Predictive model of the efficiency of hematopoietic stem cell collection in patients with multiple myeloma and lymphoma based on multiple peripheral blood markers.

INTRODUCTION: Autologous hematopoietic stem cell transplantation (ASCT) has gained extensive application in the treatment of lymphoma and multiple myeloma (MM). Plenty of studies demonstrate that peripheral blood indicators could be considered potential predictive biomarkers for hematopoietic stem cells (HSCs) collection efficiency, including white blood cell count (WBC), monocyte count (Mono), platelet count (PLT), hematocrit, and hemoglobin levels. Currently, clinically practical predictive models based on these peripheral detection indicators to quickly, conveniently, and accurately predict collection efficiency are lacking. METHODS: In total, 139 patients with MM and lymphoma undergoing mobilization and collection of ASCT were retrospectively studied. The study endpoint was successful collection of autologous HSCs. We analyzed the effects of clinical characteristics and peripheral blood markers on collection success, and screened variables to establish a prediction model. We determined the optimal cutoff value of peripheral blood markers for predicting successful stem cell collection and the clinical value of a multi-marker prediction approach. We also established a prediction model for collection efficacy. RESULTS: Univariate and multivariate logistic regression analyses showed that the mobilization regimen, Mono, PLT, mononuclear cell count (MNC), and peripheral blood CD34+ cell count (PB CD34+ counts) were significant predictors of successful collection of peripheral blood stem cells (PBSC). Two predictive models were constructed based on the results of multivariate logistic analyses. Model 1 included the mobilization regimen, Mono, PLT, and MNC, whereas Model 2 included the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts. Receiver operating characteristic (ROC) curve analysis showed that the PB CD34+ counts, Model 1, and Model 2 could predict successful HSCs collection, with cutoff values of 26.92 × 106/L, 0.548, and 0.355, respectively. Model 1 could predict successful HSCs collection with a sensitivity of 84.62%, specificity of 75.73%, and area under the curve (AUC) of 0.863. Model 2 could predict successful HSCs collection with a sensitivity of 83.52%, specificity of 94.17%, and AUC of 0.946; thus, it was superior to the PB CD34+ counts alone. CONCLUSION: Our findings suggest that the combination of the mobilization regimen, Mono, PLT, MNC, and PB CD34+ counts before collection has predictive value for the efficacy of autologous HSCs collection in patients with MM and lymphoma. Using models based on these predictive markers may help to avoid over-collection and improve patient outcomes.

Antibody responses to SARS-CoV-2 Omicron infection in patients with hematological malignancies: A multicenter, prospective cohort study.

Little is known about antibody responses to natural Omicron infection and the risk factors for poor responders in patients with hematological malignancies (HM). We conducted a multicenter, prospective cohort study during the latest Omicron wave in Chongqing, China, aiming to compare the antibody responses, as assessed by IgG levels of anti-receptor binding domain of spike protein (anti-S-RBD), to Omicron infection in the HM cohort (HMC) with healthy control cohort (HCC), and solid cancer cohort (SCC). In addition, we intend to explore the risk factors for poor responders in the HMC. Among the 466 HM patients in this cohort, the seroconversion rate was 92.7%, no statistically difference compared with HCC (98.2%, p = 0.0513) or SCC (100%, p = 0.1363). The median anti-S-RBD IgG titer was 29.9 ng/mL, significantly lower than that of HCC (46.9 ng/mL, p < 0.0001) or SCC (46.2 ng/mL, p < 0.0001). Risk factors associated with nonseroconversion included no COVID-19 vaccination history (odds ratio [OR] = 4.58, 95% confidence interval [CI]: 1.75-12.00, p = 0.002), clinical course of COVID-19 ≤ 7 days (OR = 2.86, 95% CI: 1.31-6.25, p = 0.008) and severe B-cell reduction (0-10/µL) (OR = 3.22, 95% CI: 1.32-7.88, p = 0.010). Risk factors associated with low anti-S-RBD IgG titer were clinical course of COVID-19 ≤ 7 days (OR = 2.58, 95% CI: 1.59-4.18, p < 0.001) and severe B-cell reduction (0-10/µL) (OR = 2.87, 95% CI: 1.57-5.24, p < 0.001). This study reveals a poor antibody responses to Omicron (BA.5.2.48) infection in HM patients and identified risk factors for poor responders. Highlights that HM patients, especially those with these risk factors, may be susceptible to SARS-CoV-2 reinfection, and the postinfection vaccination strategies for these patients should be tailored. Clinical trial: ChiCTR2300071830.

