Viability of Whole-Slide Imaging for Intraoperative Touch Imprint Cytological Diagnosis of Axillary Sentinel Lymph Nodes in Breast Cancer Patients.

BACKGROUND: Whole-slide imaging (WSI) is a promising tool in pathology. However, the use of WSI in cytopathology has lagged behind that in histology. We aimed to evaluate the utility of WSI for the intraoperative touch imprint cytological diagnosis of axillary sentinel lymph nodes (SLNs) in breast cancer patients. METHODS: Glass slides from touch imprint cytology of 480 axillary SLNs were scanned using two different WSI scanners. The intra- and interobserver concordance, accuracy, possible reasons for misdiagnosis, scanning time, and review time for three cytopathologists were compared between WSI and light microscopy (LM). RESULTS: A total of 4320 diagnoses were obtained. There was substantial to strong intraobserver concordance when comparing reads among paired LM slides and WSI digital slides (κ coefficient ranged from 0.63 to 0.88, and concordance rates ranged from 94.58% to 98.33%). Substantial to strong interobserver agreement was also observed among the three cytopathologists (κ coefficient ranged from 0.67 to 0.85, and concordance rates ranged from 95.42% to 97.92%). The accuracy of LM was slightly higher (average of 98.06%) than that of WSI (averages of 96.81% and 97.78%). The majority of misdiagnoses were false negative diagnoses due to the following top three causes: few cancer cells, confusing cancer cells with histiocytes, and confusing cancer cells with lymphocytes. CONCLUSIONS: This study is the first to address the feasibility of WSI in touch imprint cytology. The use of WSI for intraoperative touch imprint cytological diagnosis of SLNs is a practical option when experienced staff are not available on-site.

Clinicopathological Features of CCDC6-RET and NCOA4-RET Fusions in Thyroid Cancer: A Single-center Retrospective Cohort Study in a Chinese Population.

BACKGROUND: The rearranged during transfection (RET) proto-oncogene fusion is common in papillary thyroid cancer (PTC), varying across ethnic groups. However, comprehensive comparisons of RET fusion types are limited. This study aims to identify predominant RET fusions and analyze their clinicopathological characteristics in a cohort of Chinese thyroid cancer cases. METHODS: This single-center retrospective cohort study analyzed thyroid cancer data, utilizing next-generation sequencing on formalin-fixed, paraffin-embedded tissue samples. Detailed clinicopathological data of thyroid cancer cases with RET fusions were collected. RESULTS: Among 2300 thyroid cancer cases, RET fusions were exclusively found in PTC or differentiated high-grade thyroid carcinoma (DHGTC) cases (2234 cases), absent in other types (66 cases). Of the 2234 PTC or DHGTC cases, 113 (5.06%) exhibited RET fusions, including 100 primary cases. CCDC6-RET fusions predominated (78.0%, 78/100), with NCOA4-RET fusions representing 22.0% (22/100). NCOA4-RET fusions were more prevalent in patients aged 45 years and older (54.5% vs. 28.2%, P = 0.021) and DHGTC cases (P < 0.05), and associated with higher rates of lymph node metastases (90.9% vs. 67.9%, P = 0.032). CCDC6-RET fusion exhibited a higher prevalence of Hashimoto's thyroiditis (67.9% vs. 22.7%, P < 0.001) and elevated thyroglobulin antibody levels (14.11 [1.86-174.32] IU/mL vs. 2.01 [1.14-15.41] IU/mL, P = 0.018). Moreover, CCDC6-RET fusion predominantly occurred in classic PTC (56.4%, 44/78) and infiltrative follicular PTC (17.9%, 14/78), whereas NCOA4-RET fusion was more frequent in classic PTC (36.4%, 8/22), solid PTC (27.3%, 6/22), and DHGTC (27.3%, 6/22). RET fusions with compound mutations were associated with older age (≥45 years) and bilateral thyroid involvement. Follow-up data showed a higher recurrence rate in the RET fusion group compared to the BRAF V600E mutation group (5.0% vs. 0.0%, P = 0.018). Although the NCOA4-RET group showed a numerically higher recurrence rate compared to CCDC6-RET (9.1% vs. 3.8%), this difference was not statistically significant (P = 0.559). CONCLUSIONS: RET fusions are specific to PTC or DHGTC cases among Chinese thyroid cancer cases. CCDC6-RET and NCOA4-RET fusions exhibited distinct clinicopathological features, with NCOA4-RET being more aggressive.

Retrieval of subsurface dissolved oxygen from surface oceanic parameters based on machine learning.

