PD-1-CD28-enhanced receptor and CD19 CAR-modified tumor-infiltrating T lymphocytes produce potential anti-tumor ability in solid tumors.

The limited expansion ability and functional inactivation of T cells within the solid tumor microenvironment are major problems faced during in the application of using tumor-infiltrating lymphocytes (TILs) in vivo. We sought to determine whether TILs carrying a PD-1-CD28-enhanced receptor and CD19 CAR could overcome this limitation and mediate tumor regression. First, anti-tumor effects of PD-1-CD28-enhanced receptor or CD19 CAR modified NY-ESO-1-TCR-T cells to mimic the TILs function (hereafter "PD-1-CD28-TCR-T" or "CD19 CAR-TCR-T" cells, respectively) were tested using the NY-ESO-1 over-expressed tumor cell line in vitro and in a tumor-bearing model. Furthermore, the safety and anti-tumor ability of S-TILs (TILs modified through transduction with a plasmid encoding the PD-1-CD28-T2A-CD19 CAR) were evaluated in vivo. PD-1-CD28-TCR-T cells showed a formidable anti-tumor ability that was not subject to PD-1/PD-L1 signaling in vivo. CD19 CAR-TCR-T cells stimulated with CD19+ B cells exhibited powerful expansion and anti-tumor abilities both in vitro and in vivo. Three patients with refractory solid tumors received S-TILs infusion. No treatment-related mortality was observed, and none of the patients experienced serious side effects. One patient with melanoma achieved a partial response, and two patients with colon or kidney cancer achieved long-term stable disease following S-TILs therapy. To the best of our knowledge, this is the first study describing the safety and efficacy of the adoptive transfer of autologous S-TILs to control disease in patients with advanced cancers, suggesting that S-TILs may be a promising alternative therapy for cancer.

Cascade Reactions Catalyzed by Gold Hybrid Nanoparticles Generate CO Gas Against Periodontitis in Diabetes.

The treatment of diabetic periodontitis poses a significant challenge due to the presence of local inflammation characterized by excessive glucose concentration, bacterial infection, and high oxidative stress. Herein, mesoporous silica nanoparticles (MSN) are embellished with gold nanoparticles (Au NPs) and loaded with manganese carbonyl to prepare a carbon monoxide (CO) enhanced multienzyme cooperative hybrid nanoplatform (MSN-Au@CO). The Glucose-like oxidase activity of Au NPs catalyzes the oxidation of glucose to hydrogen peroxide (H2O2) and gluconic acid，and then converts H2O2 to hydroxyl radicals (•OH) by peroxidase-like activity to destroy bacteria. Moreover, CO production in response to H2O2, together with Au NPs exhibited a synergistic anti-inflammatory effect in macrophages challenged by lipopolysaccharides. The underlying mechanism can be the induction of nuclear factor erythroid 2-related factor 2 to reduce reactive oxygen species, and inhibition of nuclear factor kappa-B signaling to diminish inflammatory response. Importantly, the antibacterial and anti-inflammation effects of MSN-Au@CO are validated in diabetic rats with ligature-induced periodontitis by showing decreased periodontal bone loss with good biocompatibility. To summarize, MSN-Au@CO is fabricate to utilize glucose-activated cascade reaction to eliminate bacteria, and synergize with gas therapy to regulate the immune microenvironment, offering a potential direction for the treatment of diabetic periodontitis.

Allogeneic CAR-T cells with of HLA-A/B and TRAC disruption exhibit promising antitumor capacity against B cell malignancies.