A Mid-Infrared Quantum Cascade Laser Ultra-Sensitive Trace Formaldehyde Detection System Based on Improved Dual-Incidence Multipass Gas Cell.

Formaldehyde (HCHO) is a tracer of volatile organic compounds (VOCs), and its concentration has gradually decreased with the reduction in VOC emissions in recent years, which puts forward higher requirements for the detection of trace HCHO. Therefore, a quantum cascade laser (QCL) with a central excitation wavelength of 5.68 µm was applied to detect the trace HCHO under an effective absorption optical pathlength of 67 m. An improved, dual-incidence multi-pass cell, with a simple structure and easy adjustment, was designed to further improve the absorption optical pathlength of the gas. The instrument detection sensitivity of 28 pptv (1σ) was achieved within a 40 s response time. The experimental results show that the developed HCHO detection system is almost unaffected by the cross interference of common atmospheric gases and the change of ambient humidity. Additionally, the instrument was successfully deployed in a field campaign, and it delivered results that correlated well with those of a commercial instrument based on continuous wave cavity ring-down spectroscopy (R2 = 0.967), which indicates that the instrument has a good ability to monitor ambient trace HCHO in unattended continuous operation for long periods of time.

Prognostic value of nutritional status in patients with human immunodeficiency virus infection-related lymphoma.

Objective: To investigate the predictive value of nutritional status on the prognosis of patients with human immunodeficiency virus (HIV) infection-related lymphoma. Materials and methods: A total of 149 patients with HIV infection-related lymphoma who were admitted to our hospital from August 2012 to May 2022 were selected as research subjects. Based on the patient prognosis, they were divided into a poor prognosis group (n = 30) and a good prognosis group (n = 119). General data from patients in both groups were collected, and the nutritional status of the patients was evaluated using the Controlling Nutritional Status (CONUT) score. Factors affecting the prognosis of HIV infection-related lymphoma were analyzed using univariate and multivariate analyses, and a prediction model was developed based on the analyzed factors. The receiver operating characteristic (ROC) curve was used to analyze the prediction model of the CONUT score alone and included the CONUT score in the prognosis of patients with HIV infection-related lymphoma. The predictive value of the data was assessed, and a survival curve was drawn to compare the survival of patients with different nutritional statuses. Results: There were significant differences in age, B symptoms, treatment conditions, International Prognostic Index (IPI), pathological stage, Eastern Collaborative Tumor Group physical status score (ECOG PS), CD4+ cell count, ß2 microglobulin, and lactate dehydrogenase (LDH) between the poor prognosis group and the good prognosis group (p < 0.05). The CONUT score of the poor prognosis group was higher than that of the good prognosis group, and the difference was statistically significant (p < 0.05). A univariate analysis demonstrated that the age, B symptoms, treatment status, IPI, pathological stage, ECOG PS, CD4+ cell count, ß2 microglobulin, LDH, and CONUT score were prognostic factors for patients with HIV infection-related lymphoma (p < 0.05). The results of a multivariate regression analysis demonstrated that the age, B symptoms, treatment status, IPI, pathological stage, ECOG PS, and CONUT score were independent risk factors for the prognosis of patients with HIV infection-related lymphoma (p < 0.05). The prediction model was constructed according to the multivariate Cox regression analysis results. The model formula was as follows: Logit(p) = -10.687 + 1.728 × age + 1.713 × B symptoms + 1.682 × treatment status + 1.810 × IPI + 1.643 × pathological stage + 1.584 × ECOG PS + 1.779 × CONUT score. The ROC curve was used to analyze the predictive value of the CONUT score alone and the predictive model including the CONUT score on the prognosis of patients with HIV infection-related lymphoma. The predictive value of the prognosis of patients with tumors was higher (p < 0.05). According to the results of the ROC curve analysis, the patients were divided into a high CONUT group (CONUT > 6.00 points, n = 31) and a low CONUT group (CONUT ≤ 6.00 points, n = 118) based on the Optimum threshold of the CONUT score. The survival curve showed that the survival rate of the high CONUT group was lower than that of the low CONUT group (p < 0.05). Conclusion: The poor prognosis of HIV infection-related lymphoma is related to nutritional status, which is an independent risk factor affecting the prognosis of patients and can be used as a practical indicator to predict the prognosis of patients.

