[Colorectal adenocarcinoma with enteroblastic differentiation: a clinicopathological analysis of eight cases].

Objective: To investigate the clinicopathological features of colorectal adenocarcinoma with enteroblastic differentiation (CAED). Methods: Eight cases of CAED diagnosed at the Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, China from January 2017 to August 2023 were collected. The histopathological, immunohistochemical, molecular and prognostic features of 8 CAED cases were analyzed. The relevant studies were also reviewed. Results: Among the eight patients, there were six males and two females, with an average age of 58 years (range: 29-77 years, median age: 61.5 years). Preoperative serum alpha-fetoprotein levels were elevated in five patients (14.0-286.6 µg/L). Four tumors were located in the colon, and four tumors in the rectum. Two patients were clinically staged as advanced stage (stage Ⅳ), and distant metastasis occurred at the initial diagnosis (one case had liver metastasis, and the other had lung, bone and multiple lymph nodes metastases). Six patients were clinically staged as locally-advanced stage (Stage Ⅱ-Ⅲ). Three of them developed distant metastases after surgery (one case had liver metastasis, one case had lung metastasis, and one case had peritoneal metastasis). Additionally, two patients died at 9 months and 24 months after surgery, respectively. The tumors were composed of various proportions of adenocarcinoma components with enteroblastic differentiation (30%-100%) and classical tubular adenocarcinoma components. The component with enteroblastic differentiation exhibited morphology similar to embryonic intestinal epithelium: cuboidal or columnar tumor cells arranged in tubular, papillary, cribriform, or solid nest patterns, with clear cytoplasm. Immunohistochemical studies showed that tumor cells expressed at least one oncofetal protein (SALL4, Glypican-3, and AFP). In addition, focal squamous differentiation was observed in 3 cases (3/8). Compared to the primary tumor, both CAED and squamous differentiation components were increased in the metastatic tumors. Based on the sequencing results of KRAS, NRAS and BRAF of the primary and/or metastatic tumors, 5 cases were wild-type, while KRAS exon 2 (G13D) mutations were identified in 2 cases. Conclusions: CAED is a rare colorectal malignancy with a dismal prognosis. Accurate pathological diagnosis is prognostically valuable. The histological features of enteroblastic differentiation, elevated serum AFP levels, and the expression of oncofetal proteins play an important role in the tumor diagnosis.

Factors associated with long-term healthcare expense and steroid exposure in patients admitted with acute severe ulcerative colitis.

Background and Aim: Acute severe ulcerative colitis (ASUC) remains a significant cause of morbidity and healthcare utilization. This study aimed to characterize the total healthcare costs of ASUC, explore factors associated with significant cost over the 12 months following an index admission, and document outcomes including corticosteroid exposure. Methods: Patients admitted from January 2016 until January 2021 for ASUC to a tertiary inflammatory bowel disease (IBD) center in Australia were identified via retrospective chart review. Costs were calculated over a 12-month period following index admission. Results: Seventy-two patients (30 [42%] female, median age 39 [IQR 27-54] years) were included. The median length of stay of index admission was 6 days (IQR 5-10 days). The median cost of index admission was 7829 AUD, which was driven by the initial length of stay (P < 0.01) and requirement for colectomy (P < 0.01). Median total healthcare cost over the first 12 months was 13 873 AUD (IQR 9684-19 936 AUD), again predominately driven by the length of stay (P < 0.01) and requirement for colectomy (P < 0.01). Median cumulative corticosteroid use over 12 months inclusive of index hospitalization was 1760 mg (IQR 1560-2350 mg). Requirement for inpatient medical salvage therapy with infliximab was associated with increased corticosteroid requirement (P = 0.01). Conclusion: Healthcare expense related to ASUC remains high, driven predominantly by the length of stay during initial hospitalization and need for colectomy. From a healthcare cost perspective, novel methods to reduce inpatient hospital stay as well as need for colectomy may help reduce the economic and steroid burden of ASUC.

[Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH)].

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

[Analysis of 15 cases of toxic encephalopathy caused by acute benzene poisoning].

