Correlation of FDG PET/CT, tumor markers and Ki-67 index with EGFR mutation or positive ALK expression in patients with non-small cell lung cancer.

BACKGROUND: Epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) are the two most common druggable targets in non-small cell lung cancer (NSCLC). To investigate whether the EGFR mutation and ALK rearrangement could be predicted by the combination of FDG avidity, tumor markers and Ki-67 Index. METHODS: A total of 168 newly diagnosed NSCLC patients who had undergone 18F-FDG PET/CT for staging were enrolled. PET/CT parameters of primary tumors including maximum standardized uptake value (pSUVmax), metabolic tumor volume (pMTV) and total lesion glycolysis (pTLG) were measured. Five serous tumor markers for lung cancer were recorded. Ki-67 labeling index was counted by immunohistochemical staining. EGFR mutation and ALK status were detected by ARMS-PCR and RT-PCR, respectively. Univariate and multivariate analyses were applied to identify the predictors of EGFR mutation and ALK positivity. RESULTS: EGFR mutation rate was 38.1% (64/168), which were found more frequently in female, ≤60 years old, non-smokers and adenocarcinoma patients, and were not related to lymph node involvements, distant metastases, stage and serum tumor markers. Low pSUVmax, pMTV, pTLG and Ki-67 were significantly associated with EGFR mutation. Logistic regression demonstrated that pSUVmax <6.75 and gender (female) were the independent factors affecting EGFR mutation, and the combination of them had a certain predictive value with the area under the curve of 0.784. ALK positive rate was 6.0% (10/168), all of them were adenocarcinoma patients, which were more common in non-smokers, low serum cytokeratin-19 fragment antigen (CYFRA21-1) and low Ki-67, and were not related to FDG activity. No independent factor for ALK positivity was found on Logistic regression. CONCLUSIONS: Low pSUVmax, rather than tumor markers or Ki-67, was correlated with EGFR mutation independently, which could be integrated with gender (female) to improve the identification for EGFR mutation in NSCLC patients.

Impaired local Vitamin D3 metabolism contributes to IL-36g overproduction in epithelial cells in chronic rhinosinusitis with nasal polyps.

BACKGROUND: Vitamin D (VD) possesses immunomodulatory properties, but its role in chronic rhinosinusitis with nasal polyps (CRSwNP) remains poorly studied. Herein, we aim to explore the regulation and function of VD3 in CRSwNP. METHODS: 25-hydroxyvitamin D3 (25VD3) levels in serum and tissue lysates were detected by ELISA. The expression of VD receptor (VDR) and cytochrome P450 family 27 subfamily B member 1 (CYP27B1), the enzyme that converts 25VD3 to the active 1,25-hydroxyvitamin D3 (1,25VD3), and their expression regulation in human nasal epithelial cells (HNECs) were studied by RT-PCR, western blotting, immunofluorescence, and flow cytometry. RNA sequencing was performed to identify genes regulated by 1,25VD3 in HNECs. HNECs and polyp tissue explants were treated with 1,25VD3, 25VD3, and dexamethasone. RESULTS: 25VD3 levels in serum and nasal tissue lysates were decreased in patients with eosinophilic and noneosinophilic CRSwNP than control subjects. The expression of VDR and CYP27B1 were reduced in eosinophilic and noneosinophilic CRSwNP, particularly in nasal epithelial cells. VDR and CYP27B1 expression in HNECs were downregulated by interferon y and poly (I:C). Polyp-derived epithelial cells demonstrated an impaired ability to convert 25VD3 to 1,25VD3 than control tissues. 1,25VD3 and 25VD3 suppressed IL-36y production in HNECs and polyp tissues, and the effect of 25VD3 was abolished by siCYP27B1 treatment. Tissue 25VD3 levels negatively correlated with IL-36y expression and neutrophilic inflammation in CRSwNP. CONCLUSION: Reduced systemic 25VD3 level, local 1,25VD3 generation and VDR expression result in impaired VD3 signaling activation in nasal epithelial cells, thereby exaggerating IL-36y production and neutrophilic inflammation in CRSwNP.

[Analysis of clinical and genetic characteristics of the severe liver disease phenotype in patients with hepatolenticular degeneration].

