Elevated NT-proBNP predicts unfavorable outcomes in patients with acute ischemic stroke after thrombolytic therapy.

OBJECTIVE: Few studies correlated n-terminal pro-brain natriuretic peptide (NT-proBNP) with early neurological deterioration (END) and prognosis of acute ischaemic stroke (AIS) patients with rt-PA intravenous thrombolysis. Therefore this study aimed to investigate the relationship between NT-proBNP and END, and prognosis after intravenous thrombolysis in patients with AIS. METHODS: A total of 325 patients with AIS were enrolled. We performed the natural logarithm transformation on the NT-proBNP [ln(NT-proBNP)]. Univariate and multivariate logistic regression analyses were performed to assess the relationship between ln(NT-proBNP) and END, and prognosis and receiver operating characteristic (ROC) curves were used to show the sensitivity and specificity of NT-proBNP. RESULTS: After thrombolysis, among 325 patients with AIS, 43 patients (13.2%) developed END. In addition, three months follow-up showed a poor prognosis in 98 cases (30.2%) and a good prognosis in 227 cases (69.8%). Multivariate logistic regression analysis showed that ln(NT-proBNP) was an independent risk factor for END (OR = 1.450,95%CI:1.072 ~ 1.963, P = 0.016) and poor prognosis at three months follow-up (OR = 1.767, 95%CI: 1.347 ~ 2.317, P < 0.001) respectively. According to ROC curve analysis, ln(NT-proBNP) (AUC 0.735, 95%CI: 0.674 ~0.796, P < 0.001) had a good predictive value for poor prognosis, with a predictive value of 5.12 and sensitivity and specificity of 79.59% and 60.35% respectively. When combined with NIHSS to predict END(AUC 0.718, 95%CI: 0.631 ~ 0.805, P < 0.001) and poor prognosis(AUC 0.780, 95%CI: 0.724 ~ 0.836, P < 0.001), the predictive value of the model is further improved. CONCLUSION: NT-proBNP is independently associated with END and poor prognosis in patients with AIS following intravenous thrombolysis and has a particular predictive value for END and poor prognosis.

Plasma exosomes from depression ameliorate inflammation-induced depressive-like behaviors via sigma-1 receptor delivery.

A growing body of studies indicated that exosomes are one of vital players in pathological process of neuropsychiatric diseases, but their role in major depressive disorder (MDD) remains poorly understood. Here we purified plasma exosomes from depression including lipopolysaccharide (LPS)-challenged depression, chronic restraint stress (CRS)-induced depression, MDD subjects, and from control mice or volunteers. The therapeutic effect of these exogenous exosomes was assessed utilizing behavioral tests and biochemical approaches in the LPS-caused depression or microglial BV2 cells. The expression of exosomal sigma-1 receptor (Sig-1R) was evaluated by western blotting. The role of Sig-1R in the biological function of exosomes was determined using Sig-1R knockout mice and HEK 293 cells. Our results revealed that injection of exosomes from depression models or patients rather than normal controls significantly ameliorated depressive-like behaviors, deficiency of BDNF expression and neuro-inflammation in LPS-challenged mice. In addition, co-culture with exosomes from depression models or patients instead of from controls prevented LPS-induced inflammation responses in microglial BV2 cells. Moreover, Sig-1R was demonstrated for the first time to significantly be enriched in exosomes from depression models or patients compared with that from normal controls. However, Sig-1R null exosomes no longer emerged antidepressant-like action in LPS-challenged mice. Thus, we demonstrated that plasma exosomes from depression exerted antidepressant-like effects in a Sig-1R dependent manner in the LPS-induced depression. This work improves our understanding of the exosomes in depression, suggesting a novel exosomes-based approach for MDD treatment.

White Matter Hyperintensity, Immediate Antihypertensive Treatment, and Functional Outcome After Acute Ischemic Stroke.