BACKGROUND: Although chimeric antigen receptor T (CAR-T) cells have been proven to be an effective way of treating B cell malignancies, a lot of patients could not benefit from it because of failure in CAR-T cell manufacturing, disease progression, and unaffordable price. The study aimed to explore universal CAR-T cell products to extend the clinical accessibility. METHODS: The antitumor activity of CRISPR/Cas9-edited allogeneic anti-CD19 CAR-T (CAR-T19) cells was assessed in vitro, in animal models, and in patients with relapsed/refractory (R/R) acute B cell lymphoblastic leukemia (B-ALL) or diffuse large B cell lymphoma. RESULTS: B2M-/TRAC- universal CAR-T19 (U-CAR-T19) cells exhibited powerful anti-leukemia abilities both in vitro and in animal models, as did primary CD19+ leukemia cells from leukemia patients. However, expansion, antitumor efficacy, or graft-versus-host-disease (GvHD) was not observed in six patients with R/R B cell malignancies after U-CAR-T19 cell infusion. Accordingly, significant activation of natural killer (NK) cells by U-CAR-T19 cells was proven both clinically and in vitro. HLA-A-/B-/TRAC- novel CAR-T19 (nU-CAR-T19) cells were constructed with similar tumoricidal capacity but resistance to NK cells in vitro. Surprisingly, robust expansion of nU-CAR-T19 cells, along with rapid eradication of CD19+ abnormal B cells, was observed in the peripheral blood and bone marrow of another three patients with R/R B-ALL. The patients achieved complete remission with no detectable minimal residual disease 14 days after the infusion of nU-CAR-T19 cells. Two of the three patients had grade 2 cytokine release syndrome, which were managed using an IL-6 receptor blocker. Most importantly, GvHD was not observed in any patient, suggesting the safety of TRAC-disrupted CAR-T cells generated using the CRISPR/Cas9 method for clinical application. CONCLUSIONS: The nU-CAR-T19 cells showed a strong response in R/R B-ALL. nU-CAR-T19 cells have the potential to be a promising new approach for treating R/R B cell malignancies.

The correlation between the main and minor lesions of synchronous multiple gastric neoplasms assessed gastroscopically and microscopically.

BACKGROUND: Patients with early gastric cancer (EGC) are at high risk of developing synchronous multiple gastric neoplasms (SMGNs) after undergoing endoscopic submucosal dissection (ESD). However, most previous studies have had small sample sizes, and few have focused on association studies. AIMS: This study aimed to analyze the associations between SMGN lesion data from patients with EGC treated with ESD and their correlation coefficients. METHODS: The clinical ESD data from two hospitals from January 2008 to January 2021 were retrospectively analyzed. The main lesions were defined as those with a significant depth of infiltration. The larger tumor diameter was considered the main lesion if the lesions had the same infiltration depth. RESULTS: Of the 1013 post-ESD cases examined, 95 cases (223 lesions) had SMGN, and 25 patients had more than three lesions. For the correlation analysis, 190 lesions were included. The study revealed a similarity in pathological type between main and minor lesions (rs = 0.37) and a positive correlation in infiltration depth (rs = 0.58). The mean diameter sizes of the main and minor lesions were 20.7 ± 8.3 mm and 13.1 ± 6.4 mm, respectively, with statistically significant differences (P < 0.001). A linear correlation was observed between the diameter size and a linear regression model was constructed, producing r = 0.38 [95% confidence interval (CI) 0.19-0.54], b = 0.29 (95% CI 0.14-0.44), t = 3.94, P < 0.001]. A correlation was identified between the vertical distribution of the main and minor lesions, the horizontal distribution, and the gross endoscopic morphology (ϕc = 0.25, P = 0.02; ϕc = 0.32, P < 0.001; ϕc = 0.60, P < 0.001). CONCLUSIONS: The correlation coefficients for microscopic characteristics were higher than those for gastroscopy. There is a significant positive correlation between the main and minor lesions regarding pathological stage and depth of infiltration, respectively. The spatial distribution of the lesions and the gastroscopic morphology were similar.

The m6A Reader YTHDC2 Suppresses Lung Adenocarcinoma Tumorigenesis by Destabilizing MRPL12.