Oceanic dissolved oxygen (DO) is crucial for oceanic material cycles and marine biological activities. However, obtaining subsurface DO values directly from satellite observations is limited due to the restricted observed depth. Therefore, it is essential to develop a connection between surface oceanic parameters and subsurface DO values. Machine learning (ML) methods can effectively grasp the complex relationship between input attributes and target variables, making them a valuable approach for estimating subsurface DO values based on surface oceanic parameters. In this study, the potential of ML methods for subsurface DO retrieval is analyzed. Among the selected ML methods, namely support vector regression (SVR), random forest (RF) regression, and extreme gradient boosting (XGBoosting) regression, the RF method generally demonstrates superior performance. As the depth increases, the accuracy of DO estimates tends to initially decrease, then gradually improve, with the poorest performance occurring at the depth of 600 dbar. The range of determination coefficients (R2) and root mean square error (RMSE) values based on the test dataset at different depths lies between 0.53 and 47.59 µmol/kg to 0.99 and 4.01 µmol/kg. In addition, compared to sea surface salinity (SSS) and sea surface chlorophyll-a (SCHL), sea surface temperature (SST) plays a more significant role in DO retrieval. Finally, compared to the pelagic interactions scheme for carbon and ecosystem studies (PISCES) model, the RF method achieves higher retrieval accuracies at depths above 700 dbar. In the deep ocean, the primary differences in DO values obtained from the RF method and the PISCES model-based method are noticeable in the vicinity of the equatorial region.

Two-sample Mendelian randomization studies revealed a causal relationship between insulin use and osteoporosis: An observational study.

OBJECTIVE: To investigate causal associations between diabetes, insulin treatment and osteoporosis using LDSC analysis with a 2-way Mendelian randomization study. METHODS: LDSC analysis was used to estimate the likelihood-scale heritability of the genome-wide association study used with genetic correlation between the 2 genome-wide association study used. Then a 2-sample Mendelian randomization study was performed using 3 methods including inverse variance weighted, MR Egger, and weighted median. RESULTS: The genetic correlation between diabetes, insulin treatment (h2_Z = 3.70, P = 2.16e-4), osteoporosis (h2_Z = 4.93, h2_p = 8.13e-7) and genes was significant. There was a significant genetic correlation (rg = 0.122, P = 0.0211). There was a causal association between diabetes, insulin treatment and osteoporosis [P = 0.003754, OR (95%CI) = 0.998876 (0.998116-0.999636)], while no causal association existed between osteoporosis and insulin use (P = 0.998116-0.999636) causal association existed (P = 0.333244). CONCLUSION: There was a strong genetic correlation between diabetes, insulin treatment and osteoporosis, a causal association between diabetes, insulin treatment and osteoporosis, and no causal association between osteoporosis and diabetes, insulin treatment.

Prognosis, Risk Factors, and Clinical Features of Intraocular Recurrence in Primary Vitreoretinal Lymphoma.

PURPOSE: To investigate the clinical features, risk factors, and prognosis of the intraocular recurrence in primary vitreoretinal lymphoma (PVRL). DESIGN: Retrospective case-control study. PARTICIPANTS: Ninety-seven eyes of 51 patients diagnosed with PVRL between December 2011 and January 2021 were enrolled in this study. Fourteen patients among them had experienced intraocular recurrence. METHODS: Data on demographic and ophthalmic characteristics, results of diagnostic tests, treatments, and prognosis of intraocular recurrence and nonrecurrence for PVRL patients were collected and compared. Multivariate logistic regression was used to identify independent risk factors. Receiver operating characteristic curves were used to determine the cutoff values. MAIN OUTCOME MEASURES: Clinical features and risk factors. RESULTS: Fourteen (19 eyes) of 51 PVRL patients had intraocular recurrences, resulting in a recurrence rate of 27.5% over a mean follow-up period of 42.5 months. No difference was observed in central nervous system lymphoma (CNSL) relapse rate (54.3% vs. 64.3%, P = 0.52) or median time to CNSL (36.5 months; 95% confidence interval [CI], 24.6-48.3 vs. 37.3 months; 95% CI, 24.8-49.8; P = 0.78) between intraocular nonrecurrence and intraocular recurrence groups. Furthermore, there were no statistically significant differences in the survival outcomes, such as mortality (28.6% vs. 29.7%, P = 1.00) and median overall survival (70.8 months; 95% CI, 54.0-87.7 vs. 59.2 months; 95% CI, 44.8-73.6; P = 0.30), between these 2 groups. Younger onset age (odds ratio [OR] 0.90; 95% CI, 0.84-0.98; P = 0.010), isolated PVRL (OR, 35.3; 95% CI, 2.08-600.0; P = 0.014), and no history of intravitreal chemotherapy (OR, 7.72; 95% CI, 1.37-43.6; P = 0.021) were identified as independent risk factors for intraocular recurrences. Of the patients with intraocular recurrence, 23.6% were asymptomatic and were diagnosed during routine follow-up. The rate of interleukin-10 (IL-10)/interleukin-6 > 1 was significantly lower than that at diagnosis (43.8% vs. 92.3%, P = 0.008). However, the rate of IL-10 ≥ 50 pg/mL was high (81.3%) and not significantly different from that at diagnosis (92.3%, P = 0.61). CONCLUSIONS: This study did not identify an impact of intraocular recurrence on CNS manifestations or survival outcomes in patients with PVRL. Younger patients have a higher risk of intraocular recurrence, and combined systemic and intravitreal chemotherapy may reduce intraocular recurrence. Regular ophthalmic follow-up and IL-10 testing are recommended to detect intraocular recurrence. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Causal association of metformin and osteoporosis: A 2-sample Mendelian randomization study.

