ObjectiveTo construct a novel KPC mouse model of type 2 diabetes mellitus （T2DM） comorbid with spontaneous pancreatic cancer based on the gene editing-metabolic intervention dual-driven strategy， and to compare it with traditional models. MethodsA total of 14 male KPC mice were randomly divided into novel model group （T2DM-KPC group with 7 mice） and control group （KPC group with 7 mice）， and 14 male BALB/c-nu nude mice were randomly divided into traditional model group （T2DM-pancreatic cancer group with 7 mice） and control group （pancreatic cancer group with 7 mice）. The mice in the KPC group and the pancreatic cancer group were fed with normal diet， and those in the T2DM-KPC group and the T2DM-pancreatic cancer group were fed with a high-fat diet. After 4 weeks， the mice in the T2DM-KPC group and the T2DM-pancreatic cancer group were given intraperitoneal injection of streptozotocin. Subsequently， the mice in the KPC group and the T2DM-KPC group developed primary pancreatic tumor spontaneously over time， while those in the T2DM-pancreatic cancer group and the pancreatic cancer group were inoculated with tumor cells to form subcutaneous tumor xenograft at 2 weeks after stabilization of blood glucose. The 4 groups were observed in terms of tumor formation rate， tumor formation time， body weight， and the change in blood glucose； RNA sequencing was performed for tumors from the KPC group and the T2DM-KPC group， and then molecular subtyping was performed； HE staining， Masson staining， and immunohistochemical staining were used to assess the histopathological features and tumor microenvironment of pancreatic tumor from the T2DM-KPC group， which were compared with those of the T2DM-pancreatic cancer group. A one-way analysis of variance was used for comparison of continuous data between multiple groups， and the least significant difference t-test was used for further comparison between two groups； the Fisher’s exact test was used for comparison of categorical data between multiple groups. ResultsThe T2DM-KPC group had a tumor formation rate of 85.71% and a tumor formation time of 104.40±2.87 days， while the T2DM-pancreatic cancer group had a tumor formation rate of 71.43% and a tumor formation time of 95.20±9.47 days， and there were no significant differences between the two groups in tumor formation rate， tumor formation time， body weight， and blood glucose （all P>0.05）. Molecular subtyping showed that the model in the KPC group highly resembled the pancreatic progenitor subtype of human pancreatic ductal adenocarcinoma （PDAC）， and the model in the T2DM-KPC group highly resembled the immunogenic subtype of PDAC. HE staining showed that tumor cells in the T2DM-KPC group were arranged into glandular tubular structures of varying shapes， exhibiting significant cellular atypia， and this model faithfully recapitulated the pathological features of primary pancreatic cancer and showed greater invasiveness than the KPC group. Immunohistochemical staining and Masson staining showed that compared with the T2DM-pancreatic cancer group， the T2DM-KPC group had significantly higher degrees of tumor proliferation （assessed by Ki-67 expression） and fibrosis （assessed by α-SMA and Masson） （all P<0.05）， suggesting that the mouse model in the T2DM-KPC group could better recapitulate the features of hyperproliferation and pronounced desmoplasia in human pancreatic cancer. ConclusionA novel KPC mouse model of T2DM comorbid with spontaneous pancreatic cancer is successfully constructed in this study. This model can accurately mimic the histopathological architecture and stromal microenvironment of T2DM comorbid with pancreatic cancer， realize the longitudinal simulation of the progression of pancreatic tissue from intraepithelial neoplasia to invasive carcinoma and metastasis in the presence of T2DM， and support the translational research on immunotherapy， thereby providing a novel experimental carrier for in vivo studies on spontaneous pancreatic cancer in T2DM.

