ObjectiveTo explore the potential mechanism underlying electroacupuncture therapy with the midnight-noon ebb-low method with hour-prescription for chronic obstructive pulmonary disease （COPD） with lung-qi deficiency syndrome from the perspective of brain and muscle basic helix-loop-helix ARNT-like 1 （BMAL1） as well as neutrophil extracellular traps （NETs）. MethodsThe experiment was conducted in two phases. For the therapeutic effectiveness observation， 24 rats were randomly allocated into control group 1， model group 1， midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group， with 6 rats per group. Rat models of COPD with lung-qi deficiency syndrome were established via cigarette smoke exposure combined with intratracheal instillation of lipopolysaccharide （LPS）. After successful modelling， rats in midnight-noon electro-acupuncture group 1 received electro-acupuncture at acupoints "Taiyuan （LU 9）"， "Feishu （BL 13）" and "Zusanli （ST 36）" during 05：00—07：00， 30 minutes per treatment once every other day for 14 consecutive days （7 sessions in total）. Rats in the conventional electro-acupuncture group received identical electroacupuncture manipulation at random daytime hours （08：00—18：00）. Pulmonary function parameters including forced expiratory volume in 0.3 second （FEV_0.3）， forced vital capacity （FVC） and FEV_0.3/FVC ratio were detected. Pulmonary histopathological changes were observed via hematoxylin-eosin （HE） staining. Plasma levels of pro-inflammatory factors interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α）， as well as pulmonary reactive oxygen species （ROS） content， BMAL1 protein expression and the levels of neutrophil extracellular traps （NETs） biomarkers such as myeloperoxidase （MPO）， neutrophil elastase （NE）， and citrullinated histone H3 （CitH3） in lung tissue were determined. For the mechanistic verification phase， 36 rats were divided into control group 2， model group 2， midnight-noon electro-acupuncture group 2， overexpression empty group， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group， with 6 rats in each group. At the 5th week of model construction， rats in the overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group received intratracheal instillation of 100 μl adenoviral suspension carrying overexpressed Bmal1 gene. Rats in the overexpression empty group were injected with an equal titer and equal volume of blank adenovirus without the Bmal1 coding sequence into the lung at the identical time point. Midnight-noon electro-acupuncture group 2 and overexpression with midnight-noon electro-acupuncture group were consistent with the aforementioned protocol. Finally， pulmonary levels of MPO， NE and CitH3 were measured in all groups. ResultsCompared with the control group 1， the model group 1 exhibited decreased FEV_0.3， FVC and FEV_0.3/FVC ratio， elevated plasma IL-1β， TNF-α and pulmonary ROS levels， downregulated lung BMAL1 protein expression， and increased contents of MPO， NE and CitH3 （all P＜0.05）； typical NETs-like structures with sparse granular substances attached to fibrous networks were observed under scanning electron microscopy； HE staining revealed damaged alveolar architecture accompanied by inflammatory cell infiltration. Compared with model group 1， both the midnight-noon electro-acupuncture group 1 and conventional electro-acupuncture group achieved obvious improvements in all above indicators， with superior therapeutic effects in midnight-noon electro-acupuncture group 1 （P＜0.05）. Consistently， midnight-noon electro-acupuncture group 1 showed more prominent alleviation of NETs-like structure formation and lung pathological injury compared to the conventional electro-acupuncture group. Mechanistic validation results demonstrated that compared with model group 2， the average optical density of MPO as well as the protein levels of MPO， NE and CitH3 were markedly reduced in midnight-noon electro-acupuncture group 2， overexpression BMAL1 group and overexpression with midnight-noon electro-acupuncture group （P＜0.05）； furthermore， these parameters were significantly lower in the overexpression with midnight-noon electro-acupuncture group than in midnight-noon electro-acupuncture group 2 （P＜0.05）. ConclusionElectro-acupuncture based on the midnight-noon ebb-low method with hour-prescription may alleviate pulmonary inflammation in COPD by upregulating the expression of clock protein BMAL1 and inhibiting excessive accumulation of NETs in lung tissue.

