Limits on gas impermeability of graphene.

Despite being only one-atom thick, defect-free graphene is considered to be completely impermeable to all gases and liquids1-10. This conclusion is based on theory3-8 and supported by experiments1,9,10 that could not detect gas permeation through micrometre-size membranes within a detection limit of 105 to 106 atoms per second. Here, using small monocrystalline containers tightly sealed with graphene, we show that defect-free graphene is impermeable with an accuracy of eight to nine orders of magnitude higher than in the previous experiments. We are capable of discerning (but did not observe) permeation of just a few helium atoms per hour, and this detection limit is also valid for all other gases tested (neon, nitrogen, oxygen, argon, krypton and xenon), except for hydrogen. Hydrogen shows noticeable permeation, even though its molecule is larger than helium and should experience a higher energy barrier. This puzzling observation is attributed to a two-stage process that involves dissociation of molecular hydrogen at catalytically active graphene ripples, followed by adsorbed atoms flipping to the other side of the graphene sheet with a relatively low activation energy of about 1.0 electronvolt, a value close to that previously reported for proton transport11,12. Our work provides a key reference for the impermeability of two-dimensional materials and is important from a fundamental perspective and for their potential applications.

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.

A small proton charge radius from an electron-proton scattering experiment.

Elastic electron-proton scattering (e-p) and the spectroscopy of hydrogen atoms are the two methods traditionally used to determine the proton charge radius, rp. In 2010, a new method using muonic hydrogen atoms1 found a substantial discrepancy compared with previous results2, which became known as the 'proton radius puzzle'. Despite experimental and theoretical efforts, the puzzle remains unresolved. In fact, there is a discrepancy between the two most recent spectroscopic measurements conducted on ordinary hydrogen3,4. Here we report on the proton charge radius experiment at Jefferson Laboratory (PRad), a high-precision e-p experiment that was established after the discrepancy was identified. We used a magnetic-spectrometer-free method along with a windowless hydrogen gas target, which overcame several limitations of previous e-p experiments and enabled measurements at very small forward-scattering angles. Our result, rp = 0.831 ± 0.007stat ± 0.012syst femtometres, is smaller than the most recent high-precision e-p measurement5 and 2.7 standard deviations smaller than the average of all e-p experimental results6. The smaller rp we have now measured supports the value found by two previous muonic hydrogen experiments1,7. In addition, our finding agrees with the revised value (announced in 2019) for the Rydberg constant8-one of the most accurately evaluated fundamental constants in physics.

[The mechanism of NRF2 inhibiting ROS induced autophagy to reduce ovarian granulosa cells damage].

This study explores the effects and possible mechanisms of nuclear factor E2 related factor 2 (NRF2) on ovarian granulosa cells, providing a scientific basis to prevent premature ovarian failure. An ovarian cell injury model was constructed by treating human ovarian granulosa cell (KGN cell) with 4-Vinylcyclohexene dioxide (VCD). Firstly, KGN cells were treated with different concentrations of VCD, and cell counting kit 8 (CCK-8) was used to detect ovarian cell proliferation. After determining IC50 by CCK8, the levels of estradiol and progesterone in the cell supernatant were detected using enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) assay kit was used to detect the content of ROS in ovarian cells, real-time fluorescence quantitative polymerase chain reaction (qRT PCR) was used to detect the mRNA expression level of NRF2, and Western blot was used to detect the protein expression level of NRF2. Further, NRF2 silence (siNRF2) and overexpression (NRF2-OE) cell models were constructed through lentivirus transfection, and the effects of regulating NRF2 on VCD treated cell models were investigated by detecting hormone levels, oxidative stress indicators (ROS, SOD, GSH-Px), and autophagy (LC3B level). The results showed that VCD intervention inhibited the proliferation of ovarian granulosa cells in a time-dependent and dose-dependent manner (F>100, P<0.05), with an IC50 of 1.2 mmol/L at 24 hours. After VCD treatment, the level of estradiol in the cell supernatant decreased from (56.32±10.18) ng/ml to (24.59±8.75) ng/ml (t=5.78, P<0.05). Progesterone decreased from (50.25±7.03) ng/ml to (25.13±6.67) ng/ml (t=6.54, P<0.05). After VCD treatment, the SOD of cells decreased from (44.47±7.71) ng/ml to (30.92±4.97) ng/ml (t=3.61, P<0.05). GSH-Px decreased from (68.51±10.17) ng/ml to (35.19±6.59) ng/ml (t=5.73, P<0.05). Simultaneously accompanied by an increase in autophagy and a decrease in NRF2. This study successfully constructed KGN cell models that silenced NRF2 and overexpressed NRF2. Subsequently, this study treated each group of cells with VCD and found that the cell proliferation activity of the siNRF2 group was significantly reduced (t=8.37, P<0.05), while NRF2-OE could reverse the cell activity damage caused by VCD (t=3.37, P<0.05). The siNRF2 group had the lowest level of estradiol (t=5.78, P<0.05), while NRF2-OE could reverse the decrease in cellular estradiol levels caused by VCD (t=5.58, P<0.05). The siNRF2 group had the lowest progesterone levels (t=3.02, P<0.05), while NRF2-OE could reverse the decrease in cellular progesterone levels caused by VCD (t=2.41, P<0.05). The ROS level in the siNRF2 group was the highest (t=2.86, P<0.05), NRF2-OE could reverse the increase in ROS caused by VCD (t=3.14, P<0.05), the SOD enzyme content in the siNRF2 group was the lowest (t=2.98, P<0.05), and NRF2-OE could reverse the decrease in SOD enzyme content caused by VCD (t=4.72, P<0.05). The GSH-Px enzyme content in the siNRF2 group was the lowest (t=3.67, P<0.05), and NRF2-OE could reverse the decrease in antioxidant enzyme content caused by VCD (t=2.71, P<0.05). The LC3B level was highest in the siNRF2 group (t=2.45, P<0.05), and NRF2-OE was able to reverse the LC3B elevation caused by VCD (t=9.64, P<0.05). In conclusion, NRF2 inhibits ROS induced autophagy, thereby playing a role in reducing ovarian granulosa cell damage, which may be a potential target for premature ovarian failure.

