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.

Objective:To investigate the therapeutic effects of Akkermansia muciniphila (AKK) on liver injury induced by cholestasis and its mechanisms in regulating bile acid metabolism. Methods:The cholestatic mouse model was established by bile duct ligation (BDL). A total of 35 male C57BL/6J mice (8 weeks old) were divided into 5 groups using a random numder table method (7 mice per group): group A (control group), group B (BDL group), group C (BDL+AKK group), group Z (BDL+AKK+Z/E-guggulsterone group), and group G (BDL+AKK+Gly-β-muricholic acid group). Preoperative and postoperative changes in liver function and bile acid metabolism indicators was observed of mice in groups A, B, and C. The liver function and fibrosis markers were compared between groups, as well as serum, liver, and fecal total bile acid levels, fecal bile acid composition, liver histopathology, and the mRNA expression of key proteins involved in the bile acid enterohepatic circulation and the farnesoid X receptor (FXR) signaling pathway were compared. Multiple groups of data were compared using analysis of variance or nonparametric Kruskal Wallis H test. Results:Twelve days after BDL, in groups A, B, and C, mice in group C exhibited milder postoperative jaundice and their body weights on postoperative days 4-5 and 7-11 were heavier than those in group B mice (all P<0.05). The liver tissues of mice in group C were milder than those in group B in terms of appearance, histopathology, inflammation and liver fibrosis (all P<0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, as well as the expression levels of liver α-smooth muscle actin and type Ⅰ collagen, and the levels of total liver bile acid and fecal β-murine bile acid in the C group mice were all lower than those of group B mice ((46±20) vs. (90±34) U/L, (96±17) vs.(122±31) U/L, (2.01±0.11)% vs. (7.55±0.21)%, (1.92±0.10)% vs. (7.28±0.51)%, (62±14) vs. (124±39) μmol/mg, 3 052 (1 522, 6 406) vs. 14 756 (6 582, 33 474) ng/g,all P<0.05). And the mRNA expression levels of cholesterol 7α-hydroxylase and bile salt export pump of the ileum, etc. in group C mice were lower than those in group B mice (all P<0.05), while the mRNA expression levels of FXR and fibroblast growth factor 15 in the intestine were higher than those in group B mice (all P<0.05). In groups B, C, Z, and G, compared with group C, mice in groups Z and G had aggravated liver injury and fibrosis, increased total bile acid levels in the liver, and increased serum alanine aminotransferase, total bilirubin, and expression levels of liver α-smooth muscle activator protein and type I collagen (all P<0.05). There was no statistically difference in the above indicators between group Z and group G (all P<0.05). Conclusion:AKK reduces liver bile acid synthesis, regulates bile acid metabolism, alleviate liver function damage and fibrosis, and improves clinical phenotypes by activating the intestinal FXR-fibroblast growth factor 15 signaling pathway.

Objective:To investigate the therapeutic effects of Akkermansia muciniphila (AKK) on liver injury induced by cholestasis and its mechanisms in regulating bile acid metabolism. Methods:The cholestatic mouse model was established by bile duct ligation (BDL). A total of 35 male C57BL/6J mice (8 weeks old) were divided into 5 groups using a random numder table method (7 mice per group): group A (control group), group B (BDL group), group C (BDL+AKK group), group Z (BDL+AKK+Z/E-guggulsterone group), and group G (BDL+AKK+Gly-β-muricholic acid group). Preoperative and postoperative changes in liver function and bile acid metabolism indicators was observed of mice in groups A, B, and C. The liver function and fibrosis markers were compared between groups, as well as serum, liver, and fecal total bile acid levels, fecal bile acid composition, liver histopathology, and the mRNA expression of key proteins involved in the bile acid enterohepatic circulation and the farnesoid X receptor (FXR) signaling pathway were compared. Multiple groups of data were compared using analysis of variance or nonparametric Kruskal Wallis H test. Results:Twelve days after BDL, in groups A, B, and C, mice in group C exhibited milder postoperative jaundice and their body weights on postoperative days 4-5 and 7-11 were heavier than those in group B mice (all P<0.05). The liver tissues of mice in group C were milder than those in group B in terms of appearance, histopathology, inflammation and liver fibrosis (all P<0.05). The levels of serum alanine aminotransferase, aspartate aminotransferase, as well as the expression levels of liver α-smooth muscle actin and type Ⅰ collagen, and the levels of total liver bile acid and fecal β-murine bile acid in the C group mice were all lower than those of group B mice ((46±20) vs. (90±34) U/L, (96±17) vs.(122±31) U/L, (2.01±0.11)% vs. (7.55±0.21)%, (1.92±0.10)% vs. (7.28±0.51)%, (62±14) vs. (124±39) μmol/mg, 3 052 (1 522, 6 406) vs. 14 756 (6 582, 33 474) ng/g,all P<0.05). And the mRNA expression levels of cholesterol 7α-hydroxylase and bile salt export pump of the ileum, etc. in group C mice were lower than those in group B mice (all P<0.05), while the mRNA expression levels of FXR and fibroblast growth factor 15 in the intestine were higher than those in group B mice (all P<0.05). In groups B, C, Z, and G, compared with group C, mice in groups Z and G had aggravated liver injury and fibrosis, increased total bile acid levels in the liver, and increased serum alanine aminotransferase, total bilirubin, and expression levels of liver α-smooth muscle activator protein and type I collagen (all P<0.05). There was no statistically difference in the above indicators between group Z and group G (all P<0.05). Conclusion:AKK reduces liver bile acid synthesis, regulates bile acid metabolism, alleviate liver function damage and fibrosis, and improves clinical phenotypes by activating the intestinal FXR-fibroblast growth factor 15 signaling pathway.