Objective: To investigate the clinical and genetic characteristics and predictive role of the severe liver disease phenotype in patients with hepatolenticular degeneration (HLD). Methods: Inpatients with HLD confirmed at Xinhua Hospital affiliated with Shanghai Jiao Tong University School of Medicine from January 1989 to December 2022 were selected as the research subjects. Clinical classification was performed according to the affected organs. Patients with liver disease phenotypes were classified into the liver disease group and further divided into the severe liver disease group and the ordinary liver disease group. The clinical characteristics and genetic variations were compared in each group of patients. The predictive indicators of patients with severe liver disease were analyzed by multiple regression. Statistical analysis was performed using the t-test, Mann-Whitney U test, or χ(2) test according to different data. Results: Of the 159 HLD cases, 142 were in the liver disease group (34 in the severe liver disease group and 108 in the ordinary liver disease group), and 17 were in the encephalopathy group. The median age of onset was statistically significantly different between the liver disease group and the encephalopathy group [12.6 (7.0, 13.3) years versus 16.9 (11.0, 21.5) years, P<0.01]. 156 ATP7B gene mutation sites were found in 83 cases with genetic testing results, of which 54 cases carried the p.Arg778Leu gene mutation (allele frequency 46.2%). Compared with patients with other types of gene mutations (n=65), patients with homozygous p.Arg778Leu mutations (n=18) had lower blood ceruloplasmin and albumin levels, a higher prognostic index, Child-Pugh score, an international normalized ratio, and prothrombin time (P<0.05). Hemolytic anemia, corneal K-F ring, homozygous p.Arg778Leu mutation, and multiple laboratory indexes in the severe liver disease group were statistically significantly different from those in the ordinary liver disease group (P<0.05). Multivariate logistic regression analysis showed that the predictive factors for severe liver disease were homozygous p.Arg778Leu mutation, total bilirubin, and bile acids (ORs=16.512, 1.022, 1.021, 95% CI: 1.204-226.425, 1.005-1.039, and 1.006-1.037, respectively, P<0.05). The drawn ROC curve demonstrated a cutoff value of 0.215 3, an AUC of 0.953 2, and sensitivity and specificity of 90.91% and 92.42%, respectively. Conclusion: Liver disease phenotypes are common in HLD patients and have an early onset. Total bilirubin, bile acids, and the homozygous p.Arg778Leu mutation of ATP7B is related to the severity of liver disease in HLD patients, which aids in predicting the occurrence and risk of severe liver disease.

Occupational stress, respect, and the need for psychological counselling in Chinese nurses: a nationwide cross-sectional study.

OBJECTIVES: This study aimed to explore occupational stress, perceived respect, and the need for psychological counselling among nurses in China. STUDY DESIGN: This was a nationwide cross-sectional study. METHODS: Chinese nurses from 311 cities were randomly selected through a simple random sampling method. Occupational stress, perceived respect, and psychological counselling need were assessed using an online questionnaire validated by experts. The underlying associated factors were analysed using multiple logistic regression analyses. RESULTS: We collected and analysed 51,406 valid online questionnaires. Family factors and low income were the most commonly cited sources of occupational stress, and 91.9% and 80.0% of nurses, respectively, perceived that individuals in society and patients did not give adequate respect. Furthermore, 75.5% and 79.7%, respectively, believed they were not respected by clinical managers and doctors. As a result, 64.7% nurses believed they had a moderate or high need for psychological counselling. However, 80.7% indicated that receiving adequate respect could decrease the need for stress-related psychological counselling. Indeed, multiple logistic regression analyses showed that lower respect perceived by nurses was associated with higher need for psychological counselling, particularly regarding criticism that nurses perceived from nursing managers (a little: odds ratio [OR], 1.597; 95% confidence interval [CI], 1.176-2.170; P = 0.003; moderately: OR, 1.433; 95% CI, 1.180-1.741; P < 0.001) and the difficulty of receiving respect from patients and their families (a little: OR, 1.389; 95% CI, 1.044-1.850; P = 0.024). CONCLUSIONS: Nurses in China perceive high levels of occupational stress and low levels of respect and often seek psychological counselling.

[The efficacy and side effects of rigosertib combined with chemotherapy in KRAS mutant colorectal cancer mice].