Objective:To explore the therapeutic mechanism of moxibustion in Crohn disease(CD)-associated intestinal fibrosis by observing its effects on the angiotensin-converting enzyme(ACE)/angiotensin Ⅱ(Ang Ⅱ)/angiotensin Ⅱ type 1 receptor(AT1R)axis in CD mouse models.Methods:Six randomly selected male C57BL/6 mice were assigned to a normal group,while the remaining mice were administered 0.1 mL of 2,4,6-trinitrobenzene sulfonic acid via enema to establish a CD intestinal fibrosis model.After successful modeling,the mice were randomly divided into a model group,a moxibustion group,and a Western medication group,with 6 rats in each group.The normal group and the model group only received grabbing without intervention.In the moxibustion group,mild moxibustion was applied to Qihai(CV6)and bilateral Tianshu(ST25)once a day for 10 min each time over 7 consecutive days.The Western medication group was administered mesalazine suspension via oral gavage once a day for 7 consecutive days.At the end of the intervention,the general condition,disease activity index(DAI)score,and gross colon score of mice in each group were evaluated.Hematoxylin-eosin staining was used to observe and score the histological changes in the colon tissue in each group.Masson staining was used to observe colonic fibrosis and the ratio of collagen-positive areas was analyzed;the expression of Ang Ⅱ in the colon tissue was detected by the enzyme-linked immunosorbent assay;immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction were used to detect the protein and mRNA expression of ACE and AT1R in the colon tissue,respectively;Western blotting was used to detect the expression of transforming growth factor(TGF)-β1 and connective tissue growth factor(CTGF)in the colon tissue.Results:Compared to the normal group,the DAI score,gross colon score,colonic histological score,collagen-positive area ratio,ACE protein and mRNA,Ang Ⅱ protein,AT1R protein and mRNA,TGF-β1 protein,and CTGF protein in the colon tissue in the model group increased significantly(P<0.01).In contrast,the above indicators in both the moxibustion group and the Western medication group reduced significantly compared to the model group(P<0.01 or P<0.05).There was no statistical difference in these indicators between the moxibustion group and the Western medication group(P>0.05).Conclusion:Moxibustion can alleviate intestinal fibrosis in CD mice,and its therapeutic mechanism may be associated with the regulation of colonic ACE/AngⅡ/AT1R axis.

Objective:To explore the therapeutic mechanism of moxibustion in Crohn disease(CD)-associated intestinal fibrosis by observing its effects on the angiotensin-converting enzyme(ACE)/angiotensin Ⅱ(Ang Ⅱ)/angiotensin Ⅱ type 1 receptor(AT1R)axis in CD mouse models.Methods:Six randomly selected male C57BL/6 mice were assigned to a normal group,while the remaining mice were administered 0.1 mL of 2,4,6-trinitrobenzene sulfonic acid via enema to establish a CD intestinal fibrosis model.After successful modeling,the mice were randomly divided into a model group,a moxibustion group,and a Western medication group,with 6 rats in each group.The normal group and the model group only received grabbing without intervention.In the moxibustion group,mild moxibustion was applied to Qihai(CV6)and bilateral Tianshu(ST25)once a day for 10 min each time over 7 consecutive days.The Western medication group was administered mesalazine suspension via oral gavage once a day for 7 consecutive days.At the end of the intervention,the general condition,disease activity index(DAI)score,and gross colon score of mice in each group were evaluated.Hematoxylin-eosin staining was used to observe and score the histological changes in the colon tissue in each group.Masson staining was used to observe colonic fibrosis and the ratio of collagen-positive areas was analyzed;the expression of Ang Ⅱ in the colon tissue was detected by the enzyme-linked immunosorbent assay;immunohistochemistry and real-time quantitative reverse transcription polymerase chain reaction were used to detect the protein and mRNA expression of ACE and AT1R in the colon tissue,respectively;Western blotting was used to detect the expression of transforming growth factor(TGF)-β1 and connective tissue growth factor(CTGF)in the colon tissue.Results:Compared to the normal group,the DAI score,gross colon score,colonic histological score,collagen-positive area ratio,ACE protein and mRNA,Ang Ⅱ protein,AT1R protein and mRNA,TGF-β1 protein,and CTGF protein in the colon tissue in the model group increased significantly(P<0.01).In contrast,the above indicators in both the moxibustion group and the Western medication group reduced significantly compared to the model group(P<0.01 or P<0.05).There was no statistical difference in these indicators between the moxibustion group and the Western medication group(P>0.05).Conclusion:Moxibustion can alleviate intestinal fibrosis in CD mice,and its therapeutic mechanism may be associated with the regulation of colonic ACE/AngⅡ/AT1R axis.

