AIM:To investigate the therapeutic effect of menstrual blood-derived endometrial stem cells(MenSCs)on chemotherapy-induced intestinal mucositis and flora disorders in mice,and to explore the potential mecha-nism.METHODS:The mice were randomly divided into 3 groups including normal treatment,cisplatin(Cis)treatment and Cis+MenSC treatment,with 10 mice in each group.To induce intestinal mucositis,the mice were treated with Cis(2 mg·kg-1·d-1)by intraperitoneal injection for 5 consecutive days.Control mice for normal group were received equal vol-umes of normal saline.For Cis+MenSC treatment,MenSCs(1×106)was transplanted into the mice of Cis treated mice through tail vein.The performances and weight changes of mice were examined during the experiment.After the treat-ment,the small intestine and colon were isolated for subsequent HE staining,the ratio of F4/80 and IL-6 positive cells in small intestine were detected by immunohistochemical staining,and the expression of tight junction,inflammation and apoptosis related proteins was detected by Western blot.16S rDNA amplicon sequencing was performed to detect the diver-sity and richness of intestinal flora in mice.RESULTS:Compared to the Cis group,the MenSCs-treated mice showed sig-nificantly increased body weight,relieved intestinal lymphocytes infiltration,alleviated intestinal villous edema,and or-derly arranged glands in intestinal tissues.Further analysis indicated that MenSCs transplantation significantly up-regulat-ed the expression of intestinal tight junction related proteins ZO-1 and occludin in Cis-treated mice(P＜0.05).Subse-quently,MenSCs transplantation significantly inhibited the macrophages infiltration in intestinal tissues(P＜0.01),down-regulated the expression of pro-inflammatory factors IL-1 and IL-6 and pro-apoptotic protein Bax(P＜0.01),while up-regu-lated anti-inflammatory factor IL-10 and anti-apoptotic protein Bcl-2(P＜0.01).Additionally,further microflora sequenc-ing indicated that MenSCs transplantation prevented mice from Cis-induced intestinal flora disorder,and significantly re-duced the abundance of harmful bacteria such as isenbergiella tayi and Anaerotruncus colihominis(P＜0.01).At the same time,the abundance of beneficial bacteria Lactobacillus apodemi was increased(P＜0.05),thereby restoring the composi-tion and function of healthy intestinal flora.CONCLUSION:MenSCs transplantation alleviates the chemotherapy-in-duced damage of intestinal structure,relieves the symptoms of chemotherapy-induced mucositis and restores the homeosta-sis of intestinal flora in mice.

Objective To investigate the mechanism of micellar curcumol (MC) regulating the immune microenvi-ronment of ovarian cancer by promoting the polarization of M2-type macrophages to M1-type in ovarian cancer asci-tes.Methods ① After the mice were divided into groups, a mouse ovarian cancer ascites model was constructed by using the mouse ovarian cancer cell line ID8.Then weight changes were observed, tumor tissue and ascites were collected.The expression of CD86 and CD206 on macrophages of the tumor tissue and ascites was detected by flow cytometry.The expression of protein kinase B (PKB/Akt)/mammalian target of rapamycin (mTOR) was detected by Western blot.②A human monocytic leukemia cell line (THP-1) was induced to transform into M2 macrophage (THP-1 M2 macrophage) in vitro, and then treated with 10μg/ml MC.The apoptosis was detected by flow cytom-etry.The mRNA levels of macrophage mannose receptor (CD206), transforming growth factor-β(TGF-β), inter-leukin (IL)-1β and tumor necrosis factor-α (TNF-α) were detected by qRT-PCR.The expression of CD86 and CD206 was detected by flow cytometry, and Akt/mTOR expression and phosphorylation was detected by Western blot.Results ① In vitro study showed that the average body weight of the MC group was lower than that of the control group.Compared with the control group, CD206 expression of macrophages decreased in tumor tissue and ascites in the MC group, while the expression of CD86 increased.The Akt and mTOR phosphorylation level of mac-rophages in the MC group's ascites was lower than that in control group.②In vivo study showed that there was no difference in apoptosis rate among the groups detected by flow cytometry.The mRNA expression level of CD206, TGF-β and the protein expression level of CD206 in MC group were significantly lower than those in the control group, while the mRNA expression of IL-1β, TNF-α and the protein expression level of CD86 were significantly higher than those in the control group.Compared with the control group, the phosphorylation level of Akt and mTOR in the MC group decreased.Conclusion MC promotes M1 polarization of macrophages in ascites to regulate the immune microenvironment of ovarian cancer, which may be related to the Akt/mTOR pathway.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective:To investigate effect of mesalazine(MSLZ)on improvement of colonic barrier in mice with ulcerative colitis(UC),and its regulatory mechanism on wingless-type mouse mammary tumor virus integration site1(Wnt1)signaling pathway.Methods:C57BL/6 mice were randomly divided into normal control group(Control),model group(UC),MSLZ group and MSLZ+sh-Wnt1 group.Except for Control group,other groups were treated with sodium dextran sulfate(DSS)to establish UC model.Mice in Control,UC and MSLZ groups were intraperitoneally injected 5×109 pfu/ml NC-shRNA.Mice in MSLZ+sh-Wnt1 group were intraperi-toneally injected 5×109 pfu/ml shRNA-Wnt1.Mice in MSLZ group and MSLZ+sh-Wnt1 group were gavaged with 400 mg/kg MSLZ every day,and mice in Control and UC groups were gavaged with sterile distilled water of same dose every day.Colon length of mice in each group was detected.Kit was used to detect contents of D-lactate(D-LA),lipopolysaccharide(LPS)and activity of diamine oxidase(DAO)in serum of mice in each group.TUNEL staining was used to detect apoptosis in colon tissue of mice in each group.Immunohistochemistry was used to detect expressions of mucin 2(MUC2)and Occludin in colon tissues.Western blot was used to detect expressions of Wnt1,β-catenin,B cell lymphoma-2(Bcl-2)and Bcl-2 associated X protein(Bax).Results:MSLZ could signi-ficantly increase length of colon,increase expressions of MUC2,Occludin,Wnt1,β-catenin and Bcl-2 in colon tissue,decrease levels of D-LA,LPS,DAO in serum,cell apoptosis rate and expression of Bax in colon tissue,while MSLZ+sh-Wnt1 could partially reverse protective effect of MSLZ on colon barrier function(all P<0.05).Conclusion:MSLZ can inhibit apoptosis of colon mucosa in UC mice,alleviate pathological damage of colon tissue,and ameliorate barrier function of colon mucosa,which may be related to activation of Wnt1 signaling pathway.

