Objective To observe the effects of grain-sized moxibustion on Th1 cell/Th2 cell(Th1/Th2)balance and transcription factors T-box transcription factor(T-bet)and GATA binding protein 3(GATA3)in immunosuppressive mice induced by chemotherapy.Methods According to the random number table method,32 SPF male CD-1(ICR)mice were randomly divided into the normal group,model group,levamisole hydrochloride group,and grain-sized moxibustion group,with eight mice per group.Except for the normal group,the immunosuppressive model was established by intraperitoneal injection of cyclophosphamide(80 mg/kg,once daily for three consecutive days).Mice in the levamisole hydrochloride group were given levamisole hydrochloride solution(10 mg/kg)by gavage.Mice in the grain-sized moxibustion group was given grain-sized moxibustion at"Guanyuan"(CV4),bilateral"Zusanli"(ST36),and bilateral"Sanyinjiao"(SP6),with three Zhuang at each acupoint for approximately 30 s each.The intervention was administered once daily for seven consecutive days.The general condition of mice was observed.The spleen mass and spleen index were detected.The pathological changes of spleen tissue were observed by HE staining.The protein and mRNA expressions of T-bet,GATA3,interferon-γ(IFN-γ),and interleukin(IL)-4 in spleen tissue of mice were detected by Western blotting and real-time PCR.The contents of IFN-γ,IL-2,and IL-4 in serum of mice were detected by enzyme-linked immunosorbent assay.Results Compared with the normal group,the mice in the model group were slow in response,unstable in gait;the spleen weight and spleen index were increased(P<0.05);the structure of spleen tissue was disordered,the mRNA and protein expressions of T-bet and IFN-γ in spleen tissue were decreased,and the mRNA and protein expressions of GATA3 and IL-4 were increased(P<0.05);the contents of IFN-γ and IL-2 in serum were decreased,and the content of IL-4 was increased(P<0.05).Compared with the model group,the general condition of mice in the levamisole hydrochloride group and the grain-sized moxibustion group was improved,the structure of spleen tissue was improved,the mRNA and protein expressions of T-bet and IFN-γ in spleen tissue were decreased,and the mRNA and protein expressions of GATA3 and IL-4 were increased(P<0.05);the contents of IFN-γ and IL-2 in serum were decreased,and the content of IL-4 was increased(P<0.05).Conclusion Grain-sized moxibustion can significantly improve the immunosuppressive symptoms induced by chemotherapy.The mechanism may be through regulating the expressions of transcription factors T-bet and GATA3,regulating Th1/Th2 balance,and thus restoring the immune balance.

ObjectiveTo explore the effect of grain-sized moxibustion at "Zhongwan （RN12）" "Tianshu （ST25）" and "Shangjuxu （ST37）" on the colon tissue of mice with ulcerative colitis （UC）， and to analyze the potential mechanism. MethodsForty C57BL/6 male mice were randomly divided into blank group， model group， moxibustion group and mesalazine group， with 10 mice in each group. In all the groups except for the blank group， UC mouse model was prepared by freely drinking 3% sodium dextran sulfate solution. After successful modeling， the moxibustion group was treated with grain-sized moxibustion at Zhongwan， Tianshu and Shangjuxu ， 3 cones per acupoint， 30 s of each cone. The mesalazine group was given 300 mg/kg of mesalazine enteric-coated tablet solution by gavage. The blank group and the model group were only fixed by grasping without any intervention. Each group was intervened once a day for 7 consecutive days. The general condition of mice in each group was observed， and the disease activity index （DAI） score was evaluated. The colon length， intestinal weight and colon mucosal injury score were detected. The contents of serum intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α） were detected by ELISA. The pathological changes of colon tissue were observed by HE staining. The mRNA and protein expressions of non-receptor tyrosine protein kinase 2 （JAK2）， signal transducer and activator of transcription 3 （STAT3） and suppressor of cytokine signaling 3 （SOCS3） in colon tissue of mice were detected by real-time fluorescence quantitative PCR and immunohistochemistry， respectively. The mean fluorescence intensity of JAK2 and SOCS3 in colon tissue of mice was detected by immunofluorescence double staining. ResultsCompared to the blank group， the mice in the model group had unclean perianal area， unformed stool， destroyed colonic mucosal morphology， shortened body weight and colon length， increased DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels， increased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and decreased mRNA and protein expression of SOCS3 （P＜0.01）. Compared to those in the model group， the perianal area of mice in the moxibustion group and the mesalazine group was improved， and the colonic mucosal morphology was more complete； body weight and colon length increased， while DAI score， intestinal weight index， colonic mucosal injury and pathological score， serum ICAM-1， IL-6 and TNF-α levels decreased， with decreased mRNA and protein expression of JAK2 and STAT3 in colon tissue， and increased SOCS3 mRNA and protein expression （ P＜0.01 or P＜0.05 ）. There was no significant difference in any index between the moxibustion group and the mesalazine group. ConclusionGrain-sized moxibustion at "Zhongwan"， "Tianshu" and "Shangjuxu" can improve the damage of colon mucosa in UC model mice， and the mechanism may be related to the key factors regulating JAK2 / STAT3 signaling pathway based on SOCS3.

