[Interpretation of the Implant Dentistry Core Outcome Set and Measurement international consensus report].

Selection and measurement of clinical outcome are key components of clinical research in implant dentistry. Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine took the lead and collaborated with multiple internationally renowned colleges of stomatology to develop an international consensus on the core outcome set and measurement in implant dentistry, which took two years and was published in May, 2023 in Journal of Clinical Periodontology and Clinical Oral Implants Research simultaneously. The consensus, aiming at identifying the full spectrum of benefits and harms of interventions, provides a comprehensive, agreed, and standardized set of outcomes that should be measured and reported as a minimum in clinical trials relating with implant dentistry, bone augmentation, and soft tissue augmentation. The present review describes the methodology and key elements of the consensus to help Chinese clinical researchers fully understand and appropriately apply the core outcome set and improve the overall quality of Chinese clinical research in implant dentistry.

Stabilization of labile active ingredients in an oil-water emulsion cosmetics by freeze-drying.

BACKGROUND: Due to the instability in oil/water emulsion, certain labile active ingredients were often not used in cosmetics. OBJECTIVE: The present study has tested the effect of freeze-drying to stabilize an oil/water cosmetic emulsion. MATERIALS AND METHODS: A preliminary freeze-drying process was established at the basis of calorimetric and freeze-drying microscope studies. The stability of labile molecules in the cosmetic emulsion was evaluated at 48 degree C after freeze-drying. RESULTS: The accelerated stability experiment showed that the freeze-dried emulsion retained 90.1% vitamin C after 28 days at 48 degree C, whereas the oil-water emulsion retained only 28.3% vitamin C. The freeze-dried emulsion had significantly less oil oxidation than did the oil-water emulsion. CONCLUSION: Freeze-drying improved the stability of vitamin C and oily active ingredients in cosmetic emulsions. DOI: 10.54680/fr23210110312.

[LncRNA DRAIC regulates the proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells by targeting let-7i-5p].

Objective: To investigate the effects of lncRNA DRAIC on proliferation, apoptosis, migration and invasion of lung adenocarcinoma cells and its mechanism. Methods: Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to detect the expression of DRAIC in lung cancer tissues and corresponding adjacent normal tissues of 40 patients with lung adenocarcinoma who underwent surgery in Tangshan People's Hospital from 2019 to 2020. Lung adenocarcinoma cells A549 and H1299 were cultured in vitro and divided into si-NC group, si-DRAIC group, miR-NC group, let-7i-5p mimics group, si-DRAIC+ inhibitor-NC group, and si-DRAIC+ let-7i-5p inhibitor group. CCK-8 method and clone formation experiment were used to detect cell proliferation. Flow cytometry was used to detect cell apoptosis. Transwell array was used to detect the cell migration and invasion. Western blot was used to detect the protein expressions of Caspase-3, Caspase-9, Bcl-2 and Bax. The double luciferase reporter gene experiment was used to verify the regulatory relationship between DRAIC and let-7i-5p. Independent sample t test was used for comparison between two groups, one-way ANOVA was used for comparison between multiple groups, and Pearson correlation analysis was used for correlation analysis. Results: Compared with adjacent tissues, the expression level of DRAIC in lung adenocarcinoma tissues increased (P<0.05), but the expression level of let-7i-5p decreased (P<0.05). The expression levels of DRAIC and let-7i-5p in lung adenocarcinoma tissues were negatively correlated (r=-0.737, P<0.05). The absorbance value of A549 and H1299 cells in the si-DRAIC group at 48, 72 and 96 hours were lower than those in the si-NC group (P<0.05), the number of clones formed [(91.00±6.08 vs. 136.67±6.51); (50.67±1.53 vs. 76.67±4.51)], the number of migration [(606.67±31.34 vs. 960.00±33.06); (483.33±45.96 vs. 741.67±29.67)], the number of invasion [(185.00±8.19 vs. 447.33±22.05); (365.00±33.87 vs. 688.00±32.97)] were lower than those in the si-NC group (P<0.05). However, the apoptosis rates of cells [(13.43±2.79)% vs. (4.53±0.42)%; (23.77±1.04)% vs. (6.60±1.42)%] were higher than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC group were higher than those in si-NC group, and the protein expression of Bcl-2 was lower than that in si-NC group (P<0.05). DRAIC is located in the cytoplasm. DRAIC targeted and negatively regulated the expression of let-7i-5p. The absorbance values of A549 and H1299 cells in the let-7i-5p mimics group at 48, 72 and 96 hours were lower than those in the miR-NC group (P<0.05), the number of clones formed [(131.33±14.47 vs. 171.33±6.11); (59.33±4.93 vs. 80.33±7.09)], the number of migration [(137.67±3.06 vs. 579.33±82.03); (425.00±11.14 vs. 669.33±21.13)], the number of invasion [(54.00±4.36 vs. 112.67±11.59); (80.00±4.58 vs. 333.33±16.80)] were lower than those in the miR-NC group (P<0.05). However, the apoptosis rates of cells [(14.57±1.10)% vs. (6.97±1.11)%; (23.97±0.42)% vs. (7.07±1.21)%] were higher than those in the miR-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in let-7i-5p mimics group were higher than those in miR-NC group, and the protein expression of Bcl-2 was lower than that in miR-NC group (P<0.05). The absorbance values of A549 and H1299 cells in the si-DRAIC+ let-7i-5p inhibitor group at 48, 72 and 96 hours were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05), the number of clones formed [(82.00±5.29 vs. 59.00±5.57); (77.67±4.93 vs. 41.33±7.57)], the number of migration [(774.33±35.81 vs. 455.67±19.04); (569.67±18.72 vs. 433.67±16.77)], the number of invasion [(670.33±17.21 vs. 451.00±17.52); (263.67±3.06 vs. 182.33±11.93)] were higher than those in the si-DRAIC+ inhibitor-NC group (P<0.05). However, the apoptosis rates of cells [(7.73±0.45)% vs. (19.13±1.50)%; (8.00±0.53)% vs. (28.40±0.53)%] were lower than those in the si-NC group (P<0.05). The protein expressions of Caspase-3, Caspase-9 and Bax in si-DRAIC+ let-7i-5p inhibitor group were higher than those in si-DRAIC+ inhibitor-NC group, and the protein expression of Bcl-2 was lower than that in si-DRAIC+ inhibitor-NC group (P<0.05). Conclusion: DRAIC is highly expressed in lung adenocarcinoma, and DRAIC promotes the proliferation, migration and invasion of lung adenocarcinoma cells and inhibits apoptosis by targeting let-7i-5p.