Objective:To systematically evaluate and Meta-synthesize qualitative studies on the home management needs of patients with spinal cord injury (SCI) to understand their actual self-management needs and improve the quality of home management for patients with SCI in China.Methods:A comprehensive search was conducted in databases including CNKI, Wanfang, CBM, PubMed, Embase, Web of Science, CINAHL, and Cochrane Library for qualitative research on the home management needs of patients with SCI, with a search timeframe up to November 30, 2023. The methodological quality of the included studies was evaluated using the Joanna Briggs Institute (JBI) Qualitative Assessment and Review Instrument (2016). Results were integrated and analyzed using Meta-synthesize methods.Results:A total of 15 studies were included, from which 58 distinct research findings were extracted. These were categorized into 10 new categories, which were further integrated into four main results: the need for positive emotional support, daily living-related needs, healthcare service needs, and social support needs.Conclusions:Healthcare providers should deeply understand the home management needs of patients with SCI. Utilizing artificial intelligence technology, an integrated support model encompassing hospital, home, and society can be constructed. Establishing a comprehensive home rehabilitation platform for patients with SCI can focus on psychological issues and enhance social support levels, thereby improving patients' quality of life.

Objective:To integrate qualitative research on the real experience of patients with spinal cord injury (SCI) returning to society after discharge, so as to provide a basis for developing transitional care intervention program, and promote patients' reintegration into society.Methods:Qualitative research on the real experience of patients with SCI returning to society after discharge was electronically retrieved on China National Knowledge Infrastructure, WanFang Data, VIP, China Biomedical Literature Service System, Cochrane Library, PubMed, Embase, Web of Science, CINAHL, and so on .The search period was from database establishment to August 30, 2023. The quality evaluation criteria for qualitative research of the JBI Evidence-Based Health Care Center (2016) was used to assess the quality of literature, and Meta-synthesis was used to integrate the results.Results:A total of 16 articles were included, and 51 research results were extracted. Similar research results were summarized and combined to form 12 new categories, which were then synthesized into four integrated results, including experiencing physical and mental discomfort following discharge, facing challenges in reintegrating into society, seeking social support, and adapting to social life through self-adjustment role changes.Conclusions:Patients with SCI have multiple psychological experiences in the process of reintegration into society. Medical and nursing staff should attach importance to their inner needs, help them overcome stress and challenges, provide them with personalized continuous care, and promote their role adaptation and reintegration into society.