This study was designed to investigate the effects of wheat grain moxibustion on the immune function of mice immunosuppressed by cyclophosphamide,and to delve into the potential mechanisms by analyzing factors related to NF-κB signaling pathway.Sixty SPF-grade ICR mice were randomly allocated into four groups:blank group,model group,traditional Chinese medicine group and wheat grain moxibustion group,with 15 mice in each group.Immunosuppression was induced in mice of the model,traditional Chinese medicine and wheat grain moxibustion groups by intraperitoneal injection of cyclophosphamide at 80 mg/kg daily for three days,while mice of the blank group received an equivalent volume of saline.The traditional Chinese medicine group was treated with oral administration of Zhēn Qí Fú Zhèng granules,and the wheat grain moxibustion group was treated with wheat grain moxibustion at"Da Zhui,"bilateral"Zu San Li,"and bilateral"San Yin Jiao"once a day for seven consecutive days.After corresponding treatment,spleens were harvested from the mice of different groups for pathological examination,and enzyme-linked immunosorbent assay(ELISA)was utilized to measure the serum levels of IL-2,IL-4,TNF-α and IFN-γ.Additionally,Western blot analysis was conducted to assess the protein expression levels of IκBα and P-IκBα in spleen tissue.Compared with the blank group,mice in the model group exhibited poorer general conditions,significantly reduced white blood cell(WBC)count(P＜0.01),extensive damage in spleen tissue,significant decreases in serum IL-4 and IL-2 concentrations,increases in TNF-α and IFN-γ levels(P＜0.01),lower level of P-IκBα protein in spleen tissue(P＜0.01),and higher level of IκBα protein(P＜0.01).These changes mentioned above were reversed in mice of both the wheat grain moxibustion group and the traditional Chinese medicine group(P＜0.01).Compared to the traditional Chinese medicine group,on the last day of treatment,the wheat grain moxibustion group showed slightly higher WBC counts(P＜0.05),better tissue repair,and lower levels of IFN-γ(P＜0.01).In conclusion,wheat grain moxibustion can affect the activity of NF-κB signaling pathway by regulating the relative expression of IκBα and P-IκBα,and then regulate the immune response of the body,thus play a role in alleviating the immunosuppression caused by cyclophosphamide.

Objective:To conduct clinical practice applicability evaluation and barrier analysis on the guideline for Facilitating Client Centered Learning. Methods:From September to October 2021, 11 experts were selected to use the expert meeting method to evaluate the clinical applicability of the recommended guidelines. From March to May 2022, 140 nurses from 10 pilot wards of the China-Japan Friendship Hospital were selected to conduct a survey using the self-designed Facilitating Client Centered Learning Guideline Clinical Practice Barrier Questionnaire. The barrier association rules were mined based on the Apriori algorithm. Results:Expert opinions showed that all 15 recommendations had clinical significance and all agreed to be implemented in clinical practice. In terms of current development status, ≥ 6 experts expressed that the item 2, 6, and 7 were very well implemented in clinical practice, and≥ 6 experts expressed that the item 3, 4, and 10 needed improvement, and ≥ 6 experts stated that the item 11, 12, and 14 were not carried out in clinical practice. In the investigation of barriers, a total of 140 questionnaires were distributed, and the effective response rate of the questionnaire was 92.86% (130/140). 25.38% (33/130) of nurses believed that all four factors were unobstructed. After professional screening, four association rules between barriers were summarized.Conclusions:The recommendations of the Facilitating Client Centered Learning guideline can be applied in clinical practice, but there is still a gap between clinical practice and guideline theory. The biggest barriers that may exist in clinical applications are insufficient labor and a lack of relevant nursing documents.

