Phosphoric Acid-Catalyzed Alkene Difunctionalization of 2-Vinylpyridines via HOMO/LUMO Biactivated Diels-Alder Reaction.

The difunctionalization of vinylpyridines based on the cyclization strategy remains rare and underdeveloped, in contrast to the well-developed hydrogen functionalization. Current exploration on [4 + 2] cyclization of vinylpyridines mainly relies on extremely high temperatures and the LUMO activation of vinylpyridines using boron trifluoride as a strong Lewis acid. Herein, we established a phosphoric acid-catalyzed [4 + 2] cyclization reaction of 3-vinyl-1H-indoles and 2-vinylpyridines by means of the LUMO/HOMO bifunctional activation model. This protocol features mild reaction conditions, high functional group tolerance, broad substrate compatibility, and high diastereoselectivity, enabling the efficient construction of various functionalized pyridine-substituted tetrahydrocarbazoles with prominent potential in drug discovery.

Morphology, photosynthetic and molecular mechanisms associated with powdery mildew resistance in Kentucky bluegrass.

Kentucky bluegrass (Poa pratensis L.), one of the most widely used cool-season turfgrasses around the world, is sensitive to powdery mildew (PM; Blumeria graminis). The PM strain identification and regulation mechanisms of Kentucky bluegrass in response to pathogens still remain unclear. Through morphological and molecular analyses, we identified that the pathogen in Kentucky bluegrass was B. graminis f. sp. poae. The infection of B. graminis led to a reduction of the sclerenchyma area, expansion of vesicular cells and movement of chloroplasts. The infected leaves had significantly lower values in net photosynthesis, stomatal conductance and transpiration rate, maximal quantum yield of PSII photochemistry, photochemical quenching and non-regulated energy dissipation compared to mock-inoculated leaves. Expressions of light-harvesting antenna protein genes LHCA and LHCB and photosynthetic electron transport genes petE and petH decreased significantly in infected leaves. Furthermore, upregulations of genes involved in plant-pathogen interaction, such as HSP90, RBOH, and RPM and downregulations of EDS, RPS and WRKY were observed in infected leaves. The findings may help design a feasible approach to effectively control the PM disease in Kentucky bluegrass and other related perennial grass species.

Modification of carbapenemase inhibition test and comparison of its performance with NG-Test CARBA 5 for detection of carbapenemase-producing Enterobacterales.

AIMS: Adequately and accurately identifying carbapenemase-producing Enterobacterales (CPE) is vital for selecting appropriate antimicrobial therapy and implementing effective infection control measures. This study aims to optimize the phenotypic detection method of carbapenemase for routine diagnostics in clinical microbiology laboratories. METHODS AND RESULTS: Carbapenemase genes in 2665 non-duplicate CRE clinical strains collected from various regions of China were confirmed through whole-genome sequencing (WGS). The carbapenemase inhibition test (CIT) was conducted and interpreted using different methods and breakpoints, then compared with the NG-Test CARBA 5 for carbapenemase detection. The diagnostic performance of the CIT method was optimal when the carbapenemase types were determined by comparing the inhibition zone diameters of the imipenem disc with 3-aminophenylboronic acid (APB) plus ethylenediaminetetraacetic acid (EDTA) to those of the imipenem disc with either APB or EDTA alone, with a breakpoint of 4 mm. The overall sensitivities of the current CIT, the modified CIT, and NG-Test CARBA 5 were 91.4%, 94.9%, and 99.9%, respectively. For detecting isolates co-producing Klebsiella pneumoniae carbapenemase (KPC) and metallo-ß-lactamases (MBLs), the modified CIT method had higher sensitivity than the current method (70.0% vs. 53.3%), though this difference was not statistically significant (P = 0.063). The NG-Test CARBA 5 showed excellent performance for multi-carbapenemases diagnosis, with sensitivity and specificity of 97.1% and 100%, respectively. CONCLUSIONS: Optimizing and standardizing the CIT method for clinical use is necessary. It has certain advantages in diagnosing multi-carbapenemase and rare carbapenemase production. However, for identifying common carbapenemase types, the NG-Test CARBA 5 demonstrated superior performance.

Effectiveness and safety of REBACIN as a non-invasive intervention for persistent high-risk human papillomavirus infection: A real-world prospective multicenter cohort study.

