Objective To understand the predictors and prognostic significance of cranial nerve impairment in non-acquired immune deficiency syndrome (AIDS) patients with cryptococcal meningitis.Methods A total of 145 non-AIDS patients with cryptococcal meningitis admitted to Huashan Hospital,Fudan University from Jan 2000 to Dec 2010 were reviewed retrospectively.Clinical characteristics,initial antifungal therapies and outcome of these patients were analyzed.Continuous variables were analyzed using t test and categorical variables were compared by x2 test or Fisher's exact test.Multivariate analysis was performed by binary Logistic regressions.Results Out of 145 patients,52 (35.9％) patients had cranial nerve impairment at enrollment.Optic (25/52,48.1％) and oculomotor (22/52,42.3％) nerves were the most commonly involved,followed by auditory (12/52,23.1％),abducens (6/52,11.5％),olfactory (4/52,7.7％) and facial (3/52,5.8％) nerves.The best predictive factor of cranial nerve injury was duration of diagnosis (OR =1.056,95％ CI:1.002-1.111).The risk of cranial injury would increase by 5.6％ with one-week delay of diagnosis.Intracranial hypertension and low cerebrospinal fluid cell count were also the independent predictive factors (both P＜0.05).In the follow-up period,73.3％ patients who had cranial nerve injuries were fully recovered,with a median time of 3 (0.5-24.0) months.The independent predictors of recovery were numbers of nerve involved (OR =0.230,95 ％ CI:0.066-0.800,P=0.021) and amphotericin B (AmB) plus 5-fluorocytosine,triazole antifungal agent therapy (OR=10.317,95％CI:2.086-51.025,P=0.004).Conclusions Cranial nerve impairment occurs in one-third of non-AIDS patients with cryptococcal meningitis.Delay in diagnosis,intracranial hypertension and low cerebrospinal fluid cell count are independent predictive factors.Less cranial nerve involvement and AmB plus triazole therapy predict recovery.

Objective To introduce the tibial intercondylar eminence hole (TIEH) and study its structure.Explore the connection between TIEH and the pathway how proximal tibial aggressive tumor break into the bony structure from articular cavity.Methods This retrospective study included 200 patient's CT 3-dimensional reconstruction materials from May 2017 to November 2017 in Qilu hospital randomly.There were 115 males and 85 females,the average age was 49 years (ranged from 12 to 90 years).To observe the existence of TIEH and identify its location and measurement with imaging techniques.According to 50 tibial plateau specimen after TKA and 5 specimen after car accident or amputation due to tumor,physical proof the existence of TIEH.The specific location,peripheral structure,coverage,content of TIEH as well as its top,walls and bottom were researched and analysed.Pathological staining was used and 1 cases undertook preoperation contrast agent observation.1 cases of typical cases were reviewed.Results TIEH was ubiquity according to all of the 200 cases.TIEH was located on the depression of tibial plateau,between the attachments of ACL and PCL.The hole was round type,and the diameter was 1.6±0.3 mm,the depth was 9.1±2.1 mm.1-3 Paraforamen (semidiamete≤7 mm) were found around the main TIEH in 53％ patients (106/200),the diameter and depth was less than the main hole.The CT value showed the orifice (472.5±30.1 HU) ＞ the pore wall (312.3±22.5 HU) ＞ the pore bottom (202.4±17.3 HU) ＞ the pore (118.3±10.4 HU) ＞ the orifice covering (75.0±11.1 HU).The synovial tissue septum was only 1 mm between the top of hole and the articular cavity.The top of TIEH was surrounded by articular cartilage,the walls and bottom were spongy bone,the content was dense connective tissue that didn't attach to the walls tightly.The peripheral spongy bone was easy to infiltrate by methylene blue.Preoperation radiography showed that TIEH had poor barrier function.Conclusion Tibial intercondylar eminence hole is an intrinsic structure of the human body.The coverage is weak,and it is easy to cause the tumor to hide and recur.The tumor may pass through this hole and bidirectionally enter between the proximal humerus and the joint cavity.

