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.

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.

[Expression levels of ubiquitin C-terminal hydrolase-L1 and serum glial fibrillary acidic protein and its clinical significance in patients with acute cerebral infarction].

OBJECTIVE: To determine expression levels of ubiquitin C-terminal hydrolase-L1 (UCH-L1) and serum glial fibrillary acidic protein (GFAP) in patients with acute cerebral infarction and their clinical significance.
 Methods: A total of 80 patients with acute cerebral infarction in Chongqing Cancer Hospital from January 2014 to February 2016 were enrolled as an observation group. Another 80 healthy people served as a control group. The expression levels of UCH-L1 and GFAP in the 2 groups were detected.
 Results: Sensibility and specificity for UCH-L1 and GFAP were 75.0%, 87.5% and 81.3%, 90.0%, respectively. Receiver operating characteristic curve areas of UCH-L1 and GFAP were 0.670 and 0.757, respectively. There were no significant significance in age, gender, drinking, smoke, diabetes, and hyperlipidemia in the 2 groups (P>0.05). High blood pressure rate in the observation group was higher than that in the control group (P<0.05). Spearson/Pearson analysis showed that serum UCH-L1 and GFAP levels were positively correlated with hypertension, but they were negatively correlated with sex, age, diabetes, hyperlipidemia, alcohol consumption, smoking, and other factors. General data at different time in the observation group was not statistically different (P>0.05). The expression levels of UCH-L1 and GFAP in the observation group was higher than that in the control group (P<0.05). UCH-L1 and GFAP levels at different time in the 2 groups were not statistically different (P>0.05). UCH-L1 and GFAP levels in the light, medium, and heavy groups were higher than those in the control group (P<0.05), while UCH-L1 and GFAP levels in the medium and heavy groups were higher than those in the light group (P<0.05). There was significant difference between levels of UCH-L1 or GFAP and infarction size at different time in the observation group (P<0.05). The results of Pearson correlation analysis showed that the levels of serum UCH-L1 and GFAP were positively correlated (r=0.634, P=0.001).
 Conclusion: The levels of serum UCH-L1 and GFAP are significantly increased at the early stage of acute cerebral infarction, and they have a certain correlation with the severity of cerebral infarction, which can provide a basis for early clinical diagnosis and treatment.

MSCs can be a double-edged sword in tumorigenesis.

Mesenchymal stem cells (MSCs) have been used to treat various diseases including Alzheimer's disease and cancer. In particular, the immunomodulatory function of MSCs plays a major role in cancer therapy using stem cells. However, MSCs exert promotive and inhibitory effects on cancer. The immunomodulatory effects of MSCs in the tumor microenvironment (TME) are ambiguous, which is the primary reason for the different outcomes of MSCs therapies for tumors. This review discusses the use of MSCs in cancer immunotherapy and their immunomodulatory mechanisms in cancers.

Long non-coding RNA small nucleolar RNA host gene 1 alleviates the progression of epilepsy by regulating the miR-181a/BCL-2 axis in vitro.

PURPOSE: Long non-coding RNAs (lncRNAs) have been reported to be involved in regulating epilepsy. The purpose of this study is to investigate the possibly regulatory mechanism of small nucleolar RNA host gene 1 (SNHG1) on epilepsy. METHODS: Quantitative real-time PCR was utilized to detect the expression of SNHG1, microRNA (miR)-181a, and B-cell lymphoma-2 (BCL-2). Through an enzyme-linked immunosorbent assay, the levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and cyclooxygenase-2 (COX-2) were determined. The viability and apoptosis of CTX-TNA2 cells were measured using MTT assay and flow cytometry analysis, respectively. Western blot assay was performed to analyze the protein levels of Bcl-2, BCL2-associated X, and Caspase-3. The relationships between miR-181a and SNHG1/BCL-2 were confirmed by the dual-luciferase reporter assay. RESULTS: SNHG1 expression was down-regulated in EP tissues and kainic acid (KA)-induced CTX-TNA2 cells. The apoptosis and release of inflammatory factors (TNF-α, IL-1ß, IL-6, and COX-2) in KA-induced CTX-TNA2 cells were suppressed by SNHG1 overexpression and promoted by miR-181a up-regulation. In addition, we confirmed that SNHG1 targeted miR-181a, whereas BCL-2 was a target gene of miR-181a. Negative correlations between SNHG1 and miR-181a, as well as miR-181a and BCL-2 were exhibited. Both the up-regulation of miR-181a and down-regulation of BCL-2 reversed the inhibiting effects of SNHG1 on apoptosis and inflammatory response of KA-induced CTX-TNA2 cells, and the promoting effect upon cell viability. CONCLUSIONS: SNHG1 alleviated the progression of EP by modulating the miR-181a/BCL-2 axis in vitro, thus SNHG1 could act as a possible therapeutic target for treating EP.