N6-methyladenosine (m6A) is the most common posttranscriptional RNA modification and plays significant roles in physiological and pathological progression. Here, we probed the functions and mechanism of the m6A reader YTH domain containing 2 (YTHDC2) in Lung Adenocarcinoma (LUAD) tumorigenesis. Levels of genes and proteins of YTHDC2 and Mitochondrial ribosomal protein L7/L12 (MRPL12) were assayed by quantitative real-time polymerase chain reaction, western blotting and Immunohistochemistry (IHC) analyses. In vitro analysis was conducted using 5-ethynyl-2'-deoxyuridine (EdU), colony formation, flow cytometry, and transwell assays, respectively. In vivo assay was performed by using the mouse lung adenocarcinoma model. The methylated RNA immunoprecipitation (MeRIP) assay was used to detect the m6A modification profile of MRPL12 mRNA. YTHDC2 was lowly expressed in lung adenocarcinoma tissues and cells. Overexpression of YTHDC2 suppressed the proliferation, invasion and migration of lung adenocarcinoma cells, but induced cell apoptosis. As expected, forced expression of YTHDC2 hindered lung adenocarcinoma tumor growth in vivo. Mechanistically, YTHDC2 preferentially bound to m6A-modified MRPL12 mRNA and destabilized its expression. MRPL12 was highly expressed in lung adenocarcinoma tissues and cells, and MRPL12 silencing repressed the growth and mobility of lung adenocarcinoma cells. Moreover, MRPL12 upregulation attenuated the anticancer activity of YTHDC2 in lung adenocarcinoma cells. In vivo assay also showed YTHDC2 suppressed tumor growth in the lung adenocarcinoma mouse model via downregulating MRPL12. The m6A reader YTHDC2 repressed lung adenocarcinoma tumorigenesis by destabilizing MRPL12 in an m6A-dependent manner.

The safety and anti-tumor effect of multiple peptides-pulsed dendritic cells combined with induced specific cytotoxic T lymphocytes for patients with solid tumors.

Objective: The aim of this study was to explore the safety and efficacy of multiple peptide-pulsed autologous dendritic cells (DCs) combined with cytotoxic T lymphocytes (CTLs) in patients with cancer. Methods: Five patients diagnosed with cancer between November 2020 and June 2021 were enrolled and received DC-CTLs therapy. Peripheral blood was collected and antigenic peptides were analyzed. The phenotype and function of DC-CTLs and the immune status of patients were detected using flow cytometry or IFN-γ ELISPOT analysis. Results: DCs acquired a mature phenotype and expressed high levels of CD80, CD86, CD83, and HLA-DR after co-culture with peptides, and the DC-CTLs also exhibited high levels of IFN-γ. Peripheral blood mononuclear cells from post-treatment patients showed a stronger immune response to peptides than those prior to treatment. Importantly, four of five patients maintained a favorable immune status, of which one patient's disease-free survival lasted up to 28.2 months. No severe treatment-related adverse events were observed. Conclusion: Our results show that multiple peptide-pulsed DCs combined with CTLs therapy has manageable safety and promising efficacy for cancer patients, which might provide a precise immunotherapeutic strategy for cancer.

The value of FT4/TSH ratio in the differential diagnosis of Graves' disease and subacute thyroiditis.

Objective: To explore the value of the FT4/TSH ratio in the etiological diagnosis of newly diagnosed patients with thyrotoxicosis. Methods: The retrospective study was conducted on 287 patients with thyrotoxicosis (122 patients with subacute thyroiditis and 165 patients with Graves' disease) and 415 healthy people on their first visit to our hospital. All patients underwent thyroid function tests including the measurement of T3, T4, FT3, FT4, TSH, T3/TSH, and T4/TSH. The receiver operating characteristic (ROC) curve was employed to evaluate the value of FT4/TSH in the differential diagnosis of Graves' disease and subacute thyroiditis, and compared with other related indicators. Results: The area under the curve of FT4/TSH for diagnosing Graves' disease and thyroiditis was 0.846, which was significantly larger than the area under the curve of T3/T4 ratio (P< 0.05) and FT3/FT4 ratio (P< 0.05). When the cut-off value of the FT4/TSH ratio was 5731.286 pmol/mIU, the sensitivity was 71.52%, the specificity was 90.16%, the positive predictive value was 90.77% and the negative predictive value was 70.06%. The diagnostic accuracy was 79.44%. Conclusion: FT4/TSH ratio can be used as a new reference index for the differential diagnosis of thyrotoxicosis.