Objective To assess the efficacy and the survival rate of the hip joint following the treatment of osteonecrosis of the femoral head(ONFH)with ultrasound-guided percutaneous intra-articular platelet-rich plasma(PRP)injection in combination with percutaneous silver needle thermalolysis.Methods Fifty-six patients diag-nosed with ARCO(Association Research Circulation Osseous)stage Ⅱ ONFH were randomly allocated into two groups.The first group,designated as the PRP injection combined with silver needle thermalolysis group(Group R,n=28),and the second group,the steroid injection combined with silver needle thermalolysis group(Group S,n=28).Both groups underwent three injections(administered at 4-week intervals)and one session of silver needle thermalolysis.Outcome measures,including the Numerical Rating Scale(NRS)for pain assessment,Harris Hip Score(HHS),daily consumption of non-steroidal anti-inflammatory drugs(etoricoxib)and tramadol,progression to ARCO stage Ⅲ,and the rates of surgical intervention,were recorded at baseline,3 days,and 1,3,6,and 12 months after the treatment.Results When compared to the baseline,both groups manifested significant decreases in NRS scores and enhancements in HHS at all follow-up time points(P<0.05).Specifically,Group R demonstrated more favorable outcomes compared to Group S.At 3,6,and 12 months,Group R had lower NRS scores(P<0.01)and more notable improvements in HHS(P<0.01).Additionally,the daily analgesic consumption(etoricoxib and tramadol)in Group R was significantly lower than that in Group S at 3,6,and 12 months(P<0.01).Moreover,Group R exhibited a significantly lower progression rate to ARCO stage III and a lower hip replacement surgery rate(P<0.05).Conclusions Ultrasound-guided intra-articular PRP injection in combination with silver needle therma-lolysis expedites pain alleviation,enhances hip function,reduces analgesic dependence,and retards the progression of ONFH.This approach thus represents a clinically viable option for early-stage intervention.

This study was aimed at investigating the immunoregulatory function of Mycobacterium tuberculosis Rv3641c gene in modulating host type Ⅰ interferon responses.The shuttle plasmid pMV261 was used to construct Rv3641c overexpression recombinant Mycobacterium smegmatis,and the biological characteristics of the recombinant bacteria were analyzed to explore the effect of Rv3641c on the growth curve,colony morphology and stress resistance of Mycobacterium.Subsequently,RAW264.7 cells were infected with Rv3641c overexpressing Mycobacterium smegmatis,and the transcriptional expression of genes related to the inhibition of type I inter-feron pathway was determined by RT-PCR.The expression level of IFN-βprotein was determined by ELISA,and the intracellular sur-vival level was determined.As a result,the recombinant rMS::pMV261-Rv3641c was successfully constructed.The results of biologi-cal characteristics analysis showed that Rv3641c did not affect the growth of mycobacteria,but significantly changed the colony mor-phology of mycobacteria and improved its resistance to H2O2.The results of recombinant bacteria infection experiments showed that Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1β in host cells,and Rv3641c significantly down-regulated the transcription levels of IFN-α,IFN-βand downstream ISGs genes CXCL10,IFIT2 and IL-1βin host cells.The results of intracellular colonization experiments showed that the intracellular mycobacte-ria in the overexpression recombinant bacteria infection group were significantly higher than those in the empty vector group,indicat-ing that Rv3641c could promote the intracellular surviv al of mycobacteria.In summary,the Rv3641c gene of M.tuberculosis can inhibit the host type I interferon response and promote the intracellular survival of M.tuberculosis,which provides a new idea for further explor-ing the immune escape function of M.tuberculosis and the discovery of new targets for anti-tuberculosis drugs.

