ObjectiveTo investigate the effects of hypoxia-treated mesenchymal stem cell （MSCs） exosomes （Exo） and their loading with curcumin on microglial inflammatory responses， and to explore the enhancing effect of hypoxia treatment on the function of MSCs Exo. MethodsThe supernatants of human umbilical cord （hUC）-MSCs cultured under normal and hypoxic conditions were collected， and Exo were isolated using ultracentrifugation. After identification by transmission electron microscopy and Western blot， curcumin was loaded using the co-incubation method. The lipopolysaccharide （LPS）-induced microglial inflammation model was treated with dimethyl sulfoxide （DMSO）， curcumin， normoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin， respectively. The expression of the M1-type marker inducible nitric oxide synthase （iNOS） in BV2 cells was detected by immunofluorescence （IF）. Western blot and enzyme-linked immunosorbent assay （ELISA） were used to measure the expression and secretion levels of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and IL-6 in the cells and their culture supernatants. ResultsNormoxia Exo， hypoxia Exo， normoxic Exo loaded with curcumin， and hypoxic Exo loaded with curcumin exhibited a "saucer-like" shape with a diameter ranging from 30~150 nm， and the expression of exosomal markers CD9， CD81， and TSG101 were positive. After treating the BV2 cell inflammation model， IF results showed that， compared with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression of iNOS. Moreover， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， the expression level of iNOS significantly decreased after treatment with hypoxic Exo loaded with curcumin. The results of Western blot and ELISA indicated that， in comparison with the normoxia Exo group， treatment with hypoxic Exo significantly reduced the expression and secretion of the inflammatory cytokines TNF-α， IL-1β， and IL-6. Additionally， when compared with the curcumin group and the normoxic Exo loaded with curcumin group， both the expression and secretion of TNF-α， IL-1β， and IL-6 significantly decreased after treatment with hypoxic Exo loaded with curcumin. ConclusionHypoxia preconditioning can enhance the ability of hUC-MSCs-Exo in the inhibition of microglial polarization and inflammatory factors’ secretion. Additionally， using Hypoxia-MSCs-Exo as a drug-delivery carrier of curcumin can improve its solubility and stability， facilitating its absorption by cells and exerting the therapeutic effect of combination therapy.

OBJECTIVE To explore the changes of serum inflammatory factors and immune function indexes in the children with asthma induced by Mycoplasma pneumoniae infection so as to make a new breakthrough in diagnosis and treatment of the children with M.pneumoniae infection-induced asthma.METHODS A total of 118 children with M.pneumoniae infection who were treated in pediatrics department of The Affiliated Hospital of Binzhou Medical College from Jan.2020 to May 2023 were enrolled in the study and were divided into the asthma group with 26 cases and the no asthma group with 92 cases according to the status of induction of asthma.The levels of peripheral blood interleukin(IL)-1β,IL-18,tumor necrosis factor-α(TNF-α)and immune function indexes(CD3+,CD4+,CD8+and CD4+/CD8+)were observed and compared between the two groups.The values of the above indexes in diagnosis of the M.pneumoniae infection-induced asthma were analyzed by means of receiver op-erating characteristic(ROC)curves.RESULTS There were significant differences in the levels of inflammatory factors and immune function indexes between the asthma group and the no asthma group(P＜0.05).The levels of TNF-α,IL-1β,IL-18 and CD8+of the asthma group were(46.33±5.30)pg/ml,(50.60±6.33)pg/ml,(40.26±4.89)pg/ml and(40.11±6.85)％,respectively,higher than those of the no asthma group;the levels of CD3+,CD4+and CD4+/CD8+of the asthma group were(43.33±5.89)％,(15.62±3.61)％and(0.35±0.12),re-spectively,lower than those of the no asthma group.In the asthma group,the levels of TNF-α,IL-1β,IL-18 and CD8+of the MP-Immunoglobulin M(IgM)-positive children were higher than those of the MP-IgM-negative chil-dren(P＜0.05),while the levels of CD3+,CD4+and CD4+/CD8+of the MP-IgM-positive children were lower than those of the MP-IgM-negative children(P＜0.05).The areas under the ROC curves(AUCs)of the serum TNF-α,IL-1β,IL-18,CD3+,CD4+,CD8+and CD4+/CD8+were 0.812,0.805,0.795,0.814,0.768,0.805 and 0.841,respectively,in diagnosis of the M.pneumoniae infection-induced asthma.CONCLUSION The serum TNF-α,IL-1β,IL-18,CD3+,CD4+,CD8+and CD4+/CD8+of the children with M.pneumoniae infection can be used for prediction of the asthma.