[Health Risk Assessment and Environmental Benchmark of Heavy Metals in Cultivated Land in Wanjiang Economic Zone].

Focusing on the cultivated land in Wanjiang Economic Zone, 338 sets of soil samples of rice, wheat, and their roots were collected; the concentrations of five heavy metals (As, Cd, Cr, Hg, and Pb) were determined; the soil-crop pollution characteristics were evaluated using the method of geo-accumulation index and comprehensive evaluation; the human health risk of ingesting heavy metals from crops was assessed; and the soil environmental reference value of the regional cultivated land was inverted based on the species sensitive distribution model (SSD). The results showed that in the study area, the soil of rice and wheat was polluted by heavy metals (As, Cd, Cr, Hg, and Pb) in varying degrees, among which Cd was the primary pollution factor of rice, with the over-standard rate of 13.33%, and Cr was the main over-standard factor of wheat, with the over-standard rate of 11.32%. The cumulative index showed that the percentage of Cd pollution in rice was 80.7%, and that in wheat was 35.85%. Contrary to the high pollution level of soil heavy metals, only 17.19% and 7.55% of Cd in rice and wheat exceeded the national food safety limit, and the accumulation capacity of the heavy metal Cd was rice>wheat. The health risk assessment indicated that heavy metals had high non-carcinogenic risk and unacceptable carcinogenic risk to adults and children in this study. The carcinogenic risk of rice intake was higher than that of wheat, and the health risk of children was higher than that of adults. SSD inversion showed that the reference values of As, Cd, Cr, Hg, and Pb in paddy soil in the study area were an HC5 of 6.24, 0.13, 258.27, 0.12, and 53.61 mg·kg-1 and an HC95 of 68.81, 5.71, 1068.92, 0.80, and 174.22 mg·kg-1, respectively. The reference values of As, Cd, Cr, Hg, and Pb in wheat soil HC5 were 32.99, 0.04, 271.14, 0.09, and 47.53 mg·kg-1, and the values of HC95 were 225.28, 0.71, 998.58, 1.43, and 241.99 mg·kg-1, respectively. The reverse analysis showed that the HC5 of heavy metals in rice and wheat were lower than the soil risk screening values in the current standard to varying degrees. The current soil standard had loosened for the evaluation results of this region.

Intravascular Large B-Cell Lymphoma Identified by PET/CT.

ABSTRACT: Intravascular large B-cell lymphoma is a rare subtype of extranodal invasive non-Hodgkin lymphoma, and the diagnosis is challenging. Here we report findings of 18 F-FDG PET/CT study in a case of intravascular large B-cell lymphoma invading bilateral lungs and kidneys in a 63-year-old woman. The PET/CT images showed diffuse increased FDG uptake in bilateral lungs and kidneys. Unexpectedly, there was no abnormal density on the CT images. The 18 F-FDG PET/CT seems to be valuable and sensitive in the diagnosis of intravascular large B-cell lymphoma.

[Heavy Metal Pollution Characteristics and Health Risk Assessment of Soil-crops System in Anhui Section of the Yangtze River Basin].

In order to explore the pollution characteristics and health risks of heavy metals in a soil-crop system in the Anhui section of the Yangtze River basin, a total of 338 groups of soil samples from rice, wheat, and their roots were collected, and the contents of eight types of heavy metals were determined. Additionally, the pollution index method, potential ecological hazard, multivariate statistical analysis, and health risk were used to evaluate the heavy metal content in rice and wheat root soil. The results showed that Cd, Cu, Cr, and Ni in the soil had an obvious accumulation effect, and the pollution of rice root soil was more serious than that of wheat soil. The potential ecological risk was mild to moderate, which mainly came from the elements Cd and Hg. Multivariate statistical analysis showed that Cu, Pb, Zn, and Cd were industrial sources and agricultural sources; Cr and Ni were natural sources; and As and Hg were agricultural sources. The absorption and enrichment intensity of heavy metals by rice was in the order of Cd>Zn>Cu>Hg>Ni>As>Cr=Pb, and those in wheat were ordered as Zn>Cd>Cu>Hg>Ni>As=Pb>Cr. The root soil heavy metal health risk assessment indicated that oral intake was the main exposure route of non-carcinogenic risk, and children were more vulnerable to heavy metal pollution. Non-carcinogenic risk assessment showed that wheat root soil posed non-carcinogenic risk to children but no carcinogenic risk. Intake of rice and wheat had some degree of non-carcinogenic risk and unacceptable carcinogenic risk for both adults and children.