[Expression and prognostic significance of KAP1 gene in malignant pleural mesothelioma].

Objective: To explore the expression of KAP1 (KRAB-associated protein 1, KAP1) in Malignant pleural mesothelioma (MPM) based on the cancer genome atlas (TCGA) and clinical trials. And elucidate the correlation between the expression of KAP1 and the clinical pathological parameters of patients with MPM and its prognosis. Methods: In April 2022, Based on the second generation KAP1mRNA sequencing data and clinicopathological data of MPM patients downloaded from TCGA database, the correlation between KAP1mRNA expression and clinical parameters was analyzed, and the correlation between KAP1 protein expression and clinicopathological parameters and its prognostic value were analyzed based on Chuxiong data set cohort clinical samples. The expression of KAP1 mRNA in MPM samples and matched normal tumor adjacent tissues was detected by qRT-PCR, and the expression of KAP1 protein in MPM and normal pleural tissues was detected by immunohistochemistry and Westernblotting. To construct a Kaplan-Meier model to explore the effect of KAP1 expression on the prognosis of MPM patients, and to analyze the prognostic factors of MPM patients by Cox regression. Results: qRT-PCR and Western blotting detection showed that the expression levels of KAP1 gene in four different MPM cells (NCI-H28, NCI-H2052, NCI-H2452, and MTSO-211H) were significantly higher than those in normal pleural mesothelial cells Met-5A. qRT-PCR, Western blotting and IHC results demonstrated that the mRNA and protein expression levels of KAP1 in MPM tissues was significantly higher than that in matching normal mesothelial tissues, and the expression level of KAP1 protein was correlated with TP 53 protein expression levels and serum CEA levels (P<0.05) . The mRNA expression level was significantly correlated with the prognosis, The overall survival time of mesothelioma patients with high KAP1mRNA expression was significantly shorter (HR=3.7, Logrank P<0.001) . Tumor type, age and the mRNA expression were related to the prognosis of MPM patients (P<0.05) . Multivariate analysis showed that tumor type and KAP1 mRNA expression level were independent prognostic factors of MPM patients (P<0.05) . Conclusion: In this study, TCGA database and Chuxiong cohort experiment samples were used to collect the relevant information of KAP1 expression in malignant melanoma tissues. It was confirmed that KAP1 is highly expressed in MPM tissues. The mRNA expression level and pathological type are correlated with the prognosis of patients.

Ceruloplasmin regulating fibrosis in orbital fibroblasts provides a novel therapeutic target for Graves' orbitopathy.

PURPOSE: In diagnosing the pathogenesis of Graves' orbitopathy (GO), there is a growing interest in fibrosis generated by orbital fibroblasts (OFs); nevertheless, the involvement of ceruloplasmin (CP) in OFs remains unknown. METHODS: Differentially expressed genes (DEGs) were identified through bioinformatic analysis. OFs were isolated from orbital tissue and identified with immunofluorescent staining. The levels of DEGs were validated in GO tissue samples and TGF-ß-challenged OFs, and CP was selected for the following laboratory investigations. CP overexpression or knockdown was achieved, and cell viability and fibrosis-associated proteins were investigated to assess the cell phenotype and function. Signaling pathways were subsequently investigated to explore the mechanism of CP function in OFs. RESULTS: CP and cathepsin C (CTSC) are two overlapped DEGs in GSE58331 and GSE105149. OFs were isolated and identified through fibrotic biomarkers. CP and CTSC were downregulated in GO tissue samples and TGF-ß-challenged OFs. CP overexpression or knockdown was achieved in OFs by transducing a CP overexpression vector or small interfering RNA against CP (si1-CP or si2-CP) and verified using a qRT-PCR. CP overexpression inhibited cell viability and reduced the levels of α-SMA, vimentin, fibronectin, and collagen I, whereas CP knockdown exerted opposite effects on OFs. CP overexpression inhibited the phosphorylation of Smad3, Erk1/2, p38, JNK, and AKT; conversely, CP knockdown exerted opposite effects on the phosphorylation of factors mentioned above. CONCLUSION: CP was downregulated in GO and suppressed the expression of fibrosis-associated proteins in both GO and normal OFs. CP might serve as a promising therapeutic agent in the treatment regimens for GO.