To investigate the causal relationship between metformin use and osteoporosis and different subtypes of osteoporosis using a 2-sample Mendelian randomization method. Data from genome-wide association studies were analyzed, with the exposure factor being metformin and the outcome variables being osteoporosis and different subtypes. Mendelian randomization was performed using Inverse Variance Weighted (IVW), MR-Egger, and weight median (WM) methods, and heterogeneity tests, horizontal multivariate analyses, and sensitivity analyses were performed. The IVW method analysis with metformin and osteoporosis showed P = 1.53E-04, OR (95%CI) = 1.81E-02 (2.27E-02-1.44E-01); the IVW method analysis with metformin and postmenopausal osteoporosis with pathologic fracture showed P = 2.22E-01, OR (95%CI) = 4.89E-02 (3. 83E-04-6.23E + 00); the IVW method using metformin with osteoporosis with pathological fracture showed that P = 2.14E-01, OR (95%CI) = 1.64E + 00(5.78E-02-6.44E-04); the IVW method using metformin with pharmacological osteoporosis with pathological fracture showed that P = 9. 83E- 01, OR (95%CI) = 1.11E + 00 (3.99E-05-3.11E + 04); IVW method of metformin use and pharmacological osteoporosis showed that P = 5.99E-01, OR (95%CI) = 2.27E + 01 (2.00E-04-2.57E + 06); there is a causal relationship between metformin use and osteoporosis, but there is no causal relationship between metformin use and postmenopausal osteoporosis with pathological fracture, osteoporosis with pathological fracture, pharmacological osteoporosis, and pharmacological osteoporosis with pathological fracture, and metformin use is a protective factor for osteoporosis.

Study on the safety and effectiveness of low-dose vs. regular-dose fondaparinux in preventing venous thromboembolism prophylaxis following total knee arthroplasty.

Background: This study aims to evaluate the effectiveness and safety of low-dose (1.5 mg) fondaparinux for venous thromboembolism (VTE) prophylaxis in patients post-total knee arthroplasty (TKA). Methods: We retrospectively identified 314 patients who carried out the primary TKAs and received fondaparinux for VTE chemoprophylaxis between July 2020 and December 2021. A total of 141 TKA patients were excluded according to the exclusion criteria. Two groups of patients were established: the low-dose group included 84 patients who injected 1.5 mg of fondaparinux, and the regular-dose group included 89 patients who injected 2.5 mg of fondaparinux. The pre-operative blood analysis and coagulation assays were performed. The surgical time, the incidence of symptomatic VET, blood loss, wound complication, bleeding, drainage, and mortality of patients were determined and assessed. Results: The pre-operative blood analysis, body mass index, sex, age, and coagulation assays of patients in both groups were comparable. In terms of symptomatic pulmonary embolism and deep vein thrombosis, there was no significant difference (variation) between the two groups. However, patients in both groups showed a substantial difference in terms of blood loss, drain volume, wound complication, and transfusion rate. Conclusion: In prevention of VET in patients post-TKA, low-dose fondaparin is as effective as conventional dose fondaparinux. A significant decrease in blood loss, post-surgical transfusion rates, and wound complications were detected in patients given low-dose fondaparinux compared to those receiving regular-dose fondaparinux.

Association of elevated plasma CCL5 levels with high risk for tic disorders in children.

