[Ultrasonographic features of thyroid carcinoma of different sizes: comparison between medullary thyroid carcinomas and papillary thyroid carcinomas].

Objective: To investigate the ultrasonographic features of medullary thyroid carcinomas (MTCs) of different sizes and supply valid information for separating MTCs from papillary thyroid carcinomas (PTCs). Methods: There were 87 patients with MTC and 220 patients with PTC detected by ultrasonography and confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from June 2018 to March 2022. Nodules were divided into the large nodule group (the maximum diameter of the tumor was＞1 cm) and the small nodule group (the maximum diameter of the tumor was ≤1 cm). There were 97 cases in the small nodule group, including 28 cases of MTC and 69 cases of PTC. There were 210 cases in the large nodule group, including 59 cases of MTC and 151 cases of PTC. After stratification by thyroid nodules, ultrasonographic features of thyroid nodules and metastatic lymph nodes, preoperative serum calcitonin (CT) and carcinoembryonic antigen (CEA) levels were compared between MTC and PTC patients. Results: In the small nodule group, the proportion of MTCs exhibiting hypoecho, smooth margins, and having blood flow signals was higher than that of PTCs, with statistically significant differences (all P＜0.05). In the large nodule group, the proportion of MTCs showing cystic solidity, hypoecho, smooth margins, blood flow, and the type Ⅳvascular distribution was higher than PTCs, and the difference of calcification type between them was also statistically significant (all P＜0.05). In contrast, the differences in the number of lesions and aspect ratio between MTCs and PTCs were not statistically significant regardless of nodule size (all P＞0.05). In the small nodule group,6 metastatic lymph nodes of medullary thyroid carcinoma (LNM-MTC) and 11 metastatic lymph nodes of papillary thyroid carcinoma (LNM-PTC) were correctly diagnosed by ultrasound, respectively. The diagnostic compliance rate of ultrasound was 78.6% (22/28) and 78.3% (54/69), respectively, with no statistically significant difference (P=0.973). In the large nodule group, 28 LNM-MTC and 11 LNM-PTC were correctly diagnosed by ultrasound, respectively. The diagnostic compliance of ultrasound was 88.1% (52/59) and 73.5% (111/151), respectively, which was statistically significant (P=0.022). Among them, 82.1% of LNM-MTC and 56.6% of LNM-PTC showed abnormal blood flow signals, with a statistically significant difference (P=0.016). There were significant differences in preoperative serum CT and CEA levels of different sizes of MTCs (all P＜0.05). Conclusions: Different sizes of MTCs require diverse demonstrative criteria. Abnormal blood flow signal is of great significance in the diagnosis of LNM-MTC. Within the absence of ultrasonic characteristics, preoperative serum CT test can provide confidence for the diagnosis of MTC.

[Correlation of MYB/NFIB gene fusion with the grade and prognosis of head and neck adenoid cystic carcinoma and the concordance of two detection methods].

Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade Ⅰ-Ⅱ, grade Ⅲ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade Ⅲ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.

Optimal biopsy site for the diagnosis of oral pemphigus vulgaris and mucous membrane pemphigoid: a systematic review and meta-analysis.

The aim of this study was to critically evaluate the diagnostic yields of direct immunofluorescence (DIF) analysis on perilesional and normal-appearing mucosa biopsy samples, to determine the optimal biopsy site for patients presenting with oral pemphigus vulgaris (PV) or mucous membrane pemphigoid (MMP). Electronic databases and article bibliographies were searched in December 2022. The primary outcome was the rate of DIF positivity. Of 374 records identified after the elimination of duplicates, 21 studies with 1027 samples were ultimately included. Meta-analysis revealed a pooled DIF positivity rate of 99.6% (95% confidence interval (CI) 97.4-100.0%, I2 = 0%) for PV and 92.6% (95% CI 87.9-96.5%, I2 = 44%) for MMP for biopsies from perilesional sites, and of 95.4% (95% CI 88.6-99.5%, I2 = 0%) for PV and 94.1% (95% CI 86.5-99.2%, I2 = 42%) for MMP for biopsies from normal-appearing sites. For MMP, there was no significant difference in the rate of DIF positivity between the two biopsy sites (odds ratio 1.91, 95% CI 0.91-4.01, I2 = 0%). The results suggest that the perilesional mucosa remains the optimal biopsy site for DIF diagnosis of oral PV, while the normal-appearing mucosa biopsy is optimal for oral MMP.

[AF4/FMR2 and IL-10 gene single nucleotide polymorphisms are correlated with disease susceptibility and immune infiltration in ankylosing spondylitis].

