Objective To investigate the effect of wogonin(WOG)on retinal ganglion cell(RGC)damage in chron-ic glaucoma rats and its relationship with the regulation of the JAK2/STAT3 signaling pathway.Methods A chronic glau-coma rat model was established in SPF-grade healthy male SD rats(50 modeled successfully).Successfully modeled rats were randomly divided into 6 groups(n=10 per group).The model group received an equal volume of normal saline(once daily,10 mL·kg-1 by gavage and 1 mL·kg-1 by intraperitoneal injection).The low-dose WOG group(L-WOG),medium-dose WOG group(M-WOG),and high-dose WOG group(H-WOG)received WOG at 7 mg·kg-1,14 mg·kg-1,and 28 mg·kg-1 by gavage,respectively(once daily,gavage volume 10 mL·kg-1).The high-dose WOG+Colivelin group(H-WOG+Colivelin)received WOG by gavage(28 mg·kg-1,once daily,10 mL·kg-1)plus intraperitoneal injection of the JAK2/STAT3 pathway activator Colivelin(1 mg·kg-1,once daily,injection volume 1 mL·kg-1).An additional 10 normal rats served as the sham-operated control group(Control group),undergoing surgery to expose the superior episcleral vein without cauterization,and receiving normal saline postoperatively in the same manner as the model group.All treatments lasted for 8 weeks.Intraocular pressure was measured using a tonometer.Retinal morphological changes and RGC apopto-sis were assessed by hematoxylin-eosin(HE)staining and TUNEL staining,respectively.Superoxide dismutase(SOD)ac-tivity and malondialdehyde(MDA)content in retinal tissue were measured by ELISA.Protein expression changes in the JAK2/STAT3 signaling pathway in retinal tissue were detected by Western blot.Results Retinal structure was normal in the Control group,with clear layers and densely arranged cells.Compared to the Control group,the model group showed significantly thinner retinal tissue,disorganized structure,sparsely arranged cells,and vacuolation.Compared to the model group,the L-WOG,M-WOG,and H-WOG groups exhibited increased retinal thickness and more orderly cell arrangement.Compared to the H-WOG group,the H-WOG+Colivelin group showed relatively thinner retinal tissue and sparser cell ar-rangement.After intervention,the RGC apoptosis rate in the model group(7.32％±1.07％)was significantly higher than that in the Control group(0.61％±0.12％)(P＜0.05).The apoptosis rates in the L-WOG group(5.67％±0.63％),M-WOG group(3.34％±0.75％),and H-WOG group(1.12％±0.35％)were significantly lower than that in the model group(all P＜0.05),showing a dose-dependent decreasing trend.The apoptosis rate in the H-WOG+Colivelin group(6.83％±1.56％)was significantly higher than that in the H-WOG group(P＜0.05).Compared to the Control group,SOD activity in the retinal tissue of the model group was significantly decreased(P＜0.05),while MDA content was significantly increased(P＜0.05).Compared to the model group,SOD activity was significantly increased and MDA content was significantly de-creased in the L-WOG,M-WOG,and H-WOG groups(all P＜0.05),with this effect being dose-dependent(i.e.,H-WOG group＞M-WOG group＞L-WOG group).Compared to the H-WOG group,the H-WOG+Colivelin group showed signifi-cantly decreased SOD activity and significantly increased MDA content(P＜0.05).Compared to the Control group,the ra-tios of p-JAK2/JAK2 and p-STAT3/STAT3 expression in the retinal tissue of the model group were significantly upregulated(all P＜0.05).Compared to the model group,the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 expression were significantly downregulated in the L-WOG,M-WOG,and H-WOG groups(all P＜0.05).Compared to the H-WOG group,the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 expression were significantly upregulated in the H-WOG+Colivelin group(all P＜0.05).Conclusion WOG may alleviate retinal tissue damage in chronic glaucoma rats by inhibiting the JAK2/STAT3 signaling pathway,thereby reducing oxidative stress and RGC apoptosis.

