The accumulation of uremic toxins such as urea nitrogen, blood creatinine, and uric acid of patients with renal failure in vivo would lead to aggravated kidney damage. In this study, coated aldehyde oxy-starch (CAO) was used as an adsorbent to investigate its in vitro adsorption performance on renal failure indexes for urea, indoxyl sulfate (INS), monomethylamine (MMA), dimethylamine (DMA), uric acid (UA), and creatinine (Cr). The effects of variables such as pH, temperature, concentration, dosage, and time on the adsorption capacity of CAO were systematically investigated, employing analytical techniques of high-performance liquid chromatography (HPLC) and gas chromatography (GC). The results revealed that CAO exhibited a strong adsorption capacity for urea, INS, and MMA, alongside a moderate adsorption capacity for DMA, UA, and Cr. The adsorption kinetics and thermodynamic studies indicated that the adsorption of urea and UA by CAO were fitted in pseudo-first-order kinetics, and the adsorption isotherm aligned with the Freundlich adsorption model. The enthalpy change ΔH of urea in adsorption was in the range of 40 to 60 kJ·mol^-1, which demonstrated the presence of strong adsorption force due to the interactions of coordinating groups. The ΔH of UA was greater than 80 kJ·mol^-1, indicating the generation of chemical bonds during the adsorption. Both of them, Gibbs free energy ΔG was less than 0, within the range of -20 to 0 kJ·mol^-1, suggested that the adsorption of urea and UA by CAO occurred spontaneously as physical adsorption process. The adsorption entropy ΔS of urea and UA was > 0, which indicated an increase in entropy throughout the adsorption. The infrared spectroscopygram showed the formation of a chemical bond, specifically the imine bond, following the adsorption of urea by CAO, thereby indicating a chemical reaction during the adsorption. This study elucidates the adsorption mechanism of CAO on various indexes of renal failure, providing a scientific basis for its clinical usage.

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Malignant pleural mesothelioma(MPM)is a rare cancer with high malignancy and aggressiveness on the pleural,caused by the following risk factors including asbestos inhalation,genetic factors,and genetic mutation.The pres-ent chemotherapy,antiangiogenic therapy,and immunotherapy methods are ineffective and the survival time of patients is very short.There is an urgent need to find potential therapeutic targets for MPM.At present,it has been found the following types of targets:gene mutation targets such as BRCA associated protein 1(BAP1)and cyclin-dependent kinase 2A(CDKN2A);epigenetic targets such as lysine(K)-specific demethylase 4A(KDM4A)and lysine-specific demethylase 1(LSD1),and signal protein targets such as glucose-regulated protein 78(GRP78)and signal transducer and activator of transcription 3(STAT3).So far,available clinical trials include phase Ⅱ clinical trials of histone methyltransferase inhibitor Tazemetostat,poly(ADP-ribose)polymerase(PARP)inhibitor Rucaparib and cyclin-dependent kinases 4 and 6(CDK4/6)inhibitor Abemaciclib,as well as phase Ⅰ clinical trials of mesothelin-targeting chimeric antigen receptor T-cell immunotherapy(CAR-T)cell injection in the thoracic cavity and TEA domain family member(TEAD)inhibitor VT3989 and IK-930,and the results of these trials have showed certain clinical efficacy.