OBJECTIVE: To explore the correlation of polymorphisms of AF4/FMR2 family genes and IL-10 gene with genetic susceptibility to ankylosing spondylitis (AS) and identify the high-risk factors of AS. METHODS: This case-control study was conducted among 207 AS patients and 321 healthy individuals. The tag single nucleotide polymorphisms (SNPs) rs340630, rs241084, rs10865035, rs1698105, and rs1800896 of the AF4/FMR2 family gene and IL-10 gene of the AS patients were genotyped, and the distribution frequencies of the genotypes and alleles were analyzed to explore the relationship between different genetic models and AS and the gene-gene and gene-environment interactions. RESULTS: Gender ratio, smoking history, drinking history, hypertension, erythrocyte sedimentation rate and C-reactive protein differed significantly between the case group and the control group (P < 0.05). The dominant model and recessive model of AFF1 rs340630, the recessive model of AFF3 rs10865035, and the recessive model of IL-10 rs1800896 were significantly different between the two groups (P=0.031, 0.010, 0.031, and 0.019, respectively). Gene-environment interaction analysis suggested that the interaction model incorporating AFF1 rs340630, AFF2 rs241084, AFF3 rs10865035, AFF4 rs1698105, IL-10 rs1800896, smoking history and drinking history was the best model. The genes related with AF4/FMR2 and IL-10 were enriched in the biological processes of AF4 super extension complex, interleukin family signal transduction, cytokine stimulation and apoptosis. The expression levels of AF4/FMR2 and IL-10 were positively correlated with immune infiltration (r > 0). CONCLUSION: The SNPs of AF4/FMR2 and IL-10 genes are associated with the susceptibility to AS, and the interactions of AF4/FMR2 and IL-10 genes with the environmental factors contributes causes AS through immune infiltration.

[A brief history of the evolution of lung cancer operation].

Surgical operation is one of the significant parts of the comprehensive therapeutic methods of lung cancer. In the history of the development of lung cancer operation, scholars and predecessors at home and abroad have gradually established the current status of lung cancer operation and the framework of comprehensive treatment after continuous understanding of local anatomy of lung, continuous innovation of surgical equipment and continuous reform of surgical methods. In the continuous development and improvement of lung cancer surgical diagnosis and treatment procedures, a set of standardized diagnosis and treatment process of lung cancer screening, early diagnosis and treatment, standardized surgery process, rapid perioperative recovery, postoperative adjuvant treatment and follow-up has been formed. The achievements of lung cancer operation are achieved by scholars standing on the shoulders of giants. In the process of pioneering and innovating, we should go back and review the road that our predecessors have taken, and draw energy from it to continue to create new brilliance in lung cancer operation. In this paper, the evolution history of lung cancer surgery is summarized in order to improve the clinician's understanding of the history of lung cancer surgery.

Application of combined anterior and posterior approaches for the treatment of cervical tuberculosis with anterior cervical abscess formation and kyphosis using a Jackson operating table: a case report and literature review.

BACKGROUND: There have been insufficient reports to date regarding the treatment of cervical spinal tuberculosis, and the optimal surgical approaches to treating this condition have yet to be established. CASE REPORT: This report describes the treatment of a case of tuberculosis associated with a large abscess and pronounced kyphosis through the use of a combined anterior and posterior approach with the aid of the Jackson operating table. This patient did not exhibit any sensorimotor abnormalities of the upper extremities, lower extremities, or trunk, and presented with symmetrical bilateral hyperreflexia of the knee tendons, while being negative for Hoffmann's sign and Babinski's sign. Laboratory test results revealed an erythrocyte sedimentation rate (ESR) of 42.0 mm/h and a C-reactive protein (CRP) of 47.09 mg/L. Acid-fast staining was negative, and spine magnetic resonance imaging revealed the destruction of the C3-C4 vertebral body and a posterior convex deformity of the cervical spine. The patient reported a visual analog pain score (VAS) of 6, and exhibited an Oswestry disability index (ODI) score of 65. Jackson table-assisted anterior and posterior cervical resection decompression was performed to treat this patient, and at 3 months post-surgery the patient's VAS and ODI scores were respectively reduced to 2 and 17. Computed tomography analyses of the cervical spine at this follow-up time point revealed good structural fusion of the autologous iliac bone graft with internal fixation and improvement of the originally observed cervical kyphosis. CONCLUSIONS: This case suggests that Jackson table-assisted anterior-posterior lesion removal and bone graft fusion can safely and effectively treat cervical tuberculosis with a large anterior cervical abscess combined with cervical kyphosis, providing a foundation for future efforts to treat spinal tuberculosis.

[Comparison of off-pump coronary artery bypass grafting alone or combined with mitral valve plasty for coronary heart disease with moderate ischemic mitral insufficiency].