Unexpected catalytic activity of nanorippled graphene.

Graphite is one of the most chemically inert materials. Its elementary constituent, monolayer graphene, is generally expected to inherit most of the parent material's properties including chemical inertness. Here, we show that, unlike graphite, defect-free monolayer graphene exhibits a strong activity with respect to splitting molecular hydrogen, which is comparable to that of metallic and other known catalysts for this reaction. We attribute the unexpected catalytic activity to surface corrugations (nanoscale ripples), a conclusion supported by theory. Nanoripples are likely to play a role in other chemical reactions involving graphene and, because nanorippling is inherent to atomically thin crystals, can be important for two-dimensional (2D) materials in general.

[Comparative analysis of work-related musculoskeletal disorders catalogues].

Work-related musculoskeletal disorders (WMSDs) refer to musculoskeletal disorders caused by work or work as the main cause, which are characterized by high prevalence and heavy burden of disease as a global problem. The classification and catalog of occupational diseases is of great significance for guiding the prevention and control of occupational diseases and safeguarding the rights and interests of workers. The types of WMSDs included in the list of occupational diseases vary greatly from country to country, and the regulations on specific pathogenic factors are also inconsistent. By sorting out and analyzing the lists and characteristics of WMSDs at home and abroad, and using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) in occupational health to standardize of WMSDs in various countries, which would lay the foundation for future multi-country WMSDs occupational health registration and disease burden research, and provide a reference for China to revise the WMSDs list.

[Dihydromyricetin mediates epithelial mesenchymal transformation and regulates the proliferation and apoptosis of esophageal squamous cell carcinoma cells].