Background and Purpose- It remains unknown that whether white matter hyperintensity (WMH) severity influences the effect of antihypertensive treatment in acute ischemic stroke. We aimed to investigate the effects of early antihypertensive treatment on death and disability among patients with acute ischemic stroke according to WMH severities. Methods- This study was a secondary analysis of the data from CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). Severity of WMH was evaluated using Fazekas rating scale score among 303 participants with available magnetic resonance imaging data and was categorized into none-mild WMH (Fazekas score 0-2) and moderate-severe WMH (Fazekas score 3-6). Functional outcome was death or major disability (modified Rankin Scale score of ≥3) at 14 days or hospital discharge and within 3 months. Results- WMH severity was significantly associated with an increased risk of death or major disability. Each 1 score increase in Fazekas score was associated with an adjusted odds ratio (95% CI) of 1.25 (1.03-1.51) for 14 days or hospital discharge and 1.39 (1.12-1.72) for 3-month functional outcome. There were no significant interactions between antihypertensive treatment and WMH severity (both P>0.1) on functional outcome at 14 days or hospital discharge and within 3 months. The neutral effects of immediate antihypertensive treatment were observed both in patients with moderate-severe WMH and none-mild WMH. Conclusions- Participants with higher WMH burden had increased risk of death or major disability after acute ischemic stroke. Early antihypertensive treatment had a neutral effect on clinical outcomes among acute ischemic stroke patients with a variety of WMH severities. Registration- URL: https://www.clinicaltrials.gov; Unique identifier: NCT01840072.

Up-regulated lnc-lung cancer associated transcript 1 enhances cell migration and invasion in breast cancer progression.

Breast cancer remains a leading cause of tumor-related deaths in the world. The pathogenesis contributing to breast cancer progression has not been fully understood. Increasing evidence suggests that long noncoding RNA (lncRNA) is implicated in various kinds of malignant cancers, including breast cancer. In the study, we attempted to explore the expression and effects of lnc-lung cancer associated transcript 1 (LUCAT1) on breast cancer development. Our results indicated that the expression of lnc-LUCAT1 was highly up-regulated in breast cancer tissues and cell lines. Over-expression of lnc-LUCAT1 enhanced cell proliferation, migration and invasion in breast cancer cell lines. Moreover, lnc-LUCAT1 was found to be a target of miR-7-5p. There was a negative correlation between lnc-LUCAT1 and miR-7-5p. The reduction of miR-7-5p was required in the augmentation of breast cancer development induced by lnc-LUCAT1 over-expression. In addition, SOX2 acted as a target of miR-7-5p. SOX2 was an oncogene in breast cancer through promoting cell proliferation, migration and invasion. The in vivo study confirmed the role of lnc-LUCAT1 in promoting tumor growth, accompanied with down-regulated SOX2 expression, whereas up-regulated miR-7-5p. Collectively, the lnc-LUCAT1/miR-7-5p-SOX2 regulatory pathway might provide a new and effective therapeutic strategy to prevent breast cancer development.

Tim-3 promotes cell aggressiveness and paclitaxel resistance through NF-κB/STAT3 signalling pathway in breast cancer cells.

OBJECTIVE: Although T-cell immunoglobulin and mucin-domain containing molecule-3 (Tim-3) has been recognized as a promising target for cancer immunotherapy, its exact role in breast cancer has not been fully elucidated. METHODS: Tim-3 gene expression in breast cancer and its prognostic significance were analyzed. Associated mechanisms were then explored in vitro by establishing Tim-3-overexpressing breast cancer cells. RESULTS: In a pooled analysis of The Cancer Genome Atlas (TCGA) database, Tim-3 gene expression levels were significantly higher (P<0.001) in breast cancer tissue, compared with normal tissues. Tim-3 was a prognosis indicator in breast cancer patients [relapse-free survival (RFS), P=0.004; overall survival (OS), P=0.099]. Tim-3 overexpression in Tim-3low breast cancer cells promoted aggressiveness of breast cancer cells, as evidenced by enhanced proliferation, migration, invasion, tight junction deterioration and tumor-associated tubal formation. Tim-3 also enhanced cellular resistance to paclitaxel. Furthermore, Tim-3 exerted its function by activating the NF-κB/STAT3 signalling pathway and by regulating gene expression [cyclin D1 (CCND1), C-Myc, matrix metalloproteinase-1(MMP1), TWIST, vascular endothelial growth factor (VEGF) upregulation, concomitant with E-cadherin downregulation). Lastly, Tim-3 downregulated tight junction-associated molecules zona occludens (ZO)-2, ZO-1 and occludin, which may further facilitate tumor progression. CONCLUSIONS: Tim-3 plays an oncogenic role in breast cancer and may represent a potential target for antitumor therapy.

Association of PTPN1 polymorphisms with breast cancer risk: A case-control study in Chinese females.