Objective·To detect immunoglobulin(Ig)expression levels in newly diagnosed multiple myeloma(MM)patients before and after induction therapy,and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy,infection occurrence,and prognosis.Methods·Clinical data from 142 MM patients treated at the Department of Hematology,The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed.Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone(VRD)regimen were assessed.Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal.Patients were stratified by immunoparesis severity(mild,moderate,severe,extremely severe).ANOVA,rank-sum tests,and x2 tests were used to analyze correlations with baseline characteristics.The relationship between the improvement in immunoparesis and the induction efficacy,infection occurrence,and prognosis was analyzed based on the dynamic changes in immunoparesis.Results·Normal Igs were severely reduced in newly diagnosed MM patients.Immunoparesis was present in 128 patients(90.1%),with severe or extremely severe immunoparesis accounting for 76.1%.Patients with extensive immunoparesis(all uninvolved Ig levels below the lower normal limit)were more likely to have severe immunoparesis(P<0.05).There were no statistically significant differences in age,gender,presence of severe renal insufficiency,and high-risk cytogenetics among MM patients with different degrees of immunoparesis(P>0.05),but there were statistically significant differences in MM staging(P=0.008)and typing(P=0.010).Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System(R-ISS)and were of the IgG type.At diagnosis,the levels of the involved Ig or light chain were negatively correlated with normal Ig levels(P<0.05).Improvement in immunoparesis after induction therapy was positively correlated with treatment response(P=0.006).The infection rate was high(26.8%),but no significant correlation was found between immunoparesis and infection occurrence(P>0.05).After induction therapy,patients showing improvement in immunoparesis had significantly longer progression-free survival(PFS)(median PFS:not reached vs 38 months,P=0.025),but no significant impact on overall survival(OS)was observed(P=0.450).Conclusion·Immunoparesis is common and severe in newly diagnosed MM patients,with severity correlating with disease stage and subtype.VRD therapy can partially reverse immunoparesis,and improvement is positively associated with treatment response and PFS benefit.Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies.Humoral immune deficiency may serve as a prognostic indicator in MM,but its impact on OS requires further investigation.

Objective To investigate the effect of wogonin(WOG)on retinal ganglion cell(RGC)damage in chron-ic glaucoma rats and its relationship with the regulation of the JAK2/STAT3 signaling pathway.Methods A chronic glau-coma rat model was established in SPF-grade healthy male SD rats(50 modeled successfully).Successfully modeled rats were randomly divided into 6 groups(n=10 per group).The model group received an equal volume of normal saline(once daily,10 mL·kg-1 by gavage and 1 mL·kg-1 by intraperitoneal injection).The low-dose WOG group(L-WOG),medium-dose WOG group(M-WOG),and high-dose WOG group(H-WOG)received WOG at 7 mg·kg-1,14 mg·kg-1,and 28 mg·kg-1 by gavage,respectively(once daily,gavage volume 10 mL·kg-1).The high-dose WOG+Colivelin group(H-WOG+Colivelin)received WOG by gavage(28 mg·kg-1,once daily,10 mL·kg-1)plus intraperitoneal injection of the JAK2/STAT3 pathway activator Colivelin(1 mg·kg-1,once daily,injection volume 1 mL·kg-1).An additional 10 normal rats served as the sham-operated control group(Control group),undergoing surgery to expose the superior episcleral vein without cauterization,and receiving normal saline postoperatively in the same manner as the model group.All treatments lasted for 8 weeks.Intraocular pressure was measured using a tonometer.Retinal morphological changes and RGC apopto-sis were assessed by hematoxylin-eosin(HE)staining and TUNEL staining,respectively.Superoxide dismutase(SOD)ac-tivity and malondialdehyde(MDA)content in retinal tissue were measured by ELISA.Protein expression changes in the JAK2/STAT3 signaling pathway in retinal tissue were detected by Western blot.Results Retinal structure was normal in the Control group,with clear layers and densely arranged cells.Compared to the Control group,the model group showed significantly thinner retinal tissue,disorganized structure,sparsely arranged cells,and vacuolation.Compared to the model group,the L-WOG,M-WOG,and H-WOG groups exhibited increased retinal thickness and more orderly cell arrangement.Compared to the H-WOG group,the H-WOG+Colivelin group showed relatively thinner retinal tissue and sparser cell ar-rangement.After intervention,the RGC apoptosis rate in the model group(7.32％±1.07％)was significantly higher than that in the Control group(0.61％±0.12％)(P＜0.05).The apoptosis rates in the L-WOG group(5.67％±0.63％),M-WOG group(3.34％±0.75％),and H-WOG group(1.12％±0.35％)were significantly lower than that in the model group(all P＜0.05),showing a dose-dependent decreasing trend.The apoptosis rate in the H-WOG+Colivelin group(6.83％±1.56％)was significantly higher than that in the H-WOG group(P＜0.05).Compared to the Control group,SOD activity in the retinal tissue of the model group was significantly decreased(P＜0.05),while MDA content was significantly increased(P＜0.05).Compared to the model group,SOD activity was significantly increased and MDA content was significantly de-creased in the L-WOG,M-WOG,and H-WOG groups(all P＜0.05),with this effect being dose-dependent(i.e.,H-WOG group＞M-WOG group＞L-WOG group).Compared to the H-WOG group,the H-WOG+Colivelin group showed signifi-cantly decreased SOD activity and significantly increased MDA content(P＜0.05).Compared to the Control group,the ra-tios of p-JAK2/JAK2 and p-STAT3/STAT3 expression in the retinal tissue of the model group were significantly upregulated(all P＜0.05).Compared to the model group,the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 expression were significantly downregulated in the L-WOG,M-WOG,and H-WOG groups(all P＜0.05).Compared to the H-WOG group,the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 expression were significantly upregulated in the H-WOG+Colivelin group(all P＜0.05).Conclusion WOG may alleviate retinal tissue damage in chronic glaucoma rats by inhibiting the JAK2/STAT3 signaling pathway,thereby reducing oxidative stress and RGC apoptosis.