In this paper, the MRI manifestations of 15 patients with benzene toxic encephalopathy were analyzed, and the lesion location, shape, scope and signal were observed. The clinical manifestations of 15 patients were mainly central nervous system damage, and the MRI manifestations were characteristic, with a wide range of lesions, and the shapes were "sunflower-like", "flame-like", "bracket-like" and "butterfly-like", and the MRI signal was sheet-like long T(1), long T(2), fluid attenuated inversion recovery (FLAIR) sequence and diffusion weighted imaging (DWI) high signal, apparent diffusion coeffecient (ADC) map low, equal or high signals. When the patient's diagnosis is unclear, MRI examination may provide clinical basis for diagnosis.

[A novel attention fusion network-based multiple instance learning framework to automate diagnosis of chronic gastritis with multiple indicators].

Objective: To explore the performance of the attention-multiple instance learning (MIL) framework, an attention fusion network-based MIL, in the automated diagnosis of chronic gastritis with multiple indicators. Methods: A total of 1 015 biopsy cases of gastritis diagnosed in Fudan University Cancer Hospital, Shanghai, China and 115 biopsy cases of gastritis diagnosed in Shanghai Pudong Hospital, Shanghai, China were collected from January 1st to December 31st in 2018. All pathological sections were digitally converted into whole slide imaging (WSI). The WSI label was based on the corresponding pathological report, including "activity" "atrophy" and "intestinal metaplasia". The WSI were divided into a training set, a single test set, a mixed test set and an independent test set. The accuracy of automated diagnosis for the Attention-MIL model was validated in three test sets. Results: The area under receive-operator curve (AUC) values of Attention-MIL model in single test sets of 240 WSI were: activity 0.98, atrophy 0.89, and intestinal metaplasia 0.98; the average accuracy of the three indicators was 94.2%. The AUC values in mixed test sets of 117 WSI were: activity 0.95, atrophy 0.86, and intestinal metaplasia 0.94; the average accuracy of the three indicators was 88.3%. The AUC values in independent test sets of 115 WSI were: activity 0.93, atrophy 0.84, and intestinal metaplasia 0.90; the average accuracy of the three indicators was 85.5%. Conclusions: To assist in pathological diagnosis of chronic gastritis, the diagnostic accuracy of Attention-MIL model is very close to that of pathologists. Thus, it is suitable for practical application of artificial intelligence technology.

[Gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma: a clinicopathological study].

Objective: To investigate the clinicopathological features, immunohistochemical characteristics, differential diagnosis and prognosis of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinomas. Methods: Two cases of gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma were collected at Fudan University Shanghai Cancer Center, Shanghai, China from 2017 to 2018. The clinicopathological characteristics were analyzed. Hematoxylin and eosin, and immunohistochemical stains were performed, and the relevant literatures were reviewed. Results: The two patients were both male, aged 60 and 74 years, respectively. Their symptoms were both abdominal pain. The tumor arose in the esophagogastric junction in case 1, and the cardia to the fundus and the posterior wall of the upper part of gastric body in case 2. Both tumors were present as an ulcerative mass. The patients died of tumor 11 months and 8 months after surgery, respectively. Histologically, the tumor cells arranged in sheets, nests, cords or trabecular patterns, and pseudoavleolar structure. The tumor cells were epithelioid with uniform morphology, while the tumors showed scant stroma and massive necrosis. Variable rhabdoid cells and multinucleated giant cells were seen in both cases. SMARCA4 encoding protein BRG1 was undetectable in both tumors, while SMARCB1 encoding protein INI1 was detected. The tumor cells were diffusely positive for vimentin and negative for epithelial marker (CKpan), gastrointestinal stromal tumor markers (CD117 and DOG1), myogenic markers (desmin and myogenin), melanoma markers (S-100 protein, SOX10 and HMB45), and lymphohematopoietic markers (LCA and CD20). Conclusions: Gastric SWI/SNF-complex deficient undifferentiated/rhabdoid carcinoma is a rare and highly aggressive tumor with poor prognosis. The detection of subunits protein expression of SWI/SNF complex is important for diagnosis of the tumor.

[The impact of obstructive sleep apnea hypopnea syndrome on the perioperative and long-term outcome in patients with Stanford type A aortic dissection].

