[Clinicopathological features of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma].

Objective: To investigate the clinicopathological features, immunophenotype and gene alterations of thyroid-like low-grade nasopharyngeal papillary adenocarcinoma (TL-LGNPPA). Methods: Fifteen case of TL-LGNPPA diagnosed at Zhejiang Cancer Hospital (5 cases) and the First Affiliated Hospital, Zhejiang University School of Medicine (10 cases) from November 2011 to August 2020 were collected. Clinical and pathological examinations, immunohistochemical staining and next-generation sequencing were performed. The clinicopathological and molecular characteristics were summarized, and relevant literature was reviewed. Results: Fifteen patients were identified and included. Their median age was 36 years (range, 20-60 years). The male-female ratio was 1.0∶1.1. The most common symptoms were epistaxis and nasal obstruction. The neoplasms were located on the roof of the nasopharynx or the posterior margin of the nasal septum. The pathological features included complex papillary and glandular structures mainly composed of single or pseudostratified cubic and columnar cells, with mild to moderate cytological atypia. In some cases, spindle cell features, nuclear grooves, ground glass nuclei, squamous metaplasia, or scattered psammoma bodies were identified. In addition, nuclear polar reversal cells, hobnail cells and micropapillary structures were found, but have not been reported in previous literature. Immunohistochemistry showed that the tumor cells were diffusely positive for TTF1, CK7, vimentin and CKpan; focally positive for p40, CK5/6 and p16; and negative for Tg, NapsinA, CK20, CDX2, S-100 and PAX8. The Ki-67 positive rates ranged from 1% to 20% and were≤10% in thirteen cases (13/15). EBER in situ hybridization was negative in all cases. DNA sequencing of 6 specimens was performed and all specimens were found harboring gene mutations (EWSR1, SMAD2, ROS1, JAK3, GRIN2A, ERRCC5, STAT3, and TET2), but no hot spot gene alterations were found. No MSI-H and MMR related gene changes were detected. All tumors showed low tumor mutation burden. All 15 patients underwent endoscopic surgery, and only 1 of them underwent radiotherapy postoperatively. All patients were recurrence free and alive at the end of follow-up periods (range: 23 to 129 months). Conclusions: TL-LGNPPA is a rare indolent tumor of the nasopharynx and exhibits a unique morphology and immunophenotype. Endoscopic resection is an effective treatment for TL-LGNPPA with excellent overall prognosis.

The clinical landscape of cell-free DNA alterations in 1671 patients with advanced biliary tract cancer.

BACKGROUND: Targeted therapies have transformed clinical management of advanced biliary tract cancer (BTC). Cell-free DNA (cfDNA) analysis is an attractive approach for cancer genomic profiling that overcomes many limitations of traditional tissue-based analysis. We examined cfDNA as a tool to inform clinical management of patients with advanced BTC and generate novel insights into BTC tumor biology. PATIENTS AND METHODS: We analyzed next-generation sequencing data of 2068 cfDNA samples from 1671 patients with advanced BTC generated with Guardant360. We carried out clinical annotation on a multi-institutional subset (n = 225) to assess intra-patient cfDNA-tumor concordance and the association of cfDNA variant allele fraction (VAF) with clinical outcomes. RESULTS: Genetic alterations were detected in cfDNA in 84% of patients, with targetable alterations detected in 44% of patients. Fibroblast growth factor receptor 2 (FGFR2) fusions, isocitrate dehydrogenase 1 (IDH1) mutations, and BRAF V600E were clonal in the majority of cases, affirming these targetable alterations as early driver events in BTC. Concordance between cfDNA and tissue for mutation detection was high for IDH1 mutations (87%) and BRAF V600E (100%), and low for FGFR2 fusions (18%). cfDNA analysis uncovered novel putative mechanisms of resistance to targeted therapies, including mutation of the cysteine residue (FGFR2 C492F) to which covalent FGFR inhibitors bind. High pre-treatment cfDNA VAF was associated with poor prognosis and shorter response to chemotherapy and targeted therapy. Finally, we report the frequency of promising targets in advanced BTC currently under investigation in other advanced solid tumors, including KRAS G12C (1.0%), KRAS G12D (5.1%), PIK3CA mutations (6.8%), and ERBB2 amplifications (4.9%). CONCLUSIONS: These findings from the largest and most comprehensive study to date of cfDNA from patients with advanced BTC highlight the utility of cfDNA analysis in current management of this disease. Characterization of oncogenic drivers and mechanisms of therapeutic resistance in this study will inform drug development efforts to reduce mortality for patients with BTC.