Objective: To study the effects of dihydromyricetin (DMY) on the proliferation, apoptosis and epithelial mesenchymal transition (EMT) of esophageal squamous cell carcinoma (ESCC) cell KYSE150 and KYSE410. Methods: KYSE150 and KYSE410 cells were treated with different concentrations of DMY (0, 25, 50, 100, 150, 200 µmol/L) for 24 hours. The median inhibition concentration (IC50) values of KYSE150 and KYSE410 were detected by cell counting kit-8 (CCK-8) method. Then 0.5‰ dimethyl sulfoxide (DMSO) was used as control group, dihydromyricetin (DMY), dihydromyricetin and transforming growth factor-ß1 (DMY+ TGF-ß1), transforming growth factor-ß1 (TGF-ß1) were used as experimental group. Cell proliferation and apoptosis rates were measured by clonal formation and flow cytometry. Transwell invasion and wound healing assay were used to detect cell invasion and migration. The protein expression levels of Caspase-3, Caspase-9, Bcl-2, Bax, Smad2/3, phosphorylation-Smad2/3 (p-Smad2/3) and Vimentin were detected by western blot. Results: The IC50 values of DMY on KYSE410 and KYSE150 cells were 100.51 and 101.27 µmol/L. The clone formation numbers of KYSE150 and KYSE410 in DMY group [(0.53±0.03) and (0.31±0.03)] were lower than those in DMSO group [(1.00±0.10) and (1.00±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in DMY group [(1.84±0.22)% and (2.80±0.07)%] were higher than those in DMSO group [(1.00±0.18)% and (1.00±0.07)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in DMY group [(0.42±0.03) and (0.29±0.05)] were lower than those in DMSO group [(1.00±0.08) and (1.00±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in DMY group [(0.65±0.14)% and (0.40±0.17)%] were lower than those in DMSO group [(1.00±0.10)% and (1.00±0.08)%, P<0.05]. The clone formation numbers of KYSE150 and KYSE410 in TGF-ß1 group [(1.01±0.08) and (0.99±0.25)] were higher than those in DMY+ TGF-ß1 group [(0.73±0.10) and (0.58±0.05), P<0.05]. The apoptosis rates of KYSE150 and KYSE410 cells in TGF-ß1 group [(0.81±0.14)% and (1.18±0.10)%] were lower than those in DMY+ TGF-ß1 group [(1.38±0.22)% and (1.85±0.04)%, P<0.05]. The invasion numbers of KYSE150 and KYSE410 cells in TGF-ß1 group [(1.19±0.11) and (1.39±0.11)] were higher than those in DMY+ TGF-ß1 group [(0.93±0.09) and (0.93±0.05), P<0.05]. The migration rates of KYSE150 and KYSE410 cells in TGF-ß1 group [(1.87±0.19)% and (1.32±0.04)%] were higher than those in DMY+ TGF-ß1 group [(0.86±0.16)% and (0.77±0.12)%, P<0.05]. The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY group were higher than those in DMSO group, while the protein expression level of Bcl-2 was lower than that in DMSO group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in DMY group were lower than those in DMSO group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in TGF-ß1 group were lower than those in DMY+ TGF-ß1 group, and the protein expression level of Bcl-2 was higher than that in DMY+ TGF-ß1 group (P<0.05). The protein expression levels of Bax, Caspase-3 and Caspase-9 in KYSE150 and KYSE410 cells in DMY+ TGF-ß1 group were lower than those in DMY group, and the protein expression level of Bcl-2 was higher than that in DMY group (P<0.05). The protein expression levels of p-Smad2/3, Smad2/3 and Vimentin in KYSE150 and KYSE410 cells in TGF-ß1 group were higher than those in DMY+ TGF-ß1 group (P<0.05). Conclusion: DMY can inhibit the proliferation and EMT of ESCC mediated by TGF-ß1 and promote cell apoptosis.

Exponentially selective molecular sieving through angstrom pores.

Two-dimensional crystals with angstrom-scale pores are widely considered as candidates for a next generation of molecular separation technologies aiming to provide extreme, exponentially large selectivity combined with high flow rates. No such pores have been demonstrated experimentally. Here we study gas transport through individual graphene pores created by low intensity exposure to low kV electrons. Helium and hydrogen permeate easily through these pores whereas larger species such as xenon and methane are practically blocked. Permeating gases experience activation barriers that increase quadratically with molecules' kinetic diameter, and the effective diameter of the created pores is estimated as ∼2 angstroms, about one missing carbon ring. Our work reveals stringent conditions for achieving the long sought-after exponential selectivity using porous two-dimensional membranes and suggests limits on their possible performance.

[Exploration of the high-risk factors of catheter-related thrombosis in breast cancer].

