POEMS syndrome is a rare condition associated with plasma cell disorders， and it often involves multiple systems and has diverse clinical manifestations. This article reports two cases of POEMS syndrome with hepatosplenomegaly as the initial manifestation. During the course of the disease， the patients presented with lower limb weakness， hepatosplenomegaly， lymph node enlargement， ascites， hypothyroidism， positive M protein， and skin hyperpigmentation， and ¹⁸F-FDG PET-CT imaging revealed bone lesions mainly characterized by osteolytic changes and plasma cell tumors. There was an increase in the serum level of vascular endothelial growth factor. The patients were finally diagnosed with POEMS syndrome， and the symptoms were relieved after immunomodulatory treatment.

Poly(ADP-ribose) polymerase 1 (PARP1) is a multifunctional protein involved in diverse cellular functions, notably DNA damage repair. Pharmacological inhibition of PARP1 has therapeutic benefits for various pathologies. Despite the increased use of PARP inhibitors, challenges persist in achieving PARP1 selectivity and effective blood-brain barrier (BBB) penetration. The development of a PARP1-specific positron emission tomography (PET) radioligand is crucial for understanding disease biology and performing target occupancy studies, which may aid in the development of PARP1-specific inhibitors. In this study, we leverage the recently identified PARP1 inhibitor, AZD9574, to introduce the design and development of its ¹⁸F-isotopologue ([¹⁸F]AZD9574). Our comprehensive approach, encompassing pharmacological, cellular, autoradiographic, and in vivo PET imaging evaluations in non-human primates, demonstrates the capacity of [¹⁸F]AZD9574 to specifically bind to PARP1 and to successfully penetrate the BBB. These findings position [¹⁸F]AZD9574 as a viable molecular imaging tool, poised to facilitate the exploration of pathophysiological changes in PARP1 tissue abundance across various diseases.

Background::Acute pulmonary embolism (APE) is a fatal cardiovascular disease, yet missed diagnosis and misdiagnosis often occur due to non-specific symptoms and signs. A simple, objective technique will help clinicians make a quick and precise diagnosis. In population studies, machine learning (ML) plays a critical role in characterizing cardiovascular risks, predicting outcomes, and identifying biomarkers. This work sought to develop an ML model for helping APE diagnosis and compare it against current clinical probability assessment models.Methods::This is a single-center retrospective study. Patients with suspected APE were continuously enrolled and randomly divided into two groups including training and testing sets. A total of 8 ML models, including random forest (RF), Na?ve Bayes, decision tree, K-nearest neighbors, logistic regression, multi-layer perceptron, support vector machine, and gradient boosting decision tree were developed based on the training set to diagnose APE. Thereafter, the model with the best diagnostic performance was selected and evaluated against the current clinical assessment strategies, including the Wells score, revised Geneva score, and Years algorithm. Eventually, the ML model was internally validated to assess the diagnostic performance using receiver operating characteristic (ROC) analysis.Results::The ML models were constructed using eight clinical features, including D-dimer, cardiac troponin T (cTNT), arterial oxygen saturation, heart rate, chest pain, lower limb pain, hemoptysis, and chronic heart failure. Among eight ML models, the RF model achieved the best performance with the highest area under the curve (AUC) (AUC = 0.774). Compared to the current clinical assessment strategies, the RF model outperformed the Wells score ( P = 0.030) and was not inferior to any other clinical probability assessment strategy. The AUC of the RF model for diagnosing APE onset in internal validation set was 0.726. Conclusions::Based on RF algorithm, a novel prediction model was finally constructed for APE diagnosis. When compared to the current clinical assessment strategies, the RF model achieved better diagnostic efficacy and accuracy. Therefore, the ML algorithm can be a useful tool in assisting with the diagnosis of APE.