[Relationship between onco-immunological and morphologic characteristics of lymphoepithelioma-like carcinoma and lymphocyte subtypes of peripheral blood].

Objective: To study the relationship between the onco-immunological and morphologic characteristics of lymphoepithelioma-like carcinoma (LELC) and peripheral blood lymphocyte subtypes and its clinical significance. Methods: The pathologic and clinical data of 117 LELC patients who were admitted to the Tumor Hospital of the University of Chinese Academy of Sciences from 2006 to 2018 were collected. The histological classification was based on previously reported morphological classification method. The onco-immunological and morphologic characteristics of the tumors such as lymphoid follicle formation and interstitial fibrous hyperplasia, patient's peripheral blood lymphocyte subtypes and prognosis data were collected. The relationship between various factors and their impact on prognosis were analyzed. Results: There were 117 patients, including 61 females and 56 males. The male to female ratio was 0.9∶1.0. The age of onset was 24-89 years (median 52 years). Primary sites included head and neck (68 cases), lungs (26 cases), stomach (15 cases), and others (eight cases). Morphologically, 54 cases were type Ⅰ, 62 cases were type Ⅱ, and one case could not be classified. The onco-immunological and morphologic features of the LELC tumors showed a continuous spectrum. Interstitial TILs were noted from focally to diffuse, and the interstitial fibrous tissues were from hardly visible to obvious sclerotic. Formation of lymphoid follicles was seen in 42 patients; obvious fibrosis was seen in 31 cases. Data of peripheral blood lymphocyte subtyping by flow cytometry were available in 73 cases. These data included CD3+total T cells, CD3+CD4+helper T cells, CD3+CD8+cytotoxic T cells, CD3-CD56+natural killer (NK) cells, CD3-CD19+B cells, CD4+CD45RA-T helper induction subgroup, CD4+CD45RA+ T suppression induction subgroup, CD4+CD45RO+memory T cell subgroup, CD45RA+CD45RO+activated T cell subgroup, CD8+CD38+activated cytotoxic T cell, and CD25+lymphocytes and CD44+lymphocyte. The proportion of lymphocytes of each subtype was normal in most patients, but the proportion of CD44+lymphocytes in 61 cases (83.6%) was increased; the proportion of T cell suppression induced subgroups was decreased in 53 cases (72.6%). Correlation analysis found a significant correlation between clinical stage and NK cells (P=0.023); tumor histologic type and cytotoxic T cells were significantly positively correlated (P=0.012); while tumor cell morphologic differentiation was significantly related to total T cells (P=0.003) and NK cells (P=0.026); Formation of interstitial lymphoid follicles was positively correlated with memory T cell subsets (P=0.025); Tumor interstitial fibrosis was significantly positively correlated with T suppression-induced subpopulations (P=0.004), and was significantly negatively correlated with total T cells (P=0.023) and with the expression of CD44 adhesion molecules (P=0.003). Survival analysis found that lymphoid follicle formation was a favorable prognostic factor for LELC (P=0.001). Conclusions: The onco-immunological and morphologic features in LELC show a continuous spectrum; the tumor clinicopathological characteristics and onco-immunological morphology are closely related to peripheral blood T lymphocyte subtypes, and the formation of interstitial lymphoid follicles is a favorable prognostic factor for LELC.

[Pathological features related to onco-immunity and their clinical significance of pancreatic ductal adenocarcinoma].

