Theoretical Analysis of Selectivity Differences in Ketoreductases toward Aldehyde and Ketone Carbonyl Groups.

Lactobacillus kefir alcohol dehydrogenase (LkADH) and ketoreductase from Chryseobacterium sp. CA49 (ChKRED12) exhibit different chemoselectivity and stereoselectivity toward a substrate with both keto and aldehyde carbonyl groups. LkADH selectively reduces the keto carbonyl group while retaining the aldehyde carbonyl group, producing optically pure R-alcohols. In contrast, ChKRED12 selectively reduces the aldehyde group and exhibits low reactivity toward ketone carbonyls. This study investigated the structural basis for these differences and the role of specific residues in the active site. Molecular dynamics (MD) simulations and quantum chemical calculations were used to investigate the interactions between the substrate and the enzymes and the essential cause of this phenomenon. The present study has revealed that LkADH and ChKRED12 exhibit significant differences in the structure of their respective active pockets, which is a crucial determinant of their distinct chemoselectivity toward the same substrate. Moreover, residues N89, N113, and E144 within LkADH as well as Q151 and D190 within ChKRED12 have been identified as key contributors to substrate stabilization within the active pocket through electrostatic interactions and van der Waals forces, followed by hydride transfer utilizing the coenzyme NADPH. Furthermore, the enantioselectivity mechanism of LkADH has been elucidated using quantum chemical methods. Overall, these findings not only provide fundamental insights into the underlying reasons for the observed differences in selectivity but also offer a detailed mechanistic understanding of the catalytic reaction.

Public Knowledge and Awareness of Anesthesiology and Anesthesiologists in China: A Cross-Sectional National Survey of 1 Million Participants.

BACKGROUND: In the past 20 years, anesthesiology has become one of the most advanced specialties and has undergone rapid development. However, public awareness regarding anesthesiology and anesthesiologists is limited, especially in developing countries. It is important for anesthesiologists to make the public aware of their role during surgery. Therefore, a nationwide survey was set up to investigate public awareness of anesthesiology and anesthesiologists in China. METHOD: A cross-sectional nationwide survey was performed from June 2018 to June 2019 in 34 provinces, municipalities, and autonomous regions across China and an overseas region. The questionnaires of the survey were divided into 2 main parts: general items and research items. General items included the demographic characteristics of the participants; research items consisted of 10 questions about the public's awareness of anesthesiologists and anesthesiology. Data quality control was undertaken by the investigation committee throughout the survey process. RESULTS: The nationwide survey enrolled 1,001,279 participants (male, 40.7%). We found that most of the participants regarded anesthesiologists as doctors. However, public knowledge of anesthesiologists' work and duties during surgery was quite low, with correct response rate ranging from 16.5% to 52.9%, and anesthesiologist responsibilities were often mistakenly attributed to surgeons or nurses. It is disappointing that more than half of participants still thought that, once the patient fell asleep after receiving anesthetics, the anesthesiologist could leave the operating room. Finally, the correct response rate was positively correlated with the economic levels of the regions. CONCLUSIONS: Public awareness regarding anesthesiology and anesthesiologists in China remains inadequate. Due to the biases and characteristics of the participants, the actual situation of the general Chinese public is likely even worse than reflected here. Therefore, extensive measures should be undertaken to improve public knowledge of anesthesiology and anesthesiologists.

Prognostic Nutritional Index (PNI) as a potential predictor and intervention target for perioperative ischemic stroke: a retrospective cohort study.