BACKGROUND: Breast cancer (BC) risk, development, and prognosis were closely related to obesity, diabetes mellitus, and metabolic syndrome. Protein tyrosine phosphatase, non-receptor type 1 (PTPN1) located on chromosome 20q13, could negatively regulate insulin and leptin signaling. In this study, we determined the association of PTPN1 polymorphisms with BC risk. METHODS: We analyzed the distribution of 11 selected PTPN1 single nucleotide polymorphisms in Chinese female patients with BC (n = 953) and healthy controls (n = 963) based on a multicenter case-control study. The association of PTPN1 genotypes and haplotypes frequencies with BC risk were determined by logistic regression analysis. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), diabetes mellitus history, and fasting plasma glucose level. The eQTL (expression Quantitative Trait Loci) analysis for PTPN1 was conducted by GTEx database. RESULTS: There were significant differences between BC cases and control groups in menopausal status, number of births, and BMI. Four single nucleotide polymorphisms (SNPs; rs3215684, rs3787345, rs718049, and rs718050) decreased overall BC risk, and other seven SNPs showed no significant association with BC risk. In multivariate analysis, BMI and rs3215684 DT + DD genotype were identified as independent risk factors for BC, and mutated genotypes of rs3215684 were correlated with increased PTPN1 expression. There are no haplotypes showed different frequencies between cases and controls. In the stratified analysis, rs2206656 showed a significant association with decreased BC risk in the subgroup of BMI ≤ 24 kg/m 2 , while rs3215684 and rs718049 showed lower BC risk in the subgroup of WHR > 0.85. Seven SNPs showed lower BC risk in the subgroup with diabetes mellitus history and/or fasting plasma glucose level ≥ 7 mM, while rs754118 decreased BC risk in the subgroup of fasting plasma glucose level < 7 mM. CONCLUSION: Our findings suggest that PTPN1 SNPs associated with BC susceptibility in Chinese females, which also suggested a novel mechanism between obesity, diabetes mellitus, and BC risk.

CD21lo/medCD27+ proinflammatory B cells are enriched in breast cancer patients and promote antitumor T cell responses.

Breast cancer is a common malignancy and a major cause of death in women worldwide. The immunomodulatory role of B cells is being increasingly recognized in autoimmune diseases and cancers. In recent years, immunotherapeutic strategies that upregulate the patient's own antitumor T cell responses have shown promise in treating solid tumors and are being developed for breast cancer. In this study, we discovered that the B cells in breast cancer patients were enriched with interferon (IFN)-γ-expressing cells and presented high potency for IFN-γ production. These IFN-γ-expressing B cells were enriched in, but did not completely overlap with, the CD21lo/medCD27+IgM-IgD-IgG+IgA- B cell subset, which was consistent with IgG-expressing memory B cells. Compared to CD27+IgG- B cells, the CD27+IgG+ B cells expressed significantly higher IFN-γ expression. Given that B cells demonstrate important antigen-presenting function to T cells, we incubated CD27+IgG- B cells and CD27+IgG+ B cells with autologous CD4+ T cells. Compared to the CD4+ T cells that were incubated with CD27+IgG- B cells, the CD4+ T cells that were incubated with CD27+IgG+ B cells presented significantly higher TBX21 and lower FOXP3 expression, suggesting that the CD27+IgG+ B cells, but not the CD27+IgG- B cells, promoted Th1 and suppressed regulatory T cell responses. IFN-γ-expressing B cells were further enriched in the intratumoral environment of breast cancer patients. Together, we discovered that breast cancer patients presented an upregulation of IFN-γ-expressing proinflammatory B cells with the potency to promote Th1 responses.

Distinct Effects of Body Mass Index and Waist/Hip Ratio on Risk of Breast Cancer by Joint Estrogen and Progestogen Receptor Status: Results from a Case-Control Study in Northern and Eastern China and Implications for Chemoprevention.