Risk Predictive Model Based on Three DDR-Related Genes for Predicting Prognosis, Therapeutic Sensitivity, and Tumor Microenvironment in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is the seventh most common malignancy and the second most common cause of cancer-related deaths. Tumor mutational load, genomic instability, and tumor-infiltrating lymphocytes were associated with DNA damage response and repair gene changes. The goal of this study is to estimate the chances of patients with HCC surviving their disease by constructing a DNA damage repair- (DDR-) related gene profile. The International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA) provided us with the mRNA expression matrix as well as clinical information relevant to HCC patients. Using Cox regression and LASSO analysis, DEGs strongly related to general survival were discovered in the differentially expressed gene (DEG) study. In order to assess the model's accuracy, Kaplan-Meier (KM) and receiver operating characteristic (ROC) were used. In order to compute the immune cell infiltration score and immune associated pathway activity, a single-sample gene set enrichment analysis was performed. A three-gene signature (CDC20, TTK, and CENPA) was created using stability selection and LASSO COX regression. In comparison to the low-risk group, the prognosis for the high-risk group was surprisingly poor. In the ICGC datasets, the predictive characteristic was confirmed. A receiver operating characteristic (ROC) curve was calculated for each cohort. The risk mark for HCC patients is a reliable predictor according to multivariate Cox regression analysis. According to ssGSEA, this signature was highly correlated with the immunological state of HCC patients. There was a significant correlation between the expression levels of prognostic genes and cancer cells' susceptibility to antitumor therapies. Overall, a distinct gene profile associated with DDR was identified, and this pattern may be able to predict HCC patients' long-term survival, immune milieu, and chemotherapeutic response.

Clinical characteristics and outcomes of newly diagnosed patients with HIV-associated aggressive B-cell NHL in China.

Little is known about the incidence, clinical characteristics and prognostic factors in HIV associated lymphoma as these are less common than HIV-negative lymphoma in China. Currently, there are no standard guidelines for treatment of these patients. Therefore, we performed a study to analyse the clinical characteristics and outcomes of newly diagnosed HIV-associated aggressive B-cell non-Hodgkin's lymphoma (NHL) patients in Chongqing University Cancer Hospital (CUCH). Totally 86 newly diagnosed HIV-associated aggressive B-cell NHL patients in CUCH, southwest China, from July 2008 to August 2021, were analysed. In the entire cohort, median age was 48 years (range, 23-87 years), and more patients were male (87.2%). Most patients had elevated lactate dehydrogenase (LDH) (82.6%), advanced ann arbor stage (80.2%) and high IPI score (IPI score, 3-5) (62.7%) at diagnosis. Median CD4+ T-cell count at diagnosis was 191/µl (range, 4-1022), 84 patients (97.7%) were on combination antiretroviral therapy (cART) at lymphoma diagnosis. In DLBCL patients, cox multivariate analysis showed that age ≥ 60 (HR = 2.251, 95%CI 1.122-4.516; p = 0.012), elevated LDH (HR = 4.452, 95%CI 1.027-19.297; p = 0.041) and received less than two cycles of chemotherapy (HR = 0.629, 95%CI 0.589-1.071; p = 0.012) were independent risk factors for adverse prognosis based on PFS. Age ≥ 60 (HR = 3.162, 95%CI 1.500-6.665; p = 0.002) and received less than two cycles of chemotherapy (HR = 0.524, 95%CI 0.347-0.791; p = 0.002) were also independent risk factor for adverse prognosis based on OS. In BL patients, cox multivariate analysis showed that elevated LDH and received less than two cycles of chemotherapy were independent risk factors for adverse prognosis. In the DLBCL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 12 months, respectively (p = 0.006). Median OS times were not reached and 36 months, respectively (p = 0.021). In the BL group, median PFS times in the received rituximab and no received rituximab groups were not reached and 4.8 months, respectively (p = 0.046). Median OS times were not reached and 10.1 months, respectively (p = 0.035). Overall, these data indicated that standardized anti-lymphoma therapy and rituximab administration were significantly associated with improved outcomes in patients with HIV-associated DLBCL and BL.

Generation and Release of OH Radicals from the Reaction of H2 O with O2 over Soot.

OH radicals in the air maintain the oxidizing power of the troposphere. A conventional view is that particulate matter (PM) in the atmosphere is a major sink of OH radicals, thereby lowering the oxidizing power of atmosphere in the event of high-level PM. By contrary, our joint experimental/theoretical study reveals a new mechanism for the generation of gaseous OH radicals by carbonaceous soot particles. We show that water and O2 react on carbonaceous surfaces and give rise to gaseous OH radicals under irradiation. With ample delocalized π electrons, carbonaceous surfaces enable the easy desorption of hydroxyl groups to produce gaseous OH radicals, evidenced by direct observation of the steady generation of OH radicals on a carbonaceous surface. Our results reveal a new chemical mechanism for the production of OH radicals.