Objective: To explore the high risk factors of catheter-related thrombosis (CRT) in breast cancer patients, and provide the basis for the development of appropriate prevention and treatment strategies. Methods: A total of 1 432 breast cancer patients scheduled to receive central venous catheterization in National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College from January 1, 2015 to August 31, 2019 were selected. Baseline information and catheterization information of patients were collected. The occurrence of CRT was confirmed by vascular ultrasound examination, and the influencing factors of CRT were analyzed. Results: The total number of catheter days were 121, 980 days in 1 432 patients with breast cancer, and the average number of catheter days in each patient was 85.2 days. The incidence of CRT was 6.8% (97/1 432), which was 0.79 cases/1 000 catheter days. Among 815 patients with centrally inserted central venous catheters (CICC), 43 (5.3%) had CRT, which was 0.70 cases/1 000 catheter days. Among 617 patients with peripherally inserted central venous catheters (PICC), 54 (8.8%) developed CRT, which was 0.90 cases/1 000 catheter days. CRT was most common in subclavian vein (63.9%). Multivariate regression analysis showed that age ≥ 60 years old (OR=1.712, 95% CI: 1.056-2.775, P=0.029), PICC (OR=1.732, 95% CI: 1.130-2.656, P=0.012), the catheter position except subclavian vein (OR=10.420, 95% CI: 1.207-89.991), secondary adjustment of catheter position (OR=3.985, 95% CI: 1.510-10.521, P=0.005) and high D-Dimer level (OR=1.129, 95% CI: 1.026-1.241, P=0.012)were independent risk factors for CRT. Conclusions: The CRT problem can't be ignored in the clinical treatment of breast cancer patients with central venous catheterization. Screening the appropriate age of patients and the type of central venous catheters, reducing the secondary adjustment of catheter position, and timely monitoring the level of D-dimer are helpful to the prevention and treatment of CRT.

A preliminary study on colour Doppler ultrasound for the evaluation of intervertebral stenosis of the vertebral artery.

AIM: To determine the optimal thresholds for assessing intervertebral segment stenosis through haemodynamic parameters of colour Doppler ultrasound compared with computed tomography (CT) angiography. MATERIALS AND METHODS: Fifty-four patients diagnosed with intervertebral stenosis on colour Doppler imaging were included. Twenty patients with normal vertebral arteries constituted a control group. Peak systolic velocity at the intervertebral stenosis (PSVIV-S) and the intervertebral segment distal to the stenosis (PSVIV-D), end diastolic velocity at the intervertebral stenosis (EDVIV-S), and the intervertebral segment distal to the stenosis (EDVIV-D) were measured, and the ratios of PSVIV-S/PSVIV-D and EDVIV-S/EDVIV-D were calculated. Cut-off values for the diagnosis of <50%, 50-69%, and 70-99% stenosis were determined using a receiver operating characteristics curve. RESULTS: The optimal cut-off values of haemodynamic parameters for evaluating the intervertebral artery for <50% stenosis were PSVIV-S ≥81.5 cm/s, EDVIV-S ≥24.5 cm/s, PSVIV-S/PSVIV-D ≥1.49, and EDVIV-S/EDVIV-D ≥1.28; for 50-69% stenosis were PSVIV-S ≥137.5 cm/s, EDVIV-S ≥36.5 cm/s, PSVIV-S/PSVIV-D ≥3.14, and EDVIV-S/EDVIV-D ≥2.75; and for 70-99% stenosis were PSVIV-S ≥216 cm/s, EDVIV-S ≥55 cm/s, PSVIV-S/PSVIV-D ≥4.31, and EDVIV-S/EDVIV-D ≥4.16. PSVIV-S/PSVIV-D was the most superior haemodynamic parameter, with areas under the curve of 1.000, 0.906, and 0.968 for the diagnosis of <50%, 50-69%, and 70-99% stenosis, respectively. CONCLUSION: Colour Doppler sonography reliably identifies intervertebral stenosis. The results can be used as a preliminary reference for evaluating intervertebral stenosis.

[The effects of stelleta ganglion resection on heart failure in response to pressure overload].