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 observe the effect of human umbilical cord mesenchymal stem cell-derived exo-somes(HUC-MSC-Exo)on microglial polarization in neonatal rats with white matter injury(WMI).Methods Three-day-old Sprague-Dawley rats were randomly divided into sham group(Sham),hypoxia-ischemia group(HI)and HUC-MSC-Exo group,with 12 rats in each group.Unilateral common carotid artery ligation combined with hy-poxia(8％oxygen and 92％nitrogen)was used to construct a WMI rat model.Exosomes were extracted by ultra-high-speed centrifugation and characterized by nanoflow cytometry,western blot experiments and transmission electron mi-croscopy.Brain stereotaxic-assisted inferior ventricular transplantation exo(2×108 particles/μL)was performed and brain tissue samples were collected 14 days after HI.Hematoxylin-eosin(HE)staining was used to observe morpho-logical changes of brain tissue.Nissl staining was used to observe Nissl body formation in brain tissue;Luxol fast blue(LFB)staining was used to observe the formation of myelin sheath in brain tissue.Immunofluorescence staining was used to observe the localized expression of ionic calcium binds adaptor molecule 1(Iba1).The protein expres-sion levels of cluster of differentiation 86(CD86),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),CD206,arginase-1(Arg-1),IL-10 and transforming growth factor-β(TGF-β)were detected by western blot.Results The results of nanoflow cytometry,western blot and transmission electron microscopy showed that the diameter of HUC-MSC-Exo particles was between 30 and 150 nm,and the oval-like shape and membrane-like structure were visible,and the exo markers CD9,CD63 and TSG101 were positive,while calnexin was negative.HE staining,Nissl staining and LFB staining showed that compared with the Sham group,the HI group had brain tissue structure destruction,which was manifested by cell morphological changes,nerve fiber ar-rangement disorder and vacuolation,Nissl body dissolution or even disappearance,and myelination was blocked.HUC-MSC-Exo significantly reversed the pathological changes in the HI group.The results of immunofluorescence staining and western blot showed that the microglial marker Iba1 was mainly expressed in the subventricular zone(SVZ),and the expression of Iba1 protein in the SVZ region increased after HI compared with the Sham group(t=15.95、20.31,P<0.01).HUC-MSC-Exo significantly reduced the expression of Iba1 protein in the HI group(t=10.35、11.01,P<0.01).The results of western blot showed that the expressions of M1 microglia markers(CD86 and iNOS)and pro-inflammatory cytokines(TNF-α and IL-1β)were significantly increased after HI(t=10.98、7.68、15.13、13.13,both P<0.01),and the expressions of M2 microglia markers(CD206 and Arg-1)and anti-inflammatory cytokines(IL-10 and TGF-β)were also increased after HI(t=14.26、9.38、8.82、7.42,both P<0.01).HUC-MSC-Exo decreased the protein expression of CD86,iNOS,TNF-α and IL-1β(t=9.79、5.81、8.06、7.03,all P<0.01)and increased the protein expression levels of CD206,Arg-1,IL-10 and TGF-β compared to the HI group(t=12.90、8.16、8.98、9.49,both P<0.01).Conclusion HUC-MSC-Exo attenuates WMI in neonatal rats by regulating microglial polarization.

Objective To observe the effect of human umbilical cord mesenchymal stem cell-derived exo-somes(HUC-MSC-Exo)on microglial polarization in neonatal rats with white matter injury(WMI).Methods Three-day-old Sprague-Dawley rats were randomly divided into sham group(Sham),hypoxia-ischemia group(HI)and HUC-MSC-Exo group,with 12 rats in each group.Unilateral common carotid artery ligation combined with hy-poxia(8％oxygen and 92％nitrogen)was used to construct a WMI rat model.Exosomes were extracted by ultra-high-speed centrifugation and characterized by nanoflow cytometry,western blot experiments and transmission electron mi-croscopy.Brain stereotaxic-assisted inferior ventricular transplantation exo(2×108 particles/μL)was performed and brain tissue samples were collected 14 days after HI.Hematoxylin-eosin(HE)staining was used to observe morpho-logical changes of brain tissue.Nissl staining was used to observe Nissl body formation in brain tissue;Luxol fast blue(LFB)staining was used to observe the formation of myelin sheath in brain tissue.Immunofluorescence staining was used to observe the localized expression of ionic calcium binds adaptor molecule 1(Iba1).The protein expres-sion levels of cluster of differentiation 86(CD86),inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),CD206,arginase-1(Arg-1),IL-10 and transforming growth factor-β(TGF-β)were detected by western blot.Results The results of nanoflow cytometry,western blot and transmission electron microscopy showed that the diameter of HUC-MSC-Exo particles was between 30 and 150 nm,and the oval-like shape and membrane-like structure were visible,and the exo markers CD9,CD63 and TSG101 were positive,while calnexin was negative.HE staining,Nissl staining and LFB staining showed that compared with the Sham group,the HI group had brain tissue structure destruction,which was manifested by cell morphological changes,nerve fiber ar-rangement disorder and vacuolation,Nissl body dissolution or even disappearance,and myelination was blocked.HUC-MSC-Exo significantly reversed the pathological changes in the HI group.The results of immunofluorescence staining and western blot showed that the microglial marker Iba1 was mainly expressed in the subventricular zone(SVZ),and the expression of Iba1 protein in the SVZ region increased after HI compared with the Sham group(t=15.95、20.31,P<0.01).HUC-MSC-Exo significantly reduced the expression of Iba1 protein in the HI group(t=10.35、11.01,P<0.01).The results of western blot showed that the expressions of M1 microglia markers(CD86 and iNOS)and pro-inflammatory cytokines(TNF-α and IL-1β)were significantly increased after HI(t=10.98、7.68、15.13、13.13,both P<0.01),and the expressions of M2 microglia markers(CD206 and Arg-1)and anti-inflammatory cytokines(IL-10 and TGF-β)were also increased after HI(t=14.26、9.38、8.82、7.42,both P<0.01).HUC-MSC-Exo decreased the protein expression of CD86,iNOS,TNF-α and IL-1β(t=9.79、5.81、8.06、7.03,all P<0.01)and increased the protein expression levels of CD206,Arg-1,IL-10 and TGF-β compared to the HI group(t=12.90、8.16、8.98、9.49,both P<0.01).Conclusion HUC-MSC-Exo attenuates WMI in neonatal rats by regulating microglial polarization.