Objective: To investigate the tumor immunity-related pathologic features and clinical significance in pancreatic ductal adenocarcinoma (PDAC). Methods: All pathologic materials and clinical information of 192 PDAC patients from the Cancer Hospital of the University of Chinese Academy of Sciences from January 2010 to December 2020 were collected. The onco-immune microenvironment associated morphologic features were evaluated, and MHC-Ⅰ, PD-L1, CD3, and CD8 expression were detected by immunohistochemistry (IHC). Then the correlation between the factors and their influence on prognosis was analyzed. Results: There were 163 cases of non-specific adenocarcinoma (163/192, 84.90%), 18 cases of adeno-squamous carcinoma (18/192, 9.37%), and 11 cases of other rare subtypes (11/192, 5.73%). Perineural invasion was observed in 110 cases (110/192, 57.29%) and vascular invasion in 86 cases (86/192, 44.79%). There were 84 cases (84/182, 46.15%) with severe chronic inflammation. Tumor infiltrating immune cell numbers (TII-N) were increased in 52 cases (52/192, 27.08%). Lymphocytes and plasma cells were the main infiltrating immune cells in 60 cases (60/192, 31.25%), whereas in 34 cases (34/192, 17.71%) the tumors were mainly infiltrated by granulocytes, and 98 cases (98/192, 51.04%) showed mixed infiltration. CD3+T cells were deficient in 124 cases (124/192, 66.31%). CD8+T cells were deficient in 152 cases (152/192, 79.58%). MHC-Ⅰ expression was down-regulated in 156 cases (156/192, 81.25%), and PD-L1 was positive (CPS≥1) in 46 cases (46/192, 23.96%). Statistical analysis showed that TII-N was negatively correlated with vascular invasion (P=0.035), perineural invasion (P=0.002), stage (P=0.004) and long-term alcohol consumption (P=0.039). The type of immune cells correlated positively with chronic pancreatic inflammation (P=0.002), and negatively with tumor differentiation (P=0.024). CD8+T cells were positively correlated with CD3+T cells (P=0.032), MHC-Ⅰ expression (P<0.001) and PD-L1 expression (P=0.001), and negatively correlated with long-term smoking (P=0.016). Univariate analysis showed that histological nonspecific type (P=0.013) and TII-N (P<0.001) were the factors for good prognosis. Vascular invasion (P=0.032), perineural invasion (P=0.001), high stage (P=0.003) and long-term alcohol consumption (P=0.004) were adverse prognostic factors. COX multivariate risk analysis found that TII-N was an independent favorable factor for PDAC, while perineural invasion was an independent adverse risk factor. Conclusions: TII-N is an independent superior prognostic factor for PDAC, and significantly correlated with many factors; chronic alcohol consumption and smoking may inhibit onco-immunity in PDAC patients.

[Clinical characteristics of patients infected with 2019-nCoV Omicron variants BA.2 and BA.5 in Xi'an city, China].

Objective: To analyze the epidemiological and clinical characteristics of patients infected with different subtype of 2019-nCoV Omicron variants BA.2 and BA.5 in Xi'an city. Methods: A retrospective observational study was conducted to collect data of 168 patients infected with Omicron variant admitted to the designated hospital for COVID-19 charged by Xi'an Chest Hospital during 2022. Data were collected including epidemiological, clinical features, laboratory and viral load, and the difference between BA.2 and BA.5 subtype was analyzed. Results: A total of 168 patients were admitted, including 122 cases infected with BA.2 subtype, and 46 cases infected with BA.5 subtype. Patients infected with BA.2 subtype had a higher rate of cough than BA.5 subtype (43.44%∶23.91%; P=0.021). Compared with the Omicron variant BA.2, patients infected with BA.5 subtype had a higher proportion of asymptomatic and mild infections (89.13%∶68.85%; P<0.001), higher rate of vaccination (95.66%∶68.03%; P<0.001), shorter time to nucleic acid negative conversion (8.62; P=0.047), and a higher viral load at admission (P=0.005, P=0.017). Conclusions: The Omicron variant is extremely infectious with aggregated onset, but its clinical symptoms are mild. The vaccine, especially the booster vaccination, remains effective in preventing severe stage progression and improving prognosis in patients with Omicron variant infection.

Effects of guanidinoacetic acid and coated folic acid supplementation on growth performance, nutrient digestion and hepatic gene expression in Angus bulls.

To evaluate the impacts of guanidinoacetic acid (GAA) and coated folic acid (CFA) on growth performance, nutrient digestion and hepatic gene expression, fifty-two Angus bulls were assigned to four groups in a 2 × 2 factor experimental design. The CFA of 0 or 6 mg/kg dietary DM folic acid was supplemented in diets with GAA of 0 (GAA-) or 0·6 g/kg DM (GAA+), respectively. Average daily gain (ADG), feed efficiency and hepatic creatine concentration increased with GAA or CFA addition, and the increased magnitude of these parameters was greater for addition of CFA in GAA- diets than in GAA+ diets. Blood creatine concentration increased with GAA or CFA addition, and greater increase was observed when CFA was supplemented in GAA+ diets than in GAA- diets. DM intake was unchanged, but rumen total SCFA concentration and digestibilities of DM, crude protein, neutral-detergent fibre and acid-detergent fibre increased with the addition of GAA or CFA. Acetate:propionate ratio was unaffected by GAA, but increased for CFA addition. Increase in blood concentrations of albumin, total protein and insulin-like growth factor-1 (IGF-1) was observed for GAA or CFA addition. Blood folate concentration was decreased by GAA, but increased with CFA addition. Hepatic expressions of IGF-1, phosphoinositide 3-kinase, protein kinase B, mammalian target of rapamycin and ribosomal protein S6 kinase increased with GAA or CFA addition. Results indicated that the combined supplementation of GAA and CFA could not cause ADG increase more when compared with GAA or CFA addition alone.