Objective: To observe the impact and difference of resection of left stellate ganglion (LSG) or right stellate ganglion (RSG) on rats with heart failure. Methods: Thirty male SD rats were divided into 3 groups (n=10 each) by random number table method: control group, LSG group, RSG group. All three groups underwent TAC surgery to establish a pressure-overloaded heart failure model. Then, LSG and RSG were bluntly separated and removed in rats assigned to the LSG group or RSG group by surgery, while rats in the control group underwent sham operation. The changes in blood pressure and heart rate before operation, 30 minutes and 10 weeks after operation were recorded; echocardiography was performed before operation and 10 weeks after operation to detect the thickness of the ventricular septum, left ventricle posterior wall diameter, left ventricular end diastolic diameter, left ventricular end diastolic volume, and calculate the left ventricular fractional shortening and left ventricular ejection fraction. HE staining and Masson staining were performed to observe the degree of myocardial hypertrophy and myocardial fibrosis, and to judge the ventricular remodeling. Results: The heart rates of the three groups of rats were (352.4±4.3), (320.3±4.0) and (297.9±5.9) beats/min, and the blood pressure was (142.8±2.3), (123.4±2.7) and (129.6±2.9) mmHg(1 mmHg=0.133 kPa) at thirty minutes after surgery; the heart rates of the three groups of rats were (352.9±4.0), (321.6±3.4) and (301±4.1) beats/min, and the blood pressure was (145.6±1.9), (124.8±1.7) and (130.4±4.4) mmHg at 10 weeks after surgery. The heart rate and blood pressure in the LSG group and RSG group at 30 min and 10 weeks after surgery were significantly lower than those in the control group; at 10 weeks after surgery, the heart rate in the RSG group was significantly lower than that in the LSG group (P both<0.001). After 10 weeks, rats in the control group developed severe left ventricular dilatation. Degree of left ventricular hypertrophy was significantly reduced in the LSG group and RSG group than in the control group, the thickness of the ventricular septum was (3.2±0.3), (2.5±0.1) and (2.5±0.1) mm; the left ventricular end-diastolic diameters were (7.5±0.3), (5.5±0.3) and (5.7±0.2) mm; the left ventricular end-diastolic volume was (9.5±0.3), (4.5±0.2) and (4.8±0.2) ml; the left ventricular fractional shortening was (21.6±1.3)%, (49.1±3.9)% and (47.4±1.5)%; and the left ventricular ejection fraction was (50.9±2.5)%, (81.9±2.1)% and (80.0±2.3)%, respectively in the control group, LSG group and RSG group. Compared with the control group, the left ventricular posterior wall diameter, left ventricular end-diastolic diameter and left ventricular end-diastolic volume were significantly lower and the left ventricular fractional shortening and left ventricular ejection fraction were significantly higher in the LSG group and RSG group (all P<0.001). 10 weeks after operation, the values of type Ⅰ collagen in the control group, LSG group, and RSG group were (0.354±0.013), (0.211±0.012) and (0.243±0.013), respectively. Ratio of type Ⅰ/Ⅲ collagen was (1.109±0.065), (0.737±0.055) and (0.839±0.075), respectively. Compared with the control group, the ratio of type Ⅰcollagen and ratio of type Ⅰ/Ⅲ collagen were significantly lower in the LSG group and RSG group (P<0.001). Conclusion: Both left and right stellate ganglion resection can similarly reduce ventricular remodeling caused by pressure overload and delay the progression of heart failure in tis TAC rat model.

[Susceptibility genes and risk prediction model of cardiovascular toxicity related to antineoplastic therapy in tumor patients].

Cardiovascular toxicity of cancer patients in antineoplastic therapy is gradually paid widespread attention. Although many high-risk factors of cardiovascular toxicity associated with chemotherapy, targeted therapy or immunotherapy have been identified, it is still difficult to establish accurate risk prediction model. Traditional risk prediction model cannot adequately explain the differences in cardiovascular toxicity susceptibility among patients, makes it difficult to accurately screen high-risk groups, early diagnose and prevent cardiovascular toxicity. Finding susceptible genes of cardiovascular toxicity associated with antineoplastic therapy and incorporating single-nucleotide polymorphisms into risk prediction model can significantly improve the identification of high-risk population of cardiovascular toxicity.

[The metabolism of blood glucose and lipid in breast cancer patients after the first chemotherapy].

Objective: To analyze the metabolism of blood glucose and lipid in breast cancer patients after the first chemotherapy. Methods: Breast cancer patients who received chemotherapy for the first time from December 2016 to January 2020 were collected in our hospital, and their blood glucose and lipid levels were monitored. Patients were grouped according to different treatment plans. Non-parametric rank sum test was used for statistical analysis on SPSS software. Results: There were 1 356 female breast cancer patients were enrolled, blood glucose and lipid levels were compared before and after chemotherapy. Our results showed that baseline medium blood glucose was 5.2 mmol/L, lower than 5.3 mmol/L after chemotherapy (P<0.05). The baseline triglyceride (TG) was 1.2 mmol/L, lower than 1.6 mmol/L after chemotherapy (P<0.05). The baseline small dense low-density lipoprotein (sdLDL) was 0.7 mmol/L, lower than 0.8 mmol/L after chemotherapy (P<0.05). The baseline high density lipoprotein (HDL) was 1.3 mmol/L, higher than 1.2 mmol/L after chemotherapy (P<0.05). Patients' menstrual status and body mass index were related with blood glucose, TG, LDL and sdLDL (all P< 0.05). Conclusions: Abnormal metabolism of blood glucose and lipid are observed in breast cancer patients after the first chemotherapy. More awareness of cardiovascular disease in breast cancer patients might ensure their overall clinical benefits.