Objective: To compare the efficacy of off-pump coronary artery bypass grafting (CABG) or CABG plus mitral valve plasty (MVP) in patients with coronary heart disease complicated with moderate ischemic mitral insufficiency. Methods: The clinical data of 1 050 patients with coronary heart disease complicated with moderate ischemic mitral insufficiency who underwent surgical procedures from January 2009 to December 2020 were analyzed retrospectively. There were 733 males and 317 females, aging (63.3±9.0) years (range: 31 to 83 years). Patients were divided into CABG+MVP group and CABG group according to surgical methods, and the two groups of patients were matched for 1∶4 by the propensity score matching method. There were 107 patients in the CABG+MVP group and 406 patients in the CABG group after matching. The t test, Mann-Whitney U test, χ2 test, Fisher's exact probability method and repeated measures anova were used to compare the surgical outcomes and overall survival in the two groups. Results: There were no significant differences in perioperative death and postoperative complications between the two groups (all P>0.05). Compared with CABG group, CABG+MVP group had longer operation time ((5.6±1.2) hours vs. (4.2±1.0) hours, t=11.528, P<0.01), ICU stay(M(IQR))(43.0(47.3) hours vs. 25.0(33.6) hours, Z=2.483, P=0.013), and postoperative hospital stay (8(4) days vs. 7(5) days, Z=2.143, P=0.032). The amount of erythrocyte and platelet used in CABG+MVP group was significantly increased (2.0(6.5) U vs. 0(2.0) U, Z=7.084, P<0.01; 0(0.5) U vs. 0(0) U, Z=5.210, P<0.01). A total of 463 cases (93.9%) were followed up. Median follow-up was 32(31) months (range: 3 to 105 months). There was no significant difference in overall survival and no major adverse cardic and cerebrovascular events survival between CABG group and CABG+MVP group (P=0.196,P=0.305). Echocardiography showed that there was no significant difference in ejection fraction left ventricular end-diastolic diameter between the two groups (F=0.322, P=0.571; F=0.681, P=0.410). However, CABG+MVP improved mitral regurgitation better than CABG (F=160.222, P<0.01). Conclusions: For patients with coronary heart disease with moderate ischemic mitral insufficiency, the rates of all-cause mortality and major adverse cardiac and cerebrovascular events are similar between the two surgeries. Although CABG+MVP improves mitral regurgitation better than CABG, it increases the duration of surgery, ICU stay, postoperative hospital stay, and blood transfusion requirement.

[Pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma].

Objective: To investigate the pathological characteristics and clinical prognosis of nodular sclerosis grade 2 of classic Hodgkin's lymphoma (cHL-NS2) in our cancer center. Methods: A retrospective collection of 23 cases of cHL-NS2 admitted in Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from July 2008 to April 2019 was performed. Fifty-five cases of nodular sclerosis grade 1 of classical Hodgkin's lymphoma (cHL-NS1) during the same period were selected as control group. Survival curves were plotted using the Kaplan-Meier method, and Cox regression model was used to analyze the influencing factors for survival. Results: The median age of 23 cases of cHL-NS2 was 30 years old. Five cases had extra nodal invasion, and 19 cases were Ⅰ-Ⅱ stage based on Ann Arbor system. The pathological morphology of cHL-NS2 showed that the lymph node structure was completely destroyed and was divided into nodules by thick collagen. The tumor cells in the nodules were abundant and proliferated in sheets. The boundaries between the tumor cells were not clear. The incidence of tumor necrosis in cHL-NS2 was 43.5% (10/23), which was significantly higher than 18.2% (10/55) in cHL-NS1 (P=0.040). The 3-year progression-free survival (PFS) rate of patients in the cHL-NS2 group was 58.1%, which was significantly lower than 89.7% in the cHL-NS1 group (P=0.002). In all of 78 cases, the 3-year PFS rate of patients who did not obtain complete response (CR) was 67.1%, which was significantly lower than 92.2% in patients who achieved CR (P=0.030). Multivariate Cox regression analysis demonstrated that both cHL-NS2 and failure to obtain CR by first-line treatment were independent indicators for short PFS time (P<0.05). Conclusions: In cHL-NS2, the morphology of tumor cells are diverse, and tumor necrosis can be easily found. Under the current first-line treatments of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) or bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP), cHL-NS2 is an independent indicator for worse PFS.

[Application value of superb microvascular imaging for diagnosis of different size renal solid tumors].