Objective: To investigate the effect of rigosertib (RGS) combined with classic chemotherapy drugs including 5-fluorouracil, oxaliplatin, and irinotecan in colorectal cancer. Methods: Explore the synergy effects of RGS and 5-fluorouracil (5-FU), oxaliplatin (OXA), and irinotecan (IRI) on colorectal cancer by subcutaneously transplanted tumor models of mice. The mice were randomly divided into control group, RGS group, 5-FU group, OXA group, IRI group, 5-FU+ RGS group, OXA+ RGS group and IRI+ RGS group. The synergy effects of RGS and OXA on KRAS mutant colorectal cancer cell lines in vitro was detected by CCK-8. Ki-67 immunohistochemistry and TdT-mediated dUTP nick-end labeling (TUNEL) staining were performed on the mouse tumor tissue sections, and the extracted tumor tissue was analyzed by western blot. The blood samples of mice after chemotherapy and RGS treatment were collected, blood routine and liver and kidney function analysis were conducted, and H&E staining on liver sections was performed to observe the side effects of chemotherapy and RGS. Results: The subcutaneously transplanted tumor models were established successfully in all groups. 55 days after administration, the fold change of tumor size of OXA+ RGS group was 37.019±8.634, which is significantly smaller than 77.571±15.387 of RGS group (P=0.029) and 92.500±13.279 of OXA group (P=0.008). Immunohistochemical staining showed that the Ki-67 index of tumor tissue in control group, OXA group, RGS group and OXA+ RGS group were (100.0±16.8)%, (35.6±11.3)%, (54.5±18.1)% and (15.4±3.9)%, respectively. The Ki-67 index of OXA+ RGS group was significantly lower than that in control group (P=0.014), but there was no significant difference compared to OXA group and RGS group (OXA: P=0.549; RGS: P=0.218). TUNEL fluorescence staining showed that the apoptotic level of OXA+ RGS group was 3.878±0.547, which was significantly higher than 1.515±0.442 of OXA group (P=0.005) and 1.966±0.261 of RGS group (P=0.008). Western blot showed that the expressions of apoptosis related proteins such as cleaved-PARP, cleaved-caspase 3 and cleaved-caspase 8 in the tumor tissues of mice in the OXA+ RGS group were higher than those in control group, OXA group and RGS group. After the mice received RGS combined with chemotherapy drugs, there was no significant effect on liver and kidney function indexes, but the combined use of oxaliplatin and RGS significantly reduced the white blood cells [(0.385±0.215)×10(9)/L vs (5.598±0.605)×10(9)/L, P<0.001] and hemoglobin[(56.000±24.000)g/L vs (153.333±2.231)g/L, P=0.001] of the mice. RGS, chemotherapy combined with RGS and chemotherapy alone did not significantly increase the damage to liver cells. Conclusions: The combination of RGS and oxaliplatin has a stronger anti-tumor effect on KRAS mutant colorectal cancer. RGS single agent will not cause significant bone marrow suppression and hepatorenal injury in mice, but its side effects may increase correspondingly after combined with chemotherapy.

[Factors influencing the clinical phenotype of hepatolenticular degeneration].

Hepatolenticular degeneration is an autosomal recessive genetic disease caused by mutations in the ATP7B gene. More than 800 mutations have been identified in the ATP7B gene so far, with significant differences in clinical phenotypes among different mutation sites. Totally different clinical phenotypic mutations can even exist in the same gene. Although copper accumulation due to gene mutation is the basis of the pathogenesis of hepatolenticular degeneration, more and more evidence demonstrates that it is difficult to explain the diversity of clinical manifestations solely from the perspective of gene mutation. Therefore, this article reviews the research progress on the factors influencing genotype, modifier genes, epigenetics, age, gender, diet, and other factors on the phenotype of patients with hepatolenticular degeneration.

[Clinical and imaging characteristics of optic nerve tumors as the differencial diagnosis of optic neuritis].