[Risk prediction of venous thromboembolism in non-small cell lung cancer patients based on COMPASS-CAT risk assessment model].

Objective: To verify the risk prediction efficacies of COMPASS-cancer associated thrombosis (COMPASS-CAT) risk assessment model and the new prediction probability model established based on COMPASS-CAT for venous thromboembolism (VTE) in hospitalized patients with non-small cell lung cancer (NSCLC). Methods: We retrospectively collected the clinical data of 373 patients with NSCLC admitted to National Clinical Research Center for Cancer/Cancer Hospital from March 2013 to June 2017. All of them were divided into VTE group (63 cases) and non-VTE group (310 cases) according to VTE occurred or not. According to the COMPASS-CAT risk assessment model, all patients were scored and classified by risk. Chi-square test was used to compare the clinical features between two groups, and multivariate logistic regression analysis was used to evaluate the independent risk factors of VTE in NSCLC patients. Based on the COMPASS-CAT risk assessment model, D-dimer≥1.03 mg/L and hemoglobin<10 g/dl were included to construct a new COMPASS-CAT prediction probability model, the ROC curve was also drawn. We used MedCalc software to compare the difference of ROC curves and analyze the application value of different risk assessment models in predicting VTE risk of NSCLC patients. Results: The incidence of VTE was 16.9% (63/373). The COMPASS-CAT score of VTE group was 6.37±3.40, which was higher than 2.74±2.04 of non-VTE group (P<0.001). Univariate analysis showed that the proportion of patients with KPS≤80, COMPASS-CAT≥7, D-dimer≥1.03 mg/L, central venous catheter (CVC), hemoglobin<10 g/L, cardiovascular complications≥2, hyperlipidemia, clinical stages Ⅲ and Ⅳ, KPS≤80 in VTE group was significantly higher than that in non-VTE group (P<0.05). Logistic regression analysis showed that D-dimer≥1.03 mg/L, compass-cat score≥7 and hemoglobin <10 g/dL were independent risk factors for VTE. Based on the COMPASS-CAT risk assessment model, a new risk assessment model of COMPASS-CAT was constructed by incorporating the variables of D-dimer ≥1.03 mg/L and hemoglobin <10 g/dl. The area under ROC curve (AUC) of COMPASS-CAT model and new COMPASS-CAT prediction probability model were 0.745 and 0.804, respectively. Compared with COMPASS-CAT model, AUC of new COMPASS-CAT prediction probability model increased by 0.059, with statistically significant difference(P=0.007). Conclusion: COMPASS-CAT risk assessment model can predict the risk of VTE in NSCLC patients, and the new COMPASS-CAT prediction probability model constructed by COMPASS-CAT model combined with D-dimer and hemoglobin variables can improve the accuracy of screening VTE risk factors in NSCLC patient.

[Genotype-phenotype analysis of a homozygous familial hypercholesterolemia pedigree].

Objective: To analyze the genetic characteristics of a five generations pedigree with homozygous familial hypercholesterolemia (HoFH). Methods: Prospective study. Twenty family members included a proband diagnosed as familial hyperlipidemia at the cardiology Department of Xi'an Children's Hospital in October 2018 were research object. Clinical data were collected. Genome DNAs were extracted. Whole exons sequencing was performed on the proband using target capture next generation sequencing. Candidate gene mutation sites identified by bioinformatics were verified by Sanger sequencing in the family members. The genotype-phenotype correlation of the pedigree was analyzed between heterozygous mutation carriers and non-carriers. Results: The proband was a 7-years and 10-month-old boy. He was born with a roundgreen bean size yellow skin protuberance in the skin of the coccyx. Since the age of 3-4 years old, xanthoma-like lesions with a diameter of 0.5-1.5 cm gradually appeared in the skin of bilateral elbow joints, knee joints and Achilles tendon. The height, weight and intellectual development of the child were the same as those of normal children at the same age. No similar xanthoma-like lesion was found in the other family members. The proband's total cholesterol (TC) reached 18.16-21.24 mmol/L, and his low density lipoproteincholesterol (LDL-C) was 14.08-15.51 mmol/L. Carotid ultrasonography showed diffuse sclerotic plaques in bilateral carotid and vertebral arteries, and color Doppler echocardiography revealed aortic valve thickening and calcification. Gene testing identified that the proband carried a homozygous mutation C. 418G>A (p. E140K) in LDLR gene inherited from his parents who had a consanguineous marriage and carried a heterozygous mutation of LDLR-E140K, respectively.The TC, LDL-C and apolipoproteinB (ApoB) of LDLR-E140K gene heterozygous carriers ((8.40±0.13), (6.79±0.01) and (1.95±0.05) mmol/L, respectively) were significantly higher than those of non-carriers ((4.59±0.28), (3.35±0.39) and (0.86±0.10) mmol/L, t=7.269, 4.595, 6.311, respectively, P<0.05). Conclusions: LDLR-E140K gene homozygous mutation is first reported to be associated with most severe phenotype HoFH. The genotype-phenotype analysis of the pedigree shows that the clinical phenotype of the proband with homozygous mutation is the most serious, and all the heterozygous mutation carriers present with hypercholesterolemia phenotype. The investigation confirms that LDLR-E140K is the pathogenic variation of familial hyperlipidemia.