Objective:To investigate the predictive value of endothelial activation and stress index(EASIX)for the prognosis of patients with mantle cell lymphoma(MCL).Methods:A retrospective analysis was conducted to assess prognosis and compare the clinical features of patients diagnosed with MCL who were admitted to the Affiliated Hospital of Xuzhou Medical University from January 2010 to June 2023,had therapeutic indications and received standard treatment.Results:A total of 66 patients were included and divided into high EASIX group and low EASIX group,according to a cutoff value of 0.97 determined by the receiver operating characteristic(ROC)curve.Multivariate Cox regression analysis showed that prealbumin＜0.2 g/L,high EASIX,and ECOG PS score ≥2 were independent risk factors influencing overall survival(OS)in MCL patients.The median OS of patients in the high and low EASIX group was 13.0 and 37.5 months,and the median progression-free survival was 8.8 and 26.0 months,respectively.The proportions of patients with ECOG PS score ≥2 and prealbumin＜0.2 g/L at onset significantly increased in the high EASIX group compared to those in the low EASIX group.Conclusion:At the time of initial diagnosis,EASIX can serve as an independent prognostic indicator impacting OS in patients with MCL.Furthermore,patients in the high EASIX group experience a poorer prognosis and shorter survival duration compared with those in the low EASIX group.

Objective:To analyze the effects of the Focused Solution Model Nursing intervention on quality of life,negative emotions of the patients with prostate cancer.Methods:A total of 82 prostate cancer patients who were diagnosed and treated at the General Hospital of Eastern Theater Command between September 2022 and September 2024 were included and randomly divided into study group and control group by the method of random number table,with 41 patients in each group.The patients in the study group were treated with Focused Solution Model Nursing intervention.And the routine care was used in the control group The quality of life and negative emotions were compared between the two groups by using the scales of World Health Organization Quality of Life-Brief(WHOQOL-BREF),HAMA and HAMD.Results:Compared to the control group,the patients in the study group exhibited signifi-cantly higher scores in the physiological,psychological,environmental,and social relationship domains of the WHOQOL-BREF scale(P＜0.05).The scores of HAMA and HAMD in study group were lower than those of the control group(P＜0.05).Additionally,all subscales of the Social Impact Scale including social exclusion,internalized shame,social isolation and economic discrimination were significantly lower than those of the study group(P＜0.05).Conclusion:Focused Solution Model Nursing intervention can effec-tively improve the quality of life and negative emotions of the prostate cancer patients in the clinical treatment.

Objective:To investigate the prevalence and risk factors of cornea guttata in patients with age-related cataract.Methods:A cross-sectional study was conducted.A total of 1 472 patients aged 50-89 years with complete medical records, who were diagnosed with age-related cataract and to undergo surgery, were enrolled at Peking University People's Hospital from August 2018 to July 2019.The presence of guttata was determined according to the specular microscopy images and the overall prevalence of guttata was calculated, as well as the prevalence rates of different gender, eye, and age distribution.Patients were divided into a guttata group (96 cases 130 eyes) and a non-guttata group (1 376 cases 2 814 eyes), and the differences in general information between groups were compared.The corneal endothelial cell density (CD), coefficient of variation of cell size (CV), fraction of hexagonal cells (6A), axial length (AL), white to white (WTW), anterior chamber depth, and corneal vertex thickness were compared between the two groups, and only the right eye of the patient with both eyes affected was included for analysis.The risk factors of guttata were analyzed by multivariate logistic regression.Differences in influencing factors among different guttata grades were compared, and the differences in biometric parameters of each eye in both eyes of guttata patients were compared.This study adhered to the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2023PHB198-001).Results:Of the 1 472 patients, 96(6.52%) patients had cornea guttata.The prevalence rate of guttata in males was 4.04%, which was significantly lower than 8.20% in females ( χ2=10.058, P=0.002).The average age of patients in the guttata group was (71.19±8.57) years old, with 24 males and 72 females, including 62 patients with monocular guttata and 39 patients with isolated guttata.Multivariate logistic regression analysis showed that female (odds ratio [ OR]=2.124, 95% confidence interval [ CI]: 1.306-3.455), greater AL ( OR=1.201, 95% CI: 1.083-1.332), shallow anterior chamber depth ( OR=0.439, 95% CI: 0.252-0.766), and greater corneal vertex thickness ( OR=1.008, 95% CI: 1.001-1.015) were risk factors for guttata.There were statistically significant differences in the proportion of monocular guttata and biocular guttata among different grades groups, and between isolated guttata and non-isolated guttata ( χ2=25.492, 15.362; both P<0.05).Differences in CD and corneal vertex thickness among different grades groups were statistically significant ( F=3.264, 5.784; both P<0.05).The CD was significanty higher and the corneal vertex thickness was significantly thinner in the grade 1 than in the grade ≥3 (both P<0.017).There was no statistically significant difference in binocular CD, CV, 6A, AL, WTW, anterior chamber depth, and corneal vertex thickness between both eyes of monocular or binocular guttata patients (all P>0.05). Conclusions:The risk factors of guttata include female, long AL, shallow anterior chamber depth, and thick corneal vertex thickness.The guttata grade of monocular guttata and isolated guttata patients is lower.With the increase of grade, the corneal vertex thickness increases.There is no difference in ocular structure between both eyes of guttata patients.