OBJECTIVE To carry out regular monitoring of carbapenem-resistant Klebsiella pneumoniae(CRKP)contamination status in the environment of intensive care unit(ICU)and take targeted prevention and control measures so as to reduce the incidence of hospital-associated infections with multidrug-resistant organisms(MDROs).METHODS The surfaces of surroundings of the patients who were colonized and infected with CRKP in the ICU of grade A tertiary hospital of Shanghai and the hands of relevant staff were sampled by stages from Jan 1,2021 to Jun 30,2024.The distribution of the CRKP strains in the surroundings were analyzed according to the locations positive for CRKP,and the disinfection measures were accordingly and continuously modified.The trend of isolation rate of CRKP strains from the ICU patients was analyzed during the time period when the measures were implemented.RESULTS Totally 266 environmental samples were collected during the baseline period(from Jan.1 2021 to Dec.31 2021),265 during intervention period(from Jan.1 2022 to Dec.31 2023),274 during con-solidation period(from Jan.1 to Jun.30 2024);the isolation rates of the CRKP strains were 4.51％,4.91％and 3.65％,respectively.The isolation rate of the strains was highest from the bed unit(10.40％),followed by the article for public use(6.74％),articles used by health care workers(2.98％)and diagnosis and treatment arti-cles(1.91％).The isolation rate of CRKP of the patients was 24.75％during the baseline period,15.48％during the intervention period,5.69％during the consolidation period,showing a continuously downward trend(x2=30.330,P＜0.001).CONCLUSION It is necessary to regularly carry out the environmental monitoring of CRKP strains,seek for the weak links of environmental disinfection and implement the intensified prevention and control measures so as to reduce the incidence of CRKP infection,which may provide theoretical bases for effective control of the CRKP strains.

Objective:To analyze the predictive role of WT1 expression levels pre-and early post-transplantation on relapse and overall survival(OS)in patients with acute myeloid leukemia(AML)undergoing allogeneic hematopoietic stem cell transplantation(allo-HSCT)during their first complete remission(CR1).Methods:A retrospective analysis was conducted on the clinical data of 107 adult AML patients who underwent allo-HSCT during their CR1 at our center between May 2012 and December 2021.The predictive role of bone marrow WT1 expression levels before transplantation and at 3 and 6 months post-transplantation on relapse and OS was explored in combination with relevant clinical factors.Results:The median follow-up time for the 107 patients was 70(range:11-117)months.Among the patients,15 cases died.Kaplan-Meier survial analysis showed that the 3-year overall survival(OS)rate was 85.0％.20 patients experienced relapse,with a median time to relapse of 8(range:0.5-44)months and a l-year cumulative relapse rate of 13.1％.The overall median value of WT1 before transplantation,3 months after transplantation,and 6 months after transplantation was 0.26％(range:0％-23.64％),with an upper quartile value of 0.74％.No statistically significant differences in WT1 expression levels were observed among the pre-transplantation,3-month post-transplantation,and 6-month post-transplantation time points(P=0.227).Univariate analysis showed that patients with WT1 levels＞0.74％at 3 months post-transplantation had a higher 1-year relapse rate(P=0.029)and lower 3-year OS rate(P＜0.001)compared to patients with WT1 levels ≤0.74％.Other significant factors affecting 1-year relapse included stem cell source(P=0.041)and chronic graft-versus-host disease(cGVHD)(P=0.013).For 3-year OS,additional influencing factors were genetic high risk(P=0.048)and stem cell source(P=0.016).Multivariate analysis revealed that WT1 level＞0.74％at 3 months post-transplantation had a trend to affect 1-year relapse rate(HR=3.309,95％CI:0.958-11.431,P=0.058),while the absence of cGVHD was an independent risk factor for 1-year relapse(HR=3.473,95％CI:0.749-16.100,P=0.037).Only WT1 level＞0.74％at 3 months post-transplantation was an independent risk factor for 3-year OS(HR=6.886,95％CI:2.402-19.738,P＜0.001).Conclusion:High WT1 expression level at 3 months post-transplantation in AML patients undergoing allo-HSCT during CR1 affects the 1-year relapse rate and 3-year OS,and is an independent risk factor affecting 3-year OS.These findings suggest that dynamic monitoring of WT1 expression levels has certain value in prognostic assessment of AML patients who received allo-HSCT during CR1.