BACKGROUND: The prognostic nutritional index (PNI) is a nutritional indicator and predictor of various diseases. However it is unclear whether PNI can be a predictor of perioperative ischemic stroke. This study aims to evaluate the association of the preoperative PNI and ischemic stroke in patients undergoing non-cardiac surgery. METHODS: The retrospective cohort study included patients who underwent noncardiac surgery between January 2008 and August 2019. The patients were divided into PNI ≥ 38.8 and PNI < 38.8 groups according to the cut-off value of PNI. Univariate and multivariate logistic regression analyses were performed to explore the association between PNI and perioperative ischemic stroke. Subsequently, propensity score matching (PSM) analysis was performed to eliminate the confounding factors of covariates and further validate the results. Subgroup analyses were completed to assess the predictive utility of PNI for perioperative ischemic stroke in different groups. RESULTS: Amongst 221,542 hospitalized patients enrolled, 485 (0.22%) experienced an ischemic stroke within 30 days of the surgery, 22.1% of patients were malnourished according to PNI < 38.8, and the occurrence of perioperative ischemic stroke was 0.34% (169/49055) in the PNI < 38.8 group. PNI < 38.8 was significantly associated with an increased incidence of perioperative ischemic stroke whether in univariate logistic regression analysis (OR = 1.884, 95% CI: 1.559-2.267, P < 0.001) or multivariate logistic regression analysis (OR = 1.306, 95% CI: 1.061-1.602, P = 0.011). After PSM analysis, the ORs of PNI < 38.8 group were 1.250 (95% CI: 1.000-1.556, P = 0.050) and 1.357 (95% CI: 1.077-1.704, P = 0.009) in univariate logistic regression analysis and multivariate logistic regression analysis respectively. The subgroup analysis indicated that reduced PNI was significantly associated to an increased risk of perioperative ischemic stroke in patients over 65 years old, ASA II, not taking aspirin before surgery, without a history of stroke, who had neurosurgery, non-emergency surgery, and were admitted to ICU after surgery. CONCLUSIONS: Our study indicates that low preoperative PNI is significantly associated with a higher incidence of ischemic stroke in patients undergoing non-cardiac surgery. Preoperative PNI, as a preoperative nutritional status evaluation index, is an independent risk factor useful to predict perioperative ischemic stroke risk, which could be used as an intervenable preoperative clinical biochemical index to reduce the incidence of perioperative ischemic stroke.

A radiomics nomogram prediction for survival of patients with "driver gene-negative" lung adenocarcinomas (LUAD).

BACKGROUND: To study the role of computed tomography (CT)-derived radiomics features and clinical characteristics on the prognosis of "driver gene-negative" lung adenocarcinoma (LUAD) and to explore the potential molecular biological which may be helpful for patients' individual postoperative care. METHODS: A total of 180 patients with stage I-III "driver gene-negative" LUAD in the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to June 2015 were retrospectively collected. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was used to screen radiomics features and calculated the Rad-score. The prediction performance of the nomogram model based on radiomics features and clinical characteristics was validated and then assessed with respect to calibration. Gene set enrichment analysis (GSEA) was used to explore the relevant biological pathways. RESULTS: The radiomics and the clinicopathological characteristics were combined to construct a nomogram resulted in better performance for the estimation of OS (C-index: 0.815; 95% confidence interval [CI]: 0.756-0.874) than the clinicopathological nomogram (C-index: 0.765; 95% CI: 0.692-0.837). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinicopathological nomogram. The clinical prognostic risk score of each patient was calculated based on the radiomics nomogram and divided by X-tile into high-risk (> 65.28) and low-risk (≤ 65.28) groups. GSEA results showed that the low-risk score group was directly related to amino acid metabolism, and the high-risk score group was related to immune and metabolism pathways. CONCLUSIONS: The radiomics nomogram was promising to predict the prognosis of patients with "driver gene-negative" LUAD. The metabolism and immune-related pathways may provide new treatment orientation for this genetically unique subset of patients, which may serve as a potential tool to guide individual postoperative care for those patients.

Anxiety and depression in patients with chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome.