Evaluation of the Efficacy of the Hospital Glycemic Management System for Patients with Malignant Tumors and Hyperglycemia.

OBJECTIVE: To explore the efficacy of the hospital glycemic management system with information integration in patients with malignant tumors and hyperglycemia. METHODS: Three hundred ninety-three patients diagnosed with malignant tumors with hyperglycemia and hospitalized in the non-endocrinology department of a specialized cancer hospital from March 2019 to November 2020 were recruited. All the patients were diagnosed and treated according to the clinical department and disease course. In total, 196 patients were divided into the control group, who received the conventional blood glucose management mode, and 197 patients were divided into the intervention group, who received the hospital glycemic management system with information integration. The average daily glucose levels were recorded before and after breakfast, lunch, and dinner, at bedtime and at night. The average glucose level, glucose compliance rate, hypoglycemia rate, hyperglycemia rate, glucose measurements per day, average number of hospitalization days and patient satisfaction were compared between the groups. RESULTS: In the intervention group, the average glucose level was significantly lower than that in the control group (P<0.05). The hyperglycemia and hypoglycemia rates in the intervention group were lower than those in the control group (P<0.05). The glucose compliance rate in the intervention group was higher than that in the control group (P<0.05). The highest blood glucose level in the intervention group was lower than that in the control group (P<0.05), and the lowest blood glucose level was higher than that in the control group (P<0.05). The glucose measurements per day in the intervention group were higher than those in the control group, and the average number of hospitalization days in the intervention group was lower than that in the control group (P<0.05). Patient satisfaction in the intervention group was higher than that in the control group (P<0.05). CONCLUSION: The hospital glycemic management system with information integration significantly improved the glycemic management of patients with malignant non-endocrine tumors and hyperglycemia, including their glucose level and glucose compliance rate, as well as patient satisfaction, and reduced the average number of hospitalization days and risk of hyperglycemia/hypoglycemia.

Measurement of tropospheric HO2 radical using fluorescence assay by gas expansion with low interferences.

An instrument to detect atmospheric HO2 radicals using fluorescence assay by gas expansion (FAGE) technique has been developed. HO2 is measured by reaction with NO to form OH and subsequent detection of OH by laser-induced fluorescence at low pressure. The system performance has been improved by optimizing the expansion distance and pressure, the influence factors of HO2 conversion efficiency are also studied. The interferences of RO2 radicals were investigated by determining the conversion efficiency of RO2 to OH during the measurement of HO2. The dependence of the conversion of HO2 on NO concentration was investigated, and low HO2 conversion efficiency was selected to realize the ambient HO2 measurement, where the conversion efficiency of RO2 derived by propane, ethene, isoprene and methanol to OH has been reduced to less than 6% in the atmosphere. Furthermore, no significant interferences from PM2.5 and NO were found in the ambient HO2 measurement. The detection limits for HO2 (S/N = 2) are estimated to 4.8 × 105 cm-3 and 1.1 × 106 cm-3 ( [Formula: see text] = 20%) under night and noon conditions, with 60 sec signal integration time. The instrument was successfully deployed during STORM-2018 field campaign at Shenzhen graduate school of Peking University. The concentration of atmospheric HOx radical and the good correlation of OH with j(O1D) was obtained here. The diurnal variation of HOx concentration shows that the OH maximum concentration of those days is about 5.3 × 106 cm-3 appearing around 12:00, while the HO2 maximum concentration is about 4.2 × 108 cm-3 appearing around 13:30.

miR-196b-5p-enriched extracellular vesicles from tubular epithelial cells mediated aldosterone-induced renal fibrosis in mice with diabetes.

