Clinical features of patients with rheumatic and musculoskeletal diseases during the coronavirus disease 2019 pandemic and the association of its relapse with infection: Across-sectional study.

AIM: The aim of this study was to investigate the clinical features of patients with rheumatic and musculoskeletal diseases (RMDs) infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the relationship between RMDs relapse and SARS-CoV-2 infection. METHODS: We carried out a cross-sectional observational study among 585 patients with RMDs and 619 individuals without RMDs. Data on demographics, the clinical features of coronavirus disease 2019 (COVID-19), antirheumatic therapy, and RMD relapse were collected. Differences between RMDs and control groups, infected and uninfected groups, relapse and non-relapse RMDs groups were examined. The influence of COVID-19 infection on medications and relapse of RMDs was also assessed. RESULTS: Among 1204 participants finally recruited for analysis, 1030 (85.5%) were infected with COVID-19. Seven hundred and ninety-five (77.2%) of infected individuals were female, and the median age was 40 years (IQR 33, 50). Patients in the RMD group had a relatively lower risk of COVID-19 symptoms whereas were significantly more likely to require hospitalization (6.7% vs. 2.2%). In the RMDs group, younger patients who were under the age of 65 were more likely to report more symptoms. More patients with RMD relapse (27, 34.6%) adjusted their medications during the period of COVID-19 infection than those without relapse (59, 13.2%). CONCLUSION: Patients with RMDs were at lower risk of symptoms of COVID-19. Rheumatic and musculoskeletal disease patients experience a higher risk of relapse especially when they adjust medications during COVID-19 infection. The long-term prognosis of infected RMDs patients need further investigation.

Evaluation of safety and efficacy of inhaled ambroxol in hospitalized adult patients with mucopurulent sputum and expectoration difficulty.

Background: Ambroxol is a widely used mucoactive drug in sputum clearance of respiratory diseases taken orally and by injection. However, there is a paucity of evidence for inhaled ambroxol in sputum clearance. Methods: This study performed a multicenter, randomized, double-blind, placebo-controlled, phase 3 trial at 19 centers in China. Hospitalized adult patients with mucopurulent sputum and expectoration difficulty were recruited. Patients were randomized by 1:1 to receive inhalation of either ambroxol hydrochloride solution 3 mL (22.5 mg) + 0.9% sodium chloride 3 mL or 0.9% sodium chloride 6 mL twice daily for 5 days, with an interval of more than 6 h. The primary efficacy endpoint was the absolute change in the sputum property score after treatment compared to the baseline in the intention-to-treat population. Results: Between 10 April 2018 and 23 November 2020, 316 patients were recruited and assessed for eligibility, of whom 138 who received inhaled ambroxol and 134 who received a placebo were included. Patients who received inhaled ambroxol had a significantly greater decrease in the sputum property score compared with patients who received inhalation of placebo (difference: -0.29; 95% CI: -0.53 to -0.05; p = 0.0215). Compared with the placebo, inhaled ambroxol also significantly reduced more expectoration volume in 24 h (difference: -0.18; 95% CI: -0.34 to -0.03; p = 0.0166). There was no significant difference in the proportion of adverse events between the two groups, and no deaths were reported. Discussion: In hospitalized adult patients with mucopurulent sputum and expectoration difficulty, inhaled ambroxol was safe and effective for sputum clearance compared with a placebo. Clinical trial registration: [https://www.chictr.org.cn/showproj.html?proj=184677], Chinese Clinical Trial Registry [ChiCTR2200066348].

Selective extended dissection for pancreaticoduodenectomy is associated with better survival in pancreatic cancer patients: retrospective cohort study.

BACKGROUND: Pancreatic ductal adenocarcinoma is a highly malignant tumor with relatively poor survival. Surgery is the first choice for treating patients with early pancreatic cancer. However, the surgical approach and the extent of resection for patients with pancreatic cancer are currently controversial. METHODS: The authors optimized the procedure of standard pancreaticoduodenectomy to selective extended dissection (SED), which is based on the extrapancreatic nerve plexus potentially invaded by the tumor. The authors retrospectively analyzed the clinicopathological data of patients with pancreatic adenocarcinoma who underwent radical surgery in our center from 2011 to 2020. Patients who underwent standard dissection (SD) were matched 2:1 to those who underwent SED using propensity score matching. The log-rank test and Cox regression model were used to analyze survival data. In addition, statistical analyses were performed for the perioperative complications, postoperative pathology, and recurrence pattern. RESULTS: A total of 520 patients were included in the analysis. Among patients with extrapancreatic perineural invasion (EPNI), disease-free survival was significantly longer in those who received SED than in those who received SD (14.5 months vs. 10 months, P <0.05). The incidence of metastasis in No. 9 and No. 14 lymph nodes was significantly higher in patients with EPNI. In addition, there was no significant difference in the incidence rate of perioperative complications between the two surgical procedures. CONCLUSION: Compared with SD, SED exhibits a significant prognostic benefit for patients with EPNI. The SED procedure aiming at specific nerve plexus dissection displayed particular efficacy and safety in resectable pancreatic ductal adenocarcinoma patients.