The impact of the metabolic score for insulin resistance on cardiovascular disease: a 10-year follow-up cohort study.

PURPOSE: To investigate whether the metabolic score for insulin resistance (METS-IR) is associated with an increased risk of cardiovascular disease (CVD). METHODS: A total of 6489 participants aged 35-70 years without a history of CVD were included in this prospective cohort study. The median follow-up time was 10.6 years. The METS-IR was calculated as ln [2 × FPG (mg/dL) + fasting TG (mg/dL)] × BMI (kg/m2)/ln [HDL-C (mg/dL)]. The primary outcome was CVD, defined as the composite of coronary heart disease (CHD) and stroke. RESULTS: During follow-up, 396 individuals developed CVD. Kaplan-Meier survival curves by quintiles of METS-IR showed statistically significant differences (log-rank test, P < 0.001). Multivariate Cox regression analysis showed that the hazard ratio [95% confidence interval (95% CI)] of CVD was 1.80 (1.24-2.61) in quintile 5 and 1.17 (1.05-1.31) for per standard deviation (SD) increase in METS-IR. In subgroup analysis, the significant association between METS-IR and CVD was mainly observed among females and subjects without diabetes mellitus. A significant interaction was found between gender and METS-IR (P-interaction = 0.001). Moreover, adding METS-IR to models with traditional risk factors yielded a significant improvement in discrimination and reclassification of incident CVD. CONCLUSION: The elevated METS-IR was independently associated with incident CVD, suggesting that the METS-IR might be a valuable indicator for risk stratification and early intervention of CVD.

[Clinical and biological features and prognosis of patients with leukemic non-nodal mantle cell lymphoma].

Objective: To investigate the clinical, biological and prognostic characteristics of leukemic non-nodal mantle cell lymphoma (nnMCL). Methods: The clinical data of 14 patients with nnMCL and 238 patients with classical mantle cell lymphoma (cMCL) in Blood Diseases Hospital, Chinese Academy of Medical Sciences from November 2000 to October 2020 were retrospectively analyzed. Among the 14 patients with nnMCL, there were 9 males and 5 females, with the age [M (Q1, Q3)] of 57.5 (52.3, 67.0) years. Among the 238 patients with cMCL, there were 187 males and 51 females, with the age of 58.0 (51.0, 65.3) years. The clinical and biological characteristics of the two groups were recorded and compared. Follow-up and efficacy evaluation were conducted by re-examination during hospital stay and telephone follow-up and so on. Results: The proportion of CD200 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [14.6% (19/130)] (P=0.001). The proportion of CD23 expression in nnMCL patients was 8/14, which was higher than that in cMCL patients [13.5% (23/171)] (P<0.001). The proportion of CD5 expression in nnMCL patients was 10/14, which was lower than that in cMCL patients [97.4% (184/189)] (P=0.001). The proportion of CD38 expression in nnMCL patients was 4/14, which was lower than that in cMCL patients [69.6% (112/161)] (P=0.005). The expression proportion of sex-determining region of Y chromosome-related high-mobility-group box 11 (SOX11) in nnMCL patients was 1/5, which was lower than that in cMCL patients [77.9% (60/77)] (P=0.014). The proportion of immunoglobulin heavy chain variable region (IGHV) mutations in nnMCL patients was 11/11, which was higher than that in cMCL patients [26.0% (13/50)] (P<0.001). As of April 11, 2021, the follow-up time for nnMCL and cMCL patients was 31 (8-89) months and 48 (0-195) months, respectively. Among the 14 nnMCL patients, 6 patients were still under observation, and 8 patients were treated. The overall response rate (ORR) was 8/8, including 4 patients with complete remission and 4 patients with partial response. The median overall survival and median progression-free survival were not reached in nnMCL patients. In the cMCL group, 50.0% (112/224) patients achieved a complete response, 24.6% (55/224) patients achieved a partial response, and ORR was 74.6% (167/224). There was no statistically significant difference in ORR between the two groups (P=0.205). Conclusions: nnMCL patients have an indolent progression, with higher expression rates of CD23 and CD200 and lower expression rates of SOX11, CD5 and CD38. Most patients have IGHV mutations, with a relatively good prognosis, and"watch and wait"approach is an optional treatment.

[Research progress on immunohistochemical diagnostic markers for malignant pleural mesothelioma].

Malignant pleural mesothelioma (MPM) is a malignant tumor originating from the pleura, characterized by insidious onset, strong local invasiveness, short survival period, and poor prognosis. Clinical diagnosis is of paramount importance for the treatment and prognosis of MPM. Currently, the gold standard for diagnosing MPM is the results of histopathological examinations. Immunohistochemistry (IHC) is an effective auxiliary method in pathological diagnosis. Preliminary examinations can use two positive markers and two negative markers to distinguish pleural metastatic tumors, with additional antibodies selected based on differential diagnosis. The combined use of IHC markers plays a crucial role in the differential diagnosis between MPM and other tumors. This article primarily introduces commonly used IHC markers in MPM and the research progress of novel IHC markers in screening and differential diagnosis, aiming to provide reference for the clinical diagnosis and treatment of MPM.

