.2％ ) suffered soft tissue injury ;16 (11.0％ )had fractures ;and 78 (53.2％ )had fear of falling.Multiple Logistic regression analysis showed that age(OR=2.41 ;95％ CI :1.69-3.05) ,history of falls(OR =2.85 ;95％ CI :1.46-3.81) ,history of stroke(OR=1.87 ;95％ CI :1.12-2.79) ,right hemiplegia(OR=2.37 ;95％ CI :1.62-4.59) ,left hemiplegia(OR= 2.47 ;95％ CI :1.46-4.78) ,paraplegia(OR= 2.55 ;95％ CI :1.57-4.98) ,visual impairment(OR=2.35 ;95％ CI :1.35-6.62) ,apraxia(OR=2.53 ;95％ CI :1.42-5.63) ,unilateral spatial neglect (OR=3.34 ;95％ CI :2.82-6.34) ,use of psychotropic medications (OR= 1.76 ;95％ CI :1.11-1.98) ,impaired physical mobility (OR = 1.58 ;95％ CI :1.82-2.91) ,low MMSE scale(OR = 3.42 ;95％ CI :1.38-7.41) ,low Barthel Index score(OR = 2.83 ;95％ CI :0.97-4.68) ,BBS scale<45(OR=2.48 ;95％ CI :1.27-4.18) ,TUG>15seconds(OR=3.56 ;95％ CI :1.91-5.23) ,and lack of rehabilitation therapy (OR=3.42 ;95％ CI :1.38-7.41)were independent predictors for falls(all P<0.05). Conclusions Falls are common among elderly patients within two years after stroke.Most falls happen indoors ,during daytime and while moving.Age ,history of falls ,history of stroke ,hemiplegia ,visual impairment ,apraxia ,unilateral spatial neglect ,use of psychotropic medications ,walk with a walker ,low MMSE scale ,low Barthel Index score ,BBS scale<45 ,TUG>15 seconds ,and lack of rehabilitation therapy are independent risk factors for falls after stroke.

Objective To establish a BALB/c mouse model of total hysterectomy and to investigate and analyze its characteristics and formation mechanism. Methods The control group was fed conventionally without any treatment. The mice in the model group were anesthetized and performed hysterectomy. The animals in the sham-operated group had abdominal cavity opened and only exposing the uterus. The changes of body weight were observed dynamically,and at the end of the fourth weeks. The concentration of serum estradiol was determined and histological structure of the ovaries was examined. Results The general status of all the mice after operation was good without obvious inflammation, and the incision healed completely. There was no significant difference in the body weight before operation among the mice, whereas the weight of model group mice was higher than the control group and sham-operation group at the end of the second,third and forth weeks(P< 0.05). The estradiol contents of the model group was significantly lower than that in control group and sham operation group(P< 0.01). The histological structure of ovaries in the control group and sham-operation group was normal,however the model group showed differences,such as irregular shape of the ovaries,changed number of mature follicles, loosely distributed granulosa cells, and apoptosis. Conclusions The mouse model of total hysterectomy established in our study can well simulate the clinical manifestations of ovarian dysfunction after operation, and is an ideal model for the study of complications after ovariectomy and screening of drugs.