PURPOSE: Psychological symptoms are increasingly being noted in patients with chronic diseases. Currently, little evidence is available on the mental health of patients with overlap syndrome (OVS, chronic obstructive pulmonary disease plus obstructive sleep apnea). This study aimed to describe the prevalence and identify influencing factors of anxiety and depression in patients with OVS. METHODS: We recruited patients admitted for chronic obstructive pulmonary disease (COPD) from July 2018 to July 2019 who also underwent polysomnography tests to assess obstructive sleep apnea (OSA). COPD patients who had an apnea-hypopnea index (AHI) ≥ 5/h were defined as OVS. COPD patients who had an AHI < 5/h were identified as pure COPD. Questionnaires were administered to evaluate depression and anxiety in all subjects. We compared the differences in scores between patients with OVS and pure COPD. RESULTS: Two hundred and fifty-two patients were included, 180 (71%) patients had OVS, while only 72 patients had pure COPD. In the OVS group, 54% of the patients had depression, and 77% of the patients had anxiety. We found that patients with OVS had higher anxiety (8.00 (4.00, 10.00) vs. 6.00 (3.00, 9.00), p = 0.018) and depression (8.00 (4.00, 10.00) vs. 5.50 (2.25, 10.00), p = 0.022) scores than patients with pure COPD. A higher proportion of patients with hypertension (41% vs. 21%) and coronary heart disease (14% vs. 4%) were found in the OVS group. Chest pain, COPD Assessment Test (CAT) score, and OVS were independent risk factors for depression (P<0.05). A positive correlation was shown between anxiety and depression (r=0.638, p < 0.001). CONCLUSIONS: Anxiety and depression were more severe in patients with OVS than in patients with pure COPD. More attention should be paid to the mental health of OVS patients. TRIAL REGISTRATION: ClinicalTrials.gov; URL: www. CLINICALTRIALS: gov . NO.: NCT03182309. Registered on June 9, 2017; https://clinicaltrials.gov/ct2/show/NCT03182309?term=NCT+03182309&draw=2&rank=1.

Predicting response to immunotherapy plus chemotherapy in patients with esophageal squamous cell carcinoma using non-invasive Radiomic biomarkers.

OBJECTIVES: To develop and validate a radiomics model for evaluating treatment response to immune-checkpoint inhibitor plus chemotherapy (ICI + CT) in patients with advanced esophageal squamous cell carcinoma (ESCC). METHODS: A total of 64 patients with advance ESCC receiving first-line ICI + CT at two centers between January 2019 and June 2020 were enrolled in this study. Both 2D ROIs and 3D ROIs were segmented. ComBat correction was applied to minimize the potential bias on the results due to different scan protocols. A total of 788 features were extracted and radiomics models were built on corrected/uncorrected 2D and 3D features by using 5-fold cross-validation. The performance of the radiomics models was assessed by its discrimination, calibration and clinical usefulness with independent validation. RESULTS: Five features and support vector machine algorithm were selected to build the 2D uncorrected, 2D corrected, 3D uncorrected and 3D corrected radiomics models. The 2D radiomics models significantly outperformed the 3D radiomics models in both primary and validation cohorts. When ComBat correction was used, the performance of 2D models was better (p = 0.0059) in the training cohort, and significantly better (p < 0.0001) in the validation cohort. The 2D corrected radiomics model yielded the optimal performance and was used to build the nomogram. The calibration curve of the radiomics model demonstrated good agreement between prediction and observation and the decision curve analysis confirmed the clinical utility. CONCLUSIONS: The easy-to-use 2D corrected radiomics model could facilitate noninvasive preselection of ESCC patients who would benefit from ICI + CT.

The Application of Biomass-Based Catalytic Materials in the Synthesis of Cyclic Carbonates from CO2 and Epoxides.

The synthesis of cyclic carbonates from carbon dioxide (CO2) and epoxides is a 100% atom economical reaction and an attractive pathway for CO2 utilisation. Because CO2 is a thermodynamically stable molecule, the use of catalysts is mandatory in reducing the activation energy of the CO2 conversion. Considering environmental compatibility and the high-efficiency catalytic conversion of CO2, there is the strong need to develop green catalysts. Biomass-based catalysts, a type of renewable resource, have attracted considerable attention due to their unique properties-non-toxic, low-cost, pollution-free, etc. In this review, recent advances in the development of biomass-based catalysts for the synthesis of cyclic carbonates by CO2 and epoxides coupling are summarized and discussed in detail. The effect of biomass-based catalysts, functional groups, reaction conditions, and co-catalysts on the catalytic efficiency and selectivity of synthesizing cyclic carbonates process is discussed. We intend to provide a comprehensive understanding of recent experimental and theoretical progress of CO2 and epoxides coupling reaction and pave the way for both CO2 conversion and biomass unitization.

Effect of Serum Vitamin D Levels on Cellular Immunity and Antiviral Effects in Chronic Hepatitis B Patients.