Objective:To introduce the discovery and nomenclature of the intercondylar foramen of femur (IFF) and foramen of tibial intercondylar eminence (FTIE) and research the close relationship between the high recurrence rate of aggressive tumors around the knee joint and the foramina around the knee joint.Methods:①Radiographic observation and measurement: 3D reconstruction of CT scan of 200 patients in our hospital were used to obverse the common feature、position and measure of Inter-condylar foramen of femur and Foramen of tibial intercondylar eminence. ②Anatomical and histological observation: To proof the existence of IFF and FTIE through the anatomy of 15 cases of car accidents or tumor amputations and 60 cases of autopsy. Then the specific location, the surrounding structure, the proximal coverage, the contents, the apical construction, the wall and the bottom tissues of the IFF and FTIE were studied and analyzed. ③Histological and pathological observation of tumor anatomy: Through the study of the distal femur and tibia malignant tumor tissues(including primary bone tumors and metastatic tumors), we observed the relationship between the foraminal structures and the tumor, judged the situation of concealed transmission and two-way spread through the foramina, and analyzed the relationship between tumor recurrence and foraminal structures. ④The synovial membrane of foramina, especially in cases where the synovium was suspected to be involved by the lesions judged by the radiography was analyzed to observe whether the synovium was infiltrated by the tumor.Results:IFF and FTIE were the inherent physical structure of the human. Their physiological function was the vascular foramina that lead the branches of arteria media genus into the Intercondylar fossa of femur and tibial intercondylar eminence. Their opening was separated with the joint cavity by the synovial tissues, so IFF and FTIE were isolated with joint cavity by the synovial tissues、meniscus and cruciate ligaments. After invading the IFF and FTIE, the aggressive tumors did not break into the joint cavity immediately, but conceal in the foramina and invade the synovium with specific biological behavior with the sequence: reactive edema, hyperplasia, degeneration, calcification, hyaline degeneration (infiltration in some cases), synovial rupture, and then tumor invasion of the articular cavity. Usually, tumors or recurrence has been observed before synovial rupture. We also observed the tendency of tumors to spread along the arteria media genus to the popliteal vessels, peripheral soft tissues and lymphatic vessels with typical radiographic performance like popliteal lymphadenectasis. Color nodules and tumors in other parts could also invade or metastasize into bone through these foramina.Conclusions:IFF and FTIE are foramina nutricium of arteria media genus. They are the inherent physical structure of the human. The foramina play an important role in the spread, concealment and recurrence of peripheralkneeaggressive tumor.

MAGED4B belongs to the melanoma-associated antigen family; originally found in melanoma, it is expressed in various types of cancer, and is especially enriched in glioblastoma. However, the functional role and molecular mechanisms of MAGED4B in glioma are still unclear. In this study, we found that the MAGED4B level was higher in glioma tissue than that in non-cancer tissue, and the level was positively correlated with glioma grade, tumor diameter, Ki-67 level, and patient age. The patients with higher levels had a worse prognosis than those with lower MAGED4B levels. In glioma cells, MAGED4B overexpression promoted proliferation, invasion, and migration, as well as decreasing apoptosis and the chemosensitivity to cisplatin and temozolomide. On the contrary, MAGED4B knockdown in glioma cells inhibited proliferation, invasion, and migration, as well as increasing apoptosis and the chemosensitivity to cisplatin and temozolomide. MAGED4B knockdown also inhibited the growth of gliomas implanted into the rat brain. The interaction between MAGED4B and tripartite motif-containing 27 (TRIM27) in glioma cells was detected by co-immunoprecipitation assay, which showed that MAGED4B was co-localized with TRIM27. In addition, MAGED4B overexpression down-regulated the TRIM27 protein level, and this was blocked by carbobenzoxyl-L-leucyl-L-leucyl-L-leucine (MG132), an inhibitor of the proteasome. On the contrary, MAGED4B knockdown up-regulated the TRIM27 level. Furthermore, MAGED4B overexpression increased TRIM27 ubiquitination in the presence of MG132. Accordingly, MAGED4B down-regulated the protein levels of genes downstream of ubiquitin-specific protease 7 (USP7) involved in the tumor necrosis factor-alpha (TNF-α)-induced apoptotic pathway. These findings indicate that MAGED4B promotes glioma growth via a TRIM27/USP7/receptor-interacting serine/threonine-protein kinase 1 (RIP1)-dependent TNF-α-induced apoptotic pathway, which suggests that MAGED4B is a potential target for glioma diagnosis and treatment.
Humans ; Tumor Necrosis Factor-alpha ; DNA-Binding Proteins/metabolism* ; Ubiquitin-Specific Peptidase 7 ; Cisplatin ; Temozolomide ; Transcription Factors ; Glioma ; Cell Proliferation ; Melanoma ; Cell Line, Tumor ; Apoptosis ; Nuclear Proteins/genetics*