[Clinical observation of the curative effect after 5-year follow-up of single tooth implant-supported restorations in the posterior region].

OBJECTIVE: To analyze the clinical curative effect after 5-year follow-up of single tooth implant-supported restorations in the posterior region. METHODS: In the study, patients with single tooth implant-supported restorations in the posterior region after loading 5-year in the Second Clinical Division of Peking University School and Hospital of Stomatology from October 2005 to May 2010 was enrolled. The implant survival rate, prosthetic conditions (including the structural integrity or loosening of the prosthesis, the retention of the materials used to fill access holes of screw-retained implant crowns, loosening or fractures of the implant abutment or screw) and marginal bone lever level around implants were determined by clinical and radiographic examination. RESULTS: The study was composed of 215 patients, the mean age was 48.6 years (range: 27 to 71), and 321 soft tissue implants were inserted. There were 9 implants loose and lost during the visit, the cumulative success rate was 97.2%. In the 312 remaining implants, 120 implants were placed in the upper jaws (38.5%) and 192 in the lower jaws (61.5%). Three different diameters as 3.3 mm (5 implants), 4.1 mm (115 implants) and 4.8 mm (192 implants) and three different lengths as 8 mm (21 implants), 10 mm (206 implants) and 12 mm (85 implants) were used, respectively. 277 (88.8%) cement-retained and 35 (11.2%) screw-retained implant-supported single crowns were made. The marginal bone loss (MBL) around dental implants after loading 5 years in the mesial and distal sides were (0.73±0.25) mm and (0.78±0.26) mm, respectively. There was no significant difference among MBL and bone quality, implant type, angle of abutment, prosthodontic type, crown-to-implant ratio, gender, and age of the patients (P > 0.05). The major mechanical complications after restoration involved loosening (8.6%) and fracture (2.9%) of the crown retainer screw, loss of resin covering the screw (11.4%), and the most frequent mechanical complications were loss of crown retention (14.1%) and fracture of porcelain (13.8%). The incidence of loss of crown retention was correlated with insufficient clinical crown height or using angle abutment (P < 0.05). CONCLUSION: After loading 5 years, the bone level around the soft-tissue-implant placed in posterior region was stable. To minimize the frequency of mechanical complications after restoration, protocols must be established from diagnosis to the completion of treatment and follow up of implant-supported prostheses, especially in terms of adequate technical steps and careful radiographic evaluation of the components.

Hippocampal subfield volumes in mood disorders.

Volume reduction and shape abnormality of the hippocampus have been associated with mood disorders. However, the hippocampus is not a uniform structure and consists of several subfields, such as the cornu ammonis (CA) subfields CA1-4, the dentate gyrus (DG) including a granule cell layer (GCL) and a molecular layer (ML) that continuously crosses adjacent subiculum (Sub) and CA fields. It is known that cellular and molecular mechanisms associated with mood disorders may be localized to specific hippocampal subfields. Thus, it is necessary to investigate the link between the in vivo hippocampal subfield volumes and specific mood disorders, such as bipolar disorder (BD) and major depressive disorder (MDD). In the present study, we used a state-of-the-art hippocampal segmentation approach, and we found that patients with BD had reduced volumes of hippocampal subfields, specifically in the left CA4, GCL, ML and both sides of the hippocampal tail, compared with healthy subjects and patients with MDD. The volume reduction was especially severe in patients with bipolar I disorder (BD-I). We also demonstrated that hippocampal subfield volume reduction was associated with the progression of the illness. For patients with BD-I, the volumes of the right CA1, ML and Sub decreased as the illness duration increased, and the volumes of both sides of the CA2/3, CA4 and hippocampal tail had negative correlations with the number of manic episodes. These results indicated that among the mood disorders the hippocampal subfields were more affected in BD-I compared with BD-II and MDD, and manic episodes had focused progressive effect on the CA2/3 and CA4 and hippocampal tail.

[Clinical observation on soft and hard tissue changes of immediate implantation and immediate reconstruction in anterior region after loading 3 years].