Objective: To investigate the clinical and imaging features of optic nerve tumors that require differential diagnosis from optic neuritis. Methods: A retrospective case series study was conducted. Clinical data of patients diagnosed with optic nerve tumors from January 2017 to December 2021 at the Second Affiliated Hospital of Zhejiang University School of Medicine were collected. A total of 29 patients (39 eyes) with clinical and magnetic resonance imaging (MRI) findings similar to optic neuritis or optic neuropathy were included. There were 15 cases of optic nerve sheath meningioma (ONSM) (17 eyes), 4 cases of optic nerve glioma (ONG) (5 eyes), and 10 cases of infiltrative optic nerve lesions (ION) (17 eyes). All patients underwent best-corrected visual acuity (BCVA), anterior and posterior segment examinations, visual field examination, and orbital or cranial MRI examination. Patient data were observed and analyzed, treatment and follow-up information were recorded, and clinical and imaging features were summarized and compared with those of optic neuritis or optic neuropathy. Results: Among the 29 patients with optic nerve tumors, 10 were male and 19 were female, with an average age of (43.3±13.8) years and a range of 11 to 72 years. The follow-up time was 6.8 (2.0, 11.0) months, with a range of 1 to 33 months. Sixteen patients (21 eyes) with optic nerve tumors were initially misdiagnosed as having acute optic neuritis and showed poor response to steroid treatment. Of these, 9 cases (11 eyes) were ONSM, 4 cases (6 eyes) were ION, and 3 cases (4 eyes) were ONG. The diagnostic delay time was 7.1 (1.5, 12.0) months, with a range of 1 to 24 months. The main clinical symptoms of all affected eyes were acute vision loss in 23 eyes, slow vision loss in 5 eyes, transient blackouts in 4 eyes, and no obvious visual symptoms in 7 eyes. The median BCVA of all affected eyes was 0.1, ranging from light perception to 1.0. Fundus examination results showed optic disc edema in 34 eyes and normal optic disc in 5 eyes among the 39 eyes with optic nerve tumors. A total of 27 patients (33 eyes) completed visual field examinations, which revealed an enlarged physiological blind spot in 11 eyes, a concentric or tubular visual field contraction in 8 eyes, a diffuse decrease in light sensitivity in 7 eyes, an arcuate scotoma in 4 eyes, and a normal visual field in 3 eyes. All affected eyes completed orbital or cranial MRI examinations, which showed mild optic nerve thickening in 22 eyes, significant thickening in 6 eyes with distortion, and no significant thickening in 6 eyes. Contrast-enhanced T1-weighted imaging (T1WI) MRI showed optic nerve parenchymal thickening in 5 eyes, all of which were ONG, and 2 of them had optic nerve parenchymal enhancement. Optic nerve sheath thickening and enhancement without optic nerve parenchymal thickening or enhancement were observed in 28 eyes, including 17 eyes of ION and 11 eyes of ONSM. There were 6 eyes with no obvious optic nerve thickening, which were all ONSM, showing mild or significant thickening and enhancement of the optic nerve sheath without optic nerve parenchymal thickening or enhancement. Conclusions: Optic nerve tumors can present with ophthalmic clinical features similar to optic neuritis, such as optic disc edema, and demonstrate MRI findings that resemble those of optic neuritis. Therefore, differentiation between the two is crucial, based on differences in their natural course and response to steroid therapy.

[An interpretation of the British Association for the Study of the Liver practice guideline for the evaluation and treatment of hepatolenticular degeneration].

Hepatolenticular degeneration is common among rare diseases. China has a higher incidence rate than Western countries, and it is increasing year by year. The disease is easy to overlook and misdiagnose due to its complexity and non-specific clinical manifestations. Therefore, the British Association for the Study of the Liver has recently issued practice guidelines for the evaluation and treatment of hepatolenticular degeneration in order to aid clinicians in improving the clinical decision-making process regarding diagnosis, treatment, and long-term follow-up management. Herein is a brief introduction and interpretation of the content of the guideline, with aim of facilitating its application in clinical practice.

[Pregnancy management in patients with hepatolenticular degeneration].

Hepatolenticular degeneration (HLD) is an autosomal recessive genetic disease with a wide range of clinical manifestations. Women of childbearing age often present with irregular or even absent menstruation. Getting pregnant can be difficult without systematic treatment, and even if someone does become pregnant, miscarriages are common. This article reviews the use of medication during pregnancy in patients with hepatolenticular degeneration and also discusses the mode of delivery, anesthetic drug selection, and breastfeeding safety.

[A novel nomogram for individualized preoperative prediction of lymph node metastasis in patients with intrahepatic cholangiocarcinoma].

