Abnormal activation of the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway is involved in the pathogenesis of diffuse large B-cell lymphoma （DLBCL）. In recent years， inhibitors targeting JAK2 and STAT3 have emerged as promising therapeutic candidates in DLBCL. This review summarizes the efficacy and safety profiles of JAK2 inhibitors （e.g.， ruxolitinib） and STAT3 inhibitors （direct small-molecule inhibitors， the antisense oligonucleotide， and proteolysis targeting chimeras， etc.） in preclinical models and clinical trials. Accumulating evidence indicates that JAK2 and STAT3 inhibitors exhibit antitumor activity and are generally well tolerated in a subset of DLBCL patients. Meanwhile， the development of novel drug delivery systems has significantly enhanced the stability， bioavailability， and targeting ability of the compounds. Furthermore， JAK2 and STAT3 inhibitors may exhibit synergistic effects when combined with other therapy strategies （such as combinations with B-cell receptor signaling pathway inhibitors， immunomodulators， or other targeted drugs）. However， current clinical applications are still in their early stages. Future research should concentrate on precision treatment strategies based on the genetic subtyping of DLBCL， and further refine the delivery systems for inhibitors as well as combination drug regimens to improve clinical outcomes.

ObjectiveTo explore the 28-day mortality risk of Klebsiella pneumoniae (KP) bloodstream infections (BSI) and its related influencing factors, thereby providing a scientific basis for the effective control of KP-BSI and improvement of patient prognosis. MethodsFrom January 2018 to December 2024, a retrospective review was conducted on hospitalized patients aged >18 years old treated for KP-BSI at a tertiary hospital in Hangzhou. Logistic and Cox regression analyses were performed to identify the epidemiological characteristics and the risk factors for the 28-day mortality associated with KP-BSI. ResultsA total of 123 patients with KP-BSI were included in this study, comprising 64 cases infected with carbapenem-resistant Klebsiella pneumoniae (CRKP) and 59 cases infected with carbapenem-susceptible Klebsiella pneumoniae (CSKP). Compared with CSKP-BSI, patients with CRKP-BSI more frequently presented with chronic pulmonary disease (χ²=4.29, P=0.038), concomitant infections at other sites (χ²=10.90, P=0.001), and a higher frequency of invasive procedures prior to infection (central venous catheterization, mechanical ventilation, and indwelling urinary catheter), as well as glucocorticoid use, hemodialysis, and blood transfusion (all P<0.05). The 28-day mortality was significantly higher in BSI cases caused by CRKP compared to that caused by CSKP (37.50% vs 5.08%, P<0.001). Cox regression analyses revealed that carbapenem resistance (HR=6.67, 95%CI: 1.48‒30.08, P=0.014) and blood transfusion (HR=3.58, 95%CI: 1.15‒11.19, P=0.028) were risk factors for the 28-day mortality in KP-BSI, while removal of central venous catheters after infection (HR=0.24, 95%CI: 0.08‒0.67, P=0.006) was associated with a reduced risk for the 28-day mortality. ConclusionCarbapenem resistance is associated with mortality outcomes in patients with KP-BSI. Strengthening infection control measures targeting the identified risk factors for CRKP-BSI may improve patient prognosis.

Objective To evaluate the degree of invasion of placental implantation by quantitative delin-eation of MRI placental bed abnormal hyperplasia vessels by 3D-Slicer software.Methods Fifty-seven pa-tients with placenta implantation requiring MRI in Quanzhou Maternal and Child Health Hospital from July 2020 to December 2023 were retrospectively collected and divided into the penetrating placenta implantation group(n=11)and the non-penetrating placenta implantation group(n=46),and the differences of MRI mor-phological signs between the two groups were analyzed.Among them,37 patients with placental bed xenogenic vessels scanned by MRI were screened and there were 11 cases in the penetrating placental implantation group and 26 cases in the non-penetrating placental implantation group.3D-Slicer software was used to delineate the surface area and volume of placental bed xenogenic vessels,the differences between the two groups were ana-lyzed.Results There were significant differences in the surface area and volume of xenogenic blood vessels in placental bed between the two groups(P＜0.05).The large surface area of xenogenic vessels in the placental bed was an independent risk factor for penetrative placental implantation,and the predicted area under the curve(AUC)of penetrative placental implantation was 0.927.When the surface area of the placental bed was 1 079.25 mm2,the sensitivity was 81.8%and the specificity was 88.5%.Conclusion According to 3D-Slicer soft-ware,the diagnostic efficacy of placental bed allogenic blood vessel surface area for penetrating placental implanta-tion is high.The larger the allogenic blood vessel surface area is,the deeper the placental invasion of uterus is.