OBJECTIVE: To observe the change of soft and hard tissue in dental immediate implantation and immediate reconstruction in anterior region after loading 3 years. METHODS: Patients with single anterior tooth loss in the Department of Second Dental Center, Peking University School and Hospital of Stomatology from October 2008 to October 2012 were enrolled. The gingival papilla height, labial gingival margin level and peri-implant bone level were measured immediately after the permanent restoration and 3 years later. RESULTS: In the study, 20 patients were treated by immediate implantation and immediate reconstruction for 22 implants; 24 patients were treated by delayed implant for 29 implants. Implant stability quotient (ISQ) value of the two groups showed no significant difference before permanent restoration (P>0.05). In all the cases after loading 3 years, the average mesial gingival papilla height in implant area of the immediate group and delayed group changed by (0.34±0.54) mm and (0.05±0.39) mm respectively (P=0.07), the distal gingival papilla height changed by (0.43±0.42) mm and (0.36±0.48) mm respectively (P=0.13), while the labial gingival margin level shrinkages were (0.70±0.40) mm and (0.62±0.34) mm respectively (P=0.23). Peri-implant bone losses in the mesial side were (1.02±0.50) mm and (0.88±0.46) mm respectively (P=0.53), while those in the distal side were (1.05±0.34) mm and (0.95±0.47) mm respectively (P=0.21). All these indicators showed no significant difference between the two groups (P>0.05); When the permanent prostheses delivered, the distributions of the gingival papilla index were different between the two groups whether in the mesial side or in the distal side (P<0.05). CONCLUSION: The changes of the soft and hard tissue of the immediate implantation and immediate reconstruction in anterior region after loading 3 years were basically equivalent to the conventional implant restoration. But, the former was obviously better than the latter in reducing the duration of treatment and in getting the ideal dental papilla aesthetic effect.

[Survival of patients with primary central nervous system diffuse large B-cell lymphoma: impact of gene aberrations and protein overexpression of bcl-2 and C-MYC, and selection of chemotherapy regimens].

Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.

Risk factors for the treatment outcome of retreated pulmonary tuberculosis patients in China: an optimized prediction model.

Retreatment of tuberculosis (TB) often fails in China, yet the risk factors associated with the failure remain unclear. To identify risk factors for the treatment failure of retreated pulmonary tuberculosis (PTB) patients, we analyzed the data of 395 retreated PTB patients who received retreatment between July 2009 and July 2011 in China. PTB patients were categorized into 'success' and 'failure' groups by their treatment outcome. Univariable and multivariable logistic regression were used to evaluate the association between treatment outcome and socio-demographic as well as clinical factors. We also created an optimized risk score model to evaluate the predictive values of these risk factors on treatment failure. Of 395 patients, 99 (25·1%) were diagnosed as retreatment failure. Our results showed that risk factors associated with treatment failure included drug resistance, low education level, low body mass index (6 months), standard treatment regimen, retreatment type, positive culture result after 2 months of treatment, and the place where the first medicine was taken. An Optimized Framingham risk model was then used to calculate the risk scores of these factors. Place where first medicine was taken (temporary living places) received a score of 6, which was highest among all the factors. The predicted probability of treatment failure increases as risk score increases. Ten out of 359 patients had a risk score >9, which corresponded to an estimated probability of treatment failure >70%. In conclusion, we have identified multiple clinical and socio-demographic factors that are associated with treatment failure of retreated PTB patients. We also created an optimized risk score model that was effective in predicting the retreatment failure. These results provide novel insights for the prognosis and improvement of treatment for retreated PTB patients.

Involvement of the MAPK pathway in the pressure-induced synovial metaplasia procedure for the temporomandibular joint.

Abnormal pressure is an important factor that contributes to bone adaptation in the temporomandibular joint (TMJ). We determined the effect of the mitogen-activated protein kinases (MAPK) pathway on the pressure-induced synovial metaplasia procedure for the TMJ, both in vitro and in vivo. Synovial fibroblasts (SFs) were exacted from rat TMJs and exposed to different hydrostatic pressures. The protein extracts were analyzed to determine the activation of ERK1/2, JNK, and p38. Surgical anterior disc displacement (ADD) was also performed on Japanese rabbits, and the proteins of TMJ were isolated to analyze pressure-induced MAPK activation after 1, 2, 4, and 8 weeks. The results showed that the activation of ERK1/2 and JNK in SFs significantly changed with increasing hydrostatic pressure, whereas p38 activation did not change. Moreover, p38 was activated in animals 1 week after surgical ADD. The levels of p38 gradually increased after 2 and 4 weeks, and then slightly decreased but remained higher than in the control 8 weeks after surgical ADD. Nevertheless, JNK was rarely activated after the ADD treatment. Our findings suggest the involvement of MAPK activation in the pressure-induced synovial metaplasia procedure with pressure loading in TMJ.