Objective: Constructing and validating a nomogram model for preoperative prediction of intrahepatic cholangiocarcinoma (ICC) lymph node metastasis to assist decision making during surgery. Methods: Retrospectively collecting the clinical and pathological data of 1 031 ICC patients who underwent partial hepatectomy at Eastern Hepatobiliary Surgery Hospital of Naval Military Medical University,General Hospital of Eastern Theater Command,or Zhongda Hospital Southeast University from January 2003 to January 2014. There were 682 males and 349 females; mean age was 54.7 years(range:18 to 82 years). There were 562 patients who underwent lymph node dissection and 469 patients who did not. Among the patients in the dissection group,Lasso regression method was used to filtrate preoperative variables related to lymph node metastasis and establish a nomogram. Bootstrap method was used to internally validate the discrimination of the nomogram,and the accuracy of the nomogram was assessed by using calibration curves. Patients were divided into low-moderate and high-risk groups based on model prediction probability. Propensity score matching(PSM) was used to analyze the overall survival (OS) and recurrence-free survival (RFS) of patients with and without lymph node dissection in the two groups,and to judge the importance of lymph node dissection in the two groups. Results: Six factors related to ICC lymph node metastasis were determined by Lasso regression,including hepatitis B surface antigen,CA19-9,age,lymphadenopathy,carcinoembryo antigen and maximum tumor diameter. These factors were integrated into a nomogram to predict ICC lymph node metastasis. The aera under curve value was 0.764,and the C-index was 0.754. Stratified analysis showed that OS and RFS in the high-risk group of lymph node metastasis were significantly lower than those in the low-medium risk group(median OS:14.6 months vs. 27.0 months,P<0.01; median RFS:9.1 months vs. 15.5 months,P<0.01). In the high-risk group,the median OS was 16.7 months and 6.3 months(Log-rank test: P=0.187;Wilcoxon test:P=0.046),and the median RFS was 11.0 months and 4.8 months(P=0.403),respectively in the lymph node dissection group and undissected group after PSM. In the low-medium-risk group,the median OS was 22.7 months and 26.7 months(P=0.288),and the median RFS was 13.0 months and 14.5 months(P=0.306),respectively in the lymph node dissection group and undissected group after PSM. Conclusions: The nomogram could be used for preoperative prediction of lymph node metastasis and prognostic stratification in patients with ICC. For patients with high risk of lymph node metastasis predicted by the model,active dissection should be performed. For patients predicted to be at low-moderate risk,lymph node dissection might be optional in some specific cases.

New biomarker for lung cancer - focus on circSETD3.

In order to explore the mechanism of gefitinib-acquired resistance in lung cancer, a new biomarker has been developed for early clinical diagnosis and intervention; human NSCLC (Non-Small Cell Lung Cancer) cell lines H292 (denoted as H292S) and PC9 (denoted as PC9S) were used to establish gefitinib-resistant NSCLC cell lines H292 and PC9 models. CCK-8 (Cell Counting Kit-8) method was used to test the drug resistance of the cells. circRNAs (circular RNAs) that were differentially expressed before and after resistance were screened by RNA sequencing technology. The effects of circSETD3 overexpression and interference on the sensitivity of gefitinib was observed to analyze the nuclear localization of circSETD3 and verify the interaction between circSETD3-miR-520h-ABCG2. The results showed that the most significant change in differential expression of human NSCLC cell lines before and after drug resistance was hsa_circ_0000567, that is, circSETD3, which is mainly present in the cytoplasm. In H292S and PC9S, compared with the negative control group, the cell proliferation ability of the overexpression group was significantly increased, and the apoptosis ability was significantly decreased. In H292R and PC9R, compared with the negative control group, the proliferation ability of the interference group was significantly decreased, and the apoptosis ability was significantly increased. Overexpression of circSETD3 to H292S and PC9S, the expression of ABCG2 increased significantly. Also, the expression of ABCG2 decreased significantly after transfection with miR-520h mimics. H292R and PC9R interfered with circSETD3, the expression of ABCG2 decreased significantly. Moreover, the expression of ABCG2 increased significantly after transfection with miR-520h inhibitor. In conclusion, circSETD3 can be used as a novel biomarker for lung cancer. It relieves miR-520h degradation of the transporter ABCG2 by down-regulating the miR-520h expression, causing gefitinib to be pumped out of the cell.

[Arthroscopic classification and management for the popliteal hiatus of the lateral meniscus tears].