Solitary Scapular Metastasis as the First Presentation of Prostate Adenocarcinoma Identified on 99mTc-MDP SPECT/CT.

ABSTRACT: Metastases of prostate carcinoma in the skeleton are usually multiple. Solitary metastasis in appendicular skeleton is extremely rare. We present bone scan findings of solitary scapular metastasis from prostate adenocarcinoma as the initial presentation of his malignancy in a 62-year-old man. The 99mTc-MDP SPECT/CT demonstrated intense activity in the coracoid process of left scapula, whereas the tracer uptakes in other bones were not typical of metastases. The subsequent pathological results of the punctured left scapula confirmed as metastasis from prostate adenocarcinoma.

Adjuvant cytokine-induced killer cell immunotherapy improves long-term survival in patients with stage I-II non-small cell lung cancer after curative surgery.

BACKGROUND AIMS: Non-small cell lung cancer (NSCLC) remains the most common cancer worldwide, with an annual incidence of around 1.3 million. Surgery represents the standard treatment in early-stage NSCLC when feasible. However, because of cancer recurrence, only approximately 53% of patients with stage I and II NSCLC survive 5 years after radical surgery. The authors performed a retrospective study to investigate the impact of cytokine-induced killer (CIK) cell immunotherapy on the long-term survival of patients with stage I-II NSCLC after curative resection. METHODS: Fifty-seven patients with NSCLC were included in the study, with 41 and 16 in the control and CIK groups, respectively. Clinical characteristics were compared using a t-test and χ2 test. Survival analysis of patients with NSCLC was performed using the Kaplan-Meier method. The phenotypes and anti-tumor functions of CIK cells were evaluated by flow cytometry. RESULTS: Patients in the CIK group exhibited significantly longer overall survival (OS) and better disease-free survival (DFS) than those in the control group. Subgroup analysis indicated that patients with a higher risk of recurrence benefited more from CIK treatment and attained longer OS and DFS compared with those in the control group. No severe adverse events related to CIK treatment occurred. CIK cells contained a higher proportion of CD3+CD56+ natural killer (NK) T cells and CD3+ and CD8+ T cells and a lower proportion of CD3-CD56+ NK cells compared with peripheral blood mononuclear cells. CIK cells exhibited potent tumor-killing ability, with longer contact times with tumor cells and a greater number of cells exposed to tumor cells. CONCLUSIONS: The authors' data suggest that adjuvant CIK cell therapy is a safe and effective therapeutic strategy for improving OS and DFS in patients with stage I-II NSCLC after curative resection.

Primary Aortic Epithelioid Angiosarcomas With Metastatic Disease Detected by 18F-FDG PET/CT.

ABSTRACT: Epithelioid angiosarcoma in the aortic arch with metastatic disease is extremely rare. We report a case of 63-year-old man with suspected bone metastases who underwent 18F-FDG PET/CT for seeking the potential primary tumor. PET/CT demonstrated intense FDG uptake in the aortic arch with multiple FDG-avid lesions involving the lung, lymph nodes, and bones. Finally, the diagnosis of primary aortic epithelioid angiosarcomas with metastatic disease was confirmed.