[The understanding of Epstein-Barr virus associated lymphoproliferative disorder].

In recent years, there are increasing articles concerning Epstein-Barr virus associated lymphoproliferative disorder (EBV+ LPD), and the name of EBV+ LPD is used widely. However, the meaning of EBV+ LPD used is not the same, which triggered confusion of the understanding and obstacles of the communication. In order to solve this problem. Literature was reviewed with combination of our cases to clarify the concept of EBV+ LPD and to expound our understanding about it. In general, it is currently accepted that EBV+ LPD refers to a spectrum of lymphoid tissue diseases with EBV infection, including hyperplasia, borderline lesions, and neoplastic diseases. According to this concept, EBV+ LPD should not include infectious mononucleosis (IM) and severe acute EBV infection (EBV+ hemophagocytic lymphohistiocytosis, fatal IM, fulminant IM, fulminant T-cell LPD), and should not include the explicitly named EBV+ lymphomas (such as extranodal NK/T cell lymphoma, aggressive NK cell leukemia, Burkitt lymphoma, and Hodgkin lymphoma, etc.) either. EBV+ LPD should currently include: (1) EBV+ B cell-LPD: lymphomatoid granulomatosis, EBV + immunodeficiency related LPD, chronic active EBV infection-B cell type, senile EBV+ LPD, etc. (2) EBV+ T/NK cell-LPD: CAEBV-T/NK cell type, hydroa vacciniforme, hypersensitivity of mosquito bite, etc. In addition, EBV+ LPD is classified, based on the disease process, pathological and molecular data, as 3 grades: grade1, hyperplasia (polymorphic lesions with polyclonal cells); grade 2, borderline (polymorphic lesions with clonality); grade 3, neoplasm (monomorphic lesions with clonality). There are overlaps between EBV+ LPD and typical hyperplasia, as well as EBV+ LPD and typical lymphomas. However, the most important tasks are clinical vigilance, early identification of potential severe complications, and treating the patients in a timely manner to avoid serious complications, as well as the active treatment to save lives when the complications happened.

Changes in the corpus callosum in women with late-stage bipolar disorder.

OBJECTIVE: This study investigated the differences in corpus callosum (CC) volumes between women with early-stage and late-stage bipolar I (BP I) disorder using the criteria previously described in the literature. METHOD: We compared women with early- and late-stage BP I using criteria described in the Staging Systems Task Force Report of the International Society for Bipolar Disorders. We included 20 patients with early stage and 21 patients with late-stage BP I and a group of 25 healthy controls. Patients and controls underwent structural magnetic resonance imaging. Information on the clinical features of bipolar disorder was collected using a standardized questionnaire. Anatomical volumes of five regions of CC were compared between the three groups. RESULTS: Women with late-stage BP I disorder had reduced posterior CC volumes compared with early-stage bipolar I patients and controls (F = 6.05; P = 0.004). The difference was significant after controlling for age, comorbidity with post-traumatic stress disorder, psychotic symptoms during mood episodes, and current use of medication. CONCLUSION: The posterior CC was significantly decreased in volume in women with late-stage bipolar disorder. These findings suggest that CC may be an anatomical target of neuroprogression in the course of bipolar disorder in women.

Effects of metal ions and hydrogen peroxide on the phenotype of yeast hom6Δ mutant.

UNLABELLED: HOM6 is a major gene in the aspartate pathway which leads to biosynthesis of threonine and methionine. The phenotypes of the gene deletion mutant (hom6∆) in a variety of cultural conditions have previously provided meaningful insights into the biological roles of HOM6 and its upstream intermediate metabolites. Here, we conducted a survey on a spectrum of metal ions for their effect on the aspartate pathway and broader sulphur metabolism. We show that manganese (Mn(2+) ) promoted the growth of hom6∆ under both anaerobic and aerobic conditions. Unexpectedly, 4 mmol l(-1) hydrogen peroxide (H2 O2 ), a dose normally causing temporary cell growth arrest, enhanced the growth of hom6∆ under the anaerobic condition only, while it had no effect on the wild type strain BY4743. We propose that Mn(2+) and H2 O2 promote the growth of hom6∆ by reducing the accumulation of the toxic intermediate metabolite-aspartate ß-semialdehyde, via directing the aspartate pathway to the central sugar metabolism-tricarboxylic acid cycle. SIGNIFICANCE AND IMPACT OF THE STUDY: This study focuses on the yeast strain which lacks homoserine dehydrogenase encoded by HOM6 gene in aspartate metabolism. The HOM6-deletion mutant (hom6Δ) was analysed in the context of varying environmental parameters such as metal ions and oxidants, under anaerobic and aerobic conditions. We demonstrated that both manganese and hydrogen peroxide can promote the growth of hom6Δ, with the latter exerting such effect only under anaerobic condition. The findings are relevant to the research areas of ageing and anti-fungal drug development. It highlights the importance of interactions between gene expression and environmental factors as well as culture conditions.