OBJECTIVE: To bring forward an arthroscopic classification of the popliteal hiatus of the lateral meniscus (PHLM) tears and to assess the effects of arthroscopic all-inside repair with suture hook in management of such injuries. METHODS: This study involved 146 patients who underwent arthroscopic operation because of PHLM tears from April 2014 to October 2017, eliminating the patients who had discoid lateral meniscus. There were 81 males and 65 females, with 54 left knees and 92 right knees. The average ages were (34.7±3.7) years. Among the selected participants, there were 107 patients with anterior cruciate ligament (ACL) injuries, 39 patients with medial collateral ligament (MCL) injuries, and 48 patients with medial meniscus tears. The average preoperative Lysholm and International Knee Documentation Committee (IKDC) scores were 57.7±9.2 and 54.1±8.9, respectively. The arthroscopic classification was based on the extent and degree of PHLM tears and using the arthroscopic all-inside repair with suture hook for such injuries. For the patients associated with ACL injuries, the ipsilateral autograft hamstring tendons use as the reconstruction graft for single bundle ACL reconstructions. The suture anchors were used for treatment of MCL Ⅲ injuries, and the arthroscopic all-inside repair for medial meniscus tears. RESULTS: A total of 146 PHLM tears in 146 patients were divided into type Ⅰ (tears not involved in popliteus tendon incisura; n=86, 58.9%), type Ⅱ (tears involved in popliteomeniscal fascicles; n=36, 24.7%), and type Ⅲ (tears involved in popliteus tendon incisura; n=24, 16.4%). For type Ⅰ, there were three subtypes, including type Ⅰa: longitudinal tear (n=53, 61.6%), type Ⅰb: horizontal tear (n=27, 31.4%), and type Ⅰc: radial tear (n=6, 7.0%). For type Ⅱ, there were also three subtypes, including type Ⅱa: anterosuperior popliteomeniscal fascicle tear (n=5, 13.9%), type Ⅱb: posterosuperior popliteomeniscal fascicle tear (n=20, 55.6%), and type Ⅱc: both tears (n=11, 30.6%). For type Ⅲ, there were two subtypes, including type Ⅲa: horizontal tear (n=9, 37.5%), type Ⅲb: radial tear (n=15, 62.5%). In the follow-up for an average of 15.3±2.6 months, all the patients had done well with significantly improved Lysholm (84.6±14.3) and IKDC (83.2±12.8) scores at the end of the last follow-up relative to preoperative scores (P > 0.01). CONCLUSION: We propose that it is possible to classify lateral meniscus tears at the popliteal hiatus region for three types, which can summarize the injury characteristics of this area. The arthroscopic all-inside repair with suture hook for the PHLM tears can avoid stitching to popliteal tendon or narrowing popliteal hiatus and have satisfactory clinical results.

[Blue light regulates the expression of brain derived neurotrophic factor in the habenula nucleus of depression-like rats induced by light deprivation].

Objective: To investigate the regulatory effect of blue light on the expression of brain derived neurotrophic factor (BDNF) in the habenula nucleus of depression-like rats induced by light deprivation. Methods: male SD rats were exposed to white light (white light control group, 20 rats) and constant darkness (depression model group, 60 rats), respectively. 18 days later rats in depression model group were randomly divided into three groups: depression model group (treated with constant darkness), blue light group (treated with blue light) and red light group (treated with red light). Rats in white light control group were kept in white light. All rats exposed to light were in a standard 12∶12 h Light/Dark condition at 20 lx for 36 days. Sucrose preference test was applied to evaluate depression-like symptoms of rats. The c-fos+cells in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus were detected. The phosphoylation of cAMP-response element binding protein (CREB) and the relative BDNF protein level in the habenula nucleus were measured. Results: Sucrose intake per kg body weight increased in rats exposed to blue light and returned to the level of control group (P>0.05). Sucrose intake per kg body weight in red light group and depression model group were lower than control group (P<0.05). More c-fos+cells were detected in the habenula nucleus, intergeniculate leaflet and ventral lateral geniculate nucleus from blue light group than those from depression model group (P<0.05). The relative BDNF protein level and the phosphoylation of CREB in the habenula nucleus from blue light group were higher than those from depression model group (P<0.05). Conclusion: Blue light could relieve depression-like symptoms in light-deprived rats. Exposure to blue light could activate neurons in the habenula nucleus to which intrinsically photosensitive retinal ganglion cells projected. Blue-light-mediated antidepressant effect might involve in the activation of CREB/BDNF signal transduction pathways in the habenula nucleus.

[Advances in the treatment of Wilson Disease].

Wilson Disease is kind of an autosomal recessive genetic disease. Early diagnosis and timely treatment are very important for prognosis. This article reviews the treatment of Wilson Disease, focusing on penicillamine, sodium dimercaptopropane sulfonate, ammonium tetrathiomolybdate and zinc, liver transplantation and gene therapy. At the same time, the problems of medication adherence and follow-up evaluation in patients with Wilson Disease are also discussed.