Objective:This study aims to explore the application effect of anticipatory risk intervention combined with health education under LEARNS mode in elderly patients with chronic heart failure(CHF).Methods:This randomized controlled enrolled 126 elderly CHF patients admitted in Panzhihua Central Hospital between January 2022 and February 2023.They were divided into control group(n=63)and intervention group(n=63).All patients received routine nursing care,patients in control group received additional health education under LEARNS mode,compared to those in intervention group receiving additional anticipatory risk intervention based on control group,both groups were intervened for 2 months.Physiological indexes,negative emotion,quality of life,sleep quality,disease perception&control and self-efficacy,as well as incidence of adverse events,were compared between two groups.Results:Compared with patients in control group after intervention,those in intervention group had signif-icant lower systolic blood pressure(SBP)[(119.84±8.60)mmHg vs.(129.49±9.24)mmHg],diastolic blood pressure(DBP)[(81.59±5.08)mmHg vs.(88.51±6.36)mmHg],N terminal pro brain natriuretic peptide(NT-proBNP)[(2604.46±204.80)ng/L vs.(3024.87±212.27)ng/L],scores of Self-Rating Anxiety Scale(SAS)[(55.90±2.43)points vs.(60.11±2.62)points],Self-Rating Depression Scale(SDS)[(57.03±2.56)points vs.(61.54±2.66)points],Minnesota Living with Heart Failure Questionnaire(MLHFQ)[(52.05±6.32)points vs.(60.46±7.10)points]and Pittsburgh Sleep Quality Index(PSQI)[(9.00±1.65)points vs.(11.05±1.96)points],and significant higher left ventricular ejection fraction(LVEF)[(51.83±7.28)％vs.(47.57±5.98)％],scores of Control Attitude Scale-Revised(CAS-R)[(35.59±2.97)points vs.(30.60±3.52)points]and Gen-eral Self-Efficacy Scale(GSES)[(36.98±4.21)points vs.(30.52±4.14)points](P＜0.001 all).Incidence of adverse events in intervention group was significantly lower than that of control group(3.17％vs.12.70％,P=0.048).Conclusion:Anticipatory risk intervention combined with health education under the LEARNS model could effectively improve the physiological indexes,quality of life and sleep,enhance disease perception and self-effica-cy,and reduce negative emotion and incidence of adverse events in elderly CHF patients.

Background and purpose:Thyroid cancer is the most common malignant endocrine tumor,particularly prevalent among the Asian population.The overall survival for thyroid cancer patients is relatively high,but there are significant survival differences among patients.Based on long-term hospital-based cancer registry database,this study analyzed the 10-year observed overall survival(OS)rate of thyroid cancer cases and the distribution of causes of death,providing real-world evidences to further survival management of thyroid cancer in China.Methods:A total of 55343 thyroid cancer patients who underwent treatment at Fudan University Shanghai Cancer center from 2005 to 2021 were included in this study.Clinical information and the follow-up endpoint data were collected through medical records review,telephone visits and death registry data linkage.The last follow-up date was October 31,2024.Kaplan-Meier method was applied in evaluating the OS rate,and survival data were described by different subgroups as age group,gender,treatment period,tumor staging and pathological characteristics.The standardized mortality ratio(SMR)and absolute excess risk(AER)were calculated using general Shanghai population as the reference,and the mortality risk was described by gender,age at diagnosis and histological subtype.Results:With a median follow-up time of 63.01 months,the overall 1-,3-,5-and 10-year OS rates of thyroid cancer patients were 99.67%(95%CI:99.62%-99.72%),99.11%(95%CI:99.03%-99.19%),98.48%(95%CI:98.36%-98.60%)and 95.81%(95%CI:95.50%-96.11%),respectively.The 10-year OS rates of stage Ⅰ,Ⅱ,Ⅲ and Ⅳ were 97.99%(95%CI:97.70%-98.28%),89.80%(95%CI:87.24%-92.37%),77.84%(95%CI:70.76%-84.92%)and 62.95%(95%CI:55.37%-70.54%),respectively.The differences in OS among patients with different age,gender and histological classification were significant.1256(2.27%)deaths occurred,of which 18.63%,50.88%and 7.32%were attributable to thyroid cancer,other cancers and cardiovascular disease(CVD),respectively.Compared with the general population,patients with different subtypes of thyroid cancer had higher all-cause mortality rates,progressively increasing with papillary,follicular,medullary and anaplastic thyroid carcinoma/poorly differentiated carcinoma.Compared with general population,the death risk was 2.24 times higher in papillary thyroid cancer patients(95%CI:2.06-2.44),9.94 times higher in follicular thyroid cancer patients(95%CI:6.79-14.09),12.16 times higher in medullary thyroid cancer patients(95%CI:8.05-17.69),and the highest risk was observed in patients with anaplastic thyroid carcinoma/poorly differentiated carcinoma[SMR=79.67(95%CI:58.38-106.31),AER=766.01/1 000 person-years].Conclusion:The 10-year long survival data and cause of death for thyroid cancer patients with different histological types were reported in China based on a large single institution hospital-based cancer registry database.Staging and histological characteristics were the most important factors directly affected the survival.Early diagnosis and individualized treatment are crucial for improving prognosis.