Objective:To analyze the clinical characteristics of different types of anomalous origin of the coronary artery.Methods:A case-series study was conducted.Based on the clinical data of children diagnosed with anomalous origin of the coronary artery at Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from January 2013 to January 2023, the diseases of different types of anomalous origin of the coronary artery were summarized.Results:A total of 177 children with anomalous origin of the coronary artery were treated.Among them, 122 children developed the anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA), including 54 males and 68 females, with a median age of 1.2 years; 6 children developed the anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA), including 3 males and 3 females, with a median age of 4.3 years; 9 children developed the anomalous left coronary artery from the right coronary sinus (ALCA), including 6 males and 3 females, with a median age of 9.5 years; 40 children developed the anomalous right coronary artery from the left coronary sinus (ARCA), including 24 males and 16 females, with a median age of 7.7 years.Most children diagnosed with ALCAPA had onset within 1 year of age, with chronic heart failure as the main manifestation, and young children were often accompanied by severe mitral regurgitation.A total of 111 children underwent surgery, and 11 children died.Six children with ARCAPA had no obvious clinical symptoms and were treated by operation according to the principle of double coronary circulation after diagnosis.Nine children with ALCA started with syncope, chest pain or abdominal pain after exercise.Eight of the children underwent surgical treatment, including 1 who received a heart transplant.Of the 40 children with ARCA, 23 children had clinical manifestations, with chest tightness, syncope, and chest pain after exercise as chief complaints; 16 children were tested positive for treadmill exercise before surgery; and a total of 13 children received surgical treatment.Conclusions:Different types of anomalous origin of the coronary artery vary in severity.The clinical manifestations of the anomalous origin of the left coronary artery are generally serious, and most of such patients have the risk of cardiac insufficiency or sudden death.Once diagnosed, surgical treatment should be performed timely.The clinical manifestations of the anomalous origin of the right coronary artery are relatively mild, and only a few may have serious consequences, which are usually treated according to the principle of individualization or double coronary circulation.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective:To analyze the prognostic nutritional index(PNI),controlling nutritional status(CONUT)and fibrinogen/albumin ratio(FAR)levels in elderly patients with multiple myeloma(MM)and their prognostic impact.Methods:The clinical data of 74 elderly MM patients diagnosed in Gansu Provincial Hospital from January 2020 to July 2022 were retrospectively analyzed.The optimal cut-off values for PNI,CONUT score and FAR were obtained by receiver operating characteristic(ROC)curve,which were used for grouping patients.The correlation of above three indexes with clinical parameters such as sex,serum calcium(Ca),β2-microglobulin(β2-MG),serum creatinine(Cr)in elderly MM patients were analyzed.The survival rates of patients with different levels of each index were compared.Univariate and multivariate analysis of the impact of clinical indicators on the prognosis of patients were performed.Results:The optimal cut-off values for PNI,CONUT score and FAR were 39.775,3.5 and 0.175,respectively,according to which the patients were divided into high and low group.Statistical analysis showed that there were significant differences in albumin level among different groups(all P＜0.05).In addition,there was a significant difference in hemoglobin between high-PNI group and low-PNI group(P＜0.05),while in sex distribution between high-FAR and low-FAR group(P＜0.05).The survival rate of elderly MM patients with increased PNI,decreased CONUT score and FAR was higher(all P＜0.05).Univariate and multivariate analysis showed that β2-MG,Cr,PNI,CONUT score and FAR were independent prognostic factors for elderly MM patients.Conclusion:PNI,CONUT score and FAR are related to some clinical indicators of elderly MM patients,and have an impact on the prognosis.