[Research progress of the role of iodide transporters and its regulatory signal pathways in carcinomas].

Iodine transporters of basement membrane of thyroid follicular epithelial cells can participate and exchange the iodine ions across intracellular and extracellular. Among all of the iodine rich organs, iodine ions which only exist in colloidal of thyroid follicular epithelial cells can be functioned as the raw materials, which after oxidation, iodization and coupling, to synthesize thyroid hormone (TH) and to exert its biological functions. Therefore, the iodine transported function of iodide transporters plays a pivotal role for TH biosynthesis. Furthermore, functional studies show that the abnormal expression or dysfunction of iodide transporters might serves as tumor promoters or inhibitors via regulated the mTOR signal pathway, the MAPKs signal pathway, and the NF-κB signal pathway, together contributed to the regulation of cell proliferation, invasion, metastasis and apoptosis, in which plays the role of non iodide transported function. Therefore, the non iodine transported function of iodide transporters may plays the crucial role of tumor occurrence and progression of carcinoma. Based on this information, present study was devoted to systematic summarize the iodine transported function and non iodine transported function (may affects occurrence and progression of carcinoma) of the classical iodide transporters [sodium iodide symporter (NIS) and pendrin] and novel iodine transporters[ (cystic fibrosis transmembrane conductance regulator (CFTR) , sodium multivitamin transporter (SMVT) , and anoctamin 1 (ANO1) ], respectively, in order to provide a theoretical basis and literature review reference for underlying the mechanism of iodine transporters and its regulated signal pathways for the occurrence and progression of carcinomas.

[Correlation between early eeg dual-frequency index monitoring combined with lactic acid clearance rate and delayed encephalopathy with acute severe carbon monoxide poisoning].

Objective: To analyze the correlation and predictive value between early BIS monitoring combined with lactic acid resolution (LCR) and delayed encephalopathy with acute severe carbon monoxide poisoning (ASCMP) . Methods: Select 96 cases of our hospital ASCMP patients were analyzed retrospectively in March 2020, and follow-up of 60 days, according to the outcome in patients with acute carbon monoxide poisoning (DEACMP) delayed encephalopathy group with good prognosis, compare two groups of general information, admission BIS average 24 h and 24 h after treatment the LCR, According to the 24h LCR test results, patients were divided into high LCR group (LCR>15%) and low LCR group (LCR≤15%) , analysis the BIS average, the correlation of the LCR with DEACMP and both individual and joint of DEACMP predictive value, Comparing clinical data of patients with high LCR and low LCR. Results: The mean BIS value of the DEACMP group 24 hours after admission was significantly lower than that of the group with good prognosis (P< 0.05) . LCR of DEACMP group was significantly lower than that of the group with good prognosis after 24 h treatment (P<0.05) . The prevalence of DEACMP in patients with high LCR was significantly lower than that with low LCR (P<0.01) ; In the early stage, BIS mean, LCR and DEACMP were negatively correlated (P< 0.05) , and the area under the curve predicted by BIS mean, LCR and their combination on DEACMP was 0.799, 0.847 and 0.902, respectively. Conclusion: Early BIS monitoring combined with LCR has a significant correlation with DEACMP, and the combined effect of the two is better. Early BIS combined with LCR detection can provide effective guidance for the prognosis assessment of ASCMP patients.

Altered resting-state functional connectivity and effective connectivity of the habenula in irritable bowel syndrome: A cross-sectional and machine learning study.

Irritable bowel syndrome (IBS) is a disorder involving dysfunctional brain-gut interactions characterized by chronic recurrent abdominal pain, altered bowel habits, and negative emotion. Previous studies have linked the habenula to the pathophysiology of negative emotion and pain. However, no studies to date have investigated habenular function in IBS patients. In this study, we investigated the resting-state functional connectivity (rsFC) and effective connectivity of the habenula in 34 subjects with IBS and 34 healthy controls and assessed the feasibility of differentiating IBS patients from healthy controls using a machine learning method. Our results showed significantly enhanced rsFC of the habenula-left dorsolateral prefrontal cortex (dlPFC) and habenula-periaqueductal grey (PAG, dorsomedial part), as well as decreased rsFC of the habenula-right thalamus (dorsolateral part), in the IBS patients compared with the healthy controls. Habenula-thalamus rsFC was positively correlated with pain intensity (r = .467, p = .005). Dynamic causal modeling (DCM) revealed significantly decreased effective connectivity from the right habenula to the right thalamus in the IBS patients compared to the healthy controls that was negatively correlated with disease duration (r = -.407, p = .017). In addition, IBS was classified with an accuracy of 71.5% based on the rsFC of the habenula-dlPFC, habenula-thalamus, and habenula-PAG in a support vector machine (SVM), which was further validated in an independent cohort of subjects (N = 44, accuracy = 65.2%, p = .026). Taken together, these findings establish altered habenular rsFC and effective connectivity in IBS, which extends our mechanistic understanding of the habenula's role in IBS.