Abnormal levels of some peripheral cytokines have been reported in children patients with tic disorders (TDs), but none of these cytokines can be a biomarker for this disease. Our aim was to systemically profile differentially expressed cytokines (DECs) in the blood of TD patients, examine their associations with TD development, and identify from them potential biomarkers for the prediction and management of the risk for TDs. In this study, a cytokine array capable of measuring 105 cytokines was used to screen for DECs in the plasma from 53 comorbidity-free and drug-naïve TD patients and 37 age-matched healthy controls. DECs were verified by ELISA and their associations with TD development were evaluated by binary logistic regression analysis. Elevation of a set of cytokines was observed in TD patients compared with controls, including previously uncharacterized cytokines in tic disorders, CCL5, Serpin E1, Thrombospondin-1, MIF, PDGF-AA, and PDGF-AB/BB. Further analysis of DECs revealed a significant association of elevated CCL5 with TD development (p = 0.005) and a significant ROC curve for CCL5 as a risk factor [AUC, 0.801 (95% CI: 0.707-0.895), p < 0.0001]. Conclusion: This study identifies associations of a set of circulating cytokines, particularly CCL5 with TD development, and provides evidence that high blood CCL5 has potential to be a risk factor for TD development. Clinical Trial Registration: identifier ChiCTR-2000029616.

Infection evaluation in the early period after liver transplantation: A single-center exploration.

BACKGROUND: Infection is a significant risk factor that impacts for perioperative morbidity and mortality in liver transplantation (LTx) patients and is difficult to evaluate quantitatively in the early posttransplantation period. Thus, a biomarker to assess the risk of infection and the prognosis of the recipient is highly desirable. METHODS: A total of 128 consecutive patients with end-stage liver diseases undergoing LTx between January 1, 2020 and December 31, 2021, at the First Affiliated Hospital of Zhejiang University School of Medicine, were screened retrospectively. Graft preservation fluid and blood samples were collected for culture, and other perioperative laboratory examination results were recorded, for assessment of infection status. RESULTS: After a follow-up period of 30 days, the survival rate among the 128 LTx recipients was 94.5%. Multivariable regression analysis showed that the logarithmically transformed neutrophil-to-lymphocyte ratio (NLR) (HR = 3.548, 95% CI: ; p = .041) on post-LTx day 1 and graft preservation fluid culture positivity (HR = 12.032, 95% CI: ; p = .006) were independent predictive factors for early prognosis after LTx. CONCLUSIONS: Positive graft preservation fluid culture and the logarithmically transformed NLR on post-LTx day 1 were independent predictive factors for early prognosis after LTx. The logarithmically transformed NLR could provide an earlier indication than culture results in clinical practice.

Cell-Free DNA Sequencing of Intraocular Fluid as Liquid Biopsy in the Diagnosis of Vitreoretinal Lymphoma.

Purpose: To seek novel diagnostic approaches, we improved the workflow of cell-free DNA (cfDNA) sequencing and evaluated its feasibility in vitreoretinal lymphoma (VRL) specimens; the profile of mutations was preliminarily analyzed for potential diagnostic value. Methods: The study was a diagnostic trial. 23 eyes of 23 patients with VRL and 25 eyes of 25 patients with inflammatory eye diseases were enrolled. Approximate 500µl undiluted vitreous humor and 10ml diluted vitreous fluid was obtained through diagnostic vitrectomy and sent for cytopathological examinations. 500µl of the diluted vitreous fluid was spared for cfDNA sequencing. For cfDNA sequencing, DNA fragmentation procedure was added to the workflow to improve the extraction efficiency; mutations detected were analyzed for potential diagnostic model. The sensitivity and specificity of the cytopathology and cfDNA sequencing were compared. The clinical manifestations were preliminarily analyzed for potential correlations with the genotypes. Results: CfDNA sequencing was accomplished in 23 eyes with VRL and 20 eyes with inflammatory eye diseases. VRL-related mutated genes included MYD88 (18 eyes, 78%), ETV6 (11 eyes, 48%), PIM1 (11 eyes,48%), BTG2 (7 eyes, 30%), IRF4 (7 eyes, 30%), CD79B (6 eyes, 26%), LRP1B (6 eyes, 26%), etc. Logistic regression based on the mutations of MYD88 and ETV6 was of the potential for the diagnosis of VRL (P<0.001, adjusted R2 = 0.789, sensitivity 0.913, specificity 0.950); by comparison, the sensitivity and specificity of the vitreous cytopathology were 0.826 and 1.000, respectively. Further analysis of the mutation profile showed that patients carrying CD79B mutation tended to have higher intraocular interleukin-10 level (P=0.030), that CARD11 mutation was correlated with younger age at ocular onset (P=0.039), and that patients with intracranial involvement carried more multiple-site mutations in the BTG2 gene (P=0.013). Conclusions: The improved workflow of CfDNA sequencing is of sound feasibility in a limited amount of vitreous humor. The logistic model based on the mutations could help to provide reliable clues for the diagnosis of VRL.