Purpose: To investigate the therapeutic potential of eliminating insulin-like growth factor-binding protein 5 (IGFBP5) expression in improving erectile function in mice with cavernous nerve injury (CNI)-induced erectile dysfunction (ED). Materials and Methods: Eight-week-old male C57BL/6 mice were divided into four groups: a sham-operated group and three CNI-induced ED groups. The CNI-induced ED groups were treated with intracavernous injections 3 days before the CNI procedure.These injections included phosphate-buffered saline, scrambled control short hairpin RNA (shRNA), or shRNA targeting mouse IGFBP5 lentiviral particles. One week after CNI, erectile function was evaluated and the penile tissue was then harvested for histological examination and western blot analysis. Additionally, the major pelvic ganglia (MPG) and dorsal root ganglia (DRG) were cultured for ex vivo neurite outgrowth assays. Results: Following CNI, IGFBP5 expression in the cavernous tissues significantly increased, reaching its peak at day 7. First, ablation of IGFBP5 expression promotes neurite sprouting in MPG and DRG when exposed to lipopolysaccharide. Second, ablating IGFBP5 expression in CNI-induced ED mice improved erectile function, likely owing to increased neurovascular contents, including endothelial cells, pericytes, and neuronal processes. Third, ablating IGFBP5 expression in CNI-induced ED mice promoted neurovascular regeneration by increasing cell proliferation, reducing apoptosis, and decreasing Reactive oxygen species production. Finally, western blot analysis demonstrated that IGFBP5 ablation attenuated the JNK/c-Jun signaling pathway, activated the PI3K/AKT signaling pathway, and increased vascular endothelial growth factor and neurotrophic factor expression. Conclusions Ablating IGFBP5 expression enhanced neurovascular regeneration and ultimately improved erectile function in CNI-induced ED mice.

Patent foramen ovale(PFO)demonstrates significant comorbidity with migraine,but its causal relationship and the efficacy of transcatheter closure remain controversial.This systematic review examines potential biomarkers and relevant imaging assessments for PFO-associated migraine,aiming to provide a theoretical foundation for clinical diagnosis and treatment.Key biomarkers include platelet activation markers,calcitonin gene-related peptide,homocysteine,and platelet-to-lymphocyte ratio.Imaging evaluations encompass right-to-left shunt grading(transthoracic echocardiography,transcranial Doppler ultrasound),cerebrovascular breath-holding index,characteristics of white matter hyperintensities,alterations in resting-state functional magnetic resonance imaging(rs-f-MRI)brain networks,in-situ thrombi detected by optical coherence tomography,and electroencephalogram(EEG)power spectral features.Research indicates that integrating biomarkers with imaging technologies enhances diagnostic discrimination and treatment outcome prediction.Current challenges include unclear causal relationships and insufficient standardization of detection methods.Future efforts require multidisciplinary collaboration to establish personalized diagnostic and therapeutic frameworks through multimodal indicators,thereby advancing precise prevention and treatment strategies for PFO-related migraine.

The presence of magnetic fields in a magnetic resonance accelerator (MR-linac) can affect the reference dosimetry, and thus the existing Code of Practices (CoPs) are inadequate for MR-linac. In this article, the characteristics of adsorbed dose to water and ionization chamber response in the presence of magnetic fields were introduced and a formalism for reference dosimetry in MR-linac was developed based on the existing CoPs, aiming to provide reference for dosimetric quality control and research work of MR-linac in China.