[Health management of breast cancer patients outside the hospital during the outbreak of 2019 novel coronavirus disease].

The outbreak of 2019 novel coronavirus disease (COVID-19) is spreading rapidly. In order to prevent cluster outbreaks, the government strengthened the management and control of personnel mobility, which had a great impact on the examination and treatment of breast cancer patients. This paper discusses how to realize scientific health management of breast cancer patients outside the hospital based on the existing epidemic situation, characteristics of breast cancer patients and public health safety factors. The breast cancer patients should synthetically consider the epidemic prevention situation of inhabitance, the disease stage and previous therapeutic schedule to decide the next therapeutic schedule. If necessary, after professional discussion and communication between doctors and patients online or offline, the hospital visiting time should be delayed through seeking alternative treatment schemes, and psychological counseling for patients should be paid attention to at the same time.

Perfect proton selectivity in ion transport through two-dimensional crystals.

Defect-free monolayers of graphene and hexagonal boron nitride are surprisingly permeable to thermal protons, despite being completely impenetrable to all gases. It remains untested whether small ions can permeate through the two-dimensional crystals. Here we show that mechanically exfoliated graphene and hexagonal boron nitride exhibit perfect Nernst selectivity such that only protons can permeate through, with no detectable flow of counterions. In the experiments, we use suspended monolayers that have few, if any, atomic-scale defects, as shown by gas permeation tests, and place them to separate reservoirs filled with hydrochloric acid solutions. Protons account for all the electrical current and chloride ions are blocked. This result corroborates the previous conclusion that thermal protons can pierce defect-free two-dimensional crystals. Besides the importance for theoretical developments, our results are also of interest for research on various separation technologies based on two-dimensional materials.

FOXA1 promotes proliferation, migration and invasion by transcriptional activating KRT7 in human gastric cancer cells.

Gastric cancer (GC) is the fourth leading cause of gynecological malignancies worldwide. 5-fluorouracil (5-FU)-mediated chemotherapy is the adjuvant treatment for patients with GC following surgical resection. Many studies have indicated the cancer-type specific roles of forkhead box protein A1 (FOXA1) and keratin 7 (KRT7) in human malignancies. However, the potential mechanism underlying the involvement of FOXA1 and KRT7 in the pathogenesis and chemoresistance of GC are still not entirely clear. In our study, gain- and loss-of-function experiments proved that FOXA1 promoted cell proliferation, migration and invasion in AGS and SGC-7901 cells. Consequently, KRT7 was identified to be transcriptional activated by FOXA1 using Dual luciferase reporter assay. Our results also indicated that FOXA1 exerted its functions in enhancing viability and invasion of AGS and SGC-7901 cells through activating KRT7. Finally, interference of FOXA1 or KRT7 increased the chemosensitivity of AGS and SGC-7901 cells to 5-fluorouracil (5-Fu) treatment by suppressing cell proliferation. In conclusion, these data indicate that FOXA1 promoted proliferation, migration, invasion, and decreased chemosensitivity of GC cells to 5-Fu treatment through transcriptional activator KRT7. The present study provides a novel therapeutic strategy for the enhancement of efficacy in GC treatment and provides important insights into the molecular mechanism underlying 5-FU-mediated chemoresistance.

[Clinical features and genetic characteristics of 33 patients with simple virilizing form of 21-hydroxylase deficiency].