[Analysis of clinicopathological features of 68 cases of malignant pleural mesothelioma].

Objective: To analyze the clinicopathological characteristics of diffuse malignant pleural mesothelioma (MPM), and explore the diagnostic methods in order to improve the early diagnosis rate. Methods: In January 2019 to January 2022, the clinical features, auxiliary examination and immunohistochemical results of 68 cases of MPM were analyzed retrospectively. The pathogenic features, histopathological morphology and the expression of related antibodies including Calretinin (CR), D2-40 and WT-1 were summarized. Results: Among the 68 patients, 40 male (58.82%), 28 female (41.18%), male to female ratio was 1.43%, median age was 58 years old; 50% of patients in Dayao County, epithelial mesothelioma 59 cases (86.76%), occurred in right chest in 39 cases (57.35%), left chest in 25 cases (36.76%), and 4 cases in both sides (5.89%). The most common initial clinical manifestations were pleural effusion (95.59%), chest pain (36.75%), chest tightness and shortness of breath (30.88%). The main imaging findings were pleural effusion in 49 cases (98.00%) and pleural thickening in 46 cases (92.00%). MPM tumor cells often expressed Calretinin, CK5/6, WT1 and D2-40, while TTF-1, NapsinA and CEA, the main markers differentiated from lung adenocarcinoma were negative. Serum CYFRA21-1 and CEA have high value in differential diagnosis of benign and malignant pleural effusions. Conclusion: Diffuse MPM has diverse histological and cytological morphology, which needs to be differentiated from a variety of diseases. Correct diagnosis of diffuse MPM through immunohistochemistry requires the combined application of a group of Mesothelium related antibodies.

[Expression of CD24 gene in human malignant pleural mesothelioma and its relationship with prognosis].

Objective: To investigate the expression of CD24 gene in human malignant pleural mesothelioma (MPM) cells and tissues, and evaluate its relationship with clinicopathological characteristics and clinical prognosis of MPM patients. Methods: In February 2021, UALCAN database was used to analyze the correlation between CD24 gene expression and clinicopathological characteristics in 87 cases of MPM patients. The TIMER 2.0 platform was used to explore the relationship between the expression of CD24 in MPM and tumor immune infiltrating cells. cBioportal online tool was used to analyze the correlation between CD24 and MPM tumor marker gene expression. RT-qPCR was used to analyze the expressions of CD24 gene in human normal pleural mesothelial cell lines LP9 and MPM cell lines NCI-H28 (epithelial type), NCI-H2052 (sarcoma type), and NCI-H2452 (biphasic mixed type). RT-qPCR was performed to detect the expressions of CD24 gene in 18 cases of MPM tissues and matched normal pleural tissues. The expression difference of CD24 protein in normal mesothelial tissue and MPM tissue was analyzed by immunohistochemistry. A Kaplan-Meier model was constructed to explore the influence of CD24 gene expression on the prognosis of MPM patients, and Cox regression analysis of prognostic factors in MPM patients was performed. Results: The CD24 gene expression without TP53 mutation MPM patients was significantly higher than that of patients in TP53 mutation (P<0.05). The expression of CD24 gene in MPM was positively correlated with B cells (r(s)=0.37, P<0.001). The expression of CD24 gene had a positive correlation with the expressions of thrombospondin 2 (THBS2) (r(s)=0.26, P<0.05), and had a negative correlation with the expression of epidermal growth factor containing fibulin like extracellular matrix protein 1 (EFEMP1), mesothelin (MSLN) and calbindin 2 (CALB2) (r(s)=-0.31, -0.52, -0.43, P<0.05). RT-qPCR showed that the expression level of CD24 gene in MPM cells (NCI-H28, NCI-H2052 and NCI-H2452) was significantly higher than that in normal pleural mesothelial LP9 cells. The expression level of CD24 gene in MPM tissues was significantly higher than that in matched normal pleural tissues (P<0.05). Immunohistochemistry showed that the expressions of CD24 protein in epithelial and sarcoma MPM tissues were higher than those of matched normal pleural tissues. Compared with low expression of CD24 gene, MPM patients with high expression of CD24 gene had lower overall survival (HR=2.100, 95%CI: 1.336-3.424, P<0.05) and disease-free survival (HR=1.800, 95%CI: 1.026-2.625, P<0.05). Cox multivariate analysis showed that compared with the biphasic mixed type, the epithelial type was a protective factor for the prognosis of MPM patients (HR=0.321, 95%CI: 0.172-0.623, P<0.001). Compared with low expression of CD24 gene, high expression of CD24 gene was an independent risk factor for the prognosis of MPM patients (HR=2.412, 95%CI: 1.291-4.492, P=0.006) . Conclusion: CD24 gene and protein are highly expressed in MPM tissues, and the high expression of CD24 gene suggests poor prognosis in MPM patients.