BACKGROUND: To study the effect of 25-hydroxyl vitamin D3 on peripheral blood T lymphocyte immune function and antiviral effects in chronic hepatitis B patients. METHODS: The clinical data for 70 patients with chronic hepatitis B were analyzed. Serum 25-hydroxyl vitamin D was determined by electrochemical luminescence, and hepatitis B virus serological markers were determined by fluorescence quantitative polymerase chain reaction. Subsets of T lymphocytes were determined by immune fluorescence labeling method. These patients were divided into three groups based on serum 25-hydroxyl vitamin D level. After six months of pegylated interferon treatment, three groups have their number of T lymphocyte, liver functions, and virological indexes examined at the corresponding time. RESULTS: The years and ratio of gender have no statistical differences in these three groups. The proportion of CD3+, CD4+ T lymphocytes and the ratio of CD4+/CD8+ significantly increased (p < 0.05) as the level of 25-hydroxyl vitamin D increased, but the proportion of CD8+ decreased. Interferon treatment can improve the T cells subgroup, and the high level group of serum 25-hydroxyl vitamin D improved more obviously. The positive ratio of HBeAg, HBsAg and the titer of HBV DNA decreased with the increase of serum vitamin D, and the difference between the high and low level 25-hydroxyl vitamin D groups was significant (p < 0.05). The treatment of interferon can obviously improve the hepatitis B virus serological markers; the high level group of serum 25-hydroxyl vitamin D can obtain better virological response. However, there was no significant difference between the three groups of serological markers of liver function. CONCLUSIONS: Vitamin D may play a part in the immunologic function adjustment and immune tolerance in the natural course of chronic HBV infection, and high levels of vitamin D may be able to achieve sustained virological response. These findings may shed light on the research and treatment of chronic hepatitis B pathogenesis.

Correlation between climatic environment and characteristic components of 14 kinds of huajiao by thermal analysis techniques, GC-MS and HS-IMS.

Huajiao (Zanthoxylum bungeanum Maxim.) is extensively cultivated in various countries, including China, Korea, and India, owing to its adaptability to diverse environments. This study comprehensively analyzed the volatile substance composition of 14 varieties of red huajiao with distinct geographical origins. Thermal analysis methods, gas chromatography-mass spectrometry (GC-MS), and headspace-ion mobility chromatography (HS-IMS) were employed to evaluate the total volatile substance composition and content. The study revealed minor variations in water content, volatile matter content, and fractions among the geographically sourced huajiao samples. Utilizing correlation analysis based on GC-MS and orthogonal partial least squares discriminant analysis (OPLS-DA) with HS-IMS, a robust classification method for the 14 types of huajiao was developed. Applying the variable importance in the projection (VIP) method, seven distinctive components were identified as potential markers for distinguishing the geographical origins of red huajiao. By integrating climatic and topographical factors of the 14 huajiao varieties, the correlation analysis of GC-MS, and OPLS-DA classification outcomes from HS-IMS elucidated the influence of geo-environmental factors on huajiao components and contents. This research provides insights into the impact of diverse geographic environments on the constituents and characteristics of huajiao. It offers valuable guidance for selecting optimal cultivation locations to enhance huajiao quality, aiding consumers in making informed choices.

Advanced cross-sectional imaging of cerebral aneurysms.

While the rupture rate of cerebral aneurysms is only 1% per year, ruptured aneurysms are associated with significant morbidity and mortality, while aneurysm treatments have their own associated risk of morbidity and mortality. Conventional markers for aneurysm rupture include patient-specific and aneurysm-specific characteristics, with the development of scoring systems to better assess rupture risk. These scores, however, rely heavily on aneurysm size, and their accuracy in assessing risk in smaller aneurysms is limited. While the individual risk of rupture of small aneurysms is low, due to their sheer number, the largest proportion of ruptured aneurysms are small aneurysms. Conventional imaging techniques are valuable in characterizing aneurysm morphology; however, advanced imaging techniques assessing the presence of inflammatory changes within the aneurysm wall, hemodynamic characteristics of blood flow within aneurysm sacs, and imaging visualization of irregular aneurysm wall motion have been used to further determine aneurysm instability that otherwise cannot be characterized by conventional imaging techniques. The current manuscript reviews conventional imaging techniques and their value and limitations in cerebral aneurysm characterization, and evaluates the applications, value and limitations of advanced aneurysm imaging and post-processing techniques including intracranial vessel wall MRA, 4D-flow, 4D-CTA, and computational fluid dynamic simulations.