BACKGROUND: We previously reported that REBACIN effectively eliminates persistent high-risk human papillomavirus (hrHPV) infection. Here, we conducted a prospective multicenter cohort study to evaluate the safety and effectiveness of REBACIN, taking into account factors such as specific hrHPV subtype and patient's age. METHODS: According to inclusion/exclusion criteria and participant willingness, 3252 patients were divided into REBACIN group while 249 patients into control group. Patients in REBACIN group received one course treatment of intravaginal administration of REBACIN while no treatment in control group. After drug withdrawal, participants in both groups were followed up. RESULTS: The clearance rate of persistent hrHPV infection in REBACIN group was 60.64%, compared to 20.08% in control group. Specifically, the clearance rates for single-type infection of HPV16 or HPV18 were 70.62% and 69.23%, respectively, which was higher than that of HPV52 (59.04%) or HPV58 (62.64%). In addition, the single, double, and triple/triple+ infections had a clearance rate of 65.70%, 53.31%, and 38.30%, respectively. Moreover, 1635 patients under 40 years old had a clearance rate of 65.14%, while it was 55.08% for 1447 patients over 40 years old. No serious adverse effects were found. CONCLUSION: This study confirmed that REBACIN can effectively and safely eliminate persistent hrHPV infection, which the clearance rate of HPV16/18 is higher than that of HPV52/58, the clearance rate of single-type infection is higher than that of multiple-type infections, and the clearance rate in young patients is higher than that in elder patients, providing a guidance for REBACIN application in clearing hrHPV persistent infection in real-world settings. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry Registration Number: ChiCTR1800015617 http://www.chictr.org.cn/showproj.aspx?proj=26529 Date of Registration: 2018-04-11.

Risk factors and molecular epidemiology of fecal carriage of carbapenem resistant Enterobacteriaceae in patients with liver disease.

BACKGROUND: Carbapenem resistant Enterobacteriaceae (CRE) colonization is a risk factor for CRE infection. CRE infection results in an increase in mortality in patients with cirrhosis. However, minimal data regarding the prevalence and the risk factors of CRE colonization in patients with liver disease yet without liver transplantation are available. The present study aimed to investigate the prevalence, risk factors and molecular epidemiology characteristics of CRE fecal carriage among patients with liver disease. METHODS: Stool specimens from 574 adult inpatients with liver disease were collected from December 2020 to April 2021. CRE were screened using selective chromogenic agar medium and identified by the Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS). Antimicrobial susceptibility was determined using the broth microdilution method. Carbapenemase genes were characterized by polymerase chain reaction (PCR) and DNA sequencing. Multilocus sequence typing (MLST) was performed for Carbapenem Resistant Klebsiella pneumoniae (CR-KPN) isolates and Carbapenem Resistant Escherichia Coli (CR-ECO) isolates. RESULTS: The total number of stool specimens (732) were collected from 574 patients with liver disease. 43 non-duplicated CRE strains were isolated from 39 patients with a carriage rate of 6.79% (39/574). The carriage rate was 15.60% (17/109) in patients with acute-on-chronic liver failure (ACLF). Multivariate analysis indicated that ACLF (P = 0.018), the history of pulmonary infection within past 3 months (P = 0.001) and the use of third generation cephalosporin/ß-lactamases inhibitor within past 3 months (P = 0.000) were independent risk factors of CRE colonization in patients with liver disease. Klebsiella Pnuemoniae (KPN) (51.28%) and Escherichia coli (ECO) (30.77%) were main strains in these patients. All CRE strains showed high resistance to most antimicrobials except for polymyxin B and tigecycline. Most (83.72%, 36/43) of the CRE carried carbapenemase genes. blaKPC-2 was the major carbapenemase gene. The molecular epidemiology of KPN were dominated by ST11, while the STs of ECO were scattered. CONCLUSIONS: The present study revealed that CRE fecal carriage rates were higher in patients with ACLF than in patients without liver failure. ACLF, the history of pulmonary infection within past 3 months and the use of third generation cephalosporin/ß-lactamases inhibitor within past 3 months were independent risk factors of CRE colonization in patients with liver disease. Regular CRE screening for hospitalized patients with liver disease should be conducted to limit the spread of CRE strain.

Comparison of Clinical Features and Prognostic Factors of Cryptococcal Meningitis Caused by Cryptococcus neoformans in Patients With and Without Pulmonary Nodules.