Objective:To evaluate the influencing factors and predictive value of renal function recovery in elderly patients with heart failure(HF)and acute renal injury(AKI)after intermittent veno-venous hemofiltration(IVVH)using critical care ultrasound.Methods:The clinical data of elderly patients with heart failure(NYHF grade Ⅲ~Ⅳ)complicated with acute kidney injury(stage 2~stage 3)who underwent intravenous veno-venous hemofiltration(IVVH)in the critical care unit(CCU)of our hospital were retrospectively analyzed.The demographic information of the patients and the changes in clinical biochemical and critical care ultrasound monitoring parameters before and after 7 days of IVVH were recorded.Based on the recovery of renal function, the patients were divided into two groups: a renal function recovery group and a renal function non-recovery group.Logistic regression and Receiver Operating Characteristic Curve(ROC)curve analysis were performed to determine the predictive value of various influencing factors on the recovery of renal function in patients.Results:A total of 178 patients were enrolled in this study.After starting IVVH treatment, renal function recovered in 143 cases at 30 days, and in 138 cases at 90 days.However, renal function did not recover in 35 cases at 30 days, and in 40 cases at 90 days.The proportion of NYHF Ⅲ patients、the proportion of diabetic patients、the decrease of Beta 2-microglobulin(β2-MC)、the decrease of Cystain C(CysC)、the increase of venous transit time index(VTI)、the increase of Cardiac Output(CO)and the decrease in renal blood flow resistance index(RI)in the recovery groups at both 30 days and 90 days was significantly higher than that in the non-recovery group(all P<0.05).The total treatment time of IVVH in the recovery group was significantly shorter than that in the non-recovery group, with 30 days and 90 days( P<0.05).Logistic analysis revealed that the total treatment time of IVVH( OR=1.067, P<0.001), VTI( OR=0.652, P=0.024), CO( OR=0.037, P<0.001), and RI(OR<0.001, P=0.010)of the interlobar artery were identified as independent factors influencing the recovery of renal function in AKI patients at 30 days and 90 days after IVVH treatment.The ROC curve demonstrated the predictive value of various independent influencing factors for 30-day renal function recovery.The area under the curve(AUC)for VTI was 0.610(95% CI: 0.513-0.707), for CO it was 0.760(95% CI: 0.656-0.864), and for RI it was 0.694(95% CI: 0.589-0.799).Similarly, the ROC curve showed the predictive value of these factors for renal function recovery at 90 days.The AUC for VTI was 0.654(95% CI: 0.564-0.744), for CO it was 0.697(95% CI: 0.605-0.789), and for interlobar artery RI it was 0.605(95% CI: 0.495-0.715). Conclusions:The venous transit time index(VTI), cardiac output(CO), and renal interlobar artery RI, monitored by critical care ultrasound, are independent factors that can be used to evaluate the recovery of renal function in elderly patients with HF and AKI after IVVH treatment.Additionally, the changes in these parameters within 7 days after IVVH treatment have a high predictive value for the improvement of renal function in elderly patients after 30 days and 90 days.

Objective:To investigate the effect of inhibitory activity of high mobility group protein B1 (HMGB1), signal transduction and activator of transcription 3 (STAT3) on myocardial ischemia-reperfusion injury in rats.Methods:In vivo and in vitro models of MIRI were established. SD rats were randomly divided into a sham group, a model group, a glycyrrhizic acid group, and a NSC74859 group, with 6 rats in each group. Rats in the sham group were not ligation, and rats in the sham group and model group were not given medication. The rats in the glycyrrhizic acid group and the NSC74859 group were injected with HMGB1 antagonist glycyrrhizic acid or STAT3 inhibitor NSC74859 5 mg/kg in the tail vein at 12 h 30 min before ischemia/reperfusion and 30 min after ischemia, respectively. Left ventricular shortening fraction (FS) and left ventricular ejection fraction (EF) were evaluated by echocardiography, and apoptosis of cardiomyocytes was evaluated by hematoxylin-eosin (HE) and TUNEL staining. The expression levels of HMGB1, STAT3, and phosphorylated STAT3 (p-STAT3) were detected by real-time fluorescence quantitative PCR and Western Blot. The viability of H9C2 cells was determined by the MTS assay, intracellular ATP content was determined, and the mitochondrial membrane potential of H9C2 cells was measured by flow cytometry to evaluate the survival of cardiomyocytes. The action mode of HMGB1/STAT3 was studied by the immunoprecipitation method. The expression and migration of HMGB1/STAT3 in the nucleus and cytoplasm were detected by immunostaining. Results:After inhibiting the expression of HMGB1 or STAT3, EF and FS were increased, and immune infiltration and apoptosis of cardiomyocytes were decreased. Inhibition of HMGB1 expression could decrease the expression of STAT3, but inhibition of STAT3 expression didn’t affect the expression of HMGB1. Hypoxia could lead to increased expression of HMGB1 and p-STAT3, and decreased expression of STAT3. After 8 hours of hypoxia, the expression level of STAT3 suddenly increased. After reoxygenation, the expression of HMGB1 and STAT3 decreased, and the expression of p-STAT3 increased, but p-STAT3 (Ser 727) didn’t participate in this process. After ischemia-reperfusion injury, HMGB1 and STAT3 binded firmly in cardiomyocytes, but inhibition of STAT3 or HMGB1 weakened this binding. Inhibition of HMGB1 or STAT3 expression could reduce myocardial ischemia-reperfusion injury. The expression of HMGB1 in reoxygenated cardiomyocytes increased after hypoxia, and HMGB1 migrated from the nucleus to the cytoplasm.Conclusions:Inhibiting the activity of the HMGB1/STAT3 axis effectively reduces MIRI in rats.

