Objective This study investigated the impact of occupational mercury(Hg)exposure on human gene transcription and expression,and its potential biological mechanisms. Methods Differentially expressed genes related to Hg exposure were identified and validated using gene expression microarray analysis and extended validation.Hg-exposed cell models and PTEN low-expression models were established in vitro using 293T cells.PTEN gene expression was assessed using qRT-PCR,and Western blotting was used to measure PTEN,AKT,and PI3K protein levels.IL-6 expression was determined by ELISA. Results Combined findings from gene expression microarray analysis,bioinformatics,and population expansion validation indicated significant downregulation of the PTEN gene in the high-concentration Hg exposure group.In the Hg-exposed cell model(25 and 10 μmol/L),a significant decrease in PTEN expression was observed,accompanied by a significant increase in PI3K,AKT,and IL-6 expression.Similarly,a low-expression cell model demonstrated that PTEN gene knockdown led to a significant decrease in PTEN protein expression and a substantial increase in PI3K,AKT,and IL-6 levels. Conclusion This is the first study to report that Hg exposure downregulates the PTEN gene,activates the PI3K/AKT regulatory pathway,and increases the expression of inflammatory factors,ultimately resulting in kidney inflammation.

Hepatohilar cholangiocarcinoma is a common malignant tumor of the biliary system,and radical surgery is one of the important treatment methods.Due to the narrow space at the hi-lum and the high rate of anatomical variation,radical surgery is challenging.By using medical imag-ing technology and 3D reconstruction,surgeons can accurately determine the stage and classifica-tion of hilar cholangiocarcinoma preoperatively.They can assess the tumor's resectability by Ac-cording to the bile duct separation limit points(U point,P point)and anticipate the impact of portal vein,bile duct,and arterial variations on the surgical plan,thereby improving the rate of radical re-section and reducing complication rates.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective:To investigate the effects and potential mechanisms of resveratrol on obesity in elderly mice.Methods:In this study, 3 groups were randomly formed for 32-week-old mice and for 48-week-old mice.The normal diet group received regular chow and 0.3 ml saline by gavage once a day, the high-fat diet group received a high-fat diet(containing 21% fat and 1.25% cholesterol)and 0.3 ml saline once a day, and the high-fat diet plus resveratrol group received a high-fat diet and resveratrol(22.4 mg/kg, dispersed in 0.3 ml saline)by gavage once a day.After 12 weeks, body weight and adipose tissues were measured.Plasma leptin concentrations were determined by an enzyme-linked immunosorbent assay(ELISA), and values for hypertrophic obesity-related indexes of mice were obtained by quantitative real-time PCR.Results:The body weight and the proportion of subcutaneous fat tissues were lower in the high-fat diet plus resveratrol group than in the high-fat diet group[(34.43±3.23)g vs.(53.16±2.16)g, (3.21±1.58)% vs.(4.86±0.64)%, P<0.01], and were similar to those in the normal diet group.Resveratrol had a more obvious inhibitory effect on leptin in elderly mice than in middle-aged mice.In elderly mice, the plasma leptin concentration was lower in the high-fat diet plus resveratrol group than in the high-fat diet group[(0.015±0.009)g/L vs.(0.100±0.027)g/L]and the normal diet group( F=19.85, P=0.001), and it was similar to that in the middle-aged mice on a normal diet.Resveratrol significantly increased the expression of peroxisome proliferator-activated receptor gamma(PPARγ)and glucose transporter 4(GLUT4)and reduced the expression of tumor necrosis factor-α(TNF-α)( F=10.79, 9.31 and 7.02, P=0.003, 0.006 and 0.010). Conclusions:Resveratrol can significantly improve hypertrophic obesity in elderly mice, and the inhibition of leptin secretion and up-regulation of PPARγ may be the key mechanisms.

Adolescent ; Androgen-Insensitivity Syndrome/genetics* ; Cytosine ; Female ; Guanine ; Humans ; Male ; Mutation ; RNA Splice Sites/genetics* ; Receptors, Androgen/genetics*

Objective To explore the efficacy of ganoderma lucidum preparation(Ling Zhi) in treating APP/PS-1 transgenic mouse models of Alzheimer's disease(AD).Methods APP/PS-1 transgenic mice of 4 months were randomly divided into model group,ganoderma lucidum treatment groups,including high [2250 mg/(kg·d)] and middle [750 mg/(kg·d)] dose groups,i.e.LZ-H and LZ-M groups,and the positive control group(treated with donepezil hydrochloride [2 mg/(kg·d)]).In addition,C57BL/6J wild mice were selected as normal group.The animals were administered for 4 months.Histopathological examinations including hematoxylin-eosin(HE) staining,immunohistochemistry,special staining,and electron microscopy were applied,and then the pathological morphology and structures in different groups were compared. Results The senile plaques and neurofibrillar tangles in the cerebrum and cerebellum were dissolved or disappeared in LZ-H and LZ-M groups.Decrease of amyloid angiopathy was found in LZ-H and LZ-M groups.The immature neurons appeared more in hippocampus and dentate nucleus of LZ-H and LZ-M groups than those in AD model and donepezil hydrochloride groups(hippcampus:F=1.738,P=0.016;dentate nucleus:F=1.924,P=0.026),and these immature neurons differentiated to be neurons.More Purkinje cells loss occurred in AD model mice than that in LZ-H and LZ-M groups(F=9.46,P=0.007;F=9.46,P=0.010).The LZ-H and LZ-M groups had more new neuron stem cells grown up in cerebellum.Electromicroscopic examination showed the hippocampal neurons in LZ-H and LZ-M group were integrated,the nuclear membrane was intact,and the mitochondria in the cytoplasm,endoplasmic reticulum,Golgi bodies,microtubules,and synapses were also complete.The microglial cell showed no abnormality.No toxicity appeared in the pathological specimens of mice treated with ganoderma lucidum preparation.Conclusion The ganoderma lucidum preparation can dissolve and decline or dismiss the senile plaques and neurofibrillar tangles in the brain of AD mice and also reduce the amyloid angiopathy.