Metabolic rate and substrate oxidation of young males with obesity at the different sleep stages.

OBJECTIVE: Insufficient and poor-quality sleep among young adults is closely related to obesity and may impact metabolic processes. The mobilization and use of endogenous substrates during sleep, especially fat oxidation, is essential for energy metabolism. This study investigated whether there are differences in sleep structure, metabolic rate, substrate oxidation, and the respiratory quotient (RQ) between young males with normal weight and obesity according to sleep stages and overnight sleep. METHODS: Fifteen young males with normal weight and fifteen with obesity posited electrodes of polysomnography (PSG) and slept in the metabolic chamber for estimation of sleep structure, sleep metabolic rate (SMR), carbohydrate oxidation (CHOO), fat oxidation (FATO), and RQ. Fat-free mass (FFM) was measured by bioelectrical impedance analysis. RESULTS: The sleep period time (p = 0.038) and total sleep time (p = 0.032) were significantly shorter in the obesity group than in the normal-weight group. The obesity group also had a longer sleep latency (p = 0.034) and more sleep-turning events (p = 0.018). CHOO/FFM and the RQ were higher in the obesity group while FATO/FFM was significantly higher in the normal-weight group. FATO/FFM was also higher in the normal-weight group in each sleep stage whereas the RQ was higher in the obesity group (p < 0.05). CONCLUSIONS: Young males with obesity showed lower fat oxidation and more dominant carbohydrate-derived fuel oxidation than normal-weight during sleep and experienced shorter sleep periods and total sleep time.

[Clinical application and value of 3 Tesla contrast enhanced whole-heart coronary magnetic resonance angiography].

OBJECTIVE: To investigate the clinical application, feasibility and value of 3 T whole-heart contrast enhanced free-breathing navigator-gated three-dimensional coronary magnetic resonance angiography (CE-CMRA). METHODS: 3 T CE-CMRA was used to examine patients with suspected coronary heart disease (CAD). Gd-BOPTA (0.2 mmol/kg) was injected intravenously with slow infusion rate (0.3 ml/s) to perform enhancement. Data were post-processed to obtain principal branches of coronary artery and picture quality was evaluated. According to results of selective coronary arteriography (SCAG), the diagnostic accuracy of CE-CMRA for diagnosing CAD was judged by means of detecting significant stenosis (> 50%) of the principal branches based on the 9 segments of coronary artery. RESULTS: Twenty-three out of 26 patients successfully completed the examination. The mean scanning time was (10.4 ± 2.1) minutes, 178 out of 202 (88.1%) SCAG demonstrated segments could be evaluated by CE-CMRA. The imaging quality was superior in proximal and middle segments of coronary artery principal branches than in distal segments. Based on patient-level, there were 9 positive cases and 14 negative cases examined by CE-CMRA compared with 11 positive cases and 12 negative cases examined by SCAG, respectively. The whole diagnose accordance rate of CE-CMRA was 91.3% (21/23) compared with SCAG. The sensitivity, specificity and negative predictive values were 81.8% (9/11), 88.5% (169/191) and 98.8% (9/31) respectively. CONCLUSIONS: 3 T CE-CMRA is a feasible non-invasive imaging modality for diagnosing CAD, especially to detect significant stenosis in proximal and middle segments of coronary artery principal branches. However, the detecting efficacy is limited in assessing stenosis of distal segment and small branches of coronary artery.

A potent weighted risk model for evaluating the occurrence and severity of diabetic foot ulcers.