Objective: To confirm the impact of obstructive sleep apnea hypopnea syndrome (OSAHS) on perioperative and long-term outcome in patients with Stanford type A aortic dissection. Methods: From June 2010 to July 2017, the clinical data of 91 patients with Stanford type A aortic dissection were analyzed. Among them, 51 patients with OSAHS were included in the study group and 40 patients without OSAHS were included in the control group. After 36 months follow-up, all-cause death was regarded as the end event. The clinical baseline data, perioperative period and 36 months survival rate of the two groups were compared. Kanplan-Meier method was used to describe the 36 month survival curve of the two groups. Cox proportional risk model was used to evaluate the risk ratio (HR) and 95%CI of 36 month survival rate. Results: The mortality rate during hospitalization was 5.9% (3 cases) in the study group and 5.0% (2 cases) in the control group, and the difference was not statistically significant (χ~2=0.03, P>0.05). The actual follow-up was (36.2±1.5) months, 88 cases were followed up and 3 cases were lost. The all cause mortality rate of 36 months was 27.5% (14/51)in the study group and 10.0%(4/40) in the control group, the difference was statistically significant (χ~2=4.30, P<0.05).By Cox proportional risk model analysis, 36 months after operation, the study group was compared with the control group after adjusting for age, male, bicuspid of aortic valve, chronic obstructive pulmonary disease, anemia, preoperative pericardial tamponade, postoperative organ dysfunction, preoperative LVEF, emergency operation, Sun's operation, coronary artery bypass grafting, hypertension, cardiac arrhythmia, and advanced avulsion of distal aortic dissection The survival rate was lower, the difference was statistically significant (P<0.05).In addition to OSAHS, coronary artery bypass grafting and preoperative pericardial tamponade were also risk factors for the increase of 36 month mortality rate (HR=11.28,95%CI: 1.98-46.25, P=0.009; HR=9.08, 95%CI: 2.22-41.3, P=0.032). Conclusions: There was no significant difference in mortality during hospitalization in patients with Stanford A aortic dissection combined with OSAHS. The survival rate of 36 months after operation was lower than that of the control group.

SPL36 Encodes a Receptor-like Protein Kinase that Regulates Programmed Cell Death and Defense Responses in Rice.

Lesion mimic mutants spontaneously produce disease spots in the absence of biotic or abiotic stresses. Analyzing lesion mimic mutants' sheds light on the mechanisms underlying programmed cell death and defense-related responses in plants. Here, we isolated and characterized the rice (Oryza sativa) spotted leaf 36 (spl36) mutant, which was identified from an ethyl methanesulfonate-mutagenized japonica cultivar Yundao population. spl36 displayed spontaneous cell death and enhanced resistance to rice bacterial pathogens. Gene expression analysis suggested that spl36 functions in the disease response by upregulating the expression of defense-related genes. Physiological and biochemical experiments indicated that more cell death occurred in spl36 than the wild type and that plant growth and development were affected in this mutant. We isolated SPL36 by map-based cloning. A single base substitution was detected in spl36, which results in a cysteine-to-arginine substitution in SPL36. SPL36 is predicted to encode a receptor-like protein kinase containing leucine-rich domains that may be involved in stress responses in rice. spl36 was more sensitive to salt stress than the wild type, suggesting that SPL36 also negatively regulates the salt-stress response. These findings suggest that SPL36 regulates the disease resistance response in rice by affecting the expression of defense- and stress-related genes.

LncRNA SNHG1 attenuates neuropathic pain following spinal cord injury by regulating CDK4 level.

OBJECTIVE: Neuropathic pain (NP) is one of the most intractable complications of spinal cord injury (SCI). This study aims to explore the role of long non-coding RNA (lncRNA) SNHG1 in influencing SCI-induced NP. MATERIALS AND METHODS: After establishment of the spinal nerve ligation (SNL) model in rats, spinal tissues were extracted. SNHG1 level in rat spinal tissues was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The role of SNHG1 in the development of NP was explored by assessing paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in model rats. The interaction between SNHG1 and CDK4 was explored by Luciferase assay and RIP (RNA-Binding Protein Immunoprecipitation). Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were conducted to determine inflammatory factor levels in rat spinal tissues. RESULTS: SNHG1 was upregulated in rats undergoing SNL. Knockdown of SNHG1 alleviated the development of NP and overexpression of SNHG1 was capable of inducing NP symptoms in uninjured rats. SNHG1 induced NP by directly regulating CDK4 level. CONCLUSIONS: SNHG1 is a novel target in the treatment of NP associated with neuroinflammation.