Use of Programmed Death Receptor-1 and/or Programmed Death Ligand 1 Inhibitors for the Treatment of Brain Metastasis of Lung Cancer.

The central nervous system (CNS) is regarded as an immune privileged environment; however, changes in the neuroimmunology paradigm have led to an increased interest in systematic immunotherapy in lung cancer therapy. The presence of the lymphatic system in the CNS as well as the physiological and biochemical changes in the blood-brain barrier in the tumor microenvironment suggests that immunocytes are fully capable of entering and exiting the CNS. Emerging clinical data suggest that inhibitors of programmed death receptor-1/programmed death ligand 1 (PD-1/PD-L1) can stimulate surrounding T cells and thus have antitumor effects in the CNS. For example, PD-1 antibody (pembrolizumab) monotherapy has displayed a 20-30% encephalic response rate in patients with brain metastases from malignant melanoma or non-small cell lung cancer. Combined application of nivolumab and ipilimumab anti-PD-1 and anti-cytotoxic T-lymphocyte-associated protein 4 showed an encephalic response rate of 55% in patients with brain metastases of melanoma. Further evidence is required to verify these response rates and identify the mechanisms of curative effects and drug tolerance. While regional treatments such as whole-brain radiosurgery, stereotactic radiosurgery, and brain surgery remain the mainstream, PD-1/PD-L1 inhibitors display potential decreased neurotoxic effects. To date, five drugs have been approved for use in patients with encephalic metastases of lung carcinoma: the anti-PD-1 drugs, pembrolizumab and nivolumab, and the anti-PD-L1 agents, atezolizumab, durvalumab, and avelumab. In recent years, clinical trials of inhibitors in combination with other drugs to treat brain metastasis have also emerged. This review summarizes the biological principles of PD-1/PD-L1 immunotherapy for brain metastasis of lung cancer, as well as ongoing clinical trials to explore unmet needs.

MicroRNA-351 Promotes the Proliferation and Invasion of Glioma Cells through Downregulation of NAIF1.

Despite the well-characterized expression profile of miR-351 in the neural system, its molecular mechanisms in glioma still remain elusive. Here we intended to assess the regulatory function of miR-351 on nuclear apoptosis-inducing factor 1 (NAIF1) and, thereby, modulation of cancerous behaviors of human glioma cell lines. Two human glioma cell lines (U87 and U251) and normal human astroglia (NHA) cell line were cultured. The cell lines were prepared and transfected with mimic, inhibitor, and negative controls (NCs) of miR-351, then MTT and wound healing assays were performed. We extracted the total protein for western blotting assay and isolated the total RNA for real-time PCR. The miR-351 expression was significantly decreased in U87 and U251 cell lines compared with the NHA cell line (P < 0.05). NAIF1 expression was significantly higher in glioma cell lines compared with the NHA cell line (P < 0.05). Moreover, the NAIF1 expression showed a negative correlation with miR-351 (P = 0.005, r = -0.522). Apoptosis was significantly decreased in both cell lines transfected with miR-351 mimics compared with the NC group at 72 and 96 h after transfection (P < 0.05) and significantly increased in the transfected group with miR-351 inhibitors compared with the NC group at 72 and 96 h after transfection (P < 0.05). According to our results, after 24 and 48 h, migration was increased in the mimic group compared with the miR-351 NC group and decreased in the inhibitory group compared with the miR-351 NC group in the U251 cell line. Our findings provide theoretical evidence that miR-351, which targets NAIF1, could be considered an important marker in the pathogenesis of glioma. Furthermore, miR-351 has valuable potential to serve as a new prognostic and diagnostic biomarker and could be considered a potential target for the treatment of this cancer in the near future.

Correction to: MicroRNA-351 Promotes the Proliferation and Invasion of Glioma Cells through Downregulation of NAIF1.

The original version of this article unfortunately contained mistakes in the Affiliation section.