Objective:To observe the effects of auricular point compression and exercise therapy on glycolipid metabolism,oxidative stress and sleep quality in type 2 diabetes mellitus(T2DM)patients with poor glycemic control.Methods:This study was a single-center randomized controlled study,86 T2DM patients with poor glycemic control who were treated in our hospital from June 2022 to June 2024 were divided into control group(received conventional treatment,n=43)and observation group(received auricular point compression and exercise therapy,n=43)by using the random number table method.The clinical efficacy,blood lipid indexes,blood glucose indexes,oxidative stress indexes and sleep quality were compared between the two groups.Results:The total clinical effective rate,high-density lipoprotein cholesterol(HDL-C),superoxide dismutase(SOD)and Glutathione peroxidase(GSH-Px)of the observation group after treatment were higher than those of the control group,and the fasting blood glucose(FBG),glycated hemoglobin(HbA1c),Homeostatic Model Assessment of Insulin Resistance(HOMA-IR),total cholesterol(TC),low-density lipoprotein cholesterol(LDL-C),triglycerides(TG),reactive oxygen species(ROS),malondialdehyde(MDA)and Pittsburgh sleep Quality Index(PSQI)score were lower than those of the control group(P＜0.05).Conclusion:Auricular point compression and exercise therapy can regulate glycolipid metabolism in T2DM patients with poor glycemic control,improve the degree of oxidative stress and sleep quality.

Objective:To investigate the prevalence and risk factors of cornea guttata in patients with age-related cataract.Methods:A cross-sectional study was conducted.A total of 1 472 patients aged 50-89 years with complete medical records, who were diagnosed with age-related cataract and to undergo surgery, were enrolled at Peking University People's Hospital from August 2018 to July 2019.The presence of guttata was determined according to the specular microscopy images and the overall prevalence of guttata was calculated, as well as the prevalence rates of different gender, eye, and age distribution.Patients were divided into a guttata group (96 cases 130 eyes) and a non-guttata group (1 376 cases 2 814 eyes), and the differences in general information between groups were compared.The corneal endothelial cell density (CD), coefficient of variation of cell size (CV), fraction of hexagonal cells (6A), axial length (AL), white to white (WTW), anterior chamber depth, and corneal vertex thickness were compared between the two groups, and only the right eye of the patient with both eyes affected was included for analysis.The risk factors of guttata were analyzed by multivariate logistic regression.Differences in influencing factors among different guttata grades were compared, and the differences in biometric parameters of each eye in both eyes of guttata patients were compared.This study adhered to the Declaration of Helsinki, and the study protocol was approved by the Ethics Committee of Peking University People's Hospital (No.2023PHB198-001).Results:Of the 1 472 patients, 96(6.52%) patients had cornea guttata.The prevalence rate of guttata in males was 4.04%, which was significantly lower than 8.20% in females ( χ2=10.058, P=0.002).The average age of patients in the guttata group was (71.19±8.57) years old, with 24 males and 72 females, including 62 patients with monocular guttata and 39 patients with isolated guttata.Multivariate logistic regression analysis showed that female (odds ratio [ OR]=2.124, 95% confidence interval [ CI]: 1.306-3.455), greater AL ( OR=1.201, 95% CI: 1.083-1.332), shallow anterior chamber depth ( OR=0.439, 95% CI: 0.252-0.766), and greater corneal vertex thickness ( OR=1.008, 95% CI: 1.001-1.015) were risk factors for guttata.There were statistically significant differences in the proportion of monocular guttata and biocular guttata among different grades groups, and between isolated guttata and non-isolated guttata ( χ2=25.492, 15.362; both P<0.05).Differences in CD and corneal vertex thickness among different grades groups were statistically significant ( F=3.264, 5.784; both P<0.05).The CD was significanty higher and the corneal vertex thickness was significantly thinner in the grade 1 than in the grade ≥3 (both P<0.017).There was no statistically significant difference in binocular CD, CV, 6A, AL, WTW, anterior chamber depth, and corneal vertex thickness between both eyes of monocular or binocular guttata patients (all P>0.05). Conclusions:The risk factors of guttata include female, long AL, shallow anterior chamber depth, and thick corneal vertex thickness.The guttata grade of monocular guttata and isolated guttata patients is lower.With the increase of grade, the corneal vertex thickness increases.There is no difference in ocular structure between both eyes of guttata patients.