[The clinical significance of osteotomy angle prediction for sagittal alignment reconstruction].

As an effective way to reconstruct the spinal alignment, osteotomy has been widely used to reconstruct the sagittal alignment of spine and achieved significant results.In order to avoid the secondary sagittal disequilibrium caused by the inaccurate osteotomy angle, it is very important to make an appropriate operation plan before the operation and evaluate the osteotomy angle accurately.At present, scholars have proposed different targets for sagittal reconstruction of the spine with different patients and diseases.They also proposed various prediction methods of osteotomy angle according to different reconstruction standards and principles, as well as the selection of osteotomy sites and methods.In this paper, the preoperative evaluation of the osteotomy angle was reviewed in terms of the target of sagittal reconstruction, the prediction of osteotomy angle and the selection of osteotomy method and osteotomy site.

Incorrect diagnoses in patients with neutralizing anti-interferon-gamma-autoantibodies.

OBJECTIVES: Early diagnosis of adult-onset immunodeficiency associated with neutralizing anti-interferon-gamma autoantibodies (anti-IFNγ Abs) remains difficult given the lack of a distinctive phenotype and a routine test. This study aimed to investigate the determinants of incorrect tentative diagnoses and useful clues for early disease recognition. METHODS: This study enrolled adult patients who had unexplained opportunistic infections diagnosed at six hospitals and identified those having neutralizing anti-IFNγ Abs (cases). Demographics, medical history, initial presentations and laboratory data, causative pathogens, tentative diagnoses, and treatment were analysed and compared among individuals having neutralizing anti-IFNγ Abs (cases) and those without (controls). RESULTS: Among the 154 patients enrolled, neutralizing anti-IFN-γ Abs were detected in 50 (71%) of 70 patients with disseminated non-tuberculous mycobacterial infection (dNTM) but not in 84 patients without dNTM. The median time from disease onset to the recognition of dNTM associated with neutralizing anti-IFNγ Abs was 1.6 years (range, 0.25-19 years). Incorrect tentative diagnoses resulted in the administration of anti-tuberculosis regimens (60%, 30/50), immunosuppressants (48%, 24/50), and systemic chemotherapy (2%, 10/50) to the 50 cases. Multivariate analysis revealed that case patients were more likely than controls to present with multiple bone lesions (adjusted odds ratio (OR), 27.16; 95% confidence interval (CI), 1.21-609.59) and leukocytosis (adjusted OR, 1.48; 95% CI, 1.12-1.95); however, the controls had a higher rate of mycobacterial bloodstream infection (adjusted OR, 0.05; 95% CI 0.00-0.66). CONCLUSIONS: The high rate of incorrect tentative diagnoses led to frequent inappropriate management in patients with neutralizing anti-IFNγ Abs, and highlighted the need for increased awareness among clinicians.

Age distribution of human papillomavirus infection and neutralizing antibodies in healthy Chinese women aged 18-45 years enrolled in a clinical trial.

OBJECTIVES: Data from clinical trials of human papillomavirus (HPV) vaccines showed that women naïve (negative for both type-specific antibodies and DNA) to vaccine types would derive benefit from vaccination; therefore, an understanding of the proportion of naïve women in different age groups is important for developing HPV vaccination strategies. METHODS: From November 2012 to April 2013, a total of 7372 healthy women aged 18-45 years were recruited in five provinces in China. Cervical specimens and serum samples were collected for each woman at entry. Cervical specimens were first tested by the HPV DNA enzyme immunoassay method; if positive, the specimens were then tested by reverse hybridization line probe assay and HPV-16 and HPV-18 specific polymerase chain reactions. Neutralizing antibodies against HPV-16 or HPV-18 were tested with a pseudovirion-based neutralization assay. RESULTS: The overall prevalence of high-risk HPV DNA was 14.8% (1088/7367, 95% CI 14.0-15.6), and the seroprevalence of neutralizing antibodies against HPV-16 and HPV-18 was 12.6% (925/7367) and 4.9% (364/7367), respectively. In younger women (18-26 years) and middle-aged women (27-45 years), 83.8% (3116/3719) and 81.4% (2968/3648) were naïve to both HPV-16 and HPV-18 (both neutralizing antibodies and DNA were negative), respectively. In addition, 98.5% (3664/3719) and 98.0% (3575/3648) of the younger or middle-aged women were naïve to at least one HPV type (HPV-16 or HPV-18). DISCUSSION: This study revealed that the majority of Chinese women aged 18-26 years and 27-45 years were naïve to both HPV-16 and HPV-18 and would thus derive full benefit from bivalent HPV vaccination.