Objective:To analyze the clinical characteristics and occurrence of thrombotic/bleeding events of patients with myeloproliferative neoplasm(MPN),and explore the main influencing factors,and create a risk prediction.Methods:The clinical data of 126 MPN patients with BCR-ABL fusion gene negative in the Department of Hematology of Gansu Provincial Hospital from January 2016 to September 2021 were collected,and their clinical characteristics,occurrence of thrombotic/bleeding events and main influencing factors were analyzed and summarized retrospectively.Then,a risk prediction model for thrombotic/bleeding events in MPN patients was constructed.Results:Among 126 MPN patients,50 patients(39.7％)had experienced thrombotic/bleeding events,including 44 patients(34.9％)with thrombotic events and 6 patients(4.8％)with bleeding events.Among thrombotic diseases,cerebral thrombosis was the most common(23/44,52.3％),followed by 9 cases of limb artery thrombosis mainly characterized by finger and toe tip artery ischemia,occlusion and gangrene(9/44,20.5％).Bleeding events included intracerebral hemorrhage and gastrointestinal hemorrhage.Univariate analysis showed that hypertension,hyperhomocysteinemia,white blood cell(WBC)≥10 × 109/L,hematocrit(HCT)≥49％,platelet(PLT)≥600 × 109/L and JAK2V617F gene mutation were risk factors for thrombotic/bleeding events in MPN patients,while CALR gene mutation was a protective factor.Multivariate analysis showed that hypertension and PLT ≥ 600 × 109/L were independent risk factors for thrombotic/bleeding events in MPN patients.The goodness of fit of the constructed risk prediction model was 0.872,and the area under the ROC curve was 0.838.The model was validated with clinical data,the sensitivity,specificity and accuracy was 78.85％,87.83％and 84.13％,respectively.Conclusion:The risk of thrombotic/bleeding events in MPN patients with high WBC count,hypertension and hyperhomocysteinemia is higher.Controlling hypertension and hyperhomocysteinemia and reducing WBC and PLT counts are helpful to prevent thrombotic/bleeding events and improve the life quality of patients.

Objective To analyze the risk factors of poor prognosis in patients with extended-spectrum β-lactamase producing enterobacterales(ESBL-E)bloodstream infection,and establish a nomogram prediction model to provide help for clinical diagnosis and treatment.Methods A total of 235 patients with ESBL-E bloodstream infection were collected from the First People's Hospital of Jiande City.According to their prognosis,the patients were divided into survival group(n=211)and death group(n=224).The clinical data of the patients were collected,and the independent risk factors of poor prognosis were screened by multivariate Logistic regression analysis.The nomogram was established and verified.Results The mortality of ESBL-E bloodstream infection patients with shock,respiratory failure,diabetes and leukemia,ICU admission,hypoproteinemia,increased or decreased white blood cells,and thrombocytopenia was higher(P＜0.05).Multivariate Logistic regression analysis showed that combined shock,respiratory failure and leukemia were independent risk factors for death from ESBL-E bloodstream infection.Conclusion The nomogram prediction model of adverse prognostic risk factors in patients with ESBL-E bloodstream infection can provide help for clinicians to judge the poor prognosis in the early stage,and it is of reference significance to take early intervention measures to reduce the mortality of patients.

Objective: To explore the effect of kynurenine pathway on the osteogenic differentiation of periodontal ligament stem cells (PDLSC). Methods: Unstimulated saliva samples were collected from 19 patients with periodontitis (periodontitis group) and 19 periodontally healthy individuals (health group) in Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University from June to October of 2022. Contents of kynurenine and the metabolites in saliva samples were analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. The expressions of indoleamine 2, 3-dioxygenase (IDO) and aryl hydrocarbon receptor (AhR) were further detected by immunohistochemistry in gingival tissues. The PDLSC used in this study were isolated from extracted teeth for orthodontic treatment in Nanjing Stomatological Hospital, Affiliated Hospital of Medical School, Nanjing University from July to November of 2022. Experiments were then conducted using the cells by incubating with (kynurenine group) or without kynurenine (control group) in