BACKGROUND: Diabetic foot ulcer (DFU) is a serious chronic complication of diabetes. This study aimed to establish weighted risk models for determining DFU occurrence and severity in diabetic patients. METHODS: This was a multi-center hospital-based cross-sectional study. A total of 1488 diabetic patients with or without an ulcer from three tertiary hospitals were included in the study. Random forest method was used to develop weighted risk models for assessing DFU risk and severity. Receiver operating characteristic curves were used to validate the models and calculate the optimal cut-off values of the important risk factors. RESULTS: We developed potent weighted risk models for evaluating DFU occurrence and severity. The top eight important risk factors for DFU onset were plasma fibrinogen, neutrophil percentage and hemoglobin levels in whole blood, stroke, estimated glomerular filtration rate, age, duration of diabetes, and serum albumin levels. The top 10 important risk factors for DFU severity were serum albumin, neutrophil percentage and hemoglobin levels in whole blood, plasma fibrinogen, hemoglobin A1c, estimated glomerular filtration rate, hypertension, serum uric acid, diabetic retinopathy, and sex. Furthermore, the area under curve values in the models using plasma fibrinogen as a single risk factor for determining DFU risk and severity were 0.86 (sensitivity 0.74, specificity 0.87) and 0.73 (sensitivity 0.76, specificity 0.58), respectively. The optimal cut-off values of plasma fibrinogen for determining DFU risk and severity were 3.88 g/L and 4.74 g/L, respectively. CONCLUSIONS: We have established potent weighted risk models for DFU onset and severity, based on which precise prevention strategies can be formulated. Modification of important risk factors may help reduce the incidence and progression of DFUs in diabetic patients.

A computed tomography (CT)-derived radiomics approach for predicting primary co-mutations involving TP53 and epidermal growth factor receptor (EGFR) in patients with advanced lung adenocarcinomas (LUAD).

BACKGROUND: Epidermal growth factor receptor (EGFR) co-mutated with TP53 could reduce responsiveness to tyrosine kinase inhibitors (TKIs) and worsen patients' prognosis compared to TP53 wild type patients in. EGFR: mutated lung adenocarcinomas (LUAD). To identify this genetically unique subset prior to treatment through computed tomography (CT) images had not been reported yet. METHODS: Stage III and IV LUAD with known mutation status of EGFR and TP53 from The First Affiliated Hospital of Sun Yat-sen University (May 1, 2017 to June 1, 2020) were collected. Characteristics of pretreatment enhanced-CT images were analyzed. One-versus-one was used as the multiclass classification strategy to distinguish the three subtypes of co-mutations: EGFR + & TP53 +, EGFR + & TP53 -, EGFR -. The clinical model, semantic model, radiomics model and integrated model were built. Area under the receiver-operating characteristic curves (AUCs) were used to evaluate the prediction efficacy. RESULTS: A total of 199 patients were enrolled, including 83 (42%) cases of EGFR -, 55 (28%) cases of EGFR + & TP53 +, 61 (31%) cases of EGFR + & TP53 -. Among the four different models, the integrated model displayed the best performance for all the three subtypes of co-mutations: EGFR - (AUC, 0.857; accuracy, 0.817; sensitivity, 0.998; specificity, 0.663), EGFR + & TP53 + (AUC, 0.791; accuracy, 0.758; sensitivity, 0.762; specificity, 0.783), EGFR + & TP53 - (AUC, 0.761; accuracy, 0.813; sensitivity, 0.594; specificity, 0.977). The radiomics model was slightly inferior to the integrated model. The results for the clinical and the semantic models were dissatisfactory, with AUCs less than 0.700 for all the three subtypes. CONCLUSIONS: CT imaging based artificial intelligence (AI) is expected to distinguish co-mutation status involving TP53 and EGFR. The proposed integrated model may serve as an important alternative marker for preselecting patients who will be adaptable to and sensitive to TKIs.

Noninvasive diagnosis of cardiac amyloidosis by MRI and echochardiography.

This study described the radiological features on echocardiography and MRI specific to cardiac amyloidosis confirmed on biopsy. Eleven cases of biopsy-proven cardiac amyloidosis were retrospectively reviewed in this study. All patients underwent biopsy, cardiac MRI and echocardiography. The main echocardiography and MRI findings were as follows: diffuse ventricular and septum wall thickening, atrial enlargement, pericardial effusion, restricted left ventricular (LV) systolic and diastolic function, characteristic granular sparkling of myocardium. MRI revealed a characteristic pattern of global subendocardial late enhancement, extending in varying degrees into the neighboring myocardium. The findings agreed with the infiltration distribution of amyloid protein. Typical abnormalities seen on echocardiography and MRI should have important diagnostic and prognostic value of cardiac amyloidosis. MRI should be considered in the diagnosis of cardiac amyloidosis if echocardiographic features are suspicious.

Effect of miRNA-200b on the proliferation and apoptosis of cervical cancer cells by targeting RhoA.