Objective·To investigate the safety and feasibility of early goal-directed mobilization in the recovery of gastrointestinal function after pancreaticoduodenectomy.Methods·The non-contemporaneous controlled studies were conducted.Subjects who underwent pancreaticoduodenectomy were included.From Sep 2022 to May 2023,forty patients were selected as the control group,and forty patients were selected from June 2023 to February 2024 as the experimental group.The general clinical data of the two groups were collected.The control group was treated with the nursing routine after pancreaticoduodenectomy,and there were no specific requirements for the time and goal of early activity.The experimental group had daily activity goals established for early mobilization,which were performed by the patients and their families,while the rest of their care was identical to that of the control group.The main index of effectiveness evaluation was the time of first flatus and first defecation,and the secondary indexes included the time of first getting out of bed,the time of oral drinking,the time of the gastric tube removal,and the postoperative levels of K+,Na+,and Cl-on the 3rd day of the postoperative period.Safety evaluations included chyle leak,postoperative pancreatic fistula,biliary leak and delayed gastric emptying,postoperative hemorrhage,unplanned reoperation,unplanned extubation,falls and death.Results·There was no statistically significant difference in the general clinical data of the patients in the 2 groups.After the implementation of early goal-directed mobilization,the time of first flatus was advanced from(3.95±1.68)d to(2.88±0.91)d(t=-3.560,P=0.001),and the time of first defecation was advanced from(4.90±1.61)d to(3.80±1.30)d(t=-3.352,P=0.001).The time of first getting out of bed was advanced from(5.18±1.77)d to(2.30±0.88)d(t=-9.205,P＜0.001),and the time of oral drinking was advanced from(4.10±1.89)d to(2.73±1.20)d(t=-3.883,P＜0.001).Significant differences were also observed in postoperative day 3 Na+(t=-2.745,P=0.008)and Cl-(t=-2.033,P=0.045)levels.Conclusion·Early goal-directed activity programs are safe and effective in promoting the recovery of gastrointestinal function after pancreaticoduodenectomy.