Objective: To analyze the clinical features and genotypes of adult patients with simple virilizing form of 21-hydroxylase deficiency (SV 21-OHD). Methods: This is a retrospective study including 33 patients with SV 21-OHD from January 2015 to March 2018 in the Ninth People's Hospital of Shanghai Jiao Tong University School of Medicine. Results: The diagnostic age of the patients was (26.3±6.5) years old. All patients presented with signs of masculinization, such as short stature (100%), clitoromegaly/microphallus (89.65%, 26/29), undeveloped breasts (82.76%, 24/29), deep voice (55.17%,16/29) and primary amenorrhea (89.65%, 26/29). The serum levels of 17-hydroxyprogesterone (17-OHP), androstenedione (AD) and testosterone were significantly elevated in 90.9%, 93.9% and 91.2% of the patients, respectively. Thirteen types of mutations were identified in CYP21A2 from these patients. Among them, I173N accounted for 40% and I2 G accounted for 18.33%. Four patients were found with multiple mutations in CYP21A2. Conclusions: Short stature, clitoromegaly/microphallus and primary amenorrhea are the most common clinical features in adult patients with SV 21-OHD. Serum levels of 17-OHP and AD are important indices for the diagnosis and monitoring of the patients. I173N and I2 G are the two most prevalent mutations in patients of the present study. Limitation of clinical recognition and delay in treatment contribute to the short stature of the SV 21-OHD patients.

[Research progress on etiology and treatment of adolescent lumbar disc herniation].

Adolescent lumbar disc herniation(ALDH) is clinically rare. Factors such as dysplasia, genetic factors, trauma, spinal sagittal aligment have been suspected as the pathogenesis of ALDH. The clinical features of ALDH are different from adult lumbar disc herniation: typical physical signs with minor complaints, higher proportion of lumbar deformities. ALDH usually involves one segment, presenting central type, and the herniated disc is larger with bone structure.Conservative treatment is suggested for ALDH patients without severe nerve injury. Operative procedures includes non-fusion intervertebral disc resection, lumbar fusion and percutaneous endoscopic lumbar discectomy, different procedure would be selected according to the type of herniated disc.

[The therapeutic effect of HSV1-hGM-CSF combined with doxorubicin on the mouse breast cancer model].

Objective: To evaluate the oncolytic effect of herpes simplex virus type 1 which carried recombined human granulocyte-macrophage colony-stimulating factor (HSV1-hGM-CSF) on the mouse breast cancer cell line 4T1 and compare the anticancer effects of HSV1-hGM-CSF, doxorubicin alone or combination on the breast cancer in mice. Methods: We investigated the cytotoxic effect on 4T1 cells in vitro, the cell growth, cell apoptosis and cell cycle of 4T1 cells treated with oncolytic HSV1-hGM-CSF at different MOIs (0, 0.5, 1 and 2) and doxorubicin at different concentrations (0, 2, 4 and 8 µg/ml). The effects of oncolytic HSV1-hGM-CSF and doxorubicin on the tumor growth, survival time and their side effects on the mouse breast cancer model were observed. Results: Both oncolytic HSV1-hGM-CSF and doxorubicin significantly inhibited the proliferation of 4T1 cells in vitro. Doxorubicin induced the G(2)/M phase arrest of 4T1 cells, while the cytotoxicity of oncolytic HSV1-hGM-CSF was no cell cycle-dependent.At day 16 after treatment with doxorubicin and HSV1-hGM-CSF, the tumor volume of 4T1 tumor bearing mice were (144.40±27.68)mm(3,) (216.80±57.18)mm(3,) (246.10±21.90)mm(3,) (327.50±44.24)mm(3,) (213.30±32.31)mm(3) and (495.80±75.87)mm(3) in the groups of doxorubicin combined with high dose HSV1-hGM-CSF, doxorubicin combined with low dose HSV1-hGM-CSF, doxorubicin alone, high dose HSV1-hGM-CSF alone, low dose HSV1-hGM-CSF alone and control, respectively.Compared with the control group, both doxorubicin and HSV1-hGM-CSF treatment exhibited significant reduction of primary tumor volume in vivo (P<0.001). The median survival times were 48, 50, 40, 42, 43 and 37 days in the six groups mentioned above, respectively. The median survival period of doxorubicin alone, high dose HSV1-hGM-CSF alone and low dose HSV1-hGM-CSF alone were significantly longer than that of control (P<0.05). Conclusion: Synergistic effect of sequential treatment with doxorubicin and oncolytic HSV1-hGM-CSF is observed in 4T1 mouse breast cancer.