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 explore the clinical characteristics and short-term prognosis of postoperative acute myocardial infarction (PAMI) after cardiac surgery. Methods A retrospective study was conducted on 45 PAMI patients who underwent coronary angiography after cardiac surgery at Zhongshan Hospital, Fudan University, from February 2015 to February 2025. General information, type of surgery, onset time and causes of PAMI, and in-hospital recovery condition were collected. Univariate logistic regression was used to analyze factors related to in-hospital survival. Results The patients’ age was (62.40±11.72) years, 31 cases (68.89%) were male, 21 cases (46.67%) had hypertension. Twenty-six patients (57.78%) underwent cardiac valve surgery, and 16 patients (35.56%) received coronary artery bypass grafting. The onset time of PAMI was 24 (0, 48) hours, with 38 cases (84.44%) developing within 48 hours after surgery. Twenty-eight patients (62.22%) presented with new lesions in coronary arteries/bypass grafts, and 20 patients (44.44%) were considered to have thrombus-induced PAMI. Nine patients died in hospital, 13 patients failed to recover and were discharged automatically, and 23 patients were discharged after recovery. Univariate logistic regression analysis showed that new lesion in coronary arteries/bypass grafts was risk factor for in-hospital survival (OR=0.235, P=0.036). Conclusions PAMI frequently occurs within 48 hours post-cardiac surgery, and thrombosis is the most common cause of PAMI. New lesions in coronary arteries/bypass grafts are closely correlated with poor short-term prognosis.

Objective To explore the efficacy of progressive exercise training based on the modified Medical Research Council dyspnea scale (mMRC) grading in respiratory rehabilitation for patients with chronic obstructive pulmonary disease (COPD) at a primary healthcare setting. Methods A total of 106 patients with COPD admitted to Zhuanqiao Community Health Service Center in Shanghai from Aug.1, 2022 to Jul. 30, 2024 were selected as research subjects. They were randomly divided into a study group and a control group in a 1∶1 ratio, with 53 patients in each group. The control group received conventional treatment, while the study group received conventional treatment combined with progressive exercise training. After 4 weeks of continuous treatment, the changes in the 6-minute walk test (6MWT), COPD assessment test (CAT) score, mMRC grading, Global Initiative for Chronic Obstructive Lung Disease (GOLD) grading and pulmonary function were compared between the two groups. Results Patients in both groups showed improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function compared to baseline (P＜0.05). Moreover, the study group had better improvements in 6MWT distance, CAT score, mMRC grading, GOLD grading, and pulmonary function than the control group (P＜0.05). Conclusions Conventional treatment combined with progressive exercise training based on mMRC grading can enhance the effect of respiratory rehabilitation in patients with COPD, particularly in improving pulmonary function and exercise tolerance.