Evaluating the Response and Safety of Inactivated COVID-19 Vaccines in Liver Transplant Recipients.

Purpose: To evaluate the response and safety of an inactivated vaccine (Sinovac Life Sciences Co., Ltd., Beijing, China) for coronavirus disease 2019 (COVID-19) in liver transplant (LTx) recipients from China. Patients and Methods: Thirty-five recipients post LTx from the First Affiliated Hospital of Zhejiang University School of Medicine who received inactivated vaccine from June to October 2021 were screened. Information regarding vaccine side effects and clinical data were collected. Results: Thirty-five LTx recipients were enrolled, with a mean age of 46 years, and most patients were male (30, 85.71%). All the participants had a negative history of COVID-19 infection. Predictors for negative response in the recipients were interleukin-2 receptor (IL-2R) induction during LTx, shorter time post LTx and application of a derivative from mycophenolate acid (MPA). No serious adverse events were observed during the progress of vaccination or after the vaccination. Conclusion: LTx recipients have a substantially partial immunological response to the inactivated vaccine for COVID-19. IL-2R induction during LTx, a shorter time post LTx and the application of a derivative from MPA seem to be predictors for a negative serological immunoglobulin G (IgG) antibody response in recipients. The findings require booster vaccination in these LTx recipients.

Diagnostic performance of next-generation sequencing and genetic profiling in thyroid nodules from a single center in China.

Objective: The data regarding the mutation landscape in Chinese patients with thyroid cancer are limited. The diagnostic performance of thyroid nodules by fine-needle aspiration (FNA) cytology needs optimization, especially in indeterminate nodules. Methods: A total of 1039 FNA and surgical resection samples tested using the targeted multigene next-generation sequencing (NGS) panel were retrospectively collected. The features of gene alterations in different thyroid tumors were analyzed, and the diagnostic efficacy was evaluated. Results: Among 1039 samples, there were 822 FNA and 217 surgical FFPE samples. Among 207 malignant thyroid resections, a total of 181 out of 193 papillary thyroid carcinomas (PTCs) were NGS-positive (93.8%), with a high prevalence of BRAF mutations (81.9%, 158/193) and a low prevalence of RAS (1.0%, 2/193) and TERT promoter mutations (3.6%, 7/193). Gene fusions, involving the RET and NTRK3 genes, were present in 20 PTCs (10.4%) and mutually exclusive with other driver mutations. Two of three follicular thyroid carcinomas harbored multiple mutations. RET gene point mutations were common in medullary thyroid carcinoma (8/11, 72.7%). The combination of cytology and DNA-RNA-based NGS analysis demonstrated superior diagnostic value (98.0%) in FNA samples. For indeterminate thyroid nodules, the diagnostic sensitivity and specificity of NGS testing were 79.2 (38/48) and 80.0% (8/10), respectively. Two mutation-positive benign cases harbored NRAS and TSHR mutations, respectively. Conclusions: Our study revealed the distinct molecular profile of thyroid tumors in the Chinese population. The combination of NGS testing and FNA cytology could facilitate the accurate diagnosis of thyroid nodules, especially for indeterminate nodules.

Peripheral lymphocyte populations in ovarian cancer patients and correlations with clinicopathological features.

BACKGROUND: To investigate the alterations of peripheral lymphocyte subpopulations in ovarian cancer patients compared to benign or borderline counterparts. The possible clinicopathological implications were also evaluated. METHODS: We enrolled 112 treatment-naive ovarian cancer patients, 14 borderline tumor patients and 44 benign tumor patients between 09/2016 and 01/2019. Flow cytometry was used to measure the peripheral lymphocyte subsets consisting of T cells (CD3+, CD3+CD4+, CD3+CD8+ and CD8+CD28+), regulatory T cells (Tregs, CD4+CD25+CD127-), natural killer cells (NK cells, CD3-CD56+) and B cells (CD19+). RESULTS: Most ovarian cancer patients were high-grade serous carcinoma (84.8%), followed by clear cell carcinoma (8.03%). Late-stage tumor (FIGO III + IV) accounted for 82.1%. The study showed that the proportions of peripheral lymphocyte subsets underwent apparent changes in ovarian cancer patients. We observed elevated levels of Treg cells in patients with both ovarian borderline and malignant tumor compared to those with benign tumors, which achieved statistic significance. In contrast, CD3+CD8+ T and CD8+CD28+ T cells were significantly lower in ovarian cancer patients. Interestingly, low level of B cells was correlated to clear cell carcinoma (P = 0.024), advanced tumor (P = 0.028) and platinum-resistant recurrence (P = 0.014). Regarding the changes of lymphocyte subsets after surgery, CD8+CD28+ T cells had a significant decreasing tendency (P = 0.007) while B cells were the opposite (P < 0.001). CONCLUSIONS: Ovarian cancer patients have altered circulating lymphocyte profile (elevated Treg cell, depressed CD3+CD8+ T and CD8+CD28+ T cells). Low level of B cells might be related to disease aggressiveness, and it recovered after the removal of tumor, which merits further study.