[Efficacy of one-stage total spondylectomy and circumferential reconstruction for axial tumors through a combined anterior retropharyngeal-posterior approach].

Objective: To elucidate the safety and efficacy of one-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach for axial tumors. Methods: A total of 20 patients with axial tumor who received total spondylectomy through a combined anterior retropharyngeal-posterior approach in Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology from February 2006 to December 2018 were retrospectively analyzed. Anterior reconstruction was performed with a special-shaped titanium mesh or three-dimensional printed (3DP) implants. The degree of local pain and neurological function was assessed by the visual analogue scale (VAS) and Frankel classification systems, respectively. Status of internal fixation and local recurrence was analyzed by radiological examination during follow-up. Results: Among the 20 patients, 12 were male and 8 were female with a mean age of (59.1±11.0) years (31 to 72 years). The mean operation time was (605.0±60.1) minutes (430 to 700 minutes) with a mean intraoperative blood loss of (1 250±347) ml (800 to 2 400 ml). The mean postoperative hospital stay was (13.2±2.8) days (8 to 20 days), and mean follow-up duration was (37.2±14.2) months(14 to 66 months). Anterior reconstructions were performed with a special-shaped titanium mesh in 14 patients and with 3DP implants in another 6 patients. Posterior occipital-cervical fixation was performed in 5 patients, while cervical fixation only in another 15 patients. The mean VAS score of pain at the last follow-up decreased significantly when compared with that before operation (1.6±0.6 vs 7.1±1.1, P<0.001). Nine patients with neurological deficits indicated significant improvement by at least 1 level at the last follow-up; among them, 2 cases of Frankel B improved to Frankel C and D, respectively; 3 cases of Frankel C all improved to Frankel D, and 4 cases of Frankel D improved to Frankel E. The perioperative complications included: 2 cases of vertebral artery injury, 2 cases of dysphagia, 3 cases of hoarseness and cough, 2 cases of cerebrospinal fluid leakage, and 1 case of greater occipital neuralgia. At the last follow-up, 5 patients died and 3 patients relapsed. Only 1 case suffered fixation failure due to local recurrence at the last follow up. Conclusions: One-stage total spondylectomy and circumferential reconstruction through a combined anterior retropharyngeal-posterior approach is safe and effective for axial tumors with favorable clinical outcomes and minor complications. Circumferential reconstruction with special-shaped titanium mesh or 3DP implant and posterior fixation can effectively reconstruct mechanical stability.

[Expression and clinical significance of COL1A1 and COL1A2 genes in malignant pleural mesothelioma tissues].

Objective: To investigate the expression levels and clinical significance of collagen typeⅠ α1 chain (COL1A1) and collagen type Ⅰ α2 chain (COL1A2) in malignant pleural mesothelioma (MPM) tissues. Methods: In January 2020, MPM tissues and adjacent normal pleural tissues were collected from 26 MPM patients, and the expression levels of COL1A1 and COL1A2 genes in the tissues were determined by quantitative reverse transcription PCR, and the efficacy of both levels in diagnosing MPM was assessed using receiver operating characteristic (ROC) curves. The relationship between COL1A1 and COL1A2 gene expression and clinicopathological features was analyzed by the Cancer Genome Atlas (TCGA) database, and the relationship between the expression levels of both and overall survival (OS) and disease-free progression survival (DFS) of MPM patients was dynamically analyzed by gene expression profiling, and the factors affecting the prognosis of MPM patients were explored by Cox proportional risk regression model. The TIMER 2.0 platform was used to explore the relationship between COL1A1 and COL1A2 gene expression in MPM and tumor immune infiltrative cells. Results: Compared with normal pleural tissues, the expression of COL1A1 and COL1A2 genes was significantly increased in MPM tissues (P<0.01) , and their expression was positively correlated (P<0.001) . The ROC curves showed that the area under the curve for COL1A1 and COL1A2 expression levels diagnostic of MPM was 0.900 and 0.897, respectively. The expression of COL1A1 gene was correlated with tumor type in MPM patients (P<0.05) , and COL1A2 gene expression was correlated with T stage in MPM patients (P<0.05) . Both COL1A1 and COL1A2 gene expression were associated with OS in MPM patients (Logrank P<0.05) , but there was no significant correlation with DFS (Logrank P>0.05) . Cox multivariate analysis showed that patients with high COL1A1 and COL1A2 gene expression and biphasic mixed MPM had a higher risk of death (P<0.05) . TIMER 2.0 platform analysis showed that COL1A1 and COL1A2 gene expression in MPM patients was positively correlated with macrophages, COL1A2 gene expression in MPM was negatively correlated with neutrophils (P<0.05) . Conclusion: High expression of COL1A1 and COL1A2 genes in MPM tissues is valuable for diagnosis, disease prediction and prognostic assessment of MPM, and both may jointly contribute to the development of MPM.

[Analysis of screening results and risk factors of high-risk populations of lung cancer in Nanchang city from 2018 to 2019].