ObjectiveThrough multimodal research methods including medication rule mining， network pharmacology， molecular docking and dynamics simulation， and in vivo animal experiments， this study aims to speculate and verify the core composition （Ginseng Radix et Rhizoma Rubra-Salviae Miltiorrhizae Radix et Rhizoma-Notoginseng Radix et Rhizoma） and efficacy （Qi-invigorating and blood-activating） of the drug combination in Yitangkang Compound for improving diabetic cardiomyopathy （DCM）， investigate the interaction relationship and binding strength between core active ingredients of the drug combination and key signaling pathway targets， and further explore the mechanism by which the Qi-invigorating and blood-activating drug combination regulates the calcium signaling pathway to improve cardiac function in DCM rats. MethodsThe Ancient and Modern Medical Cases Cloud Platform was used to construct a DCM prescription database， and the "Analysis Method" module of the platform was applied to mine and summarize medication rules， thereby determining the core composition of the Qi-invigorating and blood-activating drug combination in Yitangkang. Drug-active ingredient-signaling pathway-core target-disease analysis and visualization were conducted by combining network pharmacology with the Traditional Chinese Medicine System Pharmacology Platform （TCMSP） database， SwissTargetPrediction platform， GeneCards database， MetaScape database， CytoScape software， etc. Then， molecular docking was performed via the CB-Dock2 platform， and molecular dynamics simulation of the high-binding-strength docking complexes was carried out by Gromacs software. Finally， in vivo animal experiments were carried out. Twenty-eight Sprague Dawley （SD） rats meeting the research criteria were divided into a normal group， a model group， a drug combination group （3.3 g·kg^-1）， and a Yitangkang group （20 g·kg^-1）. A type 2 diabetes mellitus （T2DM） rat model was established by high-fat diet feeding combined with intraperitoneal injection of streptozotocin （STZ）， followed by continuous feeding for eight weeks until the DCM model was successfully established. During this period， the traditional Chinese medicine （TCM） compound and drug combination were administered for prevention and treatment intervention. Meanwhile， changes in blood glucose， body weight， and heart index of each group were monitored. Cardiac function was assessed by echocardiography， and electrophysiological signals were detected by an electrocardiogram. The heart tissue was observed for pathological changes by hematoxylin-eosin （HE） and Masson staining， and the expression of L-type calcium channel （CACNA1C）， calmodulin （CALM1）， calcium/calmodulin-dependent protein kinase Ⅱδ （CAMK2D）， and neuronal nitric oxide synthase （NOS1） proteins in the calcium signaling pathway of myocardial tissue was detected by Western blot. ResultsIn 62 DCM prescriptions， Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma were used most frequently. Their meridian tropism mainly involved the spleen， heart， and lung， and their sweet and warm properties were prominent. The drugs for tonifying or blood-activating and stasis-resolving ranked top. In association rule analysis， （Ginseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma）-Notoginseng Radix et Rhizoma had the highest lift. Network pharmacology obtained 75 active ingredients of the drug combination， 714 drug combination action targets， 2 702 disease targets， and 286 intersection targets. Protein-protein interaction （PPI） network predicted nine interaction component-targets （nine active ingredients and four calcium signaling pathway target genes）. Molecular docking showed the four complexes with the lowest binding energy were 2f3z-ginsenoside Re， 1cll-quercetin， 9blh-（6S）-6-（hydroxymethyl）-1，6-dimethyl-8，9-dihydro-7H-naphtho［8，7-g］benzofuran-10，11-dione， and 5vv0-miltionone Ⅱ. Dynamics simulation showed the CALM1-quercetin complex had the strongest binding affinity. The animal experiment results revealed that compared with the normal group， the model group showed significant changes in blood glucose， body weight， myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression levels of CACNA1C， CALM1， CAMK2D， and NOS1 proteins （P<0.05， P<0.01）. Compared with the model group， the Yitangkang group had a certain improvement effect on the above indexes （P<0.05， P<0.01）. Compared with the Yitangkang group， the drug combination group showed no significant difference in improving myocardial tissue morphology， heart index， cardiac function， electrophysiological indexes， and the expression of CACNA1C， CALM1， CAMK2D， and NOS1 proteins， except for blood glucose and body weight. ConclusionGinseng Radix et Rhizoma Rubra， Salviae Miltiorrhizae Radix et Rhizoma， and Notoginseng Radix et Rhizoma are the core Qi-invigorating and blood-activating drug combination in Yitangkang Compound. They have a good preventive and therapeutic effect on STZ-induced DCM in rats， and their mechanism of action may be related to the regulation of the calcium signaling pathway.