Whether the clinical features of cryptococcal meningitis (CM) patients vary with the coexistence of pulmonary nodules is not clear. This study aimed to compare the clinical features of CM in patients with and without pulmonary nodules detected by chest computed tomography (CT). The medical records of CM patients hospitalized in Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 1, 2010, to December 31, 2016, were retrospectively reviewed. Baseline demographics, laboratory and radiographic findings, clinical managements, and outcomes were analyzed. A total of 90 CM patients were enrolled. Forty (44.4%) patients had pulmonary nodules (PN-positive), and 50 (55.6%) patients had no pulmonary nodules (PN-negative). Compared with PN-negative patients, PN-positive patients had higher cerebrospinal fluid (CSF)/serum albumin ratios, higher rates of CSF protein > 1000 mg/L, CSF glucose < 2.5 mmol/L, worse overall treatment response, higher rates of abnormal head CT and magnetic resonance imaging manifestations, and more unfavorable clinical outcomes. Multivariate analysis showed that immunocompromise (p = 0.037) and CSF glucose < 2.5 mmol/L (p = 0.044) indicated poor outcome in PN-positive patients, while CSF glucose < 2.5 mmol/L (p = 0.025) also indicated poor outcome in PN-negative patients. Amphotericin B in the initial therapy was a protective factor for PN-negative patients (p = 0.008). Certain clinical features showed significant differences between CM patients with and without pulmonary nodules, and several independent contributing factors impacted the clinical outcomes for CM patients. Future studies should be performed to further examine these factors.

The Roles of Fatty-Acid Modification in the Activity of the Anticancer Peptide R-Lycosin-I.

We previously reported that R-lycosin-I, modified by amino acid substitution from lycosin-I, was a peptide with anticancer activity and a linear amphipathic α-helix conformation and that it can induce cancer cell apoptosis and inhibit cell proliferation. However, the anticancer activity of R-lycosin-I was not highly improved. In order to further improve the anticancer activity of R-lycosin-I, fatty acids with different chain lengths from 12 to 20 carbons were introduced to the N-terminal of R-lycosin-I to yield five lipopeptides (R-C12, R-C14, R-C16, R-C18, R-C20). The physicochemical properties of the five lipopeptides were determined by hydrodynamic size, ζ-potential, and circular dichroism spectroscopy, respectively. Then, the cytotoxic activity of these lipopeptides in A549 cells was evaluated with serum-containing and serum-free media, respectively, showing their anticancer activities were all increased through fatty-acid modification. This may be a result of the increased hydrophobicity and the enhanced interaction with the cancer cell membrane. The cytotoxic activity of R-C16 was 3-4-fold higher than that of the original R-lycosin-I and also was the strongest among all five lipopeptides, whether in serum or serum-free conditions. Compared with R-lycosin-I, the lactate dehydrogenase (LDH) leakage assay and scanning electron microscopy (SEM) indicated that R-C16 had a weakly destructive effect on the cancer cell membrane, but it might cause apoptosis to exert an anticancer activity. Finally, the impacts of fatty-acid length on the physicochemical properties and the anticancer potential of peptide were discussed. Our data consolidate work on fatty-acid-modified anticancer peptides.

Arginine modification of lycosin-I to improve inhibitory activity against cancer cells.

Lycosin-I is a linear amphipathic α-helical anticancer peptide (ACP) extracted from the spider Lycosa singoriensis, which can activate the mitochondrial death pathway to induce apoptosis in tumor cells and up-regulate p27 to inhibit cell proliferation. However, the applicability of lycosin-I as a novel anticancer drug is limited by its low cellular entry and efficacy in solid tumors. Amino acid substitution presents an effective and modest strategy to improve the anticancer activity and bioavailability of ACPs. Herein, an arginine-modified lycosin-I (named R-lycosin-I) was designed and synthesized by substituting lysine (Lys) with arginine (Arg). This peptide exhibited higher anticancer activity and penetrability against solid tumor cells than lycosin-I. They displayed noticeable differences in their physicochemical properties including the secondary structure, hydrodynamic size, and zeta potential. Fluorescence analyses have confirmed that R-lycosin-I exhibits increased cellular uptake and improved intracellular distribution. Due to its superior physical and chemical properties and high serum stability, R-lycosin-I could penetrate deeply into tumor spheroids and produce strong toxicity in the 3D tumor model. Overall, these findings suggest that arginine modification may provide an effective strategy for improving the anticancer activity of lycosin-I, and R-lycosin-I may be a useful lead for developing anticancer drugs.