BACKGROUND: Obesity is a consideration in the pharmacologic intervention for estrogen receptor (ER) positive (ER+) breast cancer risk. Body mass index (BMI) and waist/hip ratio (WHR) have demonstrated different effects on breast cancer risk in relation to estrogen receptor (ER) status, but the results have been inconsistent. Furthermore, the situation in Chinese women remains unclear. MATERIALS AND METHODS: We conducted a case-control study including 1,439 breast cancer cases in Northern and Eastern China. Both ER and progesterone receptor (PR) statuses were available for 1,316 cases. Associations between body size-related factors and breast cancer risk defined by receptor status were assessed by multiple polytomous unconditional logistic regression analysis. RESULTS: Body mass index and WHR were positively associated with overall breast cancer risk. Body mass index was positively associated with both ER+/PR positive (PR+) and ER negative (ER-)/PR negative(PR-) subtype risks, although only significantly for ER+/PR+ subtype. Waist-hip ratio was only positively correlated with ER-/PR- subtype risk, although independent of BMI. Body mass index was positively associated with risk of ER+/PR+ and ER-/PR- subtypes in premenopausal women, whereas WHR was inversely correlated with ER+/PR- and positively with ER-/PR- subtype risks. Among postmenopausal women, WHR >0.85 was associated with increased risk of ER-/PR- subtype. CONCLUSION: Both general and central obesity contribute to breast cancer risk, with different effects on specific subtypes. General obesity, indicated by BMI, is more strongly associated with ER+/PR+ subtype, especially among premenopausal women, whereas central obesity, indicated by WHR, is more specific for ER-/PR- subtype, independent of menopausal status. These results suggest that different chemoprevention strategies may be appropriate in selected individuals. IMPLICATIONS FOR PRACTICE: The results of this study suggest that general and central obesity may play different roles in different breast cancer subtypes, supporting the hypothesis that obesity affects breast carcinogenesis via complex molecular interconnections, beyond the impact of estrogens. The results also imply that different chemoprevention strategies may be appropriate for selected individuals, highlighting the need to be particularly aware of women with a high waist/hip ratio but normal body mass index. Given the lack of any proven pharmacologic intervention for estrogen receptor negative breast cancer, stricter weight-control measures may be advised in these individuals.

Differential regulation and function of tumor-infiltrating T cells in different stages of breast cancer patients.

Breast cancer survival was associated with higher frequencies of CD8(+) T cytotoxic T cells in infiltrating lymphocytes. On the other hand, the frequency of CD4(+)CD25(+)FoxP3(+) regulatory T cells was inversely correlated with clinical outcomes of breast cancer. The regulation and interaction of different types of tumor-infiltrating T cells in different stages of breast cancer patients are still unclear. In this study, we examined the functions and regulations of CD8(+) T cells and CD4(+)CD25(+)FoxP3(+) T cells from resected tumors from 12 stage I, 24 stage II, and 20 stage III untreated breast cancer patients. We found that tumor-infiltrating CD8(+) T cells from stage III patients were more refractory to T cell receptor (TCR) stimulation than those from stage I and stage II patients in terms of interferon gamma (IFN-γ) production and proliferation. On the other hand, tumor-infiltrating CD4(+)CD25(+)FoxP3(+) T cells had higher proliferation in stage III tumors than in stage I and stage II tumors. In addition, we found that tumor-infiltrating CD4(+)CD25(+) T cells can suppress CD8(+) T cell inflammation ex vivo. Altogether, our data demonstrated that stage III tumors in breast cancer patients had a more immunosuppressive microenvironment.

A prospective, multicentre, registry study of RECO in the endovascular treatment of acute ischaemic stroke.

The RECO is a novel endovascular treatment (EVT) device that adjusts the distance between two mesh segments to axially hold the thrombus. We organized this postmarket study to assess the safety and performance of RECO in acute ischaemic stroke (AIS) patients with large vessel occlusion (LVO). This was a single-arm prospective multicentre study that enrolled patients as first-line patients treated with RECO at 9 stroke centres. The primary outcome measures included functional independence at 90 days (mRS 0-2), symptomatic intracranial haemorrhage (sICH), time from puncture to recanalization and time from symptom onset to recanalization. The secondary outcome measures were a modified thrombolysis in cerebral infarction (mTICI) score of 2b or 3 after the first attempt and at the end of the procedure and the all-cause mortality rate within 90 days. From May 22, 2020, to July 30, 2022, a total of 268 consecutive patients were enrolled in the registry. The median puncture-to-recanalization time was 64 (IQR, 45-92), and the symptom onset-to-recanalization time was 328 min (IQR, 228-469). RECO achieved successful reperfusion (mTICI 2b-3) after the first pass in 133 of 268 patients (49.6%). At the end of the operation, 96.6% of the patients reached mTICI 2b-3, and 97.4% of the patients ultimately achieved successful reperfusion. Sixteen (7.2%) patients had sICH. A total of 132 (49.3%) patients achieved functional independence at 90 days, and the all-cause mortality rate within 90 days was 17.5%. In this clinical experience, the RECO device achieved a high rate of complete recanalization with a good safety profile and favourable 90-day clinical outcomes.Clinical trial registration: URL: https://www.clinicaltrials.gov/ ; Unique identifier: NCT04840719.

Clinical efficacy and biomarker analysis of neoadjuvant camrelizumab plus chemotherapy for early-stage triple-negative breast cancer: a experimental single-arm phase II clinical trial pilot study.