Objective: To collate and analyze the screening results of high-risk lung cancer populations in communities in Nanchang from 2018 to 2019, and to explore the lung-positive nodules and risk factors for lung cancer. Methods: Data of the screening subjects in 8 administrative districts and 15 street health service centers in Nanchang city, Jiangxi province from November 2018 to October 2019 were collected, people at high risk of lung cancer was assessed, clinical screening of high-risk groups of lung cancer was conducted by low-dose helical computed tomography (LDCT), and risk factors for suspected lung cancer and lung-positive nodules were analyzed. Results: Of the 25 871 people participated in screening, 5 220 were at high risk for lung cancer and 15 374 without other malignant tumors were at high risk. There were 2 417 cases participated in clinical LDCT screening, including 193 cases of lung-positive nodules, 67 cases of suspected lung cancer, 912 cases of other lung diseases, the positive rate of lung cancer or lung-positive nodules was 10.76% (260/2 417). Univariate analysis showed that age, coarse grain intake, oil intake, housing heating, passive smoking, alcohol consumption and mental trauma were associated with positive pulmonary nodules or lung cancer (all P<0.05). Multivariate analysis showed that gender, age, housing heating, smoking and drinking were related to the occurrence of lung nodules or lung cancer (all P<0.05). Conclusions: Men are more likely to develop lung cancer or lung-positive nodules than women. The age is an independent risk factor for lung-positive nodules or lung cancer. In a certain range, age will increase the incidence of lung cancer, housing heating may be the protective factor for lung cancer, while smoking and drinking are risk factors.

[Mutation analysis and prenatal diagnosis of MYO7A gene in a case of Usher syndrome type 1].

Objective: To analyze the clinical characteristics and identify the causative gene of a case with congenital deafness. Methods: Detailed medical history and clinical examination of a 4-year-old male child with congenital deafness were conducted in the First Affiliated Hospital of Army Military Medical University in June 2016. He was diagnosed with sensorineural deafness. The venous blood of the child and his parents was drawn, and genomic DNA was extracted. Proband's DNA was performed with targeted capture of high-throughput sequencing, then Sanger sequencing was used to verify the suspected mutation and segregation in this pedigree. According to the genetic diagnosis of the proband's deafness, ophthalmic examinations were performed. Genetic prenatal diagnosis was performed when the proband's mother was pregnant again. Results: The patient was detected with p.Trp1466Ter/p.Tyr2042Ter compound heterozygous mutations of MYO7A gene with targeted high-throughput sequencing. The mutation of p.Trp1466Ter was a reported mutation, while p.Tyr2042Ter has not been reported. In addition to congenital deafness, retinitis pigmentosa was also found by ophthalmologic examination, and the patient was clinically diagnosed with Usher syndrome type 1. Amniocentesis and fetal DNA sequencing were performed on the repregnancy fetus of this family at 18 weeks of gestation. The heterozygous mutation of MYO7A gene p.Tyr2042Ter was found, and the other allele was the wild type, indicating that the child will not exhibit clinical manifestations of Usher syndrome type 1. Indeed, the second child passed neonatal hearing screening. Conclusions: The clinical features and genetic variants were delineated in this family with Usher syndrome type 1. The results of the current study have enriched the phenotype and genotype data of the disease and provided a basis for genetic counseling.

[The association between myopic refraction and near work among children and adolescents based on genetic risk score].

Objective: To explore the relationship between myopic refraction and near work in children and adolescents with different genetic risks. Methods: From September to December 2016, Nankai District and Hongqiao District of Tianjin were taken as the study sites. Using the method of stratified cluster random sampling, 533 children and adolescents aged 6-14 years from one primary school and one junior middle school in each of the two districts were included as the study subjects. Refraction measurements by an auto-kerato-refractor and questionnaire survey about near work were conducted. 11 single nucleotide polymorphisms in the selected myopia susceptibility genes were detected, and the genetic risk of each individual was scored. After grouping by genetic risk score, the relationship between myopia and near work was analyzed by the multivariate logistic regression, and the relationship between near work and refraction was analyzed by the multivariate linear regression. Results: The age of 553 subjects was (9.8±2.5) years, including 295 boys (53.3%). The overall detection rate of myopia was 62.0%. The spherical equivalent refraction (SER) was (-1.30±1.85) D. The results of the multivariate logistic regression showed that in the low risk group of GRS, compared with those with continuous near work time less than half an hour, those with continuous near work time no less than half an hour had a higher risk of myopia [OR (95%CI) = 2.64 (1.07, 6.52)]. In the moderate risk group of GRS, the risk of myopia increased with the increase of daily computer use [OR (95%CI) = 2.14 (1.03, 4.77)]. In the high risk group of GRS, the risk of myopia increased with the increase of the total daily reading and writing time [OR (95%CI) = 1.27 (1.01, 1.59)]. The results of the multivariate linear regression showed that in the low risk group of GRS, with increase of 1 hour in the total daily reading and writing time and mobile phone time, the SER decreased by 0.18 D (95%CI:-0.30, -0.07) and 0.95 D (95%CI:-1.51, -0.39), respectively. In the moderate risk group of GRS, with increase of 1 hour in the total daily reading and writing time and computer use time, the SER decreased by 0.25 D (95%CI:-0.31, -0.18) and 0.57 D (95%CI:-0.97, -0.18), respectively. In the high risk group of GRS, with increase of 1 hour in the daily total reading and writing time, the SER decreased by 0.33 D (95%CI:-0.43, -0.22). Conclusion: Continuous near work time no less than half an hour, daily computer use time, the total daily reading and writing time, and daily mobile phone use time were associated with myopic refraction in children and adolescents.