Effects of hemolysis and lipemia interference on kaolin-activated thromboelastography, and comparison with conventional coagulation tests.

The effects of hemolysis and lipemia on thromboelastography (TEG) analysis have been scarcely evaluated in human samples, and neglected in clinical practice. We aimed to investigate the effects of in vitro mechanical hemolysis and lipemia on TEG analysis and conventional coagulation tests. Twenty-four healthy volunteers were enrolled in the study. Besides the controls, three groups with slight, moderate and severe mechanical hemolysis were constituted according to free hemoglobin (Hb) concentrations of 0.5-1.0, 2.0-6.0 and 7.0-13.0 g/L, respectively; and three groups with mild, moderate and high lipemia were established according to triglyceride concentrations of ∼6.0, ∼12.0, and ∼18.0 mmol/L, respectively. Four TEG parameters, reaction time (R), coagulation time (K), angle (α), and maximum amplitude (MA), were measured alongside conventional plasma tests including prothrombin time (PT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) by mechanical method, and platelet count by optical method. Results showed that the median R and MA values at moderate and severe hemolysis and K at severe hemolysis exceeded respective reference intervals, and were considered unacceptable. Median values of TEG parameters in lipemic samples were all within reference intervals. Bias values of conventional plasma tests PT, APTT and FIB in hemolyzed or lipemic samples were all lower than the Clinical Laboratory Improvement Amendments (CLIA) allowable limits. Bias values of platelet count at moderate to severe hemolysis and lipemia exceeded the CLIA allowable limits. In conclusion, the detection of TEG was in general more affected by mechanical hemolysis than plasma coagulation tests. Pre-analytical variables should be taken into account when unexpected TEG results are obtained.

The role of thromboelastography in predicting bleeding risk and guiding the administration of platelet transfusions in hematological patients: a cohort study.

The purpose of this study was to assess the accuracy of the parameters used in conventional hemostatic testing and thromboelastography (TEG) in predicting bleeding risk in patients with hematologic diseases. Patients diagnosed with a hematologic disease were divided into bleeding (n = 125) and non-bleeding (n = 509) groups according to clinical signs and symptoms. Several parameters were measured in all patients via traditional hemostatic testing and TEG, including platelet counts (PLT) and maximum amplitude (MA). The sensitivity and specificity of each parameter for predicting bleeding risk were determined via receiver operating characteristic curves. PLT had a sensitivity of 81.1 % and a specificity of 74.4 %, and MA had a sensitivity of 74.7 % and a specificity of 72.0 %. Specificity was higher for both parameters together (77.6 %) than for either alone (P < 0.01). In a subgroup analysis of patients with PLT < 20 × 10(9)/L, sensitivity was higher for both parameters together (84.6 %) than for either alone (P = 0.003). Although all parameters evaluated predicted bleeding risk, PLT and MA were especially accurate. We suggest that the combination of PLT and MA better assesses bleeding risk than do other parameters and that the use of this metric may help to guide decisions regarding platelet transfusion in patients with thrombocytopenic hematologic diseases.

Gain-of-function ADAMTS13 variants that are resistant to autoantibodies against ADAMTS13 in patients with acquired thrombotic thrombocytopenic purpura.

Thrombotic thrombocytopenic purpura (TTP) is primarily caused by immunoglobulin G (IgG) autoantibodies against A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats, 13 (ADAMTS13). Nearly all adult idiopathic TTP patients harbor IgGs, which bind the spacer domain of ADAMTS13, a region critical for recognition and proteolysis of von Willebrand factor (VWF). We hypothesize that a modification of an exosite in the spacer domain may generate ADAMTS13 variants with reduced autoantibody binding while preserving or enhancing specific activity. Site-directed mutagenesis was used to generate a series of ADAMTS13 variants, and their functional properties were assessed. Of 24 novel ADAMTS13 variants, 2 (ie, M4, R660K/F592Y/R568K/Y661F and M5, R660K/F592Y/R568K/Y661F/Y665F) exhibited increased specific activity approximately 4- to 5-fold and approximately 10- to 12-fold cleaving a peptide VWF73 substrate and multimeric VWF, respectively. More interestingly, the gain-of-function ADAMTS13 variants were more resistant to inhibition by anti-ADAMTS13 autoantibodies from patients with acquired idiopathic TTP because of reduced binding by anti-ADAMTS13 IgGs. These results shed more light on the critical role of the exosite in the spacer domain in substrate recognition. Our findings also help understand the pathogenesis of acquired autoimmune TTP. The autoantibody-resistant ADAMTS13 variants may be further developed as a novel therapeutic for acquired TTP with inhibitors.