Objective Exploring the therapeutic mechanism of Yishen Jiangzhuo Granules(YSJZG)on chronic kidney disease(CKD)based on mitochondrial dynamics and apoptosis of renal tubular epithelial cells.Methods The CKD model of rats with 5/6 nephrectomy was adopted and divided into 6 groups according to random number table:sham operation control group,model group,emodin group(500 mg/kg/d),Yishen Jiangzhuo granule low,middle and high dose groups.After 8 weeks of treatment with YSJZG,serum creatinine(SCR)and urea nitrogen(BUN),pathological changes of renal cortex,mitochondrial morphology and ultrastructure were detected,and mitochondrial kinetic protein in renal tubular epithelial cells was detected by immunohistochemistry(Drp1,Fis1)and fusion proteins(Opa1,Mfn1)were detected by Western blot,and apoptotic proteins(CytC,Bax)in cytoplasm and mitochondria were detected by real-time PCR.Results Renal injury:Compared with the model group,YSJZG groups significantly reduced the levels of SCR and BUN,renal tubular degeneration and necrosis,and mitochondrial structural damage in rats.Renal tubule mitochondrial dynamic protein:Compared with the model group,the expression of division proteins Drp1 and Fis1 was downregulated,the expression of fusion proteins Opa1 and Mfn1 was upregulated,and transmission electron microscopy observed that the mitochondrial fragmentation changes were relatively mild.Apoptosis related indicators and mtDNA copy number of renal tubular cells:Compared with the model group,the content of Bax protein in renal tubular epithelial cells of YSJZG groups increased significantly in cytoplasm(P<0.05)and decreased significantly in mitochondria(P<0.05).The content of CytC protein decreased significantly in cytoplasm(P<0.05)and increased significantly in mitochondria(P<0.05).The copy number of mtDNA increased significantly(P<0.05),and the total levels of SMAC,CytC and Bax mRNA decreased significantly(P<0.05).Correlation between mitochondrial dynamic protein and apoptosis in renal tubular cells:Pearson correlation analysis showed that the expression of Drp1 and Fis1 was negatively correlated with the expression of CytC in mitochondria,and positively correlated with the expression of CytC in cytoplasm.The expression levels of fusion proteins Opa1 and Mfn1 showed a significant positive correlation with CytC expression in mitochondria,and a significant negative correlation with CytC expression in cytoplasm.Conclusion YSJZG can significantly delay the progression of CKD,and its mechanism may be achieved by regulating mitochondrial dynamics of renal tubular epithelial cells,thereby inhibiting endogenous cell apoptosis pathway.