BACKGROUND: Triple-negative breast cancer (TNBC) is associated with a dismal prognosis. Immune checkpoint inhibitors have shown promising antitumor activity in neoadjuvant settings. This single-arm, phase II trial aimed to evaluate the efficacy and safety of camrelizumab plus chemotherapy as the neoadjuvant therapy (NAT) in early TNBC. METHODS: Patients received eight cycles of camrelizumab plus nonplatinum-based chemotherapy. The primary endpoint was total pathological complete response (pCR). Secondary endpoints included the breast pathological complete response (bpCR), adverse events (AEs). Multiomics biomarkers were assessed as exploratory objective. RESULTS: Twenty of 23 TNBC patients receiving NAT underwent surgery, with the total pCR rate of 65% (13/20) and bpCR rate of 70% (14/20). Grade ≥3 treatment-related AEs were observed in 14 (60.9%) patients, with the most common AE being neutropenia (65.2%). Tumor immune microenvironment was analyzed between pCR and non-pCR samples before and after the NAT. Gene expression profiling showed a higher immune infiltration in pCR patients than non-pCR patients in pre-NAT samples. Through establishment of a predictive model for the NAT efficacy, TAP1 and IRF4 were identified as the potential predictive biomarkers for response to the NAT. Gene set enrichment analysis revealed the glycolysis and hypoxia pathways were significantly activated in non-pCR patients before the NAT, and this hypoxia was aggravated after the NAT. CONCLUSION: Camrelizumab plus nonplatinum-based chemotherapy shows a promising pCR rate in early-stage TNBC, with an acceptable safety profile. TAP1 and IRF4 may serve as potential predictive biomarkers for response to the NAT. Aggravated hypoxia and activated glycolysis after the NAT may be associated with the treatment resistance.

Two-year follow-up of post-traumatic stress disorder symptoms in healthcare workers after the COVID-19 pandemic in China.

OBJECTIVES: This study aimed to conduct a 2-year follow-up of mental disorders in healthcare workers (HCWs) in a region of China outside the epidemic's core zone who happened to be directly or possibly exposed to persons with COVID-19. MATERIAL AND METHODS: A cognitive analysis scale was utilized in the evaluation the mental or emotional state of HCWs at Xuzhou Medical University's affiliated hospital in the city of Xuzhou, China (a non-core epidemic area) 2 years after the first assessment during the COVID-19 pandemic. A total of 165 HCWs were selected as the study subjects. In accordance to the exposure risk of COVID-19 patients, the subjects were separated into 2 categories: a group with a high risk HCW (HHCW) (HCWs working in COVID-19-positive wards; N = 91) and a group with a minimal risk HCW (LHCW) (HCWs who worked in wards without COVID-19 patients at the same hospital; N = 75). The clinical as well as demographic information of every HCWs were collected. RESULTS: The demographic data revealed significant differences in terms of occupation, remuneration, and selfless concerns amidst both categories (p < 0.05). There lacked a statistically notable difference in the occurrence of PTSD between the 2 groups. Data was analyzed for factors associated with PTSD, and the results showed that psychological resilience, job risk, and stress in the workplace were risk factors for PTSD. Additionally, the results of the logistic regression analysis showed that psychological resilience was a significant shared risk factor for PTSD in HCWs after the COVID-19 pandemic. CONCLUSIONS: The 2-year follow-up showed no statistical difference in the incidence of PTSD between the HHCW group and the LHCW group. Workplace stress, occupational hazards, and psychological resilience were the major contributing risk factors for PTSD in HCWs. Int J Occup Med Environ Health. 2023;36(3):324-32.

Comparison of the clinical value of MRI and plasma markers for cognitive impairment in patients aged ≥75 years: a retrospective study.