The impact of mgrA on progression of Staphylococcus aureus sepsis.

Sepsis induced by Staphylococcus aureus has worse outcome with the appearance of methicillin-resistant Staphylococcus aureus (MRSA) because of multi-resistance to a large group of antibiotics, which may lead to death from septic shock. Pathogenesis of S. aureus infections are involved in the production of a wide variety of virulence factors. MgrA, a noval global regulator, is a member of the MarR (multiple antibiotic resistance regulator)/SarA (staphylococcal accessory regulator A) family proteins, which plays a key role in regulating the expression of major virulence factors in S. aureus. In the present study, by using a murine model of sepsis, we investigated the role of mgrA in onset and progression of S. aureus induced sepsis. We found that mice inoculated with wild-type strain Newman had significantly higher mortality (p = 0.029), more weight lost, more bacterial load in blood, spleen and kidney, more intense inflammation response, and worse histopathology than mice inoculated with mgrA knockout strain. Our results has provided evidence that mgrA is a global regulator in S. aureus, and play an important role in S. aureus sepsis, could increase mortality and accelerate the onset and development of sepsis.

A comparison of two piezoelectric actuator concepts for fast mechanical switching in DC hybrid circuit breakers.

Amplified piezoelectric actuators have gained considerable attention due to their inherent advantages, including rapid response, reliability, and efficiency, making them promising candidates for Direct Current (DC) switching applications. They can operate in two distinct operational modes: Block-Free (B-F) and Free-Free (F-F) configurations. These two modes offer diverse mechanical constraints and are chosen based on the application's specific requirements. This study aims to present a comparative assessment between the two modes to evaluate each configuration's applicability in DC fast switching. Accordingly, the principle behind each actuation scheme was illustrated, and both designs were modeled and analyzed by the finite element method. Subsequently, two prototypes were assembled, each resembling a different operational mode. The established prototypes were then subjected to actuation and interruption tests to investigate their travel and switching performances. Comparative results revealed that while block-free could deliver a higher apparent stroke, the accumulated gap for each configuration is almost the same. Both actuators demonstrated high capability when utilized as actuation units for fast vacuum mechanical switches integrated into a hybrid circuit breaker for DC interruption. However, the free-free operation excelled in terms of fast response, as it managed to clear the mimicked fault current faster than the block-free configuration.

Salmonella Typhimurium with Eight Tandem Copies of blaNDM-1 on a HI2 Plasmid.

Carbapenem-resistant Salmonella has recently aroused increasing attention. In this study, a total of four sequence type 36 Salmonella enterica subsp. enterica serovar Typhimurium (S. Typhimurium) isolates were consecutively isolated from an 11-month-old female patient with a gastrointestinal infection, of which one was sensitive to carbapenems and three were resistant to carbapenems. Via antibiotic susceptibility testing, a carbapenemases screening test, plasmid conjugation experiments, Illumina short-reads, and PacBio HiFi sequencing, we found that all four S. Typhimurium isolates contained a blaCTX-M-14-positive IncI1 plasmid. One carbapenem-sensitive S. Typhimurium isolate then obtained an IncHI2 plasmid carrying blaNDM-1 and an IncP plasmid without any resistance genes during the disease progression. The blaNDM-1 gene was located on a new 30 kb multiple drug resistance region, which is flanked by IS26 and TnAs2, respectively. In addition, the ST_F0903R isolate contained eight tandem copies of the ISCR1 unit (ISCR1-dsbD-trpF-ble-blaNDM-1-ISAba125Δ1), but an increase in MICs to carbapenems was not observed. Our work further provided evidence of the rapid spread and amplification of blaNDM-1 through plasmid. Prompting the recognition of carbapenem-resistant Enterobacterales and the initiation of appropriate infection control measures are essential to avoid the spread of these organisms.

A national survey on fungal infection diagnostic capacity in the clinical mycology laboratories of tertiary care hospitals in China.