OBJECTIVE To explore the changes of serum inflammatory factors and immune function indexes in the children with asthma induced by Mycoplasma pneumoniae infection so as to make a new breakthrough in diagnosis and treatment of the children with M.pneumoniae infection-induced asthma.METHODS A total of 118 children with M.pneumoniae infection who were treated in pediatrics department of The Affiliated Hospital of Binzhou Medical College from Jan.2020 to May 2023 were enrolled in the study and were divided into the asthma group with 26 cases and the no asthma group with 92 cases according to the status of induction of asthma.The levels of peripheral blood interleukin(IL)-1β,IL-18,tumor necrosis factor-α(TNF-α)and immune function indexes(CD3+,CD4+,CD8+and CD4+/CD8+)were observed and compared between the two groups.The values of the above indexes in diagnosis of the M.pneumoniae infection-induced asthma were analyzed by means of receiver op-erating characteristic(ROC)curves.RESULTS There were significant differences in the levels of inflammatory factors and immune function indexes between the asthma group and the no asthma group(P＜0.05).The levels of TNF-α,IL-1β,IL-18 and CD8+of the asthma group were(46.33±5.30)pg/ml,(50.60±6.33)pg/ml,(40.26±4.89)pg/ml and(40.11±6.85)％,respectively,higher than those of the no asthma group;the levels of CD3+,CD4+and CD4+/CD8+of the asthma group were(43.33±5.89)％,(15.62±3.61)％and(0.35±0.12),re-spectively,lower than those of the no asthma group.In the asthma group,the levels of TNF-α,IL-1β,IL-18 and CD8+of the MP-Immunoglobulin M(IgM)-positive children were higher than those of the MP-IgM-negative chil-dren(P＜0.05),while the levels of CD3+,CD4+and CD4+/CD8+of the MP-IgM-positive children were lower than those of the MP-IgM-negative children(P＜0.05).The areas under the ROC curves(AUCs)of the serum TNF-α,IL-1β,IL-18,CD3+,CD4+,CD8+and CD4+/CD8+were 0.812,0.805,0.795,0.814,0.768,0.805 and 0.841,respectively,in diagnosis of the M.pneumoniae infection-induced asthma.CONCLUSION The serum TNF-α,IL-1β,IL-18,CD3+,CD4+,CD8+and CD4+/CD8+of the children with M.pneumoniae infection can be used for prediction of the asthma.

Objective:To explore the configurational factors influencing the professional commitment of Master of Nursing Specialist (MNS) students and identify effective paths to enhance their professional commitment.Methods:A convenience sample of MNS students from six hospitals in Jiangsu Province, Shanghai City, and Anhui Province was surveyed between December 2023 and October 2024. Data were collected using a general information questionnaire, the Nurses' Professional Commitment Scale (NPCS), the Connor-Davidson Resilience Scale (CD-RISC-10), the Multidimentional Perceived Social Support (MSPSS), and the Vocational Outcome Expectation Scale (VOE-R). Fuzzy-set Qualitative Comparative Analysis (fsQCA) was used to explore the configurational influences on professional commitment.Results:A total of 332 questionnaires were distributed, and 302 valid responses were obtained (effective response rate: 90.1%). The mean NPCS score among respondents was (89.30±22.42), indicating a upper-middle level of professional commitment. The fsQCA results revealed that the frequency of night shift rotation was a necessary condition affecting professional commitment. A total of three distinct configurations (paths) were identified that can enhance the professional commitment of MNS students.Conclusions:The professional commitment of MNS students is influenced by multiple interacting factors. It is recommended that hospitals, universities, and nursing educators develop targeted interventions based on these identified configurations to improve professional commitment.

Objective:To explore the configurational factors influencing the professional commitment of Master of Nursing Specialist (MNS) students and identify effective paths to enhance their professional commitment.Methods:A convenience sample of MNS students from six hospitals in Jiangsu Province, Shanghai City, and Anhui Province was surveyed between December 2023 and October 2024. Data were collected using a general information questionnaire, the Nurses' Professional Commitment Scale (NPCS), the Connor-Davidson Resilience Scale (CD-RISC-10), the Multidimentional Perceived Social Support (MSPSS), and the Vocational Outcome Expectation Scale (VOE-R). Fuzzy-set Qualitative Comparative Analysis (fsQCA) was used to explore the configurational influences on professional commitment.Results:A total of 332 questionnaires were distributed, and 302 valid responses were obtained (effective response rate: 90.1%). The mean NPCS score among respondents was (89.30±22.42), indicating a upper-middle level of professional commitment. The fsQCA results revealed that the frequency of night shift rotation was a necessary condition affecting professional commitment. A total of three distinct configurations (paths) were identified that can enhance the professional commitment of MNS students.Conclusions:The professional commitment of MNS students is influenced by multiple interacting factors. It is recommended that hospitals, universities, and nursing educators develop targeted interventions based on these identified configurations to improve professional commitment.