Experimental study on co-culture of DiI labeled rat bone marrow mesenchymal stem cells and polycaprolactone film in vitro to make a cell patch.

BACKGROUND: In stem cell therapy, due to the lack of an effective carrier, a large number of transplanted stem cells are lost and die. Therefore, finding a suitable carrier has become a further direction of stem cell therapy. OBJECTIVE: In research on the co-culture of polycaprolactone (PCL) with 1,1'-Dioctadecyl-3,3,3',3'- tetramethylindocarbocyanine perchlorate (DiI) labeled bone marrow mesenchymal stem cells (BMSCs), we observe the effect of materials on the growth and proliferation of DiI labeled stem cells, and the effect of DiI labeling on patch preparation, so as to find a kind of biomaterial suitable for the growth and proliferation of BMSCs, and find a suitable cell carrier for stem cell therapy of myocardial infarction and in vivo tracing. METHODS: Clean grade Sprague Dawley rats were selected as experimental objects, BMSCs were isolated and cultured, and the surface markers were identified by flow cytometry. After the BMSCs were cultured for 3 passages, the BMSCs were stained with DiI dye, and the BMSCs DiI and PCL biomaterial film were co-cultured. After 24 hours, the cell growth was observed under fluorescence microscope, and fixed for scanning under electron microscope. The cell proliferation was detected by CCK-8 at 1, 4, 7, 10 days of culture. The measurement data conforming to normal distribution are expressed in the form of mean ± standard deviation (X¯± s). One way ANOVA was used for comparison among groups, LSD analysis was used for pairwise comparison. The difference was statistically significant (P < 0.05). RESULTS: BMSCs were strongly positive for CD90, CD44H, but negative for CD11b/c, CD45. Under fluorescence microscope, BMSCs DiI showed red light, fusiform or polygonal. Under the scanning electron microscope, the cell patch formed by co-culture of PCL film and DiI-BMSCs had a large number of cells on the surface and normal cell state. CCK-8 assay showed that the OD value on the first day was 0.330 ± 0.025; The OD value was 0.620 ± 0.012 on the 4th day, 1.033 ± 0.144 on the 7th day and 1.223 ± 0.133 on the 10th day. There was significant difference among the time points (P < 0.05). CONCLUSIONS: The cell patch made of PCL film and DiI labeled BMSCs can survive and proliferate on the surface, so it can be used as a scaffold material for stem cell therapy in vivo.

The Efficacy of Acupuncture on Tic Disorders in Children: A Retrospective and Propensity Score-Matched Study.

Background : Acupuncture has been considered as a complementary or alternative therapy for children with tic disorders (TD), but its efficacy remains largely unknown. This study retrospectively examined the efficacy of acupuncture treatment for TD in children over the course of 12 weeks. Methods: Data were collected from Traditional Chinese Medicine clinics in a public pediatric hospital in Shanghai between June 2020 and March 2021. A total of 250 patients with TD were included in the study, with 122 patients exposed to acupuncture therapy combined with conventional treatment (observation group), and 128 patients exposed to conventional treatment alone (control group). Propensity score matching analyses were used to balance baseline characteristics, resulting in 78 matched patients for each group. Reductions in the Yale Global Tic Severity Scale (YGTSS) total score were analyzed in the two groups after 12 weeks of treatment. Results: The two groups reached equilibrium in terms of baseline demographic characteristics and YGTSS total score after the propensity score matching (P > 0.05). Compared to the control group, the reduction in the YGTSS total score after 12 weeks of treatment was greater for the observation group (OR = 2.94, 95% CI: 1.03, 8.39, P = 0.04), and this association was stronger for patients who had significant vocal tics (ß = 0.29, 95% CI: 0.88, 2.68, P = 0.001). The clinical efficacy for the observation group was significantly better than the control group. Conclusions: We provided preliminary evidence supporting the therapeutic effect of acupuncture for TD in children. Hence, our findings indicate that acupuncture could be an adjuvant treatment efficacious for TD in children, especially for vocal tics.