Retinoic acid induces differentiation of cochlear neural progenitor cells into hair cells / O ácido retinoico induz a diferenciação das células progenitoras neurais cocleares em células ciliadas

Abstract Introduction: Inner ear progenitor cells have the potential for multi-directional differentiation. Retinoic acid is an important requirement for the development of the inner ear. Blocking the Curtyr's retinoic acid signaling pathway can significantly reduce the number of hair cells. Therefore, we believe that retinoic acid may induce the regeneration of inner ear hair cells. Objective: To investigate whether the cochlear neural progenitor cells maintain the characteristics of stem cells during recovery and subculture, whether retinoic acid can induce cochlear neural progenitor cells into hair cells in vitro, and whether retinoic acid promotes or inhibits the proliferation of cochlear neural progenitor cells during differentiation. Methods: Cochlear neural progenitor cells were cultured and induced in DMEM/F12 + RA (10−6M) and then detected the expressions of hair cell markers (Math1 and MyosinVIIa) by immunofluorescence cytochemistry and realtime-polymerase chain reaction, and the proliferation of cochlear neural progenitor cells was detected by Brdu. Results: The nestin of cochlear neural progenitor cells was positively expressed. The ratios of Math1-positive cells in the control group and experimental group were 1.5% and 63%, respectively; the ratios of MyosinVIIa-positive cells in the control group and experimental group were 0.96% and 56%, respectively (p <0.05). The ratios of Brdu+-labeled cells in retinoic acid group, group PBS, and group FBS were 20.6%, 29.9%, and 54.3%, respectively; however, the proliferation rate in the experimental group decreased. Conclusion: Retinoic acid can promote cochlear neural progenitor cells to differentiate into the hair cells.

Resumo Introdução: As células progenitoras da orelha interna têm potencial para diferenciação multidirecional. O ácido retinoico é uma condição importante para o desenvolvimento da orelha interna. O bloqueio da via de sinalização do ácido retinoico no órgão de Corti pode reduzir significativamente o número de células ciliadas. Portanto, acreditamos que o ácido retinoico pode induzir a regeneração das células ciliadas do ouvido interno. Objetivo: Investigar se as células progenitoras neurais cocleares mantêm as características das células-tronco durante a recuperação e subcultura, se o ácido retinoico pode induzir a transformação de células progenitoras neurais cocleares em células ciliadas in vitro e se o ácido retinoico promove ou inibe a proliferação das células progenitoras durante a diferenciação. Método: As células progenitoras neurais cocleares foram cultivadas e induzidas em DMEM/F12+AR (106M) e, então, foram detectadas as expressões de marcadores das células ciliadas (Math1 e Myosin?a) com o uso de citoquímica por imunofluorescência e real time -polymerase chain reaction e a proliferação de células progenitoras neurais cocleares foi detectada pelo teste Brdu. Resultados: A nestina das células progenitoras neurais cocleares foi expressa positivamente. As proporções de células positivas para Math1 no grupo controle e no grupo experimental foram 1,5% e 63%, respectivamente; as proporções de células positivas para Myosin?a no grupo controle e no grupo experimental foram de 0,96% e 56%, respectivamente (p <0,05). As proporções de células marcadas com Brdu+ no grupo ácido retinoico, grupo PBS e grupo FBS foram de 20,6%, 29,9% e 54,3%, respectivamente; no entanto, a taxa de proliferação no grupo experimental diminuiu. Conclusões: O ácido retinoico pode promover a diferenciação das células progenitoras neurais cocleares em células ciliadas.

Same-day single-dose vs large-volume split-dose regimens of polyethylene glycol for bowel preparation: A systematic review and meta-analysis.