Objective:To construct a health education program for enterostomy patients based on the guideline of Facilitating Client Centered Learning. Methods:From July to October 2022, based on the adaptability survey and literature research of the previous guidelines, the first draft of the health education program for enterostomy patients was formed. A total of 13 experts were selected using purposive sampling method, and two rounds of expert consultation were conducted through the Delphi method on the first draft of the program to build the final health education program for enterostomy patients. We calculated the authority, enthusiasm, coordination, and concentration of experts.Results:The health education program for enterostomy patients included 3 first-level indicators, 9 second-level indicators, and 31 third-level indicators. The effective response rates of the first and second rounds of consultation questionnaires were both 100.0%, and the authority coefficients of experts were both greater than 0.7. In the second round of consultation, the Kendal coordination coefficients of the importance of the first, second and third level indicators were 0.231, 0.154 and 0.182 ( P<0.05), and the Kendal coordination coefficients of the feasibility of the first, second and third level indicators were 0.216, 0.154 and 0.129 ( P<0.05), with coefficients of variation < 0.25. Conclusions:The health education program for enterostomy patients based on the guideline of Facilitating Client Centered Learning is practical and scientific, and can provide guidance for clinical practice.

SAM pointed domain containing E26 transformation-specific transcription factor (SPDEF) plays dual roles in the initiation and development of human malignancies. However, the biological role of SPDEF in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, the expression level of SPDEF and its correlation with the clinical parameters of patients with HNSCC were determined using TCGA-HNSC, GSE65858, and our own clinical cohorts. CCK8, colony formation, cell cycle analysis, and a xenograft tumor growth model were used to determine the molecular functions of SPDEF in HNSCC. ChIP-qPCR, dual luciferase reporter assay, and rescue experiments were conducted to explore the potential molecular mechanism of SPDEF in HNSCC. Compared with normal epithelial tissues, SPDEF was significantly downregulated in HNSCC tissues. Patients with HNSCC with low SPDEF mRNA levels exhibited poor clinical outcomes. Restoring SPDEF inhibited HNSCC cell viability and colony formation and induced G0/G1 cell cycle arrest, while silencing SPDEF promoted cell proliferation in vitro. The xenograft tumor growth model showed that tumors with SPDEF overexpression had slower growth rates, smaller volumes, and lower weights. SPDEF could directly bind to the promoter region of NR4A1 and promoted its transcription, inducing the suppression of AKT, MAPK, and NF-κB signaling pathways. Moreover, silencing NR4A1 blocked the suppressive effect of SPDEF in HNSCC cells. Here, we demonstrate that SPDEF acts as a tumor suppressor by transcriptionally activating NR4A1 in HNSCC. Our findings provide novel insights into the molecular mechanism of SPDEF in tumorigenesis and a novel potential therapeutic target for HNSCC.
Carcinogenesis ; Cell Proliferation ; Head and Neck Neoplasms ; Humans ; Nuclear Receptor Subfamily 4, Group A, Member 1 ; Proto-Oncogene Proteins c-ets ; Squamous Cell Carcinoma of Head and Neck ; Transcription Factors

The TEA domain (TEAD) family proteins (TEAD1‒4) are essential transcription factors that control cell differentiation and organ size in the Hippo pathway. Although the sequences and structures of TEAD family proteins are highly conserved, each TEAD isoform has unique physiological and pathological functions. Therefore, the development and discovery of subtype selective inhibitors for TEAD protein will provide important chemical probes for the TEAD-related function studies in development and diseases. Here, we identified a novel TEAD1/3 covalent inhibitor (DC-TEADin1072) with biochemical IC

Objective To study the clinical value of neonatal arterial blood pH,base excess and lactate levels within 72 h after birth in assessing early brain injury in asphyxia neonates.Method From June 2015 to November 2016,a retrospective study was performed on the asphyxia newborn admitted to newborn department of Children's Hospital of Fudan University.The data of brain magnetic resonance imaging (MRI),video electroencephalogram (VEEG),and artery blood gas analysis (within 12 h and 72 h) were all collected.The neonates were assigned into brain injury group (severe or moderate injury) and control group (normal or mild injury) according to MRI and VEEG results.The differences of arterial blood pH,base excess and the level of lactate between the two groups were analyzed and indicators of brain injury were evaluated using ROC curves.Result A total of 63 cases were included in the study.Thirty patients were in the control group and 33 patients the brain injury group.The pH within 12 h was lower [(7.32 ±0.09) vs.(7.38 ±0.08)],and the lactic acid level in 12 h and at 24-72 h were significantly higher in the brain injury group than the control group [(7.9 ±4.2) mmol/L vs.(4.9 ±2.4) mmol/L and (3.7 ±3.2) mmol/L vs.(2.2 ± 1.1) mmol/L].The differences were statistically significant (P ＜0.05).The areas under the ROC curve of pH,lactate within 12 h and at 24-72 h were 0.323,0.715,0.643 (P =0.016,0.003,0.051).The cut-off value of lactic acid within 12 h in assessing of brain injury was 7.5 mmol/L,with the sensitivity of 0.46 and the specificity of 0.97.Conclusion The artery lactate level within 72 h after birth can be used to evaluate the severity of brain injury in neonatal asphyxia infants.