Objective To investigate the expression of Nanog and its regulatory relationship with MMP-2/MMP-9 proteins in esophageal squamous cell carcinoma(ESCC).Methods We detected Nanog and MMP-2/MMP-9 protein expressions in 127 ESCC tissues and 82 adjacent normal tissues using immunohistochemistry and explored their correlations with the clinicopathological parameters and prognosis of the patients.GEO database was utilized to analyze the pathways enriched with the stemness-related molecules including Nanog,and TIMER online tool was used to analyze the correlations among TβR1,MMP-2,and MMP-9 in esophageal cancer.Results Nanog and MMP-2/MMP-9 proteins were significantly upregulated in ESCC tissues and positively intercorrelated.Their expression levels were closely correlated with infiltration depth and lymph node metastasis of ESCC but not with age,gender,or tumor differentiation.The patients with high expressions of Nanog and MMP-2/MMP-9 had significantly shorter survival time.Bioinformatics analysis showed enrichment of stemness-associated molecules in the TGF-β signaling pathway,and the expressions of MMP-2/MMP-9 and TβR1 were positively correlated.In cultured ESCC cells,Nanog knockdown significantly decreased the expression of TβR1,p-Smad2/3,MMP-2,and MMP-9 and strongly inhibited cell migration.Conclusion The high expressions of Nanog,MMP-2,and MMP-9,which are positively correlated,are closely related with invasion depth,lymph node metastasis,and prognosis of ESCC.Nanog regulates the expressions of MMP-2/MMP-9 proteins through the TGF-β signaling pathway,and its high expression promotes migration of ESCC cells.

Objective To explore the effect of temperature on the risk of hand-foot-and-mouth disease (HFMD) and population susceptibility. Methods The data of HFMD cases in Chengdu from January 1, 2016 to October 31, 2022 were collected, and local meteorological data during the same period were also collected. Distributional lag nonlinear models were developed. The relative risk (RR) of morbidity at different temperatures and different lags was calculated. Differences in the relative risk levels of different populations were analyzed and compared. Results A total of 263 776 cases of HFDM were reported in Chengdu during the study period. The distribution of HFMD was periodic. For the overall population, the short-term average temperature and RR showed a ^“U^”-shaped relationship. When the lag time was 0-7 days, the cumulative RR was 1.59 (95%CI: 1.18-2.14) at the average temperature of -0.5℃ and 2.16 (95%CI: 1.60-2.91) at the average temperature of 34.5℃. The RR values under high and low temperatures decreased with increasing lag period. When the lag time was extended, the average temperature and RR showed an inverted ^“U^”-shaped relationship, with higher RR at moderate temperatures and increasing as the lag period increased. The results of the subgroups showed that the RR of onset among scattered children was higher at high and low temperatures. Conclusion The risk effect of temperature on the onset of HFMD in different populations is variable and changes with the lag period, and the prevention and control measures should be adjusted in a timely and targeted manner.

Stroke is the second leading cause of death worldwide,and oxidative stress plays a crucial role.Celastrol exhibits strong antioxidant properties in several diseases;however,whether it can affect oxidation in cerebral ischemic-reperfusion injury(CIRI)remains unclear.This study aimed to determine whether celastrol could reduce oxidative damage during CIRI and to elucidate the underlying mechanisms.Here,we found that celastrol attenuated oxidative injury in CIRI by upregulating nuclear factor E2-related factor 2(Nrf2).Using alkynyl-tagged celastrol and liquid chromatography-tandem mass spectrometry,we showed that celastrol directly bound to neuronally expressed developmentally downregulated 4(Nedd4)and then released Nrf2 from Nedd4 in astrocytes.Nedd4 promoted the degradation of Nrf2 through K48-linked ubiquitination and thus contributed to astrocytic reactive oxygen species production in CIRI,which was significantly blocked by celastrol.Furthermore,by inhibiting oxidative stress and astrocyte activation,celastrol effectively rescued neurons from axon damage and apoptosis.Our study uncovered Nedd4 as a direct target of celastrol,and that celastrol exerts an antioxidative effect on as-trocytes by inhibiting the interaction between Nedd4 and Nrf2 and reducing Nrf2 degradation in CIRI.

Objective To construct and validate a risk prediction model of hypoglycemia in emergency intensive care unit(EICU)patients.Methods A retrospective study was conducted among 2093 EICU patients in a department of a tertiary A hospital in Urumqi from January to December 2022,as research subjects.Univariate analysis and logistic regression analysis were used to determine the risk factors for hypoglycemia,and R software was used to establish a nomogram prediction model.The area urder the receiver operator characteristic(ROC)curve was used to test the model differentiation,and the Hosmer-Lemeshow test was used to test the goodness of fit of the model.The risk prediction model was validated by the prospective study with inclusion of 699 EICU patients admitted to the same hospital from January to March 2023.Results The model variables included whether hypoglycemia occurred in the past year,acute physiology and chronic health evaluation Ⅱ score at admission,coefficient of variation of blood glucose,history of renal disease,history of diabetes,insulin treatment,and serum creatinine.The Hosmer-Lemeshow test of the model was P=0.497;the area urder the ROC curve was 0.820(95％CI:0.794～0.847);the best cutoff value was 0.495;the sensitivity was 0.856;the specificity was 0.751.The model validation results showed that the Hosmer-Lemeshow test P=0.537;the area urder the ROC curve was 0.859(95％CI:0.819～0.898);the best cutoff value was 0.597;the sensitivity was 0.840;the specificity was 0.757.Conclusion The established nomogram prediction model helps clinical staff to screen patients at high risk of hypoglycemia and provides a reference for optimizing the management of hypoglycemia in EICU patients.