BACKGROUND: Split-dose regimens (SpDs) of 4 L of polyethylene glycol (PEG) have been established as the "gold standard" for bowel preparation; however, its use is limited by the large volumes of fluids required and sleep disturbance associated with night doses. Meanwhile, the same-day single-dose regimens (SSDs) of PEG has been recommended as an alternative; however, its superiority compared to other regimens is a matter of debate. AIM: To compare the efficacy and tolerability between SSDs and large-volume SpDs PEG for bowel preparation. METHODS: We searched MEDLINE/PubMed, the Cochrane Library, RCA, EMBASE and Science Citation Index Expanded for randomized trials comparing (2 L/4 L) SSDs to large-volume (4 L/3 L) SpDs PEG-based regimens, regardless of adjuvant laxative use. The pooled analysis of relative risk ratio and mean difference was calculated for bowel cleanliness, sleep disturbance, willingness to repeat the procedure using the same preparation and adverse effects. A random effects model or fixed-effects model was chosen based on heterogeneity analysis among studies. RESULTS: A total of 18 studies were included. There was no statistically significant difference of adequate bowel preparation (relative risk = 0.97; 95%CI: 0.92-1.02) (14 trials), right colon Boston Bowel Preparation Scale (mean difference = 0.00; 95%CI: -0.04, 0.03) (9 trials) and right colon Ottawa Bowel Preparation Scale (mean difference = 0.04; 95%CI: -0.27, 0.34) (5 trials) between (2 L/4 L) SSDs and large-volume (4 L/3 L) SpDs, regardless of adjuvant laxative use. The pooled analysis favored the use of SSDs with less sleep disturbance (relative risk = 0.52; 95%CI: 0.40, 0.68) and lower incidence of abdominal pain (relative risk = 0.75; 95%CI: 0.62, 0.90). During subgroup analysis, patients that received low-volume (2 L) SSDs showed more willingness to repeat the procedure using the same preparation than SpDs (P < 0.05). No significant difference in adverse effects, including nausea, vomiting and bloating, was found between the two arms (P > 0.05). CONCLUSION: Regardless of adjuvant laxative use, the (2 L/4 L) SSD PEG-based arm was considered equal or better than the large-volume (≥ 3 L) SpDs PEG regimen in terms of bowel cleanliness and tolerability. Patients that received low-volume (2 L) SSDs showed more willingness to repeat the procedure using the same preparation due to the low-volume fluid requirement and less sleep disturbance.

Hyperparathyroidism Caused by Coexisting Parathyroid Hyperplasia and Unilateral Bifocal Parathyroid Carcinoma.

ABSTRACT: The coexistence of parathyroid hyperplasia and carcinoma is uncommon. Here we report findings of 99m Tc-sestamibi SPECT/CT study in a case of unilateral bifocal parathyroid carcinoma coexisting with parathyroid hyperplasia in a 49-year-old man. The images showed 4 foci of elevated activity around the thyroid. Histopathology confirmed the 2 lesions of the left side as parathyroid hyperplasia and the other 2 lesions of the right side as parathyroid carcinoma.

Association of BIRC5 Gene Polymorphism with the Collateral Circulation and Severity of Large Artery Atherosclerotic Stroke.

Objectives: The collateral circulation near the cerebral artery occlusion can contribute to the relief of the symptoms and signs of stroke. Genetic factors play a decisive role in the difference in collateral circulation. Survivin, encoded by the baculoviral inhibitor of apoptosis (IAP) repeat-containing 5 gene (BIRC5), plays an important role in maintaining long-term endothelial integrity and homeostasis and as an angiogenic factor in the treatment of vascular diseases. We hypothesized that genetic variations in the BIRC5 gene may contribute to severity by influencing the collateral circulation. This study aimed at examining how the polymorphism of the BIRC5 gene correlated with the collateral circulation and severity of large artery atherosclerotic stroke. Methods: This study enrolled 428 patients with large artery atherosclerotic stroke. There are no statistical differences in age, sex, social behavior, such as smoking and drinking, between the groups classified by the collateral circulation and by the severity of stroke (P > 0.01). Direct sequencing was performed for the genotyping of single nucleotide polymorphism (SNP) of BIRC5 (rs2071214). The enrolled patients were divided into several subgroups based on the collateral flow grading system from the American Society of Interventional and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR), the results of the National Institutes of Health Stroke Survey (NIHSS) (6 as a threshold), and the score of the modified Rankin scale (mRS) (for the prediction of prognosis, 2 as a threshold). Differences among subgroups were identified through logistic regression. Results: The analysis of collateral circulation revealed the significant correlation of SNP of rs2071214 with the development of poor collateral circulation of large artery atherosclerotic stroke in the additive model (GG vs. AA, odds ratio (OR) = 3.592, 95% confidence interval (CI) = 1.410-9.150, and P=0.007) and the recessive model (GG vs. AA/GA, OR = 3.313, 95% CI = 1.420-7.727, and P=0.006). The analysis of stroke severity exposed the significant role of the SNP of rs2071214 in increasing stroke severity in the dominant model (GA/GG vs. AA, OR = 1.658, 95% CI = 1.017-2.703, and P=0.043) and the additive model (GA vs. AA, OR = 1.717, 95% CI = 1.021-2.888, and P=0.042). However, the analysis of the short-term outcome indicated that three genetic models were not associated with short-term outcomes in the additive model (GA vs. AA, P=0.815, GG vs. AA, and P=0.336), the dominant model (GA/GG vs. AA and P=0.589), and the recessive model (GG vs. AA/GA and P=0.342). Conclusion: Our findings identified the SNP of rs2071214 of the BIRC5 gene as a risk factor for the poor compensatory ability of collateral circulation and a predictor of stroke severity in large artery atherosclerotic stroke, which suggested that the SNP of rs2071214 can serve as an innovative therapeutic target for patients with acute ischemic stroke.