Objective:To investigate the volume management of intermittent veno-venous hemofiltration (IVVH) guided by critical care ultrasound in the treatment of acute kidney injury (AKI) in patients with heart failure (HF).Methods:A total of 216 patients with HF and AKI treated with IVVH in the coronary care unit (CCU) of the Third Central Hospital of Tianjin from April 2019 to June 2022 were selected as the study subjects, the patients were randomly divided into conventional guidance group (107 cases) and ultrasound guidance group (109 cases). According to the recovery of renal function, IVVH was performed 12 hours every day or 12 hours every other day. The conventional guidance group selected the conventional method to formulate IVVH prescription, and the ultrasound guidance group used critical care ultrasound to adjust the treatment parameters of IVVH on the basis of the conventional guidance group. Respiratory variation index (RVI) of inferior vena cava (IVC), right left ventricular end-diastolic transverse area ratio, early diastolic peak mitral flow velocity/mitral annulus velocity peak (E/E'), aortic flow velocity time integral (VTI), cardiac output (CO), bilateral lung ultrasound B-line range, bilateral renal interlobar arteries resistance index (RI) were recorded before and 3, 6, 9 hours after each treatment. The net dehydration rate was adjusted in real time according to the comprehensive results. Urine volume, serum creatinine (SCr), estimated glomerular filtration rate (eGFR), blood B-type brain natriuretic peptide (BNP), β 2-microglobulin (β 2-MG) and cystatin C (Cys C) levels of patients in both groups were monitored before and 3, 7 and 10 days after initial treatment, and renal function recovery and clinical prognostic indexes of patients in both groups were recorded. Results:The dehydration rate of the ultrasound guidance group was slow at the beginning of IVVH, and gradually increased after 6 hours, and the overall dehydration rate was significantly slower than that of the conventional guidance group. In the ultrasound guidance group using critical care ultrasound, the RVI gradually increased, the right left ventricular end-diastolic area ratio gradually decreased, the E/E' ratio gradually decreased, and the range of B-line of bilateral lungs gradually decreased, RI of bilateral renal interlobar arteries decreased. At 3, 7 and 10 days after the first IVVH, renal function related indexes in both groups were significantly improved compared with before treatment, and the decline rate of β 2-MG and Cys C in the ultrasound guidance group was faster than that in the conventional guidance group at early (3 days) [β 2-MG (mg/L): 3.69±1.31 vs. 3.99±1.45, Cys C (mg/L): 2.91±0.95 vs. 3.14±0.96, both P < 0.05], urine volume, SCr and eGFR at 7 days were also significantly improved compared with the conventional guidance group [24-hour urine volume (mL): 1 128.23±153.92 vs. 1 015.01±114.18, SCr (μmol/L): 145.86±32.25 vs. 155.64±28.42, eGFR (mL/min): 50.26±11.24 vs. 46.51±10.61, all P < 0.05]. The time of SCr recovery, the time of reaching polyuria, the total time of IVVH treatment, the time of non-invasive mechanical ventilation and the time of living in CCU in the ultrasound guidance group were shorter than those in the conventional guidance group. The incidences of hypotension, long-term RRT, incidence of major cardiovascular adverse event (MACE) and at 28-day mortality were all lower than those in the conventional guidance group. Kaplan-Meier survival curve showed that the 28-day cumulative survival rate in the ultrasound guidance group was significantly lower than that in the conventional guidance group (Log-Rank test: χ 2 = 3.903, P = 0.048). Conclusion:The strategy of IVVH guided by critical care ultrasound in the treatment of HF with AKI has unique advantages.

BACKGROUND: The switch/sucrose nonfermentable chromatin-remodeling (SWI/SNF) complex is a pivotal chromatin remodeling complex, and the genomic alterations (GAs) of the SWI/SNF complex are observed in several cancer types, correlating with multiple biological features of tumor cells. However, their role in liver metastasis of non-small cell lung cancer (NSCLC) remains unclear. Our study aims to investigate the role and potential mechanisms underlying NSCLC liver metastasis induced by the GAs of SWI/SNF complex. METHODS: The GAs of SWI/SNF complex in NSCLC cell lines (H1299, H23 and H460) were identified by whole-exome sequencing (WES). ARID1A knockout H1299 cell was constructed with the CRISPR/Cas9 technology. The mouse model of liver metastasis from NSCLC was established to simulate lung cancer liver metastasis and observe the metastasis rate under different gene mutation conditions. RNA sequencing and Western blot were conducted for differential gene expression analysis. Immunohistochemistry (IHC) analysis was used to assess protein expression levels of SWI/SNF-regulated target molecules in mouse liver metastases. RESULTS: WES analysis revealed intracellular gene mutations. The animal experiments demonstrated a correlation between the GAs of SWI/SNF complex and a higher liver metastasis rate in immunodeficient mice. Transcriptome sequencing and Western blot analysis showed upregulated expression of ALDH1A1 and APOBEC3B in SWI/SNF-mut cells, particularly in ARID1A-deficient H460 and H1299 sgARID1A cells. IHC staining of mouse liver metastases further demonstrated elevated expression of ALDH1A1 in the H460 and H1299 sgARID1A group. CONCLUSIONS This study underscores the critical role of the GAs of SWI/SNF complex, such as ARID1A and SMARCA4, in promoting liver metastasis of lung cancer cells. The GAs of SWI/SNF complex may promote liver-specific metastasis by upregulating ALDH1A1 and APOBEC3B expression, providing novel insights into the molecular mechanisms underlying lung cancer liver metastasis.
Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/genetics* ; Lung Neoplasms/genetics* ; Mutation ; Liver Neoplasms/genetics*