[Clinicopathological features and outcome of gastroenteropancreatic high-grade (WHO G3) neuroendocrine tumors: a study of 60 cases].

Objective: To investigate the clinicopathological features and outcome of gastroenteropancreatic high-grade neuroendocrine tumors. Methods: A total of 60 gastroenteropancreatic high-grade neuroendocrine tumors were collected from January 1st, 2013 to December 31th, 2018 at Fudan University Shanghai Cancer Center, with available pathology databases and clinic follow-up information. At the same time, 157 cases of gastrointestinal pancreatic neuroendocrine neoplasm (NEN) diagnosed at the hospital in 2018 were collected and the incidence of NEN at all grades was compared. Results: There were 32 males and 28 females, aged 13-80 years (mean 54 years). Pancreas primary was the most common (48%, 29/60). Nodal metastatic rate was 9/16 and distant metastatic rate was 41%(18/44). Liver was the most common site of metastasis. Among all the gastroenteropancreatic neuroendocrine neoplasms diagnosed in the hospital in 2018, the incidence of high-grade neuroendocrine tumors was the lowest (7%, 11/157). High-grade neuroendocrine tumors had typical pathologic features of well-differentiated/moderate neuroendocrine tumors, but with significant differences in mitotic rates. By immunohistochemical staining, most of the tumors expressed neuroendocrine markers and somatostatin receptor 2 was positive in 60% (12/20) of the cases. The average Ki-67 index was 30%-40%, and there was significant difference between cases (18%-80%). The overall survival of high-grade neuroendocrine tumors was 43 months, and the disease-free survival was 12 months. Conclusions: High-grade neuroendocrine tumor is a rare group of neuroendocrine tumors, with unique clinicopathological features and good prognosis. Pathological classification and grading of gastroenteropancreatic neuroendocrine neoplasms can help clinicians to select appropriate treatment and accurately evaluate prognosis.

Downregulation of miR-21 promotes tibial fracture healing in rabbits through activating ERK pathway.

OBJECTIVE: The aim of this study was to investigate the effect of micro ribonucleic acid (miR)-21 on tibial fracture healing in rabbits by regulating the extracellular signal-regulated kinase (ERK) signaling pathway, and to explore its possible underlying mechanism. MATERIALS AND METHODS: A total of 15 healthy male rabbits were randomly divided into three groups, including: model group A (fracture group, n=5), model group B (fracture treatment group, n=5), and model group C (miR-21 siRNA + treatment group, n=5). Fracture healing was observed by imaging. The content of the serum collagen I and collagen II in rabbits was detected via enzyme-linked immunosorbent assay (ELISA). The morphology of bone tissues was observed via staining. Moreover, the expressions of ERK, transforming growth factor-ß1 (TGF-ß1), and Smad in osteoblasts of tibia were observed via Western blotting and Reverse Transcription-Polymerase Chain Reaction (RT-PCR), respectively. RESULTS: There was bony callus formation in group B and C when compared with group A. Compared with group B, bony callus formation was significantly accelerated in group C, while healing cycle was shortened. Hematoxylin-eosin (HE) staining and Masson staining indicated that compared with group A, group C had more fibrous calluses, new capillaries, and fibroblasts in tissues. Meanwhile, group C exerted better maturity of collagen tissues and higher osteoid content at 20 d after modeling. Compared with group C, there were more osteoid tissues with poor maturity in group B. Meanwhile, intramembranous bone formation was deformed, and collagen content was remarkably lower in group B. The content of serum collagen I and collagen II remarkably increased in group B compared with group A (p<0.05). However, it was significantly upregulated in group C compared with group B, showing statistically significant differences (p<0.05). According to the results of Western blotting, the protein expressions of TGF-ß1, Smad, and ERK in osteoblasts were significantly upregulated in group B when compared with those in group A (p<0.05). However, they increased remarkably in group C when compared with group B (p<0.05). Besides, RT-PCR results revealed that the messenger RNA (mRNA) expressions of TGF-ß1, Smad, and ERK in osteoblasts were significantly higher in group B than those in group A (p<0.05). However, they were markedly raised in group C in comparison with group B (p<0.05). CONCLUSIONS: Down-regulation of miR-21 promotes tibial fracture healing in rabbits by activating the ERK signaling pathway.