Changes in peripheral lymphocyte populations in patients with advanced/recurrent ovarian cancer undergoing splenectomy during cytoreductive surgery.

BACKGROUND: To investigate changes in peripheral lymphocyte subsets after splenectomy during cytoreductive surgery for advanced or recurrent ovarian cancers. METHODS: We enrolled 83 patients with advanced or recurrent ovarian cancer who underwent cytoreductive surgery. Twenty patients who also underwent splenectomy were assigned to the splenectomy cohort and the rest were assigned to the non-splenectomy cohort. Flow cytometry was used to measure peripheral lymphocyte subsets consisting of T cells, regulatory T cells, natural killer cells, B cells, and activation antigens before and after surgery. RESULTS: There was no difference in the number and distribution of peripheral lymphocyte subsets between the two cohorts before surgery. After surgery, we observed elevated levels of T cells (CD3+, CD3+CD8+) in the splenectomy cohort compared to those in the non-splenectomy cohort, and the difference was statistically significant. CD8+CD28+ T cells had a significant decreasing tendency (P = 0.011) while CD3+/HLA-DR+ T cells showed the opposite trend (P = 0.001) in the splenectomy cohort. The proportion of Tregs (P = 0.005) and B cells (P < 0.001) including CD3-/HLA-DR+ B cells (P = 0.007) increased after surgery, and the absolute number of T cells and NK cells decreased to different extents (P < 0.001) in the non-splenectomy cohort. The post-operative percentage of CD8+CD28+ T cells was less than the pre-operative percentage (P = 0.022), which was similar to the splenectomy cohort. There was no significant difference in progression-free survival or overall survival between the groups after a median follow-up time of 41 months. CONCLUSIONS: The changes in peripheral lymphocyte populations were different between patients with and those without splenectomy during cytoreductive surgery for ovarian cancers. T cells were increased and activated in the splenectomy cohort, whereas, B cells were increased and activated in the non-splenectomy cohort.

CLINICAL FEATURES, DIAGNOSTIC SIGNIFICANCE, AND PROGNOSIS OF VITREORETINAL LYMPHOMA IN YOUNG PATIENTS.

PURPOSE: To investigate the clinical features, diagnostic approaches, and outcomes of young patients with vitreoretinal lymphoma. METHODS: Fifty-one vitreoretinal lymphoma patients (97 eyes) referred to the Eye and ENT Hospital of the Fudan University from 2011 to 2020 were grouped based on their onset age (age ≤50 years and age >50 years). Complete eye examinations, evaluation of systemic conditions, and biological analysis of intraocular fluids were performed. RESULTS: Young patients accounted for 31.4% (n = 16) of the cohort. More eyes had retinal/subretinal pigment epithelial infiltration (20 [64.5%] vs. 23 [34.8%]; P = 0.018) in young patients than in elderly ones. The mutation rate of Myeloid Differentiation Factor 88 gene (MYD88) was significantly lower in young patients than in elderly ones (5 [50%] vs. 21 [91.3%]; P = 0.016). The median time to new onset of central nervous system lymphoma was significantly shorter in young patients (11.7 vs. 36.2 months; P = 0.012). However, mean overall survival did not differ between the 2 groups (64.9 vs. 57.5 months; P = 0.871). CONCLUSION: Early diagnosis and central nervous system evaluation are crucial for young vitreoretinal lymphoma patients with rapid central nervous system involvement. Meanwhile, young vitreoretinal lymphoma patients have some unique features, including more retinal/subretinal pigment epithelial infiltrations and lower MYD88 mutation rates.

Clinical significance of EPHX2 deregulation in prostate cancer.

The arachidonic acid (AA) metabolic pathway participates in various physiological processes as well as in the development of malignancies. We analyzed genomic alterations in AA metabolic enzymes in the Cancer Genome Atlas (TCGA) prostate cancer (PCa) dataset and found that the gene encoding soluble epoxide hydrolase (EPHX2) is frequently deleted in PCa. EPHX2 mRNA and protein expression in PCa was examined in multiple datasets by differential gene expression analysis and in a tissue microarray by immunohistochemistry. The expression data were analyzed in conjunction with clinicopathological variables. Both the mRNA and protein expression levels of EPHX2 were significantly decreased in tumors compared with normal prostate tissues and were inversely correlated with the Gleason grade and disease-free survival time. Furthermore, EPHX2 mRNA expression was significantly decreased in metastatic and recurrent PCa compared with localized and primary PCa, respectively. In addition, EPHX2 protein expression correlated negatively with Ki67 expression. In conclusion, EPHX2 deregulation is significantly correlated with the clinical characteristics of PCa progression and may serve as a prognostic marker for PCa.