Objective: To discuss the diagnostic value of superb microvacular imaging (SMI) in renal solid tumors of different sizes. Methods: A total of 142 patients with 146 renal tumors detected by ultrasound in Tianjin Medical University Cancer Institute and Hospital from September 2017 to March 2019 were retrospectively analyzed. The maximum diameter of lesions was 0.8-7.3 cm, and patients were divided into the maximum diameter ≤3.0 cm group (61 patients, 64 lesions) and the maximum diameter >3.0 cm group (61 patients, 82 lesions). All of the tumors were separately evaluated by SMI and color Doppler flow imaging (CDFI) with Adler grade, vascular morphology and peripheral blood flow. Results: In the group with maximum diameter ≤3.0 cm, 50 lesions were malignant and 14 were benign. In the group with maximum diameter >3.0 cm, 62 lesions were malignant and 20 were benign. In the group with maximum diameter ≤3.0 cm, there were no significant differences in location, boundary, echo, homogeneity and small cystic area between malignant tumors and benign tumors (P>0.05). In the group with maximum diameter >3.0 cm, there were significant differences in echo, homogeneity and small cystic area between malignant tumors and benign tumors (P<0.05). For all of the benign tumors, there were no significant difference between CDFI and SMI in evaluating Adler grade, vascular morphology and peripheral blood flow (P>0.05). For malignant tumors with maximum diameter ≤3.0 cm, 43 lesions with Adler grade 2-3 were detected by SMI, which was higher than CDFI (32, P<0.05). There were 38 lesions with dendritic and irregular vascular morphology detected by SMI, which was higher than CDFI (7, P<0.05). The detected rate of peripheral annular or semi-annular blood flow in lesions was 80.0% (40/50), higher than CDFI (18/50, P<0.05). While in malignant tumors with maximum diameter >3 cm, the lesion with peripheral annular or semi-annular blood flow detected by SMI was 38, higher than 22 of CDFI (P<0.05). The area under the receiver operating characteristic (ROC) curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter ≤3.0 cm was 0.627 (sensitivity: 54.0%, specificity: 71.4%) and 0.791 (sensitivity: 94.0%, specificity: 64.3%), respectively, with statistically significant difference (P=0.039). The area under the ROC curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter>3.0 cm was 0.852 (sensitivity: 85.5%, specificity: 85.0%) and 0.860 (sensitivity: 91.9%, specificity: 80.0%), respectively, without statistically significance (P=0.858). Conclusions: SMI is superior to CDFI in detecting low-velocity blood flow and microvessels in both malignant and benign renal tumors, and can effectively improve the display rate of peripheral blood flow in malignant tumors. Otherwise, SMI can provide better diagnostic efficiency for renal tumors with the maximum diameter ≤3.0 cm.

[Humanized BCMA CAR-T cell salvage therapy in two refractory multiple myeloma patients who progressed after their murine BCMA CAR-T cell therapy].

Objective: To observe the efficacy and safety of humanized anti-BCMA chimeric antigen receptor modified (BCMA CAR) -T cell therapy after disease progression with their murine BCMA CAR-T cell therapy in patients with relapsed/refractory multiple myeloma (MM) . Methods: Study participants underwent leukapheresis to collect T cells for BCMA CAR-T manufacturing. Patients were pretreated with intensive chemotherapy (fludarabine combined with cytarabine) before CAR-T therapy. Adverse events (AEs) , CAR DNA expansion, and cytokine were monitored. In vitro, transfection efficacy, specific cytotoxicity, and inflammatory response were detected when co-cultured with effector and target cells. Results: Patient (PT) 1 and 2 achieved complete remission (CR) and disease stability at 3 months post murine CAR-T therapy. However, 16 and 18 months later, they experienced progression of disease (PD) , and patient 1 presented with extramedullary disease at PD. Both of the patients received humanized CAR-T therapy and achieved partial remission (PR) and very good partial remission (VGPR) post humanized CAR-T therapy. PT1 achieved CR of the soft tissue masses at 4 months post humanized CAR-T therapy. Notably, the median peak of the BCMA CAR-T cells, copy of BCMA CAR gene, persistence of BCMA CAR-T, and the peak levels of IL-6, IL-8, IL-10, IFN-γ and TNF-α were higher in humanized CAR-T therapy than those in the murine CAR-T therapy. During the murine CAR-T therapy, both of the patients experienced grade 1 CRS and no ICANS. PT1 experienced grade 3 CRS and grade 2 ICANS during humanized CAR-T therapy, which were relieved by supportive care. Grade 2 CRS was observed for patient 2 during humanized CAR-T therapy. Humanized BCMA CAR-T cells showed a higher inflammatory response and in vitro cytotoxicity than that of murine BCMA CAR-T cells with effector/targets cells at 1∶1 over 48 hours (P<0.001) . The proportions of residual cells in humanized BCMA CAR-T and murine CAR-T were (17.38±5.18) % vs (28.27±4.58) %, (13.25±1.62) % vs (22.77±1.77) % for PT1 and PT2, respectively. Conclusions: The humanized BCMA CAR-T cell therapy was efficient and safe for patients who experienced progression of disease after the murine CAR-T therapy, especially for patients with extramedullary disease.