Background: Dementia has become the main cause of disability in older adults aged ≥75 years. Cerebral small vessel disease (CSVD) is involved in cognitive impairment (CI) and dementia and is a cause of vascular CI (VCI), which is manageable and its onset and progression can be delayed. Simple and effective markers will be beneficial to the early detection and intervention of CI. The aim of this study is to investigate the clinical application value of plasma amyloid ß1-42 (Aß42), phosphorylated tau 181 (p-tau181) and conventional structural magnetic resonance imaging (MRI) parameters for cognitive impairment (CI) in patients aged ≥75 years. Methods: We retrospectively selected patients who visited the Affiliated Hospital of Xuzhou Medical University and were clinically diagnosed with or without cognitive dysfunction between May 2018 and November 2021. Plasma indicators (Aß42 and p-tau181) and conventional structural MRI parameters were collected and analyzed. Multivariate logistic regression and receiver operator characteristic (ROC) curve were used to evaluate the diagnostic value. Results: One hundred and eighty-four subjects were included, including 54 cases in CI group and 130 cases in noncognitive impairment (NCI) groups, respectively. Univariate logistic regression analysis revealed that the percentages of Aß42+, P-tau 181+, and Aß42+/P-tau181+ showed no significant difference between the groups of CI and NCI (all P > 0.05). Multivariate logistic regression analysis showed that moderate/severe periventricular WMH (PVWMH) (OR 2.857, (1.365-5.983), P = 0.005), lateral ventricle body index (LVBI) (OR 0.413, (0.243-0.700), P = 0.001), and cortical atrophy (OR 1.304, (1.079-1.575), P = 0.006) were factors associated with CI. The combined model including PVWMH, LVBI, and cortical atrophy to detect CI and NCI showed an area under the ROC curve (AUROC) is 0.782, with the sensitivity and specificity 68.5% and 78.5%, respectively. Conclusion: For individuals ≥75 years, plasma Aß42 and P-tau181 might not be associated with cognitive impairment, and MRI parameters, including PVWMH, LVBI and cortical atrophy, are related to CI. The cognitive statuses of people over 75 years old were used as the endpoint event in this study. Therefore, it can be considered that these MRI markers might have more important clinical significance for early assessment and dynamic observation, but more studies are still needed to verify this hypothesis.

Development and validation of a nomogram for predicting internal mammary sentinel node metastasis in breast cancer patients.

OBJECTIVE: Internal mammary nodes are important in breast cancer prognosis, but their diagnosis is often missed in clinical practice, leading to inaccurate staging and treatment. We developed a validated nomogram to predict the presence of internal mammary sentinel nodes (IMSN) metastasis. METHODS: A total of 864 sequential IMSN biopsy procedures from a prospective studies database of 1505 cases were used for model development and validation. Multivariable logistic regression was performed on 519 sequential IMSN biopsy procedures from multi-center data between August 2018 and July 2022 to predict the presence of IMSN metastasis. A nomogram was developed based on the logistic regression model and subsequently applied to 345 sequential IMSN biopsy procedures from single-center data between November 2011 and July 2018. The model's discrimination was assessed using the area under the receiver operating characteristic curve. RESULTS: The overall frequency of IMSN metastasis was 17.0% in our study. A predictive model for IMSN metastasis was constructed using tumor size, tumor location, lymphovascular invasion, the number of positive axillary nodes (P < 0.05 for all variables in multivariate analysis), and histological grade (P < 0.05 only in univariate analysis). The nomogram was accurate, with a concordance index of 0.84 in the bootstrapping analysis and an area under the receiver operating characteristic curve of 0.80 in the validation population. CONCLUSION: Our nomogram provides an accurate and validated multivariable predictive model for estimating the individual likelihood of having IMSN metastasis. This may be useful for personalized treatment decisions regarding internal mammary radiotherapy in breast cancer patients.

Psychotherapy and Follow-Up in Health Care Workers After the COVID-19 Epidemic: A Single Center's Experience.

Objective: The present study aims to analysis the mental health of high-risk health care workers (HHCWs) and low-risk HCWs (LHCWs) who were respectively exposed to COVID-19 wards and non-COVID-19 wards by following up on mental disorders in HCWs in China for 6 months. Methods: A multi-psychological assessment questionnaire was used to follow up on the psychological status of HCWs in the Affiliated Hospital of Xuzhou Medical University in Xuzhou City (a non-core epidemic area) at 6 months after the first evaluation conducted during the COVID-19 epidemic. Based on the risk of exposure to COVID-19 patients, the HCWs were divided into two groups: high-risk HCWs, who worked in COVID-19 wards, and low-risk HCWs, who worked in non-COVID-19 wards. Results: A total of 198 HCWs participated in the study, and 168 questionnaires were selected for evaluation. Among them, 93 (55.4%) were in the HHCW group and 75 (44.5%) were in the LHCW group. Significant differences were observed in salary, profession, and altruistic behavior between the two groups (P < 0.05). There were no significant differences in the anxiety, depression, insomnia, or posttraumatic stress disorder (PTSD) scores between the two groups. Logistic regression revealed that work stress was a major joint risk factor for mental disorders in HCWs. Among all the HCWs, a total of 58 voluntarily participated in psychotherapy; the analysis showed a significant decrease in anxiety, depression, PTSD, work stress, and work risk after attending psychotherapy. There were also significant differences in positive and negative coping styles before and after psychotherapy. Conclusion: In the present follow-up, work stress was the major contributing factor to mental disorders in HCWs. Psychotherapy is helpful in terms of stress management and should be provided to first-line COVID-19 HCWs.