The use of CD20 monoclonal antibody in the treatment of children with refractory nephrotic syndrome (RNS) is a novel drug therapy in recent years. Some CD20 monoclonal antibodies have positive efficacy and few adverse reactions, which can reduce the use of hormone drugs and immunosuppressants to a certain extent. However, the treatment of nephrotic syndrome is off-label, and the application time in clinic is not long, especially for children′s RNS, and more high-quality clinical studies are still needed for long-term efficacy and safety. The application and safety research progress of CD20 monoclonal antibody (including rituximab, ofatumumab, obinutuzumab, etc.) in the treatment of children with RNS from the aspects of mechanism of action, clinical application, pharmacokinetic characteristics, adverse reactions monitoring, and prevention are reviewed in this article, so as to provide reference for rational and safe clinical use.

Objective To explore the predictive value of systemic immuno-inflammatory index(SII)and the amplitude of change(Dclta-SII)on the efficacy of adjuvant treatment with Tislelizumab(T)in combination with Gemcitabine and Cisplatin(GC)in patients with muscle-invasive bladder carcinoma(MIBC)after radical surgery.Methods A total of 47 MIBC patients undergoing radical surgery in the Affiliated Hospital of Xuzhou Medical University during Jun.2018 and Jun.2022 were enrolled.All patients received T+GC therapy.Baseline SII before treatment(Pre-SII)and SII after 3 cycles(Post-SII)were collected,and Delta-SII was calculated.The sensitivity and specificity of Pre-SII and Delta-SII were measured using receiver operating characteristic(ROC)curves,and the best cut-off values were determined.The recurrence-free survival(RFS)rate was analyzed with Kaplan-Meier method.The risk factors of RFS were investigated with univariate and multivariate Cox proportional hazard models.Results ROC curves indicated that the best cut-off values of Pre-SII and Delta-SII were 516.31 and 0.176,respectively.The low Pre-SII group(＜516.31)and high Delta-SII group(≥0.176)were associated with longer RFS(HR=1.951,95％CI:1.063-3.581,P=0.029;HR=3.892,95％CI:2.010-7.534,P＜0.001).Cox proportional hazard models showed that high Pre-SII(≥516.31),low Delta-SII(≤0.176),T3-T4 stage,Nx stage and tumor size＞3 cm were independent risk factors for tumor recurrence.Conclusion In MIBC patients receiving T+GC therapy,the amplitude of change before treatment and after 3 cycles of treatment can be used as valuable predictors of clinical efficacy.