Objective Exploring the therapeutic mechanism of Yishen Jiangzhuo Granules(YSJZG)on chronic kidney disease(CKD)based on mitochondrial dynamics and apoptosis of renal tubular epithelial cells.Methods The CKD model of rats with 5/6 nephrectomy was adopted and divided into 6 groups according to random number table:sham operation control group,model group,emodin group(500 mg/kg/d),Yishen Jiangzhuo granule low,middle and high dose groups.After 8 weeks of treatment with YSJZG,serum creatinine(SCR)and urea nitrogen(BUN),pathological changes of renal cortex,mitochondrial morphology and ultrastructure were detected,and mitochondrial kinetic protein in renal tubular epithelial cells was detected by immunohistochemistry(Drp1,Fis1)and fusion proteins(Opa1,Mfn1)were detected by Western blot,and apoptotic proteins(CytC,Bax)in cytoplasm and mitochondria were detected by real-time PCR.Results Renal injury:Compared with the model group,YSJZG groups significantly reduced the levels of SCR and BUN,renal tubular degeneration and necrosis,and mitochondrial structural damage in rats.Renal tubule mitochondrial dynamic protein:Compared with the model group,the expression of division proteins Drp1 and Fis1 was downregulated,the expression of fusion proteins Opa1 and Mfn1 was upregulated,and transmission electron microscopy observed that the mitochondrial fragmentation changes were relatively mild.Apoptosis related indicators and mtDNA copy number of renal tubular cells:Compared with the model group,the content of Bax protein in renal tubular epithelial cells of YSJZG groups increased significantly in cytoplasm(P<0.05)and decreased significantly in mitochondria(P<0.05).The content of CytC protein decreased significantly in cytoplasm(P<0.05)and increased significantly in mitochondria(P<0.05).The copy number of mtDNA increased significantly(P<0.05),and the total levels of SMAC,CytC and Bax mRNA decreased significantly(P<0.05).Correlation between mitochondrial dynamic protein and apoptosis in renal tubular cells:Pearson correlation analysis showed that the expression of Drp1 and Fis1 was negatively correlated with the expression of CytC in mitochondria,and positively correlated with the expression of CytC in cytoplasm.The expression levels of fusion proteins Opa1 and Mfn1 showed a significant positive correlation with CytC expression in mitochondria,and a significant negative correlation with CytC expression in cytoplasm.Conclusion YSJZG can significantly delay the progression of CKD,and its mechanism may be achieved by regulating mitochondrial dynamics of renal tubular epithelial cells,thereby inhibiting endogenous cell apoptosis pathway.

Objective To investigate the efficacy and safety of self-help inflatable balloon in the treatment of refractory benign upper digestive tract stricture.Methods From November 2022 to February 2024,10 patients with refractory benign upper digestive tract stricture underwent self-help inflatable balloon were retrospectively analyzed.Preoperative treatment,intraoperative and postoperative complications,dysphagia score before and after surgery,wearing time of external self-help inflatable balloon,and the clinical efficacy were evaluated.Results All the 10 patients received self-help inflatable balloon treatment.No complications such as bleeding and perforation occurred in all patients during the wearing of the balloon.The placement time of the balloon was 60～180 d,and the average wearing time was 104.9 d.Before surgery,nine cases had a stricture segment length less than 2 cm,and one case had a stricture segment length of 6 cm.The dysphagia score before surgery was(3.60±0.52),and the dysphagia score after removal of the self-help inflatable balloon was(0.60±0.52),and there was statistical significance in preoperative and postoperative comparison(P＜0.05).The dysphagia score 3 months after removal of the external self-help inflatable balloon was(0.70±0.48),there was no significant difference in dysphagia score between the day after surgery and 3 months after surgery(P＞0.05).The diameter of the stricture before and after operation was(5.09±2.02)mm and(10.35±0.73)mm respectively,and the difference was statistically significant(P＜0.05).Sore throat,wing of nose pain and balloon displacement were the most common adverse events,with 30.0％(3/10),50.0％(5/10)and 70.0％(7/10),respectively.Conclusion It is safe,effective and feasible to treat refractory benign upper digestive tract stricture with self-help inflatable balloon in vitro.It is worthy for clinical application.