Associations between pericarotid fat density and image-based risk characteristics of carotid plaque.

OBJECTIVES: In this study, we aimed to evaluate the associations between pericarotid fat density (PFD) and various risk characteristics of carotid plaque. METHODS: We retrospectively evaluated consecutive patients who were subjected to both high-resolution MRI and carotid artery CT angiography CTA at our institution between January 2016 and April 2021. The section of the carotid artery with the most severe lumen stenosis was selected from each patient for analysis. Two separated regions of interest (ROI) (each with an area of 2.5 mm2 and located at least 1 mm from the outer margin of the carotid artery wall) were defined in the perivascular fat tissue. The mean value of PFD (mean HU) was measured on the plaque side and the same axial non-plaque side. Then, the bilateral difference (D-value HU) was calculated (plaque side mean HU minus non-plaque side mean HU). According to carotid plaque risk characteristics (American Heart Association VI type [AHA VI], intraplaque hemorrhage [IPH], thinning and/or rupture of the fibrous cap [TRFC], lipid-rich necrotic core [LRNC], and calcification [CA]), the associations between PFD and five different risk characteristic subgroups were analyzed. The Student's t-test, Mann-Whitney U test, and Chi-square test were used to compare differences between different risk subgroups. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of PFD for carotid plaque risk characteristics. P < 0.05 was considered statistically significant. RESULTS: A total of 71 eligible patients (mean age 61.25 ± 10.35 years, 57 male) were examined in this study. For the plaque side and the non-plaque side, the mean PFD values were -36.25 ± 20.65 HU and -66.87 ± 15.00 HU, respectively. In the non-AHA VI and AHA VI subgroups, the values for the mean HU of the plaque side were -49.50 ± 20.53 and -33.55 ± 19.78, respectively (P = 0.014). The D-value HU was higher for the AHA VI group compared to the non-AHA VI group (33.61 ± 16.72 vs. 15.91 ± 14.52, respectively; P = 0.001). Compared to the non-IPH subgroup, the IPH subgroup had a higher mean HU value for the plaque side (-47.68 ± 18.26 vs. -29.63 ± 19.16, respectively; P < 0.001) and a higher D-value HU (17.80 ± 13.27 vs. 38.03 ± 15.46, respectively; P < 0.001). Compared to the low risk non-TRFC subgroup, the TRFC subgroup had a higher D-value HU (24.51 ± 16.16 vs. 33.55 ± 17.65, respectively; P = 0.042). The D-value of PFD was found to be a significant predictor of both AHA VI classification (AUC: 0.79; SE: 64.41%; SP: 83.33%; P = 0.0001) and IPH (AUC: 0.83; SE: 88.89%; SP: 65.38%; P < 0.0001). CONCLUSION: Our study found that PFD was significantly associated with high risk AHA VI plaque characterization, IPH, and TRFC. Therefore, PFD has the potential to be used as an indirect clinical marker of plaque instability.

Single-Nucleotide Polymorphisms in LEP and LEPR Associated With Breast Cancer Risk: Results From a Multicenter Case-Control Study in Chinese Females.

BACKGROUND: Leptin (LEP) plays a physiological role through its specific receptor (LEPR) and is involved in the occurrence and development of breast cancer. Our current study aimed at determining the influence of single-nucleotide polymorphisms (SNPs) in the genes coding for LEP and LEPR on breast cancer risk. METHODS: In the present study, 963 breast cancer cases and 953 controls were enrolled. Five SNPs of LEP and two of LEPR were chosen to evaluate the correlation of selected SNPs with breast cancer susceptibility among women in northern and eastern China. Analyses were further stratified by body mass index (BMI), waist-hip rate (WHR), estrogen receptor, and progesterone receptor status. The expression patterns of risk variant-associated genes were detected by expression quantitative trait locus (eQTL) analysis with eQTLGen and The Cancer Genome Atlas database. RESULTS: There were significant differences between breast cancer cases and control groups in the menopausal status and family history of breast cancer. Two SNPs (rs1137101 and rs4655555) of the LEPR gene decreased overall breast cancer risk, and other five SNPs showed no significant association with breast cancer risk. rs1137101 (GA vs. GG; adjusted OR = 0.719, 95% CI = 0.578-0.894, p = 0.003) and rs4655555 (TT vs. AA; adjusted OR = 0.574, 95% CI = 0.377-0.873, p = 0.009) significantly decreased breast cancer risk after Bonferroni correction for multiple testing. In subgroup analyses, the GA and GA + AA genotypes of LEPR rs1137101 associated with decreased breast cancer risk in the subgroup of BMI ≤ 24 kg/m2 or WHR ≥ 0.85 after Bonferroni correction. Furthermore, we found that the expressions of rs4655555-associated gene LEPR and leptin receptor overlapping transcript (LEPROT) were upregulated in breast cancer tumor tissues compared with adjacent normal tissues, and a higher expression of LEPR in tumor tissues was correlated with poor prognosis of breast cancer patients using The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) data. CONCLUSION: Our study demonstrated that the polymorphisms rs1137101 and rs4655555 located in the LEPR gene decreased breast cancer risk in Chinese females, which might be a research-worthy bio-diagnostic marker and applied for early prediction and risk assessment of breast cancer.