Bioinformatic analysis of the effect of type II diabetes on skin wound healing.

We examined the relationship between type 2 diabetes and skin wound healing. GSE38396 was downloaded from the Gene Expression Omnibus database and preprocessed using the RMA function of the Affy package. Differentially expressed genes (DEGs) were identified using the limma package, then DAVID was applied to per-form Gene Ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis. MicroRNAs and their target genes were screened from the miRecords database and subjected to functional analysis. Finally, the STRING online database was applied to identify the protein-protein interaction relationships, and a combined score > 0.5 was considered to indicate an interaction. A total of 421 DEGs (208 upregulated and 213 downregulated genes) were identified in the skin lymphatic endothelial cells of patients with type II diabetes. Twenty-four microRNAs and 34 target genes were screened, including those involved in cell migration, regulation of cell proliferation, cell death, and cell adhesion regulation, among others. Protein-protein interaction network clustering analysis identified a module composed of 25 genes, and INTERPRO protein domain enrichment analysis showed that the protein domain of the clustering module main-ly contained the insulin-like growth factor binding proteins IGFBP3 and CYR61. IGFBP3 and CYR61 may play important roles in skin wound healing in diabetes patients. This information may be useful for developing methods to treat skin refractory wounds in type II diabetes.

Effects and toxicity of neoadjuvant chemotherapy preoperative followed by adjuvant chemoradiation in small cell neurdendocrine cervical carcinoma.

OBJECTIVE: To determine the efficacy and toxicity of a combined-modality regimen of neoadjuvant chemotherapy (NACT) before primary radical surgery followed by adjuvant chemoradiation in small cell neuroendocrine cervical cancer (SCNEC) patients. MATERIALS AND METHODS: The study was approved by the ethics committee of the present hospital. The records of 23 SCNEC patients who received NACT before primary radical surgery were reviewed at the Zhejiang Cancer Hospital between January 1998 and May 2010. All patients received one to four cycles of NACT and two to eight cycles of chemotherapy (NACT and adjuvant chemotherapy) on the basis of platinum, 17 (73.9%) patients received NACT using a regimen consisting of etoposide and cisplatin (EP). Eighteen (85.7%) patients received adjuvant chemotherapy using a regimen consisting of PE and EP. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: Of the 23 eligible patients, 18 had Stages I-IIA, five had Stages IIB-IIIB disease. Twelve patients (52.2%) developed grade 3 and 4 neutropenia. Fourteen patients (60.9%) developed grade 3 and 4 anemia. The majority of grade 3 and 4 neutropenia and non-hematologic toxicities were usually self-limited. Three patients (13.0%) who postoperative pathology showed pathologic complete response (CR) had better prognosis than those did not show pathologic CR; the median survival was 69.5 months (range, 51.1-177.1), 54.5 months (range: 7.3-81.5), respectively. In univariate analysis, lymphovascular space invasion (LSI) (p = 0.013), and deep stromal invasion (DSI) (p = 0.001) were considered poor prognostic factors. With a median follow-up for surviving patients was 40.8 months (range, 7-177), 12 patients recurred, 11 of which had died. The estimated three- and five-year overall survival (OS) rates for all patients were 55.8% and 39.9%, respectively. CONCLUSION: NACT before primary radical surgery followed by adjuvant chemoradiation or chemotherapy was well tolerated and seems to be effective for early stage SCNEC patients. Prospective clinical study is necessary and we hope that this research's results help to design a prospective clinical study.

Prognostic factors and treatment comparison in small cell neuroendocrine cervical carcinoma.