Progression Over 5 Years of Prelaminar Hyperreflective Lines to Optic Disc Drusen in the Copenhagen Child Cohort 2000 Eye Study.

BACKGROUND: The purpose of the study was to examine 5-year changes in eyes with optic disc drusen at baseline on optical coherence tomography (OCT) scans and the relation of incident drusen to hyperreflective prelaminar lines. METHODS: The study included children who presented at baseline, when participants were aged 11-12 years, and again 5 years later. Grading for optic disc drusen was made in all. Grading for prelaminar lines was made in all children at follow-up and in eyes with optic disc drusen at baseline. Analyses included associations with scleral canal diameter at baseline in all children with optic disc drusen and a nested control group of 115 children without optic disc drusen. Data are reported as the number of children having at least one drusen or at least one hyperreflective line per person. RESULTS: The analysis included 724 children who attended both rounds of the study. Of these, 11 (1.5%) had optic disc drusen at baseline. Five additional children had developed optic disc drusen at follow-up, whereas optic disc drusen had disappeared in none, so that 16 (2.2%) children had optic disc drusen in one or both eyes at follow-up. Children with optic disc drusen at the 5-year follow-up had had a mean scleral canal diameter of 1,364 µm (interquartile range [IQR] 81 µm), compared with 1,457 µm (IQR 197) µm in 115 nested controls without optic disc drusen (P < 0.001). Optic disc drusen at follow-up were associated with more hypermetropic refraction. All children who had optic disc drusen at follow-up also had prelaminar hyperreflective lines. In addition, such lines were found at follow-up in 24 of the remaining 708 children without optic disc drusen (P < 0.001). Prelaminar hyperreflective lines with or without optic disc drusen were associated with a narrower scleral canal (diameter 1,364 µm, IQR 119 µm) compared with absence of prelaminar lines (1,486 µm, IQR 206 µm; P < 0.0001). CONCLUSION: This study provides the first evidence from a prospective study that small optic discs and prelaminar hyperreflective lines on OCT are risk factors for the development of optic disc drusen. The association between prelaminar hyperreflective lines, hypermetropia, and a narrow scleral canal supports that a crowded disc is an essential predisposing factor for the development of optic disc drusen.

[Introduction to the APASL clinical guidelines on the management of metabolic-associated fatty liver disease].

Recently, metabolic-associated fatty liver disease has become the world's highest prevalence of chronic liver disease. Moreover, it is closely related to metabolic syndrome and related diseases, bringing a huge disease burden. Previously, the global expert consensus on renaming for non-alcoholic fatty liver disease and the diagnostic criteria for metabolic-associated fatty liver disease has increased the certainty of further clinical research and practice. Presently, the research on metabolic-associated fatty liver disease is progressing rapidly, and the opinions and data based on clinical evidence are constantly updated. Hepatology international has published the "Asian Pacific Association for the Study of liver diseases' clinical guidelines on the management of metabolic-associated fatty liver disease" , which aims to promote clinical practice and improve the efficiency of clinical research. Here, we have translated the published recommendations into Chinese language, hoping to help most health professionals make clinical decisions.

[Progress in the surgical treatment of trigeminal schwannoma].

Trigeminal schwannomas(TSs) is the second most common intracranial schwannomas next to acoustic neuroma. These uncommon, slow-growing tumors, which prove to originated from Schwann cells of the fifth brain nerve, can achieve their development into various compartments.Previous to the era of microsurgery, the total tumor resection rate was low, and the postoperative neurological function was seriously damaged.With the development of microsurgery and skull base approach, the microsurgery effect of TSs has been improved. Besides, neuroendoscopy is also used in the operation of some types of trigeminal schwannomas. Radiation therapy can be performed to control tumor growth for the patients who cannot tolerate surgery, have small tumor volume, have residual tumor tissue or relapse.