Low Serum ZAG Levels Correlate With Determinants of the Metabolic Syndrome in Chinese Subjects.

Introduction: Zinc-α2-glycoprotein (ZAG) is a novel adipokine, which is involved in metabolic syndrome (MetS). This study aimed to investigate the relationship between serum ZAG and MetS in Chinese adults, who diagnosed according to the 2005 International Diabetes Federation (IDF) criteria. Methods: A group of 151 MetS patients, 84 patients with central obesity and 70 healthy controls were enrolled. General clinical information, serum samples were obtained from all subjects and serum ZAG levels were determined via the commercial ELISA kits. Results: Serum ZAG levels were the highest in the control group, then gradually decreased with the severity of the metabolic abnormalities increased (8.78 ± 1.66 µg/mL for control vs. 8.37 ± 1.52 µg/mL for central obesity vs. 7.98 ± 0.94 µg/mL for MetS, P < 0.05). It was also decreased progressively with an increasing number of the MetS components (P for trend = 0.002). Additionally, serum ZAG/fat mass ratio was calculated and the similar changes were observed in the three groups (0.85 ± 0.53 µg/mL/kg for control vs. 0.39 ± 0.10 µg/mL/kg for central obesity vs. 0.36 ± 0.08 µg/mL/kg for MetS, P < 0.05). In the multiple regression analysis, group was a strong independent factor contributing to serum ZAG levels (P < 0.001). Furthermore, compared with subjects with the highest tertile of ZAG, subjects in the lowest tertile of ZAG had 1.946-fold higher risk of MetS (95% CI 1.419-6.117, P = 0.004). This phenomenon still existed after controlling for age, gender (Model 1), ALP, AST, Cr, UA, Urea based on Model 1 (Model 2), grip strength, smoking, drinking, birth place, current address, education level, manual labor, and exercise frequency based on Model 2 (Model 3). Receiver operation characteristic (ROC) curve analysis revealed that serum ZAG might serve as a candidate biomarker for MetS (sensitivity 57.6%, specificity 70.0% and area under the curve 0.655), and serum ZAG/fat mass ratio showed improved diagnosis value accuracy, with ROC curve area of 0.951 (95% CI, 0.920-0.983, P < 0.001), and 90.7% sensitivity and 88.6% specificity. Conclusions: Serum ZAG levels were lowered in patients with MetS and central obesity. The decreased serum ZAG levels were associated with the increased risks of MetS. Serum ZAG, especially serum ZAG/fat mass ratio might be the candidate diagnostic biomarkers for MetS.

Deep convolutional neural network VGG-16 model for differential diagnosing of papillary thyroid carcinomas in cytological images: a pilot study.

Objective: In this study, we exploited a VGG-16 deep convolutional neural network (DCNN) model to differentiate papillary thyroid carcinoma (PTC) from benign thyroid nodules using cytological images. Methods: A pathology-proven dataset was built from 279 cytological images of thyroid nodules. The images were cropped into fragmented images and divided into a training dataset and a test dataset. VGG-16 and Inception-v3 DCNNs were trained and tested to make differential diagnoses. The characteristics of tumor cell nucleus were quantified as contours, perimeter, area and mean of pixel intensity and compared using independent Student's t-tests. Results: In the test group, the accuracy rates of the VGG-16 model and Inception-v3 on fragmented images were 97.66% and 92.75%, respectively, and the accuracy rates of VGG-16 and Inception-v3 in patients were 95% and 87.5%, respectively. The contours, perimeter, area and mean of pixel intensity of PTC in fragmented images were more than the benign nodules, which were 61.01±17.10 vs 47.00±24.08, p=0.000, 134.99±21.42 vs 62.40±29.15, p=0.000, 1770.89±627.22 vs 1157.27±722.23, p=0.013, 165.84±26.33 vs 132.94±28.73, p=0.000), respectively. Conclusion: In summary, after training with a large dataset, the DCNN VGG-16 model showed great potential in facilitating PTC diagnosis from cytological images. The contours, perimeter, area and mean of pixel intensity of PTC in fragmented images were more than the benign nodules.