Objective:To identify the risk factors for functional delayed gastric emptying(FDGE)after retroperitoneal tumor resection.Meth-ods:Sixty-seven patients with postoperative FDGE after retroperitoneal tumor resection from September 2017 to December 2022 admited in Peking University International Hospital were included in the observation group,and 836 normal patients who underwent ret-roperitoneal tumor resection during the same period were included in the control group.Medical histories and clinical treatment data were obtained for each group and compared to identify the risk factors for FDGE after retroperitoneal tumor resection.Results:The overall incid-ence of postoperative FDGE was 7.42%.Factors that were significantly elevated(P<0.05)in the observation group relative to the control group included adverse mental factors(37.31%),preoperative digestive tract obstruction(41.79%),postoperative abdominal cavity complic-ations(79.10%),diabetes(29.86%),average age of(61.85±6.11)years,and blood loss(1 011.94±507.30)mL.Pre-and post-surgery albumin levels[(38.22±3.75)g/L and(30.22±3.36)g/L,respectively]were significantly reduced(P<0.05)in the observation group compared to the control group.Risk factor analyses revealed that advanced age,diabetes,preoperative digestive tract obstruction,intraoperative blood loss,perioperative albumin level,postoperative abdominal cavity complications,and adverse mental factors were correlated with postoperative FDGE.Conclusions:Diverse factors could impact the risk of FDGE after retroperitoneal tumor resection.Patients should be accurately evalu-ated;reasonable and detailed prevention and treatment plans should be developed.

【Objective】 To investigate the resource allocation status of blood testing laboratories in 14 blood stations in Gansu Province, explore the impact of differences in basic conditions on the comprehensive testing ability of laboratories, so as to promote the homogenization and standardization of blood screening capacity in blood stations in Gansu and improve blood safety and effectivenes. 【Methods】 An evaluation index system of laboratory resource allocation was constructed and a question-naire was designed. The data of human resources, infrastructure and key equipment of 14 blood stations were collected. The entropy weight -TOPSIS method was used to evaluate and rank the resource allocation of 14 blood stations. 【Results】 In the comprehensive evaluation of blood testing laboratory resource allocation in 14 blood stations in Gansu, the top three were laboratories A, B and I, and the last three were laboratories G, M and J. On the whole, the main issue was unreasonable structure of human resources: most laboratories had unreasonable age structure; except for Laboratory A, there was no personnel with bachelor's degree or above in laboratories; most laboratories had not established a team with intermediate professional titles. In terms of infrastructure, the size of seven laboratories could not meet the needs of modern laboratory testing, and all eight blood stations had no spare nucleic acid laboratories nor a mutual spare laboratory with other blood stations As for the key equipment, 5 laboratories had no automatic blood grouping diagnostic instrument, 5 laboratories only had one set of enzyme immunoassay detection system, 3 laboratories had no spare equipment for the key equipment, which means if the equipment failure could not be repaired in time, the release of results would be affected. 【Conclusion】 There were significant differences in human resources, infrastructure and key equipment of blood testing laboratories in 14 blood stations in Gansu, which had a great impact on laboratory testing capacity and subsequent development. It is suggested that governments at all levels and health administrative departments optimize the input of laboratory resource allocation according to the blood collection volume of blood stations to gradually narrow the differences in resource distribution between different regions, improve the degree of laboratory automation and optimize the personnel structure, so as to build high-quality and efficient blood testing laboratories and ensure the safety of clinical blood use.