Objective To investigate the relationship between the levels of type Ⅲ procollagen(PCⅢ)and heme-binding protein(HPX)in peripheral blood,blood lipid and liver fibrosis in patients with nonalcoholic steatohepatitis(NASH).Methods Totally 126 patients with NASH admitted to the hospital from January 2021 to December 2023 were selected as NASH group,and they were divided into 3 subgroups according to the degree of liver fibrosis:no liver fibrosis group(22 cases),mild group(63 cases),moderate and severe group(41 cases).In addition,150 healthy subjects in the same period were selected as the control group.Enzyme-linked immunosorbent assay(ELISA)was used to detect and compare the levels of PC Ⅲ and HPX in periph-eral blood of all groups,and Pearson correlation analysis was used to explore the correlation between peripher-al blood PC Ⅲ and HPX levels and related indexes of blood lipids in NASH patients.The predictive value of peripheral blood PC Ⅲ and HPX for liver fibrosis in NASH patients was evaluated by receiver operating char-acteristic(ROC)curve.Results The levels of PC Ⅲ and HPX,as well as total cholesterol(TC),triglyceride(TG)and low density lipoprotein cholesterol(LDL-C)in NASH group were higher than those in control group,and the levels of high density lipoprotein cholesterol(HDL-C)were lower than those in control group,and the differences were statistically significant(P＜0.05).Pearson correlation analysis showed that the lev-els of PCⅢ and HPX in peripheral blood of NASH patients were positively correlated with TC,TG and LDL-C(P＜0.05),while negatively correlated with HDL-C(P＜0.05).The levels of PC Ⅲ and HPX in peripheral blood of the non-fibrosis group were lower than those of the mild and moderate severe groups,and the mild group was lower than that of the moderate and severe group,and the differences were statistically significant(P＜0.05).The area under the curve(AUC)of peripheral blood PC Ⅲ and HPX in predicting liver fibrosis in NASH patients were 0.757 and 0.861,respectively,and the cut-off values were 135.51 ng/mL and 804.86 mg/L,respectively.The AUC of the combined prediction for liver fibrosis was 0.905,which was higher than that predicted by the two alone.Conclusion The level of PC Ⅲ and HPX in peripheral blood is closely related to the level of blood lipids and the degree of liver fibrosis in NASH patients,which can be used as potential bi-omarkers to predict liver fibrosis in NASH patients.

Objective To explore the expression levels and clinical significance of serum eosinophil derived neurotoxin(EDN)and prostaglandin D2(PGD2)in children with respiratory syncytial viruses(RSV)pneu-monia with wheezing.Methods A total of 96 children with RSV pneumonia admitted to the hospital from March 2021 to September 2023 were selected case group,who were divided into wheezing group(n=51)and non-wheezing group(n=45)according to whether they were combined with wheezing or not.The children a-mong wheezing group were divided into mild group(n=23),moderate group(n=17)and severe group(n=11)according to the degree of disease.And the children among wheezing group were also divided into effective group(n=41)and non-effective group(n=10)according to therapeutic effect after treatment for one week.In the same period,60 children were randomly selected as control group.Serum EDN and PGD2 levels were measured by enzyme-linked immunosorbent assay.Spearman's rank correlation was used to analyse the associ-ation between serum EDN,PGD2 and degree of disease.Logistic regression was used to analyse the association between serum EDN,PGD2 and clinical efficacy of children with wheezing and receiver operating characteristic(ROC)curve was used to evaluate the predictive value of serum EDN,PGD2 on the clinical effective of chil-dren with wheezing.Results Serum EDN and PGD2 levels were higher in case group than those in control group(P＜0.05).Serum EDN and PGD2 levels were higher in wheezing group than those in non-wheezing group(P＜0.05).Serum EDN and PGD2 levels were increased sequentially in mild group,moderate group and severe group(P＜0.05).Serum EDN and PGD2 levels were positively associated with degree of disease in children with wheezing(P＜0.05).Elevated EDN and PGD2 were risk factors for ineffective clinical efficacy in children with wheezing(OR=1.241,1.225,1.309,P＜0.05).The area under the curve of serum EDN and PGD2 and combined detection to predict the clinical efficacy was 0.778,0.785,0.879,respectively,and the predictive value of combined indicators was greater than that of single indicator(Z=1.956,1.871,P=0.029,0.033).Conclusion Up-regulation of serum EDN and PGD2 expression is involved in wheezing process of children with RSV pneumonia,which is closely related to degree of disease and clinical efficacy.Early com-bined examination of two indicators may assist in the clinical assessment of degree of disease and prediction of clinical efficacy in children with wheezing.