Cardiovascular disease has become a significant cause of death in cancer patients,partly due to the cardiovascular toxicity of cancer treatments.The referral of cardio-oncology can improve the cardiovascular health of cancer patients,and develop strategies for prevention,management,and treatment of cardiovascular toxicity induced by cancer treatment.This article summarizes the strategies and status in the referral of cardio-oncology,and proposes development suggestions for the referral model of cardio-oncology,in order to improve the awareness of medical staffin implementing referral of cardio-oncology and provide a basis for promoting the development of the referral model of cardio-oncology.

Objective:To analyze the imaging features of testicular conventional ultrasonography（US），shear wave elastography（SWE），and contrast-enhanced ultrasonography（CEUS）in subtypes of spermatogenic dysfunction（focal，arrest，and exhausted），and to evaluate the diagnostic efficacy of testicular multimodal ultrasound.Methods:A prospective study enrolled 310 spermatogenic dysfunction patients（focal type group： n=77，arrest type group： n=20，exhaustive type group： n=213）and 30 healthy volunteers（control group）at Shanghai General Hospital between October 2023 and December 2024. All patients underwent preoperative testicular US，SWE，and CEUS examinations，followed by microdissection testicular sperm extraction. Ultrasound parameters were compared among groups，and receiver operating characteristic（ROC）curves were plotted to assess the diagnostic efficacy of multimodal ultrasound for different subtypes. Results:①Testicular volume：The arrest group exhibited significantly greater volume compared to the focal group and the exhausted group（all P<0.05）. No statistically significant difference was observed between the arrest group and the normal group（ P>0.05）. ②Mean Young's modulus（Emean）：The arrest group exhibited significantly lower Emean compared with both the focal and exhausted groups（all P<0.05），but showed no significant difference versus the normal group（ P>0.05）. ③CEUS quantitative parameters：The arrival time（AT）and time to peak（TTP）in the exhausted group were higher than those in the normal group，while the peak intensity（PI）and area under the time-intensity curve（AUC）were lower（all P<0.05）. No significant differences were found in AT，TTP，or AUC among the three spermatogenic dysfunction subgroups（all P>0.05）. ④CEUS perfusion patterns：The focal group predominantly exhibited a mottled pattern（70.13%，54/77）. Both the arrest group（90.00%，18/20）and the normal group（93.33%，28/30）predominantly exhibited an rich pattern. The exhausted group predominantly exhibited a sparse pattern（56.34%，120/213）. ⑤ROC curve analysis showed that for differentiating the arrest group from the focal type group and the exhaustive type group，the combination of Emean，testicular volume，and CEUS perfusion pattern yielded an AUC of 0.931，with a sensitivity of 95.00% and specificity of 85.86%. For differentiating the focal type group from the exhaustive type group，the combination of testicular echogenicity，CEUS perfusion pattern，and Emean yielded an AUC of 0.833，with a sensitivity of 81.82% and specificity of 75.12%. Conclusions:Multimodal ultrasonography can comprehensively characterize the imaging features of different subtypes of spermatogenic dysfunction，holding promise as a noninvasive predictive tool.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Objective To systematically analyze the changes in clinical indicators including blood leukocytes and neutrophils,liver and kidney functions,coagulation function,lipids,and levels of thyroid hormones and antibodies in Graves'ophthalmopathy(GO)patients who had undergone effective treatment with tocilizumab(TCZ)and to explore their clinical significance.Methods Eighty-five patients with moderately or severely active GO who were effectively treated with TCZ were enrolled.Early morning fasting blood was collected and tested for routine blood,biochemical routine,coagulation function,thyroid hormone and antibodies,and basic information such as gender,age,duration of the disease,history of smoking,comorbidities,and medications were also collected from all patients,so changes in the clinical indicators before and after the treatment could be analyzed and correlation analyses could be carried out.Results Patients with moderately to severely active GO treated with TCZ showed a significant decrease in absolute blood leukocyte and neutrophil values compared with before,and a significant decrease in liver function(alanine transaminase,aspartate aminotransferase,creatinine),cholesterol(total cholesterol,high-density lipoprotein and low-density lipoprotein)levels were significantly higher than before,and concentrations of coagulation parameters[prothrombin time,activated partial thromboplastin time,fibrinogen(FIB)and D-dimer]were significantly decreased.The concentrations of thyroid hormone and thyroid-stimulating hormone levels increased significantly,and the antibody titer of thyrotropin receptor antibody(TRAB)was significantly down-regulated after treatment.TRAB levels were significantly correlated with FIB before treatment.Conclusion Thyroid function and antibody levels improved after TCZ treatment in patients with moderately to severely active GO,but blood leukocytes,liver function and coagulation function changed significantly compared with before.The results of this study confirm the therapeutic effect of TCZ on immune disorders in GO ophthalmopathy,while underscoring the importance of monitoring potential adverse effects in clinical treatment.