Objective To investigate the clinical application of ceftazidime/avibactam(CAZ/AVI)in lung trans-plant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli(CRGNB),and ana-lyze the factors affecting the prognosis.Methods Lung transplant recipients who had CRGNB pulmonary infection and were treated with CAZ/AVI were included in the analysis.Based on 14-day clinical response,14-day microbial response,and 30-day survival status,the recipients were divided into a clinical response group and a clinical failure group,a microbial response group and a microbial failure group,as well as a survival group and a death group,re-spectively.Univariate analysis was conducted on various data from the two groups.Factors affecting therapeutic ef-ficacy and survival were included in a binary logistic regression model.Independent risk factors for CAZ/AVI anti-infective efficacy and all-cause mortality outcomes were analyzed.Results A total of 43 recipients were included.After 14-day anti-infective treatment,32 recipients(74.42％)achieved clinical response,and 30 recipients(69.77％)achieved microbial response.34 recipients(79.07％)survived 30 days after CAZ/AVI treatment.The Charlson comorbidity index(CCI),proportion of renal dysfunction,and incidence of shock in recipients in the clini-cal response group were all lower than those in the clinical failure group(P＜0.05),while the serum albumin(ALB)level was higher(P＜0.05).The incidence of shock in recipients in the microbial response group was lower than that in the microbial failure group(P＜0.05).CCI,proportion of renal dysfunction,and incidence of shock in recipients in the survival group were all lower than those in the death group(all P＜0.05),while ALB level was higher during treatment period(P＜0.05).Multivariate analysis of 14-day clinical response and 30-day survival showed that higher CCI was an independent risk factor affecting 14-day clinical response of recipients(OR=2.22,95％CI:1.07-4.63),while lower ALB levels(OR=0.72,95％CI:0.54-0.98)and higher CCI(OR=5.27,95％CI:1.18-23.58)were independent risk factors for 30-day all-cause mortality in recipients with pulmonary in-fection after lung transplant.Conclusion CAZ/AVI may be an effective drug for treating pulmonary infection caused by CRGNB in lung transplant recipients.Higher CCI is an independent risk factor for 14-day clinical failure in recipients after CAZ/AVI treatment.Lower ALB level and higher CCI are independent risk factors for increased 30-day mortality in recipients.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To isolate pathogenic bacteria from the skin of a nude mouse exhibiting squamous skin scurfs, and perform bacterial identification, traceability analysis, and pathogenicity studies to provide a new approach for the diagnosis of pathogens in nude mice with squamous skin scurfs. MethodsSkin swab samples were collected from a nude mouse exhibiting squamous skin scurfs for nucleic acid testing, bacterial isolation and culture, biochemical identification, 16S rDNA gene amplification and sequencing, and whole genome sequencing to construct a phylogenetic tree. Fifteen BALB/c nude mice were randomized into a saline-treated control group, a high-concentration group treated with 1.8×10⁸ CFU/mL of the isolated bacterial suspension, and a low-concentration group treated with 1.8×10⁷ CFU/mL of the isolated bacterial suspension. Pathogenicity was assessed by animal infection experiments and observation of histopathological changes in skin tissue using HE staining. Results The nucleic acid test for Corynebacterium bovis was negative, excluding infection by this organism. The pathogen isolated on mannitol salt agar and blood agar, combined with Gram staining, suggested a Gram-positive Staphylococcus species. The isolated strain was identified by 16S rDNA sequencing and a fully automated microbial identification system as Staphylococcus xylosus. Phylogenetic tree analysis based on whole genome sequencing showed that the strain was most closely related to an isolate from leafy vegetables in South Korea (GenBank GCA_00207825.1). In the high-concentration group, squamous skin scurfs appeared on the head, neck, and back of nude mice on the 17th day post-infection, while in the low concentration group, similar symptoms appeared on the 20th day post-infection and gradually spread to other areas. The scaling symptoms were transient, lasting for 7 days in the high-concentration group and 3 days in the low-concentration group, after which the skin returned to normal. The infection rate was 33.33% in both the high- and low-concentration groups. No significant pathological changes were observed in the skin tissues of infected mice compared to the control group, indicating marked individual differences in the pathogenicity of the strain in nude mice. Conclusion A strain of Staphylococcus xylosus was isolated from the skin of a nude mouse exhibiting squamous skin scurfs. The strain is an opportunistic pathogen that causes transient squamous skin scurfs without significant histopathological changes, and there are individual differences in the sensitivity of nude mice to this strain. These findings can provide valuable data for pathogen identification in immunodeficient or gene knockout mice.