LINC00346 accelerates the malignant progression of colorectal cancer via competitively binding to miRNA-101-5p/MMP9.

The article "LINC00346 accelerates the malignant progression of colorectal cancer via competitively binding to miRNA-101-5p/MMP9, by W.-H. Tong, J.-F. Mu, S.-P. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (12): 6639-6646-DOI: 10.26355/eurrev_202006_21650-PMID: 32633353" has been withdrawn from the authors since they decided to perform further experiments. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/21650.

[In vitro studies on the transfer of CAR into leukemia cells due to their residue in the autologous CAR-T cell preparation system for acute B-cell acute lymphoblastic leukemia].

Objective: To investigate the characteristics and cytotoxicity in vitro of the residual leukemia cells in the culture system that caused the accidental transfer of CD19 chimeric antigen receptor (CAR) into leukemia cells during the preparation of autologous CD19 CAR-T cells of relapsed/refractory B-cell acute lymphoblastic leukemia. Methods: ①Peripheral blood mononuclear cells (PBMC) of 30 patients with relapsed/refractory B-cell acute lymphoblastic anemia (R/R B-ALL) who accepted CD19 CAR-T cell therapy and six healthy volunteers were collected. ②The residual leukemia cells were analyzed by flow cytometry in the system after the PBMCs of R/R B-ALL patients were sorted by CD3 magnetic beads. ③ CD3(+) T cells from patients and healthy volunteers were transfected with CD19 CAR and CD22 CAR lentivirus to prepare CD19 CAR-T and CD22 CAR-T cells. ④The Nalm-6 cell line was resuscitated and the Nalm-6 cells with CD19 CAR lentivirus were transfected to prepare CD19 CAR-Nalm-6 cells. The patient's primary ALL cells were transfected with CD19 CAR lentivirus at the same time. ⑤The transfection rates were analyzed by flow cytometer, the cell proliferation was analyzed by the CCK-8 method, and the cell-killing activities were detected by the lactate dehydrogenase method. Results: ① Among the 30 R/R B-ALL patients who received CD19 CAR-T cell therapy, two patients had 2.04% and 3.32% residual leukemia cells in CD3(+) T cells. After 4 days in culture, the residual leukemia cells disappeared and could not be detected by a flow cytometer with prolonged cultivation in vitro. ② The proliferation of CD19 CAR-Nalm-6 cells was higher than that of the Nalm-6 cells. ③ The killing activity of the CD19 CAR-T cells on Nalm-6 cells was higher than that of the CD19 CAR-Nalm6 cells at a target ratio of 1∶1 on 24, 48, 72 h, respectively. The cytotoxicity of CD22 CAR-T cells on CD19 CAR-Nalm-6 cells was significantly higher than that of CD19 CAR-T cells. ④ The cytotoxicity of CD22 CAR-T alone on CD19 CAR-Nalm-6 cells was higher than that of CD19 CAR-T combined with CD22 CAR-T at the same target ratio. Conclusion: The residual leukemia cells in the culture system in the preparation of CD19 CAR-T cells may lead to the introduction of CD19 CAR into leukemia cells and results in the failure of the CD19 CAR-T cell therapy. Detecting the residual leukemia cells in the culture system via flow cytometry before transfection with CD19 CAR lentivirus is needed. Thus, CD22 CAR-T cell therapy could be used as one of the salvage treatments.

[Effects of SPAG6 silencing and decitabine treatment on apoptosis and phosphatase and tensin homolog methylation in SKM-1 cells].

Objective: To investigate the effects of SPAG6 silencing and decitabine on apoptosis and phosphatase and tensin homolog (PTEN) methylation in SKM-1 cells in vitro and in vivo. Methods: SKM-1 cells were transfected with a lentiviral vector to silence the expression of SPAG6. Cell survival rate was detected by CCK8 after treatment with decitabine, and cell apoptosis was detected by flow cytometry. Protein expression and methylation of PTEN were detected using Western blot and merozoite surface protein (MSP) . An non-obese diabetic/severe combined inmunodeficiency disease (NOD/SCID) mice xenograft tumor model was established, and the apoptosis and PTEN expression of tumor tissue were observed through terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and immunohistochemistry (IHC) , respectively. Results: After lentivirus transfection, SPAG6 in the interference group was silenced successfully. CCK8 results indicated that the cell survival rate of SKM-1 cells treated with decitabine decreased. Flow cytometry showed that the apoptosis rate of cells treated with decitabine [ (17.35±3.37) %] was higher than that of the untreated group (5.09%±2.06%) and the apoptosis rate of the SPAG6 silencing combined with the decitabine treatment group was the highest [ (36.34±4.00) %]. After treatment with decitabine, the expression of DNMT1 decreased, while the expression of PTEN increased, and the promoter methylation degree of PTEN also decreased. Moreover, the increased protein level caused by PTEN demethylation was the most obvious in the SPAG6 in the interference shRNA group treated with decitabine. In NOD/SCID mice, the tumor volume of the decitabine group was significantly smaller than that of the placebo group, and the tumor volume of the SPAG6 silencing combined with the decitabine treatment group was the smallest. Additionally, the apoptosis rate was the highest (the positive ratio was 3.57±0.48) . Conclusion: SPAG6 silencing may enhance the apoptosis level and the effect of PTEN demethylation in SKM-1 cells and enhance the antitumor effect of decitabine in the NOD/SCID xenograft mouse model.