AIM: To explore the efficacy of 0.05% cyclosporine A combined with olopatadine eye drops in treating allergic conjunctivitis-related dry eye disease.METHODS: A total of 63 patients(63 eyes)with allergic conjunctivitis-related dry eye disease in the People's Hospital of Guangxi Zhuang Autonomous Region from August 2022 to April 2023 were enrolled and randomly divided into control group(n=33)and observation group(n=30). The patients of the control group were administrated with 0.1% olopatadine eye drops and 0.3% sodium hyaluronate eye drops, while the observation group was administrated with 0.1% olopatadine eye drops and 0.05% cyclosporine A eye drops. The ocular surface disease index(OSDI), total ocular symptom score(TOSS), conjunctival congestion score, conjunctival papillae and follicle score, Schirmer I test(SⅠt), tear meniscus height(TMH), meibomian gland secretion ability and property score, meibomian gland loss area score, corneal fluorescein staining(CFS), tear film break-up time(BUT), noninvasive first tear film break-up time(NIBUTf), noninvasive average tear film break-up time(NIBUTav)before and after treatment and the drug safety during the treatment period of both groups of patients were evaluated.RESULTS: After treatment, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, SⅠt, TMH, meibomian gland secretion ability score and property score, CFS, BUT, NIBUTf, and NIBUTav of the observation group showed improvements compared with those before treatment(all P<0.017). Among these, OSDI, TOSS, conjunctival congestion score, conjunctival papillae and follicle score, BUT, NIBUTf, and NIBUTav demonstrated significant improvement compared with the control group(all P<0.05). There was no statistically significant difference in meibomian gland loss area score between the two groups before and after treatment(P>0.05). During the treatment period, there were no local or systemic adverse reactions.CONCLUSION: The combined use of 0.05% cyclosporine A and olopatadine eye drops can significantly improve ocular discomfort symptoms of patients with dry eye disease associated with allergic conjunctivitis, such as red eyes, itchy eyes and foreign body sensation, promote tear film stability and have high safety.

Objective To investigate the efficacy and safety of self-help inflatable balloon in the treatment of refractory benign upper digestive tract stricture.Methods From November 2022 to February 2024,10 patients with refractory benign upper digestive tract stricture underwent self-help inflatable balloon were retrospectively analyzed.Preoperative treatment,intraoperative and postoperative complications,dysphagia score before and after surgery,wearing time of external self-help inflatable balloon,and the clinical efficacy were evaluated.Results All the 10 patients received self-help inflatable balloon treatment.No complications such as bleeding and perforation occurred in all patients during the wearing of the balloon.The placement time of the balloon was 60～180 d,and the average wearing time was 104.9 d.Before surgery,nine cases had a stricture segment length less than 2 cm,and one case had a stricture segment length of 6 cm.The dysphagia score before surgery was(3.60±0.52),and the dysphagia score after removal of the self-help inflatable balloon was(0.60±0.52),and there was statistical significance in preoperative and postoperative comparison(P＜0.05).The dysphagia score 3 months after removal of the external self-help inflatable balloon was(0.70±0.48),there was no significant difference in dysphagia score between the day after surgery and 3 months after surgery(P＞0.05).The diameter of the stricture before and after operation was(5.09±2.02)mm and(10.35±0.73)mm respectively,and the difference was statistically significant(P＜0.05).Sore throat,wing of nose pain and balloon displacement were the most common adverse events,with 30.0％(3/10),50.0％(5/10)and 70.0％(7/10),respectively.Conclusion It is safe,effective and feasible to treat refractory benign upper digestive tract stricture with self-help inflatable balloon in vitro.It is worthy for clinical application.