Objective:To investigate the incidence of osteoporosis (OP) in maintenance hemodialysis (MHD) patients at the blood purification center in Gaochun district, and analyze its influencing factors.Methods:A retrospective study was conducted on 3 622 patients who received regular MHD treatment at Nanjing Gaochun People′s Hospital and Nanjing Gaochun Traditional Chinese Medicine Hospital from January 2019 to December 2023. The demographic characteristics, comorbidities, and clinical data such as blood calcium and creatinine of patients were collected. The ultivariate Logistic regression model was applied to analyze the influencing factors of OP in MHD patients.Results:The survey revealed that 33.63% of MHD patients had decreased bone mass, and 37.24% of MHD patients experienced osteoporosis. According to the occurrence of OP, 3 622 patients were separated into the OP group (1 349 cases) and the non-OP group (2 273 cases). Univariate analysis showed that compared with the non-OP group, the albumin (ALB) level in the OP group was lower: (38.95 ± 5.17) g/L vs. (40.32 ± 5.84) g/L, there was statistical difference( P<0.05). Compared with the non-OP group, the levels of immunoreactive parathyroid hormone (iPTH) and alkaline phosphatase (ALP) in the OP group were higher: (262.29 ± 36.76) ng/L vs. (249.55 ± 32.73) ng/L, (114.74 ± 18.01) U/L vs. (109.63 ± 17.25) U/L, the proportion of patients aged≥60 years old, female and dialysis duration≥5 years was higher: 61.75%(833/1 349) vs. 47.87%(1 088/2 273), 66.35%(895/1 349) vs. 54.86%(1 247/2 273), 52.34%(706/1 349) vs. 34.36%(781/2 273), there were statistical differences( P<0.05). Multivariate Logistic regression revealed ALB ( OR = 0.724, 95% CI 0.568 - 0.920), iPTH ( OR = 1.374, 95% CI 1.095 - 1.725), ALP ( OR = 1.325, 95% CI 1.070 - 1.641), age ( OR = 2.753, 95% CI 1.664 - 4.556), gender ( OR = 2.993, 95% CI 1.611 - 5.560), and dialysis time ( OR = 4.216, 95% CI 2.365 - 7.516) were all influencing factors for the occurrence of OP in MHD patients ( P<0.05). Conclusions:The incidence of OP in MHD patients in Gaochun district is high, and its occurrence is closely related to ALB, iPTH, ALP, age, gender and dialysis time. Clinical attention should be focused on this.