MicroRNA-141-3p promoted the progression of nasopharyngeal carcinoma through targeting DLC1.

OBJECTIVE: Previous studies have shown that the function of miR-141 has tissue specificity. However, the role of miR-141-3p has not been reported in nasopharyngeal carcinoma (NPC). Therefore, this study explored the function of miR-141-3p in NPC. PATIENTS AND METHODS: MiR-141-3p expression in NPC tissues was examined via quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assay. Cell Counting Kit-8 (CCK-8) and transwell assays were used to explore the function of miR-141-3p. The relationship between miR-141-3p and DLC1 was verified by Dual-Luciferase assay. Protein expression was observed by immunocytochemical assay and Western blot analysis. RESULTS: Upregulation of miR-141-3p associated with poor prognosis was detected in NPC patients. Moreover, overexpression of miR-141-3p promoted cell proliferation, migration, and invasion in NPC cells. It was also found that miR-141-3p promoted EMT and activated the mTOR signaling pathway in NPC. Furthermore, DLC1 was indicated as a direct target of miR-141-3p and miR-141-3p negatively correlated with DLC1 expression in NPC. In particular, upregulation of DLC1 could impair the promoted effect of miR-141-3p in NPC. CONCLUSIONS: MiR-141-3p promotes the progression of NPC by targeting DLC1 and activating the mTOR pathway.

[Pathological diagnosis of lung cancer based on deep transfer learning].

Objective: To establish an artificial intelligence (AI)-assisted diagnostic system for lung cancer via deep transfer learning. Methods: The researchers collected 519 lung pathologic slides from 2016 to 2019, covering various lung tissues, including normal tissues, adenocarcinoma, squamous cell carcinoma and small cell carcinoma, from the Beijing Chest Hospital, the Capital Medical University. The slides were digitized by scanner, and 316 slides were used as training set and 203 as the internal test set. The researchers labeled all the training slides by pathologists and establish a semantic segmentation model based on DeepLab v3 with ResNet-50 to detect lung cancers at the pixel level. To perform transfer learning, the researchers utilized the gastric cancer detection model to initialize the deep neural network parameters. The lung cancer detection convolutional neural network was further trained by fine-tuning of the labeled data. The deep learning model was tested by 203 slides in the internal test set and 1 081 slides obtained from TCIA database, named as the external test set. Results: The model trained with transfer learning showed substantial accuracy advantage against the one trained from scratch for the internal test set [area under curve (AUC) 0.988 vs. 0.971, Kappa 0.852 vs. 0.832]. For the external test set, the transferred model achieved an AUC of 0.968 and Kappa of 0.828, indicating superior generalization ability. By studying the predictions made by the model, the researchers obtained deeper understandings of the deep learning model. Conclusions: The lung cancer histopathological diagnostic system achieves higher accuracy and superior generalization ability. With the development of histopathological AI, the transfer learning can effectively train diagnosis models and shorten the learning period, and improve the model performance.

[Analysis of treatment modalities and prognosis of patients with gallbladder cancer in China from 2010 to 2017].