INTRODUCTION: Aldosterone is a mediator of progressive renal disease, but the mechanisms for aldosterone-mediated renal impairment in mice with diabetes are not fully defined. METHODS: Aldosterone and/or mineralocorticoid receptor antagonist eplerenone were used to treat the db/db mice with diabetes. Proximal tubule epithelial cells (PTECs) and fibroblasts were cultured. Blood and kidney samples from patients with diabetes with or without diabetic kidney disease (DKD) were used to verify the findings from animals and cultured cells. RESULTS: We found that aldosterone promoted proteinuria and tubulointerstitial extracellular matrix (ECM) accumulation in db/db mice with diabetes while eplerenone mitigated the adverse effect of aldosterone. However, coculture of PTECs and fibroblasts found that when PTECs-derived extracellular vesicles (EVs) were taken up by fibroblasts, ECM production increased remarkably. Moreover, C57BL/6 mice injected with EVs from renal cortex of aldosterone-treated db/db mice showed increased ECM accumulation. Function of the ingredients of PTECs-derived EVs were analyzed, and RNAs were identified to be responsible for the EVs-induced fibroblast dysfunction. Furthermore, microRNA (miRNA) array analysis revealed that miR-196b-5p was the most remarkably increased miRNA in PTECs-derived EVs with aldosterone stimulation. Overexpression of miR-196b-5p in fibroblasts increased ECM production, accompanied by inhibition of the SOCS2 expression and enhanced STAT3 phosphorylation. In addition, plasma levels of miR-196b-5p was higher in patients with DKD as compared with patients without DKD and miR-196b-5p levels positively correlated with the albuminuria concentration. In kidney specimens from patients with diabetes, expression of miR-196b-5p, located mainly in PTECs, increased in patients with DKD as compared with the non-DKD. CONCLUSION: This study demonstrates the involvement of miR-196b-5p-EVs pathway as a novel mechanism in aldosterone-induced renal fibrosis in diabetes. EVs rich in miR-196b-5p mediate the crosstalk between PTECs and fibroblast during the development of renal fibrosis, which might be associated with STAT3/SOCO2 signaling pathway.

Serum cell-free DNA and progression of diabetic kidney disease: a prospective study.

AIMS: Cell-free DNA (cfDNA) is associated with diabetes and cardiovascular diseases. Our study was to evaluate whether serum cfDNA could predict the progression of diabetic kidney disease (DKD). METHODS: In this prospective study, a total of 160 patients with DKD were enrolled, and the kidney function was followed up by measurement of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio (UACR) for three consecutive years. At baseline, concentrations of serum cfDNA were measured. DKD progression was defined as two-continuous decrease in eGFR and changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at last follow-up. Regression models were used to analyze associations of serum cfDNA with the DKD progression. RESULTS: In total, 131 patients finished all the follow-up visits. At the end of the study, 64 patients showed decreased eGFR and 29 patients had changes of UACR from less than 300 mg/g at baseline to higher than 300 mg/g at follow-up. At baseline, the progression group had higher serum cfDNA levels than the non-progression group (960.49 (816.53, 1073.65) ng/mL vs 824.51 (701.34, 987.06) ng/mL, p=0.014). Serum cfDNA levels were significantly negatively associated with the 1.5-year eGFR change (r=-0.219 p=0.009) and 3-year eGFR change (r=-0.181, p=0.043). Multivariate logistic analyses showed that after adjustment of age, gender, body mass index, fast plasma glucose, smoking, triglycerides, total cholesterol, duration of diabetes, systolic blood pressure, diabetic retinopathy, eGFR, high sensitivity C-reactive protein, angiotensin receptor blocker/ACE inhibitor usage, with the increase of one SD of serum cfDNA levels, the risk of DKD progression increased by 2.4 times (OR, 2.46; 95% CI 1.84 to 4.89). CONCLUSION: Serum cfDNA is closely associated with DKD, and it might be a predictor of DKD progression in patients with type 2 diabetes.

A hydroxyl radical detection system using gas expansion and fast gating laser-induced fluorescence techniques.

An OH radical measurement instrument based on Fluorescence Assay by Gas Expansion (FAGE) has been developed in our laboratory. Ambient air is introduced into a low-pressure fluorescence cell through a pinhole aperture and irradiated by a dye laser at a high repetition rate of 8.5kHz. The OH radical is both excited and detected at 308nm using A-X(0,0) band. To satisfy the high efficiency needs of fluorescence collection and detection, a 4-lens optical system and a self-designed gated photomultiplier (PMT) is used, and gating is actualized by switching the voltage applied on the PMT dynodes. A micro channel photomultiplier (MCP) is also prepared for fluorescence detection. Then the weak signal is accumulated by a photon counter in a specific timing. The OH radical excitation spectrum range in the wavelength of 307.82-308.2nm is detected and the excited line for OH detection is determined to be Q1(2) line. The calibration of the FAGE system is researched by using simultaneous photolysis of H2O and O2. The minimum detection limit of the instrument using gated PMT is determined to be 9.4×105molecules/cm3, and the sensitivity is 9.5×10-7cps/(OH·cm-3), with a signal-to-noise ratio of 2 and an integration time of 60sec, while OH detection limit and the detection sensitivity using MCP is calculated to be 1.6×105molecules/cm3 and 2.3×10-6cps/(OH·cm-3). The laboratory OH radical measurement is carried out and results show that the proposed system can be used for atmospheric OH radical measurement.