Short-term outcomes in patients with lung cancer-associated acute ischemic stroke.

BACKGROUND: To investigate the independent risk factors of poor short-term outcomes in patients with lung cancer-associated acute ischemic stroke (LCAIS) and use them to develop an index of prognosis LCAIS (pLCAIS) which could help clinicians identify patients at high risk for poor short-term outcomes. METHODS: We retrospectively enrolled patients with lung cancer-associated acute ischemic stroke and employed the 90D modified Rankin cale (mRS) to divide them into two groups: good outcomes (score 0-2) and poor outcomes (score 3-6). Propensity score matching (PSM) was used to remove confounding factors, and multivariable logistic regression analysis was used to analyze the independent risk factors of pLCAIS. The receiver operating characteristic (ROC) and area under the ROC curve (AUC) developed a multiple model combining the independent risk factors of pLCAIS. RESULTS: A total of 172 patients were included: 67 (38.9%) with good outcomes and 105 (61.1%) with poor outcomes. After using PSM, there were 33 cases in each group. The results showed that patients with poor short-term outcomes were significantly higher in D-dimer (OR = 1.001, 95% CI: 1.000-1.002, p = 0.048), CRP (OR = 1.078, 95% CI: 1.008-1.153, p = 0.028), and neutrophil count (OR = 14.673, 95% CI: 1.802-19.500, p = 0.012). The ROC curve, used to assess the diagnostic ability of binary classifiers, showed that the product of these three independent risk factors showed high sensitivity and specificity. CONCLUSION: In this study, we have identified three independent risk factors associated with poor short-term outcomes in pLCAIS: higher NC, CRP, and D-dimer levels. These findings may be helpful for clinicians in identifying poor short-term outcomes patients.

A Novel Guidewire Aiming Device to Improve the Accuracy of Guidewire Insertion in Femoral Neck Fracture Surgery Using Cannulated Screw Fixation.

BACKGROUND The aim of this study was to improve the accuracy of guidewire insertion in the femoral neck fracture surgery using cannulated screw fixation. MATERIAL AND METHODS A novel aiming device was designed and manufactured. Between January 2010 and June 2012, 64 femoral neck fracture patients were included into the study. All 64 patients were divided into 2 groups randomly. The aiming device was used during the operation for patients in the experimental group, but not in the control group. RESULTS There were no statistically significant differences in operative time or bleed volume between the groups (P>0.05). The frequency of guidewire drilling was significantly lower in the experimental group than in the control group (P<0.05). The angle between the first cannulated screw and the central axis of the femoral neck in coronal plane and sagittal plane, and the distance between the bottom cannulated screw and the medial calcar femorale rim, were significantly smaller in the experimental group than in the control group (P<0.05). CONCLUSIONS The aiming device is simple in structure and easy to use. It could help surgeons to accurately insert cannulated screw guidewires. The aiming device is suitable for broad clinical use.

An anisotropic coarse-grained model based on Gay-Berne and electric multipole potentials and its application to simulate a DMPC bilayer in an implicit solvent model.

In this work, we aim at optimizing the performance of the anisotropic GBEMP model, which adopts a framework by combining a Gay-Berne (GB) anisotropic potential with an electric multipole (EMP) potential, in simulating a DMPC lipid bilayer in an implicit solvent model. First, the Gay-Berne parameters were initially obtained by fitting to atomistic profiles of van der Waals interactions between homodimers of molecular fragments while EMP parameters was directly derived from the expansion of point multipoles at predefined EMP sites. Second, the GB and EMP parameters for DMPC molecule were carefully optimized to be comparable to AMBER atomistic model in the calculations of the dipole moments of DMPC monomers adopting different conformations as well as the nonbonded interactions between two DMPC molecules adopting different conformations and separated at various distances. Finally, the GB parameters for DMPC were slightly adjusted in simulating a 72 DMPC bilayer system so that our GBEMP model would be able to reproduce a few important structural properties, namely, thickness (DHH), area per lipid ( AL) and volume per lipid ( VL). Meanwhile, the atomistic and experimental results for electron density profiles and order parameters were reproduced reasonably well by the GBEMP model, demonstrating the promising feature of GBEMP model in modeling lipid systems. Finally, we have shown that current GBEMP model is more efficient by a factor of about 25 than AMBER atomistic point charge model.