OBJECTIVE: This article aims to investigate the effect of miRNA-200b on the proliferation and apoptosis of cervical cancer cells by targeting RhoA. METHODS: HeLa cells of cervical cancer were divided into five groups: blank control group, negative control group (miRNA-200b mimic NC), miRNA-200b mimic group, RhoA-negative control group, and RhoA overexpression group. Cells were collected 48 h after transfection. The expression levels of miRNA-200b were detected by RT-PCR. Target relationship between miRNA-200b and RhoA was verified by the dual-luciferase reporter assay. RhoA mRNA and protein expression were detected by western blot and RT-PCR methods. Flow cytometry was used to detect the apoptosis of cells in each group, and the CCK8 method was used to detect the proliferation of cells in each group. The mRNA and protein expression of Bax and cyclin D1 were detected by RT-PCR and western blot. RESULTS: The results of the dual luciferase reporter assay showed that RhoA was the target gene of microRNA 200b. Compared with the blank control group and the miRNA-200b mimic-NC group, the proportion of apoptotic cells increased significantly in the miRNA-200b mimic group, and the proliferation of cells was inhibited (P < 0.05). After overexpression of RhoA, the percentage of apoptotic cells decreased and the ability of cell proliferation increased significantly (P < 0.05). CONCLUSION: miRNA-200b can inhibit the proliferation and promote the apoptosis of cervical cancer cells by targeting the RhoA gene.

Risk factors associated with disease aggravation among 126 hospitalized patients with COVID-19 in different places in China: A retrospective observational study.

Coronavirus disease 2019 (COVID-19) has rapidly spread on a global scale. Therefore, it is urgent to identify risk factors that could be associated with severe type of COVID-19 from common type.For this retrospective study, we recruited patients with COVID-19 in Wuhan and Zhoukou. Patients were classified into a severe group and common group based on guidelines after admission. Clinical manifestations and laboratory tests were compared, and univariate binary logistic regression and multivariate regression analyses were applied to assess potential risk factors.A total of 126 patients were recruited from January 23 to March 23, 2020. Ninety cases were identified as the common type and 36 as the severe type. The average age in the severe group was significantly older than that in the common group (P = .008). Patients with severe COVID-19 exhibited higher proportions of dyspnea (P = .001), weakness (P = .023), and diarrhea (P = .046). Moreover, there were more patients with hypertension (P = .01) or coinfection (P = .001) in the severe group than in the common group. Additionally, severe COVID-19 was associated with increased neutrophil counts (P < .001), C-reactive protein (P < .001), procalcitonin (P = .024) and decreased lymphocyte counts (P = .001), hemoglobin (P < .001), total protein (TP) (P < .001), and albumin (ALB) (P < .001). Based on logistic regression analysis, dyspnea (P < .001), TP (P = .042), and ALB (P = .003) were independent risk factors for severe disease.Patients with lower TP, ALB, and dyspnea should be carefully monitored, and early intervention should be implemented to prevent the development of severe disease.

A CT-derived deep neural network predicts for programmed death ligand-1 expression status in advanced lung adenocarcinomas.

BACKGROUND: Programmed death ligand-1 (PD-L1) expression remains a crucial predictor in selecting patients for immunotherapy. The current study aimed to non-invasively predict PD-L1 expression based on chest computed tomography (CT) images in advanced lung adenocarcinomas (LUAD), thus help select optimal patients who can potentially benefit from immunotherapy. METHODS: A total of 127 patients with stage III and IV LUAD were enrolled into this study. Pretreatment enhanced thin-section CT images were available for all patients and were analyzed in terms of both morphologic characteristics by radiologists and deep learning (DL), so to further determine the association between CT features and PD-L1 expression status. Univariate analysis and multivariate logical regression analysis were applied to evaluate significant variables. For DL, the 3D DenseNet model was built and validated. The study cohort were grouped by PD-L1 Tumor Proportion Scores (TPS) cutoff value of 1% (positive/negative expression) and 50% respectively. RESULTS: Among 127 LUAD patients, 46 (36.2%) patients were PD-L1-positive and 38 (29.9%) patients expressed PD-L1-TPS ≥50%. For morphologic characteristics, univariate and multivariate analysis revealed that only lung metastasis was significantly associated with PD-L1 expression status despite of different PD-L1 TPS cutoff values, and its Area under the receiver operating characteristic curve (AUC) for predicting PD-L1 expression were less than 0.700. On the other hand, the predictive value of DL-3D DenseNet model was higher than that of the morphologic characteristics, with AUC more than 0.750. CONCLUSIONS: The traditional morphologic CT characteristics analyzed by radiologists show limited prediction efficacy for PD-L1 expression. By contrast, CT-derived deep neural network improves the prediction efficacy, it may serve as an important alternative marker for clinical PD-L1 detection.