[Development of multiple organ dysfunction syndrome in patients with Coronavirus Disease 2019: clinical characteristics and risk factors].

Objective: To explore the clinical characteristics and risk factors of patients with Coronavirus Disease 2019 (COVID-19) when developing multiple organ dysfunction syndrome (MODS). Methods: Data from 458 inpatients of confirmed COVID-19 in Wuhan, Shanghai and Tongling from December 29, 2019 to March 24, 2020 were retrospectively collected. COVID-19 was confirmed by real-time RT-PCR of throat swab samples. Data of demographics, clinical presentation, laboratory tests, imaging findings, treatment and prognosis were obtained from medical record and compared between COVID-19 patients with and without MODS. Risk factors for the development of MODS were analyzed by univariate and multivariate logistic regression analysis. Results: Of the 458 COVID-19 patients (266 from Wuhan, 208 from Shanghai, and 24 from Tongling), 103 developed transient or persistent MODS in the course. More male patients were found in those with MODS (72.8% vs 54.6%, P=0.001). And MODS patients were of older age (72.8% vs 54.6%, P=0.001), more chronic comorbidities (68.0% vs 43.4%, P<0.001), and longer onset-to-admission interval (9.0 vs 7.0 d, P<0.001). In addition, patients with MODS had more expectoration (45.6% vs 29.9%, P=0.003) and shortness of breath (52.4% vs 19.4%, P<0.001), dysfunction of various systems, decreased cellular immunity and elevated IL-6 (9.6 vs 7.6 g/L, P=0.015) in laboratory tests, isolation of other pathogens (18.4% vs 5.6%, P<0.001), and infiltration of all five lobes (75.3% vs 57.6%, P=0.003). During hospitalization, patients with MODS needed a higher proportion of comprehensive treatment and reached a mortality rate of 66.0%. Independents risk factors for development of MODS in COVID-19 patients were: onset-to-admission interval>7 days (OR=2.17, 95%CI: 1.11-4.22, P=0.023), shortness of breath (OR=3.19, 95%CI: 1.60-6.37, P=0.001), lymphocyte count<1×109/L (OR=2.67, 95%CI: 1.31-5.46, P=0.007), blood urea nitrogen>7mol/L (OR=6.27, 95%CI: 2.80-14.08, P<0.001), procalcitonin>0.1 ng/mL (OR=2.48, 95%CI: 1.20-5.13, P=0.014), and C-reactive protein>10 mg/L (OR=3.92, 95%CI: 1.41-10.89, P=0.009). Conclusions: COVID-19 patients with MODS were of higher severity and mortality. Early identification of high-risk groups with MODS according to risk factors may be helpful for early treatment.

[Characteristics and associated factors of early refractive parameters in premature infants].

Objective: To investigate the characteristics and associated factors of early refractive parameters in premature infants. Methods: Case-control study. Premature infants who underwent the first fundus screening in the ophthalmic clinic of Xiamen children's Hospital from May 2018 to February 2019 were collected. The screening time was 4 to 6 weeks after birth or corrected gestational age from 31 to 32 weeks. The premature infants who were diagnosed with mild retinopathy of prematurity (ROP) in one eye or both eyes but did not receive any treatment were divided into ROP group and divided into zone Ⅱ subgroup and zone Ⅲ subgroup according to the region of ROP; the premature infants without ROP were divided into non-ROP group. The gestational age, birth weight, spherical equivalent, anterior chamber depth, vitreous depth, axial length, lens thickness and corneal refractive power were recorded and compared. Independent sample t-test, multiple linear regression analysis and Pearson correlation analysis were used. Results: A total of 180 premature infants, 101 males and 79 females, with gestational age of (30.82±3.10) weeks, corrected gestational age of (37.21±1.44) weeks and birth weight of (1 577.85±572.12) g were included in this study. Ninety premature infants were included in the ROP group (162 eyes, of which 85 right eyes were included in the analysis) and 90 in the non-ROP group (90 right eyes). There was no significant difference in the distribution of gestational age, birth weight and corrected gestational age between the ROP group and non-ROP group (all P>0.05), but there was significant difference in the spherical equivalent between the two groups [(1.90±1.39) D vs. (3.04±1.88) D, t=-4.653, P<0.01], and ROP group was relatively smaller. In the ROP group, the anterior chamber depth was (1.82±0.23) mm, the lens thickness was (4.54±0.18) mm, and the corneal refractive power was (43.99±0.99) D. In the non-ROP group, the anterior chamber depth was (1.91±0.94) mm, the lens thickness was (4.23±0.50) mm, and the corneal refractive power was (43.72±0.92) D. The difference between the two groups was statistically significant (all P<0.01). In ROP group, the anterior chamber depth was shallower, the lens was thicker, and the corneal refractive power was higher. In ROP group, the corneal refractive power of 48 right eyes in zone Ⅱ subgroup and 37 right eyes in Zone Ⅲ subgroup were (43.92±0.78) D and (43.39±1.05) D respectively, and the spherical equivalent were (2.08±0.95) D and (2.52±1.12) D respectively. The corneal refractive power of zone Ⅱ subgroup was higher and the spherical equivalent was smaller, and the differences were statistically significant (all P<0.05). Multiple regression analysis showed that birth weight, gestational age and corneal refractive power were the influencing factors of spherical equivalent (P<0.01). The results of Pearson correlation analysis showed that the gestational age (r=0.182), birth weight (r=0.223) and corneal refractive power (r=-0.125) of premature infants were closely related to the spherical equivalent (all P<0.05). Conclusions: In premature infants, the larger spherical equivalent is related to greater gestational age and heavier birth weight. The refractive parameters of mild ROP are characterized by shallow anterior chamber, thick lens, high corneal refractive power and small spherical equivalent. The spherical equivalent is closely related to the development of ROP. (Chin J Ophthalmol, 2021, 57: 353-357).