BACKGROUND: Both aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism and lifestyle behaviors are involved in coronary artery disease (CAD), while the interaction between them is currently unknown. METHODS: A nested case-control study was conducted in 161 patients with CAD and 495 controls in dyslipidemia population in Yinzhou District, Ningbo, Zhejiang Province, China, in August 2013. Anthropometric data and blood samples were collected, demographic characteristics and lifestyle behaviors information were obtained by a face-to-face interview, dietary intake was assessed by a food frequency questionnaire, and genomic DNA was genotyped. RESULTS: Carriers with increasing number of A alleles had an elevated CAD risk compared with G allele carriers (adjusted OR = 1.483, 95% CI = 1.114-1.974). Carriers of rs671 A/G and A/A genotypes had a higher CAD risk than carriers of G/G genotype (adjusted OR = 1.492, 95% CI = 1.036-2.148). Similarly, individuals with rs671 A/A genotype had a higher CAD risk than individuals with A/G and G/G genotypes (adjusted OR = 2.161, 95% CI = 1.139-4.101). We found a borderline additive interaction between regular fried food intake and A/A and A/G genotypes, and a significantly additive interaction between sedentary/light physical activity and A/A and A/G genotypes. CONCLUSIONS Individuals with A/A or A/G genotypes of rs671 have a higher CAD risk, if they lack physical activity and take fried food regularly, than individuals with G/G genotypes. These findings can help to provide a guide to targeted heart health management.
Adult ; Aged ; Aged, 80 and over ; Aldehyde Dehydrogenase, Mitochondrial ; genetics ; Alleles ; Case-Control Studies ; China ; Coronary Artery Disease ; blood ; genetics ; Dyslipidemias ; blood ; genetics ; Female ; Genetic Association Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Life Style ; Male ; Middle Aged ; Polymorphism, Single Nucleotide ; Risk Factors

The mesencephalic astrocyte-derived neurotrophic factor (MANF) has been recently identified as a neurotrophic factor, but its role in hepatic fibrosis is unknown. Here, we found that MANF was upregulated in the fibrotic liver tissues of the patients with chronic liver diseases and of mice treated with CCl₄. MANF deficiency in either hepatocytes or hepatic mono-macrophages, particularly in hepatic mono-macrophages, clearly exacerbated hepatic fibrosis. Myeloid-specific MANF knockout increased the population of hepatic Ly6C^high macrophages and promoted HSCs activation. Furthermore, MANF-sufficient macrophages (from WT mice) transfusion ameliorated CCl₄-induced hepatic fibrosis in myeloid cells-specific MANF knockout (MKO) mice. Mechanistically, MANF interacted with S100A8 to competitively block S100A8/A9 heterodimer formation and inhibited S100A8/A9-mediated TLR4-NF-κB signal activation. Pharmacologically, systemic administration of recombinant human MANF significantly alleviated CCl₄-induced hepatic fibrosis in both WT and hepatocytes-specific MANF knockout (HKO) mice. This study reveals a mechanism by which MANF targets S100A8/A9-TLR4 as a "brake" on the upstream of NF-κB pathway, which exerts an impact on macrophage differentiation and shed light on hepatic fibrosis treatment.