Objective To investigate the clinical application of ceftazidime/avibactam(CAZ/AVI)in lung trans-plant recipients with pulmonary infection caused by carbapenem-resistant Gram-negative bacilli(CRGNB),and ana-lyze the factors affecting the prognosis.Methods Lung transplant recipients who had CRGNB pulmonary infection and were treated with CAZ/AVI were included in the analysis.Based on 14-day clinical response,14-day microbial response,and 30-day survival status,the recipients were divided into a clinical response group and a clinical failure group,a microbial response group and a microbial failure group,as well as a survival group and a death group,re-spectively.Univariate analysis was conducted on various data from the two groups.Factors affecting therapeutic ef-ficacy and survival were included in a binary logistic regression model.Independent risk factors for CAZ/AVI anti-infective efficacy and all-cause mortality outcomes were analyzed.Results A total of 43 recipients were included.After 14-day anti-infective treatment,32 recipients(74.42％)achieved clinical response,and 30 recipients(69.77％)achieved microbial response.34 recipients(79.07％)survived 30 days after CAZ/AVI treatment.The Charlson comorbidity index(CCI),proportion of renal dysfunction,and incidence of shock in recipients in the clini-cal response group were all lower than those in the clinical failure group(P＜0.05),while the serum albumin(ALB)level was higher(P＜0.05).The incidence of shock in recipients in the microbial response group was lower than that in the microbial failure group(P＜0.05).CCI,proportion of renal dysfunction,and incidence of shock in recipients in the survival group were all lower than those in the death group(all P＜0.05),while ALB level was higher during treatment period(P＜0.05).Multivariate analysis of 14-day clinical response and 30-day survival showed that higher CCI was an independent risk factor affecting 14-day clinical response of recipients(OR=2.22,95％CI:1.07-4.63),while lower ALB levels(OR=0.72,95％CI:0.54-0.98)and higher CCI(OR=5.27,95％CI:1.18-23.58)were independent risk factors for 30-day all-cause mortality in recipients with pulmonary in-fection after lung transplant.Conclusion CAZ/AVI may be an effective drug for treating pulmonary infection caused by CRGNB in lung transplant recipients.Higher CCI is an independent risk factor for 14-day clinical failure in recipients after CAZ/AVI treatment.Lower ALB level and higher CCI are independent risk factors for increased 30-day mortality in recipients.

Objective To compare the performance and efficacy of prognostic models constructed by different machine learning algorithms in predicting the survival period of lung transplantation (LTx) recipients. Methods Data from 483 recipients who underwent LTx were retrospectively collected. All recipients were divided into a training set and a validation set at a ratio of 7:3. The 24 collected variables were screened based on variable importance (VIMP). Prognostic models were constructed using random survival forest (RSF) and extreme gradient boosting tree (XGBoost). The performance of the models was evaluated using the integrated area under the curve (iAUC) and time-dependent area under the curve (tAUC). Results There were no significant statistical differences in the variables between the training set and the validation set. The top 15 variables ranked by VIMP were used for modeling and the length of stay in the intensive care unit (ICU) was determined as the most important factor. Compared with the XGBoost model, the RSF model demonstrated better performance in predicting the survival period of recipients (iAUC 0.773 vs. 0.723). The RSF model also showed better performance in predicting the 6-month survival period (tAUC _{6 months} 0.884 vs. 0.809, P = 0.009) and 1-year survival period (tAUC _{1 year} 0.896 vs. 0.825, P = 0.013) of recipients. Based on the prediction cut-off values of the two algorithms, LTx recipients were divided into high-risk and low-risk groups. The survival analysis results of both models showed that the survival rate of recipients in the high-risk group was significantly lower than that in the low-risk group (P<0.001). Conclusions Compared with XGBoost, the machine learning prognostic model developed based on the RSF algorithm may preferably predict the survival period of LTx recipients.