The tumor suppressor NOR1 suppresses cell growth, invasiveness, and tumorigenicity in glioma.

Oxidored-nitro domain-containing protein 1 (NOR1) is a tumor suppressor downregulated in various human cancers, including nasopharyngeal carcinoma (NPC), lung cancer, and testicular cancer. NOR1 protein is highly expressed in the normal brain; however, its role in brain tumors remains unknown. In this study, we demonstrated that the NOR1 protein level was decreased in glioma tissue samples as compared to its normal counterpart. Exogenously expressed NOR1 protein in glioma U251 cells inhibits tumor cell proliferation, migration, and invasion. Re-expression of NOR1 induced cell cycle S to G2 phase arrest and suppressed its tumorigenicity in nude mice. Overexpression of NOR1 in U251 cells also led to a decrease of Ki67 expression in xenografts. Transcriptomic analysis revealed that NOR1 expression altered the expression of genes favored cell proliferation. Among the differentially expressed genes, FOXR2, a member of the FOX gene family, which promotes glioma progression, was decreased in NOR1 expressing cells. The downregulation of FOXR2 by NOR1 was validated in vitro and in vivo. Our findings suggest for the first time that NOR1 suppresses glioma progression via modulating the FOXR2 expression.

[Clinical and radiographic evaluation of oblique lumbar interbody fusion combined with posterior surgery via Wiltse approach for adult degenerative scoliosis].

Objective: To assess the clinical effect of oblique lumbar interbody fusion (OLIF) combined with posterior surgery via Wiltse approach for adult degenerative scoliosis. Methods: The clinical data of 27 patients with adult degenerative scoliosis who received OLIF operation from April 2015 to June 2018 in Tongji Hospital were analyzed retrospectively. There were 17 males and 10 females with an average age of (54±11) years. All patients were treated with OLIF combined with pedicle screw fixation via Wiltse approach. Operation time, blood loss and surgery complications were all recorded. Clinical and radiographic evaluation were investigated at 1 week, 3 months of post operation and final follow-up. Visual analog scale (VAS) for low back pain and leg pain, Oswestry disability index (ODI) for low back pain were used to evaluate the clinical efficacy of surgery. Lumbar coronal cobb angle, lumbar lordosis (LL), pelvic tilt (PT), mismatch of PI and PT, sagittal vertical axis (SVA) were investigated with full spine standing X-ray. The data were compared with factor analysis of variance. Results: All patients were followed-up for 6-52 months ((30±5) months). The operation time was (235±33) min, the blood loss was (433±62) ml. VAS for low back pain and eg pain and the ODI were significantly improved from 6.8±1.4, 7.3±1.4 and 71%±11% preoperatively to 1.1±1.2, 1.0±0.9 and 17%±6% at the latest follow-up (F=115.302,139.855,291.198, all P<0.05).Lumbar coronal Cobb angle of patients was reduced from 28°±8° preoperatively to 9°±4° at the latest follow-up (F=66.352, P<0.05). The LL was significantly increased from 20°±11° preoperatively to 33°±7° (F=17.678, P<0.05), and PT, PI-LL and SVA were significantly increased from 31°±6°,35°±12° and (90±29) mm preoperatively to 26°±5°, 21°±6° and (32±17) mm at the latest follow-up (F=6.211,23.809,53.372, all P<0.05). There was no severe vascular andnerve injuries during and after operation. Conclusion: OLIF combined with posterior surgery via Wiltse approach is a safe and effective operation in the treatment of adult degenerative scoliosis with mild to moderate sagittal imbalance, it can correct the coronal and sagittal deformity, and achieve less surgery injury, less complications and good clinical results.