Objective: To evaluate the clinical characteristics and prognosis of gallbladder cancer (GBC) patients in China. Methods: This retrospective multicenter cohort study enrolled 3 528 consecutive GBC patients diagnosed between January 2010 to December 2017 in 15 hospitals from 10 provinces. There were 1 345 (38.12%) males and 2 183 (61.88%) females.The age of diagnosis was (63.7±10.8) years old (range: 26 to 99 years old) .There were 213 patients (6.04%) in stage 0 to Ⅰ, whereas 1 059 (30.02%) in stage Ⅱ to Ⅲ, 1 874 (53.12%) in stage Ⅳ, and 382 (10.83%) unavailable. Surgery was performed on 2 255 patients (63.92%) . Three hundred and thirty-six patients received chemotherapy or radiotherapy (9.52%; of which 172 were palliative); 1 101 (31.21%) received only supportive treatment.The patient source, treatment and surgery, pathology, concomitant gallstone, and prognosis were analyzed. Results: Among the 3 528 GBC patients, 959 (27.18%) were from East China, 603 (17.09%) from East-North China, 1 533 (43.45%) from Central China, and 433(12.27%) from West China. Among the 1 578 resectable tumor, 665 (42.14%) underwent radical surgery, 913 (57.86%) underwent surgery that failed to follow the guidelines.Eight hundred and ninety-one (56.46%) patients were diagnosed before surgery, 254 (16.10%) during surgery, and 381 (24.14%) after surgery (time point of diagnosis couldn't be determined in 52 patients) .Among the 1 578 patients with resectable tumor, 759 (48.10%) had concomitant gallstone.Among the 665 patients underwent radical surgery, 69 (10.4%) showed positive resection margin, 510 (76.7%) showed negative resection margin, and 86 (12.9%) unreported margin status.The 5-year overall survival rate (5yOS) for the 3 528-patient cohort was 23.0%.The 5yOS for patients with resectable tumor was 39.6%, for patients with stage ⅣB tumor without surgery was 5.4%, and for patients with stage ⅣB tumor underwent palliative surgery was 4.7%. Conclusions: More than half GBC patients in China are diagnosed in stage Ⅳ.Curative intent surgery is valuable in improving prognosis of resectable GBC.The treatment of GBC needs further standardization.Effective comprehensive treatment for GBC is in urgent need.

Knockdown of TRIM24 suppresses growth and induces apoptosis in acute myeloid leukemia through downregulation of Wnt/GSK-3ß/ß-catenin signaling.

Tripartite motif-containing protein 24 (TRIM24) has currently emerged as a crucial cancer-related gene present in a wide range of human cancer types. However, the involvement of TRIM24 in acute myeloid leukemia (AML) has not been well investigated. The present study aims to investigate the significance, cellular function, and potential regulatory mechanism of TRIM24 in AML. We found that TRIM24 expression was significantly upregulated in AML compared with normal tissues. AML patients with low expression of TRIM24 had higher survival rates than those expressing TRIM24 at higher levels. High expression of TRIM24 was also detected in AML cells and its knockdown markedly restricted proliferation and promoted apoptosis in AML cells. Further investigation revealed that TRIM24 contributed to the regulation of Wnt/ß-catenin signaling, which was associated with modulating the phosphorylation status of glycogen synthase kinase-3ß (GSK-3ß). Inactivation of GSK-3ß partially reversed the TRIM24 knockdown-mediated antitumor effects observed in AML cells. Furthermore, knockdown of TRIM24 retarded the growth of AML-derived xenograft tumors in nude mice in vivo. Overall, these findings demonstrate that knockdown of TRIM24 impedes the AML tumor growth through the modulation of Wnt/GSK-3ß/ß-catenin signaling. These findings highlight the potential TRIM24 as an attractive anticancer target to treat AML.

LINC00346 accelerates the malignant progression of colorectal cancer via competitively binding to miRNA-101-5p/MMP9.

OBJECTIVE: To clarify the promotive effect of LINC00346 on the malignant progression of colorectal cancer (CRC) by mediating miRNA-101-5p/MMP9 axis. PATIENTS AND METHODS: Expression pattern of LINC00346 in 46 paired CRC tissues and adjacent normal tissues was determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Correlation between LINC00346 level and prognosis of CRC patients was analyzed, and the LINC00346 level in CRC cell lines was examined as well. Subsequently, potential influences of LINC00346 on cellular behaviors of CRC cells were evaluated through cell counting kit-8 (CCK-8), colony formation, transwell, and wound healing assays. Finally, Dual-Luciferase reporter gene assay was conducted to verify the binding relationship between LINC00346 and miRNA-101-5p/MMP9. RESULTS: LINC00346 was upregulated in CRC tissues and cell lines. Compared with CRC patients with low level of LINC00346, those with high level suffered a poorer prognosis, and higher metastatic rates (lymph node metastasis and distant metastasis). Transfection of sh-LINC00346 attenuated proliferative, migratory, and invasive abilities of CRC cells. In addition, LINC00346 was confirmed to bind to miRNA-101-5p, and the latter was binding to MMP9. Moreover, the overexpression of miRNA-101-5p decreased colony number, viability, and numbers of migratory and invasive cells. CONCLUSIONS: LINC00346 is upregulated in CRC and correlated with metastasis and poor prognosis of CRC. LINC00346 accelerates the malignant progression of CRC via targeting miRNA-101-5p/MMP9.

[Pathological characteristics and molecular diagnosis of non-tuberculosis Mycobacterium lung disease].