OBJECTIVE: To determine the clinicopathologic factors associated with survival in small cell neuroendocrine cervical cancer (SCNEC) patients. MATERIALS AND METHODS: The study was approved by the ethics committee of the hospital. The records of 64 SCNEC patients from 9,474 Chinese patients with cervical cancer at the Zhejiang Cancer Hospital were reviewed. Kaplan-Meier and Cox regression methods were used for analyses. RESULTS: Of 64 patients, 47 had Stages I-IIA, 12 had Stages IIB-IVA, and five had Stage IV-B disease. A total of 81.25% underwent surgery, 89.1% received chemotherapy, 62.5% received radiation, 34.4% received neoadjuvant chemotherapy (NACT), and 34.4% received concurrent chemoradiation (CCRT). The median follow-up for surviving patients was 35.7 months (range: 0.5-160), and 29 (50%) of the 58 patients with Stages I-III had either disease recurrence or progression. The median time to first relapse was 10.5 months (range: 0-88.2). The five-year overall survival of patients in Stages I-IIA and IIB-IVB disease was 54.4% and 9.8%, respectively (p = 0.001). Women with early-stage (Stages IIBIIA) disease had median survival rates of 94 months compared with 21.4 months in the advanced-stage (Stages IIB-IVB) group. In univariate analysis, advanced-stage (p = 0.001), without radical surgery (p = 0.002) and deep stromal invasion (DSI) (p = 0.000) were considered poor prognostic factors. In a multivariable analysis, tumor size > four cm (p = 0.048), postoperative radiation (p = 0.038) for early-stage patients and the FIGO stage (p = 0.040) of disease in the overall population remained as independent prognostic factor of survival. CONCLUSION: The FIGO stage was found to be an independent prognostic factor of SCNEC. In addition, tumor size > four cm and DSI was associated with poor survival. Postoperative radiation for early-stage patients may not improve survival. The role of primary and postoperative NACT or CCRT is unclear. Clinical trials are needed.

[Clinical observation of the reliability of gingival contour by using temporary crown after loading 1 year].

OBJECTIVE: To observe the gingival contour and its variation following application of implant-supported temporary crowns on gingival contour in maxillary single tooth implant procedure after loading 1 year and to explore the reliability of soft tissue intervention using temporary crowns. METHODS: In 78 (37 males and 41 females) patients with anterior maxillary single tooth loss from the Department of Second Dental Center, Peking University School and Hospital of Stomatology, the gingival contour was induced by using implant-supported temporary crowns prior to maxillary tooth implant till permanent restoration from March 2010 to November 2011. The gingival papilla height and labial gingival margin level were measured immediately after the permanent restoration and 1 year later. RESULTS: In all the cases after loading 1 year, the average mesial and distal gingival papilla heights in the implant area increased by (0.16±0.58) mm and (0.10±0.53) mm, respectively. The labial gingival margin level was changed by (0.10±0.41) mm averagely. The difference in gingival contour shaped by temporary crown was not statistically significant after 1 year (P>0.05). CONCLUSION: The soft tissue shaping technique on aesthetic rehabilitation in maxillary single tooth implant is clinically feasible with a good recent aesthetic effect under the condition that the complications are controlled stringently.

Comparison of complication rates between midline catheters and peripherally inserted central catheters: a systematic review and meta-analysis of randomized controlled trials.

Midline catheters (MCs) and peripherally inserted central catheters (PICCs) are essential for reliable vascular access in patients. Despite their prevalent use, comparative risk assessments of these catheters, particularly from randomized controlled trials (RCTs), remain scarce. This meta-analysis primarily focuses on RCTs to evaluate and compare the incidence of complications associated with MCs and PICCs. We conducted a comprehensive search of databases including the Cochrane Library, PubMed, Embase, Web of Science, ScienceDirect, Scopus and ProQuest, up to April 2024. The primary outcomes analysed were total complications and catheter-related bloodstream infections (CRBSIs), while secondary outcomes included catheter dwell time and thrombosis incidence. Meta-analyses were performed using a random-effects model. Of 831 initially identified articles, five trials involving 608 patients met the inclusion criteria. MCs exhibited a significantly higher rate of total complications compared with PICCs (relative risk = 1.95, 95% confidence interval = 1.23-3.08, P=0.005, I2= 0%). MCs also had shorter dwell times and a higher incidence of premature removal. However, no significant differences were observed in the rates of CRBSIs or thrombosis between MCs and PICCs. PICCs are associated with fewer total complications and longer dwell times compared with MCs, which tend to be more often removed prematurely. Thrombosis rates were similar between the two catheter types, underscoring the need for careful catheter selection based on specific patient conditions and treatment duration. Further research, particularly additional RCTs, is necessary to confirm these findings and guide optimal catheter selection in clinical practice.