Clinical value of Pro-GRP and T lymphocyte subpopulation for the assessment of immune functions of lung cancer patients after DC-CIK biological therapy.

The present study investigated the aptness of assessing the levels of progastrin-releasing peptide (Pro-GRP) in addition to the T lymphocyte subpopulation in lung cancer patients prior to and after therapy for determining immune function. A total of 45 patients with lung cancer were recruited and stratified in to a non-small cell lung cancer (NSCLC) and an SCLC group. Prior to and after treatment by combined biological therapy comprising chemotherapy or chemoradiotherapy followed by three cycles of retransformation of autologous dendritic cells-cytokine-induced killer cells (DC-CIK), the peripheral blood was assessed for populations of CD3+, CD4+, CD8+ and regulatory T cells (Treg) by flow cytometry, and for the levels of pro-GRP, carcinoembryonic antigen, neuron-specific enolase and Cyfra 21-1. The results revealed that in NSCLC patients, CD8+ T lymphocytes and Treg populations were decreased, and that CD3+ and CD4+ T lymphocytes as well as the CD4+/CD8+ ratio were increased after therapy; in SCLC patients, CD3+, CD4+ and CD8+ T lymphocytes were increased, while Treg cells were decreased after treatment compared with those at baseline. In each group, Pro-GRP was decreased compared with that prior to treatment, and in the SCLC group only, an obvious negative correlation was identified between Pro-GRP and the T lymphocyte subpopulation. Furthermore, a significant correlation between Pro-GRP and Tregs was identified in each group. In conclusion, the present study revealed that the immune function of the patients was improved after biological therapy. The results suggested a significant correlation between Pro-GRP and the T lymphocyte subpopulation in SCLC patients. Detection of Pro-GRP may assist the early clinical diagnosis of SCLC and may also be used to assess the immune regulatory function of patients along with the T lymphocyte subpopulation. Biological therapy with retransformed autologous DC-CIK was indicated to enhance the specific elimination of tumor cells and improve the immune surveillance function in cancer patients, and also restrained the immune evasion of the tumor, leading to decreased Pro-GRP levels.

Unusual cause of 55 years of rectal bleeding: hemolymphangioma (a case report).

RATIONALE: Hemolymphangioma is a rare developmental error of combined blood and lymphatic vasculature. To the best of our knowledge, there is only one case of rectal hemolymphangioma reported in Pubmed. Our case probably is the first reported rectal hemolymphangioma with computed tomography (CT) evaluation. PATIENT CONCERNS AND DIAGNOSIS: A 57-year-old male was presented to our hospital with 55 years of long history of episodic rectal bleeding. Past medical history showed numerous hospital visits for similar illness. Multiple diagnoses were made and different treatment modalities were applied for his benefit, but none of them relieved the symptoms permanently. He was then referred to our hospital. On admission, he was presented with intermediate rectal bleeding of fresh blood. CT examination showed isodense homogenous rectal wall thickening with heterogeneous enhancement on contrast examination. Multiple calcifications were seen in and around the lesion. INTERVENTIONS AND OUTCOMES: He underwent open abdominal surgery with total surgical excision of the lesion. Post-surgical histopathological examination of excised specimen showed submucosal multiple thin-walled vessel of varying size, some consistent with blood vessel and other with lymph vessel, thus diagnosis of hemolymphangioma was made. Follow-up for 6 months showed no recurrence. LESSIONS: Hemolymphangioma is a benign developmental lesion. Radiological findings can be challenging and range from benign cystic lesion to aggressive lesion mimicking malignancy. Therefore, combined clinical history, radiological findings, and continuous follow-up can help make proper diagnosis and provide prompt and accurate treatment.