OBJECTIVETo investigate the effects of Lactobacillus rhamnosus GG (LGG) for inhibiting E.coli K1 (E44) adhesion and invasion of an intestinal epithelial cell model with Muc2 gene knockdown established using CRISPR-Cas9 system.

METHODSTwo 20-25 bp sgRNAs targeting Muc2 were chemically synthesized to construct CRISPR expression vectors for transfection in wild-type human colonic cancer cell line Ht29. The efficiency of Muc2 knockdown was determined using Western blotting. After assessment of the viability and proliferation of the transfected cells with MTT assay, we evaluated the effects of the probiotics against E44 adhesion and invasion of the cells through a competitive exclusion assay.

RESULTSTransfection of the cells with Lenticrisprv2 plasmid vectors resulted in a cell line with stable Muc2 knockdown by 81%. The inhibitory effects of probiotics against E44 adhesion and invasion of the transfected cells were markedly attenuated, and the relative adhesion and invasion rates of E44 were 72.23% (P<0.05) and 81.49% (P<0.05), respectively.

CONCLUSIONMuc2 knockdown causes attenuation of the inhibitory effects of probiotics against E44 adhesion and invasion of the intestinal epithelial cells, suggesting that up-regulation of Muc2 may serve as an important mechanism for the probiotics to reinforce the intestinal barrier and antagonize the pathogenic bacteria, which sheds light on a new strategy for prevention and treatment of bacterial intestinal infections.

Bacterial Adhesion ; CRISPR-Cas Systems ; Epithelial Cells ; cytology ; microbiology ; Escherichia coli ; pathogenicity ; Gene Knockdown Techniques ; HT29 Cells ; Humans ; Intestines ; cytology ; Lactobacillus rhamnosus ; Mucin-2 ; genetics ; Probiotics ; Transfection ; Up-Regulation

OBJECTIVETo explore the relationship between the expression of Survivin and Ki67 with prognosis of pancreatic endocrine tumors (PETs).

METHODSImmunohistochemistry for Survivin and Ki67 was performed in 25 cases of normal pancreatic tissues and 81 cases of PETs by tissue microarrays and to observe the expression and evaluate the relationship with prognosis.

RESULTS(1)The expression of Survivin and Ki67 in PETs was significantly higher than that in normal pancreatic tissues (P <0.01); (2)The expression of Survivin and Ki67 in PETs was correlated with tissue grading and the TNM-staging (P < 0.05), but not related with tumor size, location and functional status. In addition, the expression of nuclear Survivin was association with lymph node metastasis (P < 0.05). (3)The high expression of Ki67 was related with the expression of nuclear Survivin, but not related with the expression of cytoplasmic Survivin.

CONCLUSIONSurvivin and Ki67 were both expressed in PETs, which were closely related to the clinical pathological characteristics. They could be used as new indicators in the evaluation of prognosis of PETs. The expression of Survivin in nucleus had more diagnostic significance than that in cytoplasm, and that could be highly correlated with lymph node metastasis, which would be used as a new marker of poor prognosis.

Biomarkers, Tumor ; metabolism ; Cell Nucleus ; metabolism ; Cytoplasm ; metabolism ; Humans ; Immunohistochemistry ; Inhibitor of Apoptosis Proteins ; metabolism ; Ki-67 Antigen ; metabolism ; Lymphatic Metastasis ; Neoplasm Staging ; Pancreatic Neoplasms ; diagnosis ; Prognosis

The aim of this study was to compare the pain experience among orthodontic patients treated with self-ligating brackets SmartClip® (3M Unitek, Monrovia, California, USA) and conventional brackets Victory series® (3M Unitek, Monrovia, California, USA). We used a controlled clinical trial study design to compare 69 patients treated with self-ligating to 70 patients treated by conventional brackets. The nickel-titanium archwires 0.012-in were engaged after bonding both arches on the first day; and the visual analogue scale (VAS) was used to assess the pain experience of subjects for the first seven treatment days. The pre-treatment dental study models were assessed by the Little’s irregularity index to quantify the groups’ malalignment characteristics. The self-ligating brackets reported lower pain experience than the conventional group on the first five treatment days. However, the sixth day showed 1.75 mm higher visual analogue score than conventional brackets, with almost equal pain level on the seventh day. The group differences throughout the first week were neither clinically nor statistically significant. The pain experiences in both groups decreased steadily from the third treatment day to the end of the first week of treatment. Based on the study findings, the pain experience during initial alignment is not influenced by the brackets’ ligation type. The pain experience tends to decrease steadily from the third treatment day to the end of the first week of treatment irrespective of the bracket type used.
Orthodontic Brackets, Orthodontic Appliances