Objective To understand the distribution of water iodine in the external environment of Shanxi Province, and to provide a basis for redefining and implementation of scientific iodine supplementation in iodine deficiency, iodine adequate or iodine high areas. Methods In 2012 - 2016, administrative villages (neighborhood committees)in 119 counties(cities,districts)in 11 cities of Shanxi Province were selected as the investigation units, and 1 to 5 drinking water samples were collected. Water iodine content was detected using arsenic-cerium catalytic spectrophotometry. Areas standard was designated: water iodine content < 10 μg/L as iodine deficiency areas, > 100 μg/L as iodine high areas. Results A total of 26 213 administrative villages (neighborhood committees) of 1 362 townships (towns) of 119 counties (cities, districts) were surveyed, covering 2 850.94 ten thousand people. A total of 32 766 water samples were collected and the median iodine was 5.2 μg/L. There were 18 199 villages with water iodine < 10 μg/L, accounting for 69.4% (covering 1 812.17 ten thousand people, accounting for 63.6%), 6 471 villages with water iodine 10-<50 μg/L,accounting for 24.7%(covering 787.44 ten thousand people,accounting for 27.6 %),1 166 villages with water iodine 50 - < 100 μg/L,accounting for 4.4% (covering 181.46 ten thousand people, accounting for 6.4%), 377 villages with water iodine ≥100 μg/L, accounting for 1.4%(covering 69.87 ten thousand people, accounting for 2.5%).In 1 362 townships (towns), 71.1% (969)water iodine median was<10 μg/L,24.2%(330)water iodine median was in 10-<50 μg/L,3.4%(46)water iodine median was in 50-<100 μg/L,and 1.2%(17) water iodine median was ≥100 μg/L. In 119 counties(cities,districts),there were 90 counties(accounting for 75.6%) with the water median < 10 μg/L, there were 26 counties (accounting for 21.8%) with the water median 10 - < 50 μg/L. Conclusions Most parts of Shanxi Province(or the resident population) are iodine deficiency areas, the external environment water iodine contents in the rest of the regions are different, we should adopt different iodine supplement or iodine reduction measures in regions with different water iodine levels.

Objective To study the nutritional status of pregnant women in Shanxi Province before and after the implementation of the new standards of iodized salt content,provide the basis for scientific supplementation of iodine for pregnant women.Methods According to the method of population proportion sampling,30 county-level monitoring sites were selected,a primary school was selected from each county (city,district) by the method of simple random sampling and 40 students in 2011 or 50 students in 2014 aged 8-10 years were selected in each school,direct titration was used to detect salt iodine;at the same time,20 pregnant women were selected from each town where the primary school was located and urinary iodine was determined using arsenic cerium catalytic spectrophotometry (WS/T 107-2006).Results A total of 1 182 and 1 437 salt samples was detected in Shanxi Province in 2011 and 2014,the median of salt iodine was 30.5 and 24.1 mg/kg,respectively,and the difference was statistically significant (H =567.45,P ＜ 0.01);it was 95.41％,80.31％,76.62％ of the coverage rate of iodized salt,qualified rate of iodized salt,qualified iodized salt consumption rate in 2014,respectively;which were compared with those in 2011 (97.63％,97.49％,95.18％),the differences were statistically significant (x2 =9.27,232.40,166.25,P ＜ 0.01).A total of 440 and 630 urinary samples of pregnant women were tested in 2011 and 2014,the median of urinary iodine was 279.6 and 177.1 μg/L,respectively,iodine nutrition of pregnant women was more than adequate in 2011,and iodine nutrition was suitable in 2014.The difference was statistically significant (H =153.89,P ＜ 0.01).The proportion of pregnant women's median of urinary iodine less than 150 μg/L in 2014 [41.11％ (259/ 630)] was significantly higher than that in 2011 [8.18％ (36/440),x2 =140.68,P ＜ 0.01].The constituent ratio of 250 to 500 μg/L was significantly decreased [23.65％ (149/630) vs 54.77％ (241/440),x2 =108.33,P ＜ 0.01).Conclusion It is at a reasonable level of iodine nutrition level of pregnant women in Shanxi after the adjustment of iodized salt content,but the ratio of ＜ 150 μg/L is increasing,which needs to be paid attention to.