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 explore the association between circadian syndrome (CircS), metabolic syndrome (MetS) and mild cognitive impairment (MCI) in elderly rural adults in China.Methods:From March to September 2018, totally 5 765 participants aged 60 years or older from 52 villages in Yanlou Town, Yanggu County, Shandong Province were selected. The data included demographic, underlying disease and neuropsychological data were collected by questionaire survey. Having ≥3 of the following components was defined as MetS: elevated waist circumference, high triglycerides, low high-density lipoprotein cholesterol, elevated blood pressure and elevated fasting glucose. Having ≥4 of the following components was defined as CircS: short sleep (<6 h/d), depression and five other components which were used to define MetS, with elevated waist circumference as a mandatory item. MCI was diagnosed according to Petersen's criteria and further classified into amnestic MCI (aMCI) and non-amnestic MCI (naMCI) based on whether the memory domains impaired.Data were analyzed using multivariable Logistic regression and general linear regression models by R statistical software.Results:In the total sample ( n=4 898), 1 280 participants were diagnosed with MCI, of which 1 075 were aMCI and 205 were naMCI.Compared to the normal group, CircS alone was significantly associated with increased risks of MCI ( B=0.695, P=0.039) and aMCI ( B=0.782, P=0.024), as well as lower verbal fluency scores ( B=-0.244, P=0.045). No significant associations were found between MetS alone or both MetS and CircS and cognitive impairment( P>0.05). At the component level, short sleep and depression were associated with increased risks of MCI ( B=0.167, P=0.025; B=0.605, P<0.001) and aMCI ( B=0.185, P=0.020; B=0.600, P<0.001). Conclusion:Individuals with CircS are at a higher risk of cognitive impairment, CircS is more strongly associated with cognitive impairment than MetS, with short sleep duration and depressive symptoms potentially playing key roles.

Objective:To analyze the changes in the incidence trend of liver cancer in Taizhou of Jiangsu Province, from 2012 to 2020 and provide reference for tumor prevention and control and management.Methods:Liver cancer incidence data from 2012 to 2020 were extracted from the Taizhou Center for Disease Control and Prevention's tumor registry system. Demographic data were used to calculate the crude incidence rate, age-standardized incidence rate (ASIR), Chinese age-standardized incidence rate (CASIR; based on China's 2010 standard population), and world age-standardized incidence rate (WASIR; based on Segi's world standard population). The Joinpoint regression model was applied to identify inflection points in liver cancer incidence trends during 2012-2020, and annual percentage change (APC) with average annual percentage change (AAPC) were calculated.Results:In 2020, the crude incidence ratio (CIR) of liver cancer in Taizhou was 34.6 per 100 000, with CASIR and WASIR at 19.6 per 100 000 and 14.9 per 100 000, respectively. From 2012 to 2020, the male-to-female ratio of new liver cancer cases was 2.94∶1 (10 455 males vs. 3 559 females), with male incidence consistently higher than female. Overall liver cancer incidence in Taizhou initially increased and then decreased after 2017 (2012-2017: APC=6.4%, P=0.014; 2017-2020: APC=-9.5%, P=0.035), peaking at a CASIR of 26.2 per 100 000 in 2017. The trend in male incidence mirrored the overall pattern, rising before 2017 and declining thereafter (2012-2017: APC=6.2%, P=0.005; 2017-2020: APC=-9.0%, P=0.016). Female incidence remained relatively stable (2012-2016: APC=11.0%, P=0.054; 2016-2020: APC=-6.5%, P=0.130). Conclusions:Liver cancer incidence in Taizhou increased before 2017 and declined thereafter, with 2017 as the turning point. Amid population aging, liver cancer remains a persistent public health challenge requiring sustained attention.