Objective: To investigate the clinicopathological features of non-tuberculosis mycobacterial lung disease and the role of molecular pathology in diagnosis. Methods: Forty-five formalin-fixed, paraffin embedded (FFPE) specimens were collected from the Department of Pathology, Beijing Chest Hospital from February 2016 to August 2019. The clinical, imaging and histopathologic features, bacteriologic data and morphologic characteristics of acid fast bacilli (AFB) were analyzed retrospectively. Specific gene sequence IS6110 of Mycobacterium tuberculosis (MTB) was detected by fluorescence PCR. Identification of Mycobacteria was by melting curve method. Fifty cases of pulmonary tuberculosis were selected in the same period as control. Results: The NTM lung cases included 18 cases (40.0%, 18/45) of M. intracellulare, eight cases (17.8%, 8/45) of M. xenopi, six cases (13.3%, 6/45) of M. avium, six cases (13.3%, 6/45) of M. kansasii, six cases (13.3%, 6/45) of M. chelonae and one case (2.2%, 1/45) of M. simiae. Histopathologically, there were necrotizing granulomas in 34 cases (75.6%, 34/45), non-necrotizing granuloma in one case (2.2%, 1/45) and non-granulomatous lesions in 10 cases (22.2%, 10/45). The necrosis was pink necrosis, basophilic necrosis rich in nuclear fragments and suppurative necrosis. Pulmonary TB showed more pink necrosis and basophilic necrosis, the difference was statistically significant (χ(2)=10.270, P=0.001; χ(2)=7.449, P=0.006). Seventeen cases (37.8%, 17/45) of NTM lung disease showed giant multinucleated giant cells, which were significantly different from those in pulmonary tuberculosis group (χ(2)=13.446, P<0.01). The number and morphology of AFB were also different. More AFB were found in M. intracellular cases and significant AFB were easily seen in M. kansasii infection. Conclusions: M. tuberculosis and NTM cannot be reliably differentiated by histologic features or by AFB morphology. Molecular assays are important to distinguish tuberculosis from NTM lung disease.

[Protective effects of oligomeric proanthocyanidins in mice exposed to paraquat].

Objective: To investigate the protective effect of oligomeric proanthocyanidins (OPCs) in paraquat-exposed mice. Methods: An acute lung injury model was established by a single intraperitoneal injection of paraquat (PQ) in BALB/c mice. The mice were randomized into control group, paraquat-exposed group (PQ group) , oligomeric proanthocyanidins group (OPCs group) , and paraquat and oligomeric proanthocyanidins-exposed group (PQ+OPCs group) , with 10 mice in each group. Only normal saline was intraperitoneally injected into the mice in the control group. The mice in the PQ group were divided into 8 subgroups according to the dose of poison administered, i.e., 0, 25, 50, 75, 100, 150, 200, and 300 mg/kg; the mice in each subgroup were given a single intraperitoneal injection of PQ and were observed and recorded for death at 3, 6, 12, 24, 36, 48, 60, 84, and 96 hours after PQ injection. Origin 8.0 was used to calculate the median lethal dose (LD(50)) of the mice at 24, 36, 48, and 60 hours after PQ injection, and the PQ dose (100 mg/kg, ip) was chosen based on the accumulated mortality rate. An OPCs-treated experimental model was established by an intraperitoneal injection of OPCs followed by a single PQ injection (100 mg/kg, ip) 1 hour later to observe the effects of OPCs on the apparent poisoning effect and fatality rate in PQ-induced mice. Immunohistochemistry was used to determine the effect of OPCs on PQ-induced lung tissue lesions. The peripheral blood samples of the mice were collected to determine the effects of OPCs on PQ-induced inflammatory factors such as tumor necrosis factor-α (TNF-α) , interleukine-1ß (IL-1ß) , and transforming growth factor-ß1 (TGF-ß1) using enzyme-linked immunosorbent assay. Results: The mortality rate was significantly correlated with the dose and exposure time in PQ-exposed mice; the mortality rate gradually increased with increasing dose and exposure time of the poison (P<0.05) . The LD(50) values for the mice were 216.67, 124.11, and 71.24 mg/kg at 24, 48, and 72 hours after PQ exposure, respectively. PQ could induce animal death at 12 hours after injection, and the mortality rate of the animals was 40% (4/10) at 48 hours after PQ exposure. The PQ-induced mortality rate of the mice in the PQ+OPCs group was reduced, and the mortality rate of the animals was 10% (1/10) at 48 hours after PQ exposure. Compared with treatment in the control group, OPCs exposure alone had no significant effect on the expression of TNF-α and TGF-ß1 in the peripheral blood (P>0.05) , but it significantly inhibited the expression of IL-1ß (P<0.05) . After 48 hours, the expression of TNF-α, TGF-ß1, and IL-1ß in peripheral blood significantly increased by 39%, 45%, and 38%, respectively, in the PQ group (P<0.05) , but they significantly decreased by 31%, 13%, and 22%, respectively, in the OPCs+PQ group as compared with the PQ group (P<0.05) . Conclusion: OPCs pretreatment can significantly alleviate PQ-induced poisoning effect.