BACKGROUND/PURPOSE: As the incidence of fungal infections in China increases, the demand for rapid and accurate diagnosis of mycoses is growing. Yet, information on current diagnostic capacity is scarce. METHODS: An online survey was conducted in February 2018 to collect information on mycology testing from tertiary care hospitals across China. Responses from 348 hospitals were analyzed, and a scoring system was designed and employed to assess the overall diagnostic capacity. RESULTS: Most of the surveyed hospitals did not have separate laboratory space, manpower, or equipment dedicated for fungal testing. Conventional staining methods were widely available (>70%), whereas GMS and fluorescent staining were less common. Fungal identification services were offered mostly with chromogenic medium, morphological characterization or automated identification systems, other than more advanced methods such as MALDI-TOF MS and DNA sequencing. Fungal serology testing was available in 81.1%, with G test being the most often used. Though 91.8% of the respondents had the ability to perform antifungal susceptibility testing for yeasts, less than 13% conducted such testing for molds. The percentage of laboratories participating in External Quality Assessment programs and research was 57.5% and 32.5%, respectively. The average score for the 348 surveyed hospitals was 37.2 (out of a maximum of 89 points), with only 15 hospitals scoring >60, suggesting a general lack of high-quality mycology laboratories. CONCLUSIONS: The overall clinical testing capacity for fungal infection in China is insufficient. More investment and training efforts are warranted to establish centers of excellence and promote access to high-quality diagnostic services.

The landing error scoring system as a screening tool for non-contact injury risk in college soccer athletes / 中国组织工程研究

BACKGROUND:The landing error scoring system test is a standard for assessing the risk of non-contact injuries and has not yet been developed for Chinese college soccer programs. OBJECTIVE:To establish a test evaluation standard for the landing error scoring system to provide a basis for evaluating the risk of non-contact injuries in college soccer students. METHODS:A prospective cohort study was designed in which 219 athletes from 10 college soccer teams were tested with the standard landing error scoring system,and the subjects were followed up by questionnaires and medical examinations for non-contact injuries of the lower extremities and trunk for 1 year after testing to determine sex differences and assessment criteria for the landing error scoring system test indicators. RESULTS AND CONCLUSION:The total score of the landing error scoring system was(8.22±1.65)points for 219 subjects,(8.29±1.74)for males and(8.07±1.44)for females,with no significant difference between males and females(P>0.05).Within 1 year after the test,the overall injury rate of 219 subjects was 10.05%and the morbidity rate was 15.98%;the injury rate of male subjects with non-contact injury of the lower limbs and trunk was 12.75%and the morbidity rate was 20.13%;the injury rate of female subjects with non-contact injury of the lower limbs and trunk was 4.29%and the morbidity rate was 7.14%.There were no significant differences in the injury rate between men and women(P<0.05).The total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.50±1.14)vs.(8.08±1.64),P<0.01];for male subjects,the total score of the landing error scoring system was higher in the injury group than in the non-injury group[(9.63±1.12)vs.(8.09±1.73),P<0.01].The area under the curve for the total score of the landing error scoring system was 0.773(P=0.000),which had a diagnostic value for the risk of non-contact injury of the lower extremities and trunk in male subjects,with a best cut-off point of 8.5,sensitivity of 0.842,specificity of 0.623,positive likelihood ratio of 2.233,negative likelihood ratio of 0.254,relative risk factor of 8.400,and odds ratio of 8.816;the total score of the landing error scoring system was not applicable for assessing the risk of non-contact injury of the lower extremities and trunk in female subjects.To conclude,the landing error scoring system test can be used as a criterion to assess the risk of non-contact injury to the lower extremity and trunk in Chinese college male soccer players,with an optimal cut-off point of 8.5.The risk of non-contact injury to the lower extremity and trunk is 8.40 times higher in male athletes with a landing error scoring system test score of≥8.5 than in male athletes with a score of<8.5.