Advancement of polarizable force field and its use for molecular modeling and design.

The most important requirement of biomolecular modeling is to deal with electrostatic energies. The electrostatic polarizability is an important part of electrostatic interaction for simulation systems. However, AMBER, CHARMM, OPLS, GROMOS, MMFF force fields etc. used in the past mostly apply fixed atomic center point charge to describe electrostatic energies, and are not sufficient for considering the influence of the electrostatic polarization. The emergence of polarizable force fields has solved this problem. In recent years, quickly developed polarizable force fields have involved a lot of fields. The chapter relating to polarizable force fields spread over several aspects. Firstly, we reviewed the history of the classical force fields and compared with polarizable force fields to elucidate the advancements of polarizable force fields. Secondly, it is introduced that the application of polarizable force fields to small molecules and biological macromolecules simulation, including molecular design. Finally, a brief development trend and perspective is given on rapidly growing polarizable force fields.

Folding mechanisms of Trefoil Knot proteins studied by molecular dynamics simulations and Go-model.

Most proteins need to avoid the complex topologies when folding into the native structures, but some proteins with nontrivial topologies have been found in nature. Here we used protein unfolding simulations under high temperature and all-atom Go-model to investigate the folding mechanisms for two trefoil knot proteins. Results show that, the contacts in ß-sheet are important to the formation of knot protein, and if these contacts disappeared, the knot protein would be easy to untie. In the Go-model simulations, the folding processes of the two knot proteins are similar. The compact structures of the two knot proteins with the native contacts in ß-sheet are formed in transition state, and the intermediate state has loose C-terminal. This model also reveals the detailed folding mechanisms for the two proteins.

Theoretical studies on the folding mechanisms for different DNA G-quadruplexes.

The G-quadruplex DNA formed by the stack of guanines in human telomere sequence is a promising anticancer target. In this study we used the energy landscape theory to elucidate the folding mechanisms for the thrombin aptamer, Form 1 and Form 3 G-quadruplexes. The three G-quadruplexes were simulated with all-atom Go-model. Results show that, the three G-quadruplexes fold through a two-state mechanism. In the initial stage of the folding process, the compact structures are formed. The G-quadruplexes need to form G-triplex structures on the basis of the compact structures before folding to the native states. The folding free energy barrier of Form 3 G-quadruplex is higher than thrombin aptamer and Form 1, which shows that the structure of Form 3 G-quadruplex has more stability than the other two G-quadruplexes.

Binding modes and interaction mechanism between different base pairs and methylene blue trihydrate: a quantum mechanics study.

Different quantum mechanic methods have been evaluated for the calculation of binding modes and interactions between intercalators with different DNA base pairs by comparing with the results of MP2, which is very expensive, indicating that WB97XD method under 6-311+G* basis set is able to efficiently reproduce MP2 results. We discovered that the methylene blue trihydrate intercalated into the DNA base pairs, and DNA intercalation increased the distance between DNA base pairs, depending on the types of DNA bases. According to the binding energy results, it was found that the intercalation of methylene blue trihydrate into AA-TT base pair was more favorable in the orientation of nitrogen than other directions and intercalation, and the electric charge was transferred from methylene blue trihydrate to the AA-TT base pair. The analysis of change in the charge density shows that changes often take place in the heavy atom in the middle of the system which the charge density changes most remarkable.

Coarse-grained simulations for organic molecular liquids based on Gay-Berne and electric multipole potentials.

Coarse-grained studies of CH(3)SH, CH(3)CHO and CHCl(3) liquids, based on anisotropic Gay-Berne (GB) and electric multipole potentials (EMP), demonstrate that the coarse-grained model is able to qualitatively reproduce the results obtained from the atomistic model (AMOEBA polarizable force field) and allows for significant saving in computation time. It should be pointed out that the accuracy of the coarse-grained model is very sensitive to how well the anisotropic GB particle is defined and how satisfactorily the EMP sites are chosen.