Stroke incidence and cognitive outcomes of intracranial atherosclerotic stenosis: study protocol for a multicenter, prospective, observational cohort study.

Background: Intracranial atherosclerotic stenosis (ICAS) is one of the leading causes of stroke worldwide. Current diagnostic evaluations and treatments remain insufficient to assess the vulnerability of intracranial plaques and reduce the recurrence of stroke in symptomatic ICAS. On the other hand, asymptomatic ICAS is associated with an increased risk of cognitive impairment. The pathogenesis of ICAS related cognitive decline is largely unknown. The aim of SICO-ICAS study (stroke incidence and cognitive outcomes of ICAS) is to elucidate the pathophysiology of stroke and cognitive impairment in ICAS population, comprehensively evaluating the complex interactions among life-course exposure, genomic variation, vascular risk factors, cerebrovascular burden and coexisting neurodegeneration. Methods: SICO-ICAS is a multicenter, prospective, observational cohort study. We aim to recruit 3,000 patients with symptomatic or asymptomatic ICAS (>50% or occlusion) who will be followed up for ≥12 months. All participants will undergo pre-designed magnetic resonance imaging packages, blood biomarkers testing, as well as detailed cognitive domains assessment. All participants will undergo clinical visits every 6 months and telephone interviews every 3 months. The primary outcome measurement is ischemic stroke or cognitive impairment within 12 months after enrollment. Discussion: This study will establish a large prospective ICAS cohort, hopefully discover new biomarkers associated with vulnerable intracranial plaques, identify subjects at high risk for incident ischemic stroke or cognitive impairment, and eventually propose a precise diagnostic and treatment strategy for ICAS population. Trial Registration: Chinese Clinical Trials Register ChiCTR2200061938.

MiR-203 inhibits estrogen-induced viability, migration and invasion of estrogen receptor α-positive breast cancer cells.

[This retracts the article DOI: 10.3892/etm.2017.4828.].

Clinical epidemiological characteristics of nitrous oxide abusers: A single-center experience in a hospital in China.

PURPOSE: This study investigated the clinical epidemiological characteristics of nitrous oxide (N2 O) abusers in a hospital in China, which have not been systematically reported. METHODS: The characteristics of patients abusing N2 O who were examined and treated at the Affiliated Hospital of Xuzhou Medical University from January 2017 to December 2020 were analyzed. RESULTS: A total of 61 patients (average age: 21.7 ± 3.2 years; 42 male and 19 female) were enrolled; 60.7% of the patients had an education level of high school or lower, and most (59.0%) had no stable occupation. The mean exposure time was 8.5 ± 7.7 months (range: 1-36 months). Only 52.5% of the abusers reported the physician of the relevant exposure history at the first time of visiting the doctor. The main clinical type was mixed (49.2%). The most common clinical manifestation was distal limb numbness (80.3%). The most frequent outcome was peripheral neuropathy (59%) and subacute combined degeneration (36%). Serum homocysteine level was elevated in 67.5% (27/40) of the patients, while 44.4% (20/45) showed reduced vitamin B12. Note that 61% (22/36) showed abnormal signals in the posterior or lateral funiculus of the spinal cord, and 97% (31/32) of the patients showed peripheral nerve damage by electromyography. In all cases, symptoms were alleviated after halting N2 O intake and receiving nutritional neurotherapy. CONCLUSIONS: N2 O abuse can lead to nervous system damage, especially peripheral nerve and spinal cord damage. A full understanding of its clinical epidemiological characteristics is helpful for clinicians to make a timely and clear diagnosis.