Cases analysis and etiology discussion of thymoma with alopecia areata / 中华胸心血管外科杂志

Objective:Analyzed the clinicopathological features of thymoma with alopecia areata, and discussed the pathogenesis and treatment methods.Methods:The clinicopathologic data of patients with thymoma who underwent surgery from August 1, 2015 to July 31, 2020 in Beijing Tongren Hospital, Capital Medical University were reviewed. Transversally analyzed the patients of thymoma with alopecia areata and longitudinally compared with the patients of thymoma without alopecia areata after 1﹕10 matched by propensity score matching.Results:A total of 252 patients of thymoma were enrolled, including 6 patients with alopecia areata, accounting for 2.38%. The anti-AchR antibody, CD4 + /CD8 + T inversion in serum and myasthenia gravis were present in the all 6 thymoma patients with alopecia areata, which were significantly higher than those in the group of thymoma without alopecia areata. Besides myasthenia gravis, the proportion of complicated with other autoimmune diseases in thymoma patients with alopecia areata was significantly higher than that of thymoma patients without alopecia areata[83.33%(5/6) vs. 20.00%(12/60), P=0.003]. After operation, 5 patients’ alopecia areata were improved in 6 thymoma patients with alopecia areata(83.33%, 5/6). Conclusion:The thymoma patients with alopecia areata always complicated with myasthenia gravis and other autoimmune diseases. The pathogenesis may be associated with autoimmune CD8 + T lymphocytes produced by thymoma. At present, surgery is still the most effective way to improve thymoma-associated alopecia areata.

Efficacy and safety profile of repetitive transcranial magnetic stimulation versus modified electroconvulsive therapy in combination with antidepressants in patients with major depressive disorder / 四川精神卫生

BackgroundMajor depressive disorder is one of the most disabling mental diseases. Currently， medication in combination with physiotherapy and psychotherapy remains the most commonly used treatment modality for the disease， whereas only a few randomized controlled studies have been conducted on physiotherapy， and even fewer studies have focused on medication combined with physiotherapy. ObjectiveTo explore the efficacy and safety profile of repetitive transcranial magnetic stimulation （rTMS） versus modified electroconvulsive therapy （MECT） in combination with antidepressants in the treatment of major depressive disorder， so as to provide an optimized treatment plan for patients with major depressive disorder. MethodsPatients with major depressive disorder （n=335） hospitalized in Shandong Daizhuang Hospital from January 1， 2019 to April 30， 2023 were included， all of whom met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10）. Depending on their disease condition， patients were subjected to either MECT in combination with drugs （n=141） or rTMS in combination with drugs （n=194） after admission. Depressive symptoms were assessed using Hamilton Depression Scale-24 item （HAMD-24） at the baseline and the end of the 1st， 2nd， 3rd and 4th week of treatment， and the adverse reactions were documented in patient's medical records. ResultsAnalysis of variance on HAMD-24 revealed a significant effect of time （F=3.081， P=0.042）， but no effect of group （F=1.023， P=0.313）， and the interaction effect between the time and the groups was not statistically significant （F=1.642， P=0.191）. No statistical difference was reported between two groups in response rate and full remission rate （P>0.05）. Throughout the course of treatment， 58 cases （41.13%） of recent memory impairment and 74 cases （52.48%） of headache or neck muscle pain occurred in MECT combined with drugs group， and 27 cases （13.92%） in rTMS combined with drugs group experienced headache or head skin discomfort. ConclusionAntidepressants in combination with rTMS or MECT show equivalent efficacy in the treatment of major depressive disorder， while rTMS combined with antidepressants demonstrates a superior safety profile compared to MECT.

Position Effect of Fatty Acid Modification on the Cytotoxicity and Antimetastasis Potential of the Cytotoxic Peptide Lycosin-I.

Peptide modification with fatty acids is an effective method to improve peptide performance. We previously investigated the fatty acid modification of R-lycosin-I, a cytotoxic peptide derived from lycosin-I from the venom of the spider Lycosa singoriensis. In this study, we further investigated the position effects of fatty acid modification of lycosin-I. Dodecanoic acid was covalently coupled to the α/ε-amino group of one of the seven Lys residues of lycosin-I, generating eight different lipopeptides. Although all the lipopeptides had significantly improved cytotoxicity compared with lycosin-I, they displayed different cytotoxic potencies and profiles, which might be explained by multifactors including charge, size, helicity, hydrophobicity, and so forth. Of the eight lipopeptides, L-C12 demonstrated highest cytotoxicity and antimetastasis activity in two-dimensional cells, tumor spheroids, subcutaneous transplantation mouse models, and experimental melanoma metastasis mouse models. Collectively, our finding indicated that fatty acid modification position plays important roles in physiochemical parameters and biological activities of cytotoxic peptides.