The Xiangya equation could not replace the Asian modified CKD-EPI equation in estimating glomerular filtration rate in Chinese patients with chronic kidney disease.

BACKGROUND: To evaluate the clinical practicability of the Xiangya equation in estimating glomerular filtration rate (GFR) and compare with the Asian modified Chronic Kidney Disease-Epidemiology Collaboration (CKD-EPI) equation, assessing whether the Xiangya equation could replace the Asian modified CKD-EPI equation as the preferred method for predicting GFR in the Chinese CKD patients in an external validation study. METHODS: The GFR was determined simultaneously by two methods: (a) the Asian modified CKD-EPI equation (GFRCKD-EPI); (b) the Xiangya equation (GFRXiangya); diagnostic performance of the two models was compared by the regression analysis, the Bland-Altman plot, bias, precision and P30 under the background of 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) dual plasma sample clearance method as reference method for GFR measurement (mGFR). RESULTS: A total of 158 Chinese CKD patients were included in our external study. The GFRXiangya was highly related with mGFR, with the correlation coefficient of 0.92. The regression equation was GFRXiangya = 0.55*mGFR + 28.25, where the regression coefficient was far away from one and the intercept was wide. Compared with the Asian modified CKD-EPI equation, the performance of the Xiangya equation demonstrated a poorer bias (9.5 vs - 3.3 ml/min/1.73 m2, P < 0.001), an inferior precision (23.9 vs 13.0 ml/min/1.73 m2, P < 0.001), a lower P30 (51.3% vs 73.4%, P < 0.001) and a wider 95% limit of agreement in Bland-Altman analysis (65.0 vs 44.9 ml/min/1.73 m2). CONCLUSION: Due to relatively inferior performance, the Xiangya equation could not replace the Asian modified CKD-EPI equation in estimating GFR in Chinese patients with chronic kidney disease in our external cohort.

Long-term clinical efficacy of cytokine-induced killer cell-based immunotherapy in early-stage esophageal squamous cell carcinoma.

BACKGROUND AIMS: In this retrospective clinical study, the authors investigated the impact of cytokine-induced killer (CIK) cell-based immunotherapies on the long-term survival of patients with esophageal squamous cell carcinoma (ESCC). METHODS: A total of 87 patients with ESCC who received comprehensive treatment were enrolled in the study. Of these patients, 43 were in the control group and 44 were in the CIK treatment group. Flow cytometry analysis was performed to detect the phenotype and anti-tumor function of CIK cells. Clinical characteristics were compared between these two groups, and the survival estimates of ESCC patients were determined using Kaplan-Meier analysis. RESULTS: CIK cells contained a high proportion of the main functional fraction (CD3+CD56+ group) and exhibited a strong killing ability for esophageal cancer cells in vitro. Importantly, overall survival (OS) and progression-free survival (PFS) were significantly higher in the CIK group than in the control group in early-stage ESCC. However, patients with advanced-stage ESCC did not benefit from CIK cell-based therapy in terms of OS and PFS compared with the control group. CONCLUSIONS: These results demonstrate that CIK cells combined with conventional treatments potentially prolong long-term survival of patients and may serve as a combined therapeutic approach for the treatment of early-stage ESCC.