Animal disease models are important biological tools for basic medical research.Establishing an ideal animal model is a critical prerequisite for acquiring reliable experimental data.By enabling molecular-level characterization,omics technologies can enhance the precision of animal model assessments,thereby improving the evaluation criteria.This review summarizes the current applications of omics in evaluating animal disease models,discusses their potential for quality control implementation,and proposes novel frameworks for standardized model validation.

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 evaluate the efficacy and safety of Rituximab (RTX) combined with short-term use of glucocorticoids in the treatment of the initial episode of steroid-sensitive nephrotic syndrome (SSNS).Methods:A retrospective case summary.A total of 30 children with SSNS treated in the Department of Intrarenal Rheumatism and Immunology, Xuzhou Children′s Hospital from December 2021 to March 2023, were enrolled in this study.They were given a standard dose of RTX (375 mg/m 2) and glucocorticoids for a short term.The patients were followed up for 1 year, and the general condition, changes in CD19 + B lymphocytes expression after RTX treatment, the relapse rate, the median relapse-free survival and adverse reactions of RTX were recorded.Kaplan-Meier method was used to analyze the relapse-free survival time. Results:CD19 + B lymphocytes were depleted 2 weeks after RTX treatment, and the median time required for CD19 + B lymphocytes reconstitution was 5 months after RTX treatment.The 1-year relapse-free rate was 90.00%, and the median relapse-free survival was 11 months.The glucocorticoid discontinuation rate was 93.33% in 3 months after RTX treatment, and 100% in 6 and 12 months after RTX treatment.Adverse reactions included infusion reactions in 7 cases (23.33%), neutropenia/leukopenia in 5 cases (16.67%), hypoimmunoglobulinemia in 10 cases (33.33%), infections in 4 cases.One case was complicated with severe influenza A virus infection after CD19 + B lymphocytes reconstruction. Conclusions:A standard dose of RTX can significantly reduce the relapse frequency, maintain long-term remission of proteinuria, and reduce the dose of glucocorticoids in patients at the initial episode of SSNS.Thus, it is worthy of clinical promotion.

Objective To explore the effects of oleanolic acid on NF-κB/caspase-9 signaling pathway in kidneys of rat with diabetic nephropathy.Methods The diabetic nephropathy model rats were established,and the model rats were randomly divided intooleanolic acid low,medium and high dose groups,metformin group,and model group,with another 12 healthy SD rats as control group.The levels of blood glucose were measured at weeks 1,2 and 3 post-drug administration,and blood lipid and 24h urine urinary microalbumin(UMA)were measured after entire drug administration.Furthermore,we also detected the renal histopathology of rats,apoptosis of renal tubular,glomerular cells,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and protein expression of NF-κB/caspase-9 signaling pathway.Results Compared with the control group,the model group demonstrated higher levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,higher proportion of apoptotic renal tubular and glomerular,and higher expressions of caspase-9 protein and p-NF-κB p65/NF-κB p65(P＜0.05).Compared with the model group,the pathological damage of renal tissue in the metformin group and oleanolic acid low,middle and high dose groups were alleviated,the levels of blood glucose at weeks 1,2 and 3,blood lipid,UMA,TNF-α and IL-6,the proportion of apoptotic renal tubular and glomerular,and the expressions of caspase-9 proteins and p-NF-κB p65/NF-κB p65 were decreased,and these indexes in oleanolic acid groups showed a dose-dependent manner(P＜0.05).Conclusion Oleanolic acid can improve the metabolism of glucose and lipid,reduce the pathological damage of renal tissue,inhibit the apoptosis of renal tubular and glomerular,and inhibit the NF-κB/caspase-9 pathway in diabetic nephropathy rats.