Incidence and mortality of nasopharyngeal carcinoma: interim analysis of a cluster randomized controlled screening trial (PRO-NPC-001) in southern China.

BACKGROUND: Previous mass screening studies have shown that IgA antibodies against Epstein-Barr Virus (EBV) can facilitate early detection of nasopharyngeal carcinoma (NPC), but the impact of EBV-antibody screening for NPC-specific mortality remains unknown. PATIENTS AND METHODS: A prospective, cluster randomized, controlled trial for NPC screening (PRO-NPC-001) was conducted in 3 selected towns of Zhongshan City and 13 selected towns of Sihui City in southern China beginning in 2008. Serum samples of the screening group were tested for two previously selected anti-EBV antibodies. Subjects with serological medium risk were subsequently retested annually for 3 years, and those with serological high risk were referred to otorhinolaryngologists for diagnostic check-up. An interim analysis was carried out to evaluate the primary end points of the NPC-specific mortality and the early diagnostic rate, and the secondary end point of the NPC incidence, through linkage with the database of Zhongshan City. RESULTS: Among 70 296 total subjects, 29 413 screened participants (41.8% of the total subjects) in the screening group and 50 636 in the control group, 153 (43.3 per 100 000 person-year), 62 (55.3 per 100 000 person-year) and 99 (33.1 per 100 000 person-year) NPC cases were identified. The early diagnostic rates of NPC were significantly higher in the participants (79.0%, P < 0.0001) and the screening group (45.9%, P < 0.0001) compared with the control group (20.6%). Although no differences were found between NPC-specific mortality of the screening group and the control group [relative risk (RR)= 0.82, 95% confidence interval (CI) 0.37-1.79], lower NPC-specific mortality was noticed among participants from the screening group versus the control group (RR = 0.22, 95% CI 0.09-0.49). CONCLUSION: IgA antibodies against EBV can identify high-risk population and was effective in screening for early asymptomatic NPC. Although the mortality reduction was not significant in the primary end point, we noted encouraging evidence of a mortality reduction in screening participants in this interim analysis. CLINICAL TRIAL NUMBER: NCT00941538.

MicroRNA-765 targets MTUS1 to promote the progression of osteosarcoma via mediating ERK/EMT pathway.

OBJECTIVE: Previous studies have shown that microRNA-765 (miR-765) is involved in certain biological behaviors of human cancers. However, abnormal expression and function of miR-765 have not been reported in osteosarcoma (OS). PATIENTS AND METHODS: Changes in the expression of miR-765 and MTUS1 (Microtubule-associated tumor suppressor 1) were examined via Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The function of miR-765 was investigated through Cell Counting Kit-8 (CCK-8) and transwell assays in OS. The target of miR-765 was identified using a Dual-Luciferase reporter assay. RESULTS: MiR-765 was upregulated in OS tissues. And upregulation of miR-765 promoted cell proliferation, migration and invasion in OS. In addition, MTUS1 was confirmed as a direct target gene of miR-765. Moreover, miR-765 promoted the progression of OS through targeting MTUS1. Furthermore, miR-765 was involved in tumorigenesis of OS through activating extracellular-signal-regulated kinase/ epithelial-mesenchymal transition (ERK/EMT) pathway. CONCLUSIONS: MiR-765 targets MTUS1 to promote the progression of OS via mediating the ERK/EMT pathway. Therefore, miR-765 may be used as a novel biomarker for the diagnosis of OS.