Multiple myeloma (MM) is a hematological malignancy that poses significant treatment challenges due to its heterogeneity and propensity for relapse and progression. In the last two decades, the therapeutic landscape of MM has changed dramatically, but the disease remains largely incurable, with many patients facing treatment resistance. This review evaluates the current status of MM treatments, emphasizing the limitations of traditional therapies and the emerging role of immunotherapy in improving patient outcomes. It highlights the importance of achieving and maintaining minimal residual disease negativity and a balanced immune response as key treatment goals. Furthermore, it discusses the advancements in immunotherapies that are improving the prospects for patients, particularly those with relapsed or refractory disease. Innovative strategies, such as chimeric antigen receptor T-cell therapy, bispecific antibodies, and bispecific T cell engagers, have shown significant promise by targeting the malignant cells and the bone marrow microenvironment, which are essential for disease persistence and resistance to therapy. Future research should focus on refining MM treatment strategies, including the integration of immunotherapy into earlier treatment lines and the development of predictive biomarkers for personalized treatment approaches, ultimately enhancing patient outcomes.

Objective·To detect immunoglobulin(Ig)expression levels in newly diagnosed multiple myeloma(MM)patients before and after induction therapy,and to explore the clinical significance of Ig expression levels and their dynamic changes in relation to treatment efficacy,infection occurrence,and prognosis.Methods·Clinical data from 142 MM patients treated at the Department of Hematology,The First Affiliated Hospital of Soochow University between August 2018 and September 2020 were analyzed.Baseline Ig expression levels and post-induction changes following bortezomib-lenalidomide-dexamethasone(VRD)regimen were assessed.Immunoparesis was defined as uninvolved Igs below the laboratory lower limit of normal.Patients were stratified by immunoparesis severity(mild,moderate,severe,extremely severe).ANOVA,rank-sum tests,and x2 tests were used to analyze correlations with baseline characteristics.The relationship between the improvement in immunoparesis and the induction efficacy,infection occurrence,and prognosis was analyzed based on the dynamic changes in immunoparesis.Results·Normal Igs were severely reduced in newly diagnosed MM patients.Immunoparesis was present in 128 patients(90.1%),with severe or extremely severe immunoparesis accounting for 76.1%.Patients with extensive immunoparesis(all uninvolved Ig levels below the lower normal limit)were more likely to have severe immunoparesis(P<0.05).There were no statistically significant differences in age,gender,presence of severe renal insufficiency,and high-risk cytogenetics among MM patients with different degrees of immunoparesis(P>0.05),but there were statistically significant differences in MM staging(P=0.008)and typing(P=0.010).Most patients with severe immunoparesis were at stage Ⅱ/Ⅲ based on the Revised International Staging System(R-ISS)and were of the IgG type.At diagnosis,the levels of the involved Ig or light chain were negatively correlated with normal Ig levels(P<0.05).Improvement in immunoparesis after induction therapy was positively correlated with treatment response(P=0.006).The infection rate was high(26.8%),but no significant correlation was found between immunoparesis and infection occurrence(P>0.05).After induction therapy,patients showing improvement in immunoparesis had significantly longer progression-free survival(PFS)(median PFS:not reached vs 38 months,P=0.025),but no significant impact on overall survival(OS)was observed(P=0.450).Conclusion·Immunoparesis is common and severe in newly diagnosed MM patients,with severity correlating with disease stage and subtype.VRD therapy can partially reverse immunoparesis,and improvement is positively associated with treatment response and PFS benefit.Infection risk appears unrelated to immunoparesis severity and warrants comprehensive prevention strategies.Humoral immune deficiency may serve as a prognostic indicator in MM,but its impact on OS requires further investigation.