vitro. Seven days later, alkaline phosphatase (ALP) staining and assays of ALP activity were performed. Real-time fluorescence quantitative PCR (RT-qPCR) was utilized to detect the expressions of osteogenic related genes ALP, osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), collagen type-Ⅰ (COL-Ⅰ) as well as the kynurenine pathway-associated genes AhR, cytochrome P450 family (CYP) 1A1, CYP1B1. Western blotting was used to detect the expression levels of RUNX2, osteopontin (OPN) and AhR proteins on day 10 and alizarin red staining was performed to observe the formation of mineral nodules on day 21 in control group and kynurenine group. Results: Salivary concentrations of kynurenine [8.26 (0, 19.60) nmol/L] and kynurenic acid [11.4 (3.34, 13.52) nmol/L] were significantly higher in the periodontitis group than in the health group [0.75(0, 4.25) nmol/L, 1.92(1.34, 3.88) nmol/L] (Z=-2.84, P=0.004; Z=-3.61, P<0.001). The expression levels of IDO (18.33±2.22) and AhR (44.14±13.63) in gingival tissues of periodontitis patients were significantly higher than that of the health group (12.21±2.87, 15.39±5.14) (t=3.38, P=0.015; t=3.42, P=0.027). In vitro, the ALP activity of PDLSC in the kynurenine group (291.90±2.35) decreased significantly compared with the control group (329.30±19.29) (t=3.34, P=0.029). The mRNA expression levels of ALP, OCN and RUNX2 in the kynurenine group (0.43±0.12, 0.78±0.09, 0.66±0.10) were decreased compared with the control group (1.02±0.22, 1.00±0.11, 1.00±0.01) (t=4.71, P=0.003; t=3.23, P=0.018; t=6.73, P<0.001), while the levels of AhR and CYP1A1 were increased in the kynurenine group (1.43±0.07, 1.65±0.10) compared with those in the control group (1.01±0.12, 1.01±0.14) (t=5.23, P=0.006; t=6.59, P<0.001). No significant difference was observed in COL-Ⅰ and CYP1B1 mRNA levels between groups. The protein levels of OPN, RUNX2 (0.82±0.05, 0.87±0.03) were reduced and that of AhR (1.24±0.14) was increased in the kynurenine group compared with those in the control group (1.00±0.00, 1.00±0.00, 1.00±0.00) (t=6.79, P=0.003; t=7.95, P=0.001; t=3.04, P=0.039). Conclusions: Over-activated kynurenine pathway in periodontitis patients can promote upregulation of AhR and suppress the osteogenic differentiation of PDLSC.

OBJECTIVE: To analyze the clinical features and prognosis of patients with Castleman's disease (CD) and improve the diagnosis and treatment of CD. METHODS: Clinical data of patients diagnosed with CD by pathological biopsy in Gansu Provincial Hospital from January 2009 to November 2020 were retrospectively analyzed. According to clinical classification, the patients were divided into two groups: UCD (unicentric CD) group (n=20) and MCD (multicentric CD) group (n=9). The clinical manifestations, laboratory examination, treatment regimens, pathological examination and follow-up data were statistically analyzed. RESULTS: There were no significant differences in average age and gender ratio between UCD group and MCD group. In UCD patients, 80.0% were hyaline vascular type, and 20.0% were plasma cell type. In MCD patients, 33.3% were hyaline vascular type, 55.6% were plasma cell type, and 11.1% were mixed type. There was significant difference in pathological classification between the two groups (P=0.039). The UCD patients usually presented asymptomatic single lymph node enlargement with mild clinical symptoms, while the MCD patients were characterized by multiple superficial and deep lymph node enlargement throughout the body. The incidences of asthenia, splenomegaly, serous effusion in MCD group were higher than those in UCD group (P<0.05). Meanwhile, the incidences of anemia, hypoproteinemia, increased ESR, elevated serum globulin and elevated β₂-microglobulin were significantly higher than those in UCD group too (P<0.05). There was no significant difference in the incidences of abnormal WBC, PLT and elevated LDH between the two groups (P>0.05). Among 20 patients with UCD, 13 cases reached complete remission (CR), 1 case achieved partial remission (PR). Among 9 patients with MCD, 3 cases received CR and 4 cases received PR. CONCLUSION Patients with CD requires pathological examination for diagnosis. Patients with UCD show mild clinical symptoms, good surgical treatment effect and good prognosis. Patients with MCD have diversified clinical manifestations and relatively poor prognosis, and these patients require comprehensive treatment.
Humans ; Castleman Disease/therapy* ; Retrospective Studies ; Prognosis ; Splenomegaly ; Anemia