[Purpose]To analyze the epidemiology and disease burden of gastric cancer in China,Japan and Republic of Korea from 1990 to 2021 and to predict changing trends from 2022 to 2031.[Methods]Data were obtained from the Global Burden of Disease(GBD)database.Age-stan-dardized incidence rate(ASIR),age-standardized mortality rate(ASMR),crude incidence rate(CIR),crude mortality rate(CMR),and disability-adjusted life years(DALY)rate for China,Japan and Republic of Korea from 1990 to 2021 were analyzed.Joinpoint regression software was used to analyze trends and calculate annual percentage changes.The autoregressive integrated moving average(ARIMA)model was applied to predict incidence and mortality from 2022 to 2031.[Results]In 2021,China had 611 799 new gastric cancer cases and 445 013 deaths,with an ASIR of 29.05/105 and an ASMR of 21.51/105,both significantly higher than those in Japan and Republic of Korea.Among men in China,both the ASIR(44.48/105)and ASMR(32.61/105)were the highest among the three countries,exceeding those in Japan(38.77/105,20.26/105)and Re-public of Korea(38.98/105,20.50/105).Among women,China had the highest number of new cases,but its ASIR(15.23/105)was slightly lower than Republic of Korea's(15.57/105)and higher than Japan's(14.66/105).However,China's ASMR among women(12.02/105)remained significantly higher than Japan's(7.64/105)and Republic of Korea's(8.08/105).From 1990 to 2021,ASIR,ASMR and DALY rates for gastric cancer declined in all three countries,but the reduction in China was significantly smaller than that in Japan and Republic of Korea,with Republic of Korea showing the steepest declines across all indicators.ARIMA model predictions indicated significant differences in disease burden among the three countries from 2022 to 2031.ASIR is projected to continue declining in China and Republic of Korea,reaching 22.87/105 and 12.45/105,respectively by 2031,while in Japan it is predicted to rise to 26.55/105.ASMR is projected to decline in all three countries,reaching 13.71/105(China),10.44/105(Japan),and 9.08/105(Republic of Korea)in 2031.[Conclusion]Among China,Japan and Republic of Korea,China had the highest ASIR and ASMR of gastric cancer in 2021.Moreover,from 1990 to 2021,the reductions in ASIR,ASMR and DALY rates for gastric cancer were the smallest in China compared to Japan and Republic of Korea.These findings suggest that the disease burden of gastric cancer remains substantial in China,high-lighting the need for increased efforts in gastric cancer screening and early diagnosis and treatment.

Objective:To explore the clinical risk factors and pregnancy outcomes in women with hyperglycemia in pregnancy (HIP) complicated with hypertensive disorders of pregnancy (HDP).Methods:This retrospective cohort study included 43 973 singleton live births delivered at the Obstetrics and Gynecology Hospital of Fudan University between September 2017 and December 2022. Participants were categorized into four groups: HH group (HIP with HDP, n=1 011), HIP group ( n=5 469), HDP group ( n=3 486), and control group ( n=34 007). Baseline characteristics and perinatal outcomes were compared using the Chi-square test (or Fisher's exact test). Logistic regression identified risk factors and adverse outcome risks and analyze the impact of HH on neonatal weight. Results:HH accounted for 15.6% (1 011/6 480) of HIP cases, with an overall incidence of 2.3% (1 011/43 973). HIP and HDP were strongly correlated [ OR=1.803, 95% CI: 1.672-1.945]. Advanced maternal age (≥35 years at estimated due date), primiparity, and pre-pregnancy overweight/obesity (body mass index ≥24 kg/m2) were independent risk factors for HH [ OR (95% CI): 1.305 (1.113-1.529), 1.845 (1.545-2.203), and 2.316 (1.981-2.718), respectively]. Compared to the HIP group, the HH group had significantly higher risks of preterm birth [10.3% (104/1 011) vs. 6.3% (344/5 469), OR=1.627 (95% CI:1.280-2.068)], cesarean delivery [57.0% (576/1 011) vs. 41.9% (2 289/5 469), OR=1.701 (95% CI:1.474-1.963)], and neonatal birth weight < P10 [13.9% (141/1 011) vs. 9.0% (494/5 469), OR=1.668 (95% CI:1.336-2.083)]. Stratified analysis revealed a 73.4% increased risk of birth weight < P10 in the gestational diabetes mellitus A1 with HDP subgroup ( aOR=1.734, 95% CI: 1.416-2.125). Conclusions:Advanced age, pre-pregnancy overweight/obesity, and primiparity are risk factors for HH. Compared to isolated HIP, HH is associated with elevated risks of preterm birth, cesarean delivery, and abnormal neonatal birth weight, though the impact on birth weight may vary by HIP subtype.