Clinical characteristics of patients with migraine accompanied by tremor. / åå¤´ç—›ä¼´å‘éœ‡é¢¤æ‚£è€ çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: Migraine and tremor share some genetic mutation sites, and clinical studies have also confirmed their correlation. This study aims to explore the clinical and electrophysiological characteristics of migraine patients with concomitant tremor, and to analyze the relevant influential factors of tremor occurrence. METHODS: We retrospectively analyzed the clinical data of 217 migraine patients who visited the Third Affiliated Hospital of Qiqihar Medical University from June 2022 to October 2023. The Clinical Rating Scale for Tremor (CRST), Numerical Rating Scale (NRS), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) were respectively used to assess the tremor symptoms, degree of headache, anxiety, and depression of patients. All patients underwent routine head MR scanning and electromyography examination, and were divided into a migraine with tremor group and a migraine without tremor group based on the electromyogram examination. RESULTS: The migraine with tremor group and the migraine without tremor group were included 52 patients (23.96%) and 165 patients (76.04%), respectively. Compared with the migraine without tremor group, the migraine with tremor group had a longer course and duration of headache, higher frequency of headache attacks, higher NRS score, GAD-7 score, and PHQ-9 score, and fewer weekly physical exercises. The differences were statistically significant (all P<0.05). There were no statistically significant differences in the presence or absence of prodromal headache and white matter hyperintensities (WMHs) between the 2 groups (both P>0.05). The evaluation results of the CRST showed that out of 217 migraine patients, 39 patients (17.97%) were accompanied by tremors. The electromyographic results showed that all 52 migraine patients with tremors had upper limb tremors, including 28 migraine patients with postural tremors and 24 migraine patients with static tremors. Compared with the migraine patients with static tremors, the migraine patients with postural tremors had lower average frequency, peak frequency, and headache onset frequency (all P<0.05). Multiple linear regression analysis showed that frequency of physical exercise, duration of illness, frequency of headache attacks, NRS score, GAD-7 score, and PHQ-9 score were risk factors for migraine patients with concomitant tremors (all P<0.05). CONCLUSIONS: Patients with migraine mainly experience upper limb postural tremors. Reduced physical exercise, long course of disease, long duration of headache, frequent headache attacks, severe headache, anxiety, and depression are risk factors for migraine patients with concomitant tremors.

Viral reactivation in the lungs of patients with severe pneumonia is associated with increased mortality, a multicenter, retrospective study.

Viral reactivation is widespread in patients with severe pneumonia, yet the landscape of viral reactivation in the lungs is not well-known. This study aims to assess the landscape and clinical features of viral reactivation in the early onset of severe pneumonia in ICU patients. The clinical data from 97 patients were collected retrospectively from the intensive care units of five teaching hospitals between June 2018 and July 2021. Metagenomic next-generation sequencing (mNGS) of the bronchoalveolar lavage fluid (BALF) was performed at the onset of severe pneumonia. Cytomegalovirus (CMV), herpes simplex virus-1 (HSV-1), and Epstein-Barr virus (EBV) were the most common reactivated viruses in the lower respiratory tract of patients with severe pneumonia. After adjusting for the risk of confounding and competition of age, sex, sequential organ failure assessment, acute physiology chronic health assessment II and immunosuppression status, viral reactivation resulted in an overall 2.052-fold increase in 28-day all-cause mortality (95% CI: 1.004-4.194). This study showed that CMV, HSV-1, and EBV were the most common reactivated viruses in the lungs of patients with severe pneumonia. The existence of viral reactivations was associated with an increased risk of mortality. The simultaneous reactivation of multiple viruses needs to be considered in the design of clinical trials.

Prenylation of dimeric cyclo-L-Trp-L-Trp by the promiscuous cyclo-L-Trp-L-Ala prenyltransferase EchPT1.

Prenyltransferases (PTs) from the dimethylallyl tryptophan synthase (DMATS) superfamily are known as efficient biocatalysts and mainly catalyze regioselective Friedel-Crafts alkylation of tryptophan and tryptophan-containing cyclodipeptides (CDPs). They can also use other unnatural aromatic compounds as substrates and play therefore a pivotal role in increasing structural diversity and biological activities of a broad range of natural and unnatural products. In recent years, several prenylated dimeric CDPs have been identified with wide range of bioactivities. In this study, we demonstrate the production of prenylated dimeric CDPs by chemoenzymatic synthesis with a known promiscuous enzyme EchPT1, which uses cyclo-L-Trp-L-Ala as natural substrate for reverse C2-prenylation. High product yields were achieved with EchPT1 for C3-N1' and C3-C3' linked dimers of cyclo-L-Trp-L-Trp. Isolation and structural elucidation confirmed the product structures to be reversely C19/C19'-mono- and diprenylated cyclo-L-Trp-L-Trp dimers. Our study provides an additional example for increasing structural diversity by prenylation of complex substrates with known biosynthetic enzymes. KEY POINTS: • Chemoenzymatic synthesis of prenylated cyclo-L-Trp-L-Trp dimers • Same prenylation pattern and position for cyclodipeptides and their dimers. • Indole prenyltransferases such as EchPT1 can be widely used as biocatalysts.

[Cross-sectional analysis of libido status and risk factors in male patients with chronic headache].

OBJECTIVE: Exploring the libido status of male chronic headache patients and analyzing its relationship with headache symptoms, sleep, anxiety, and depression, providing reference for the comprehensive treatment of male chronic headache. METHODS: 179 patients with chronic headache who visited the Third Affiliated Hospital of Qiqihar Medical College from January 2022 to February 2023 were selected. The male Self Rated Libido Scale , Visual Analog Scale for Pain, Migraine Disability Assessment Scale, Pittsburgh Sleep Quality Index, Generalized Anxiety Disorder Scale-7, and Patient Health Questionnaire-9 were used to evaluate the libido status, headache severity, disability level, sleep quality, anxiety, and depression of the research subjects, respectively. RESULTS: Among 179 male chronic headache patients, 97 were chronic migraine (CM) patients and 82 were chronic tension type (CTT) patients, and 47 were screened for low libido. The influencing factors of libido in male chronic headache patients include age, smoking, frequency of exercise, course of disease, severity of pain, frequency of headache, disability score, sleep quality, anxiety and depression (all P<0.05). Compared with male CTT patients, male CM patients have higher pain severity, headache frequency, disability score, and anxiety score, while lower libido score (all P<0.05). The results of multivariate analysis showed that age, frequency of exercise, course of disease, severity of pain, frequency of headache, degree of disability, sleep quality, anxiety, and depression were the influencing factors for the decline of libido in male chronic headache patients. CONCLUSION: It is common for male chronic headache patients to experience decreased libido, with male chronic migraine (CM) patients exhibiting more severe reductions. Advanced age, decreased physical activity, longer disease duration, severe pain intensity, frequent headaches, higher disability levels, poor sleep, anxiety, and depression are risk factors for decreased libido in male chronic headache patients.

Correction to: Expanding tryptophan-containing cyclodipeptide synthase spectrum by identification of nine members from Streptomyces strains.

The original version of this article contained mistake. After careful re-examination of the LC-MS data, the products of CDPSs "WP_031028810" and "BAU83478" should be cFL instead of cPY. We apologize for any inconvenience that this may have caused.

Expanding tryptophan-containing cyclodipeptide synthase spectrum by identification of nine members from Streptomyces strains.

Cyclodipeptide synthases (CDPSs) comprise normally 200-300 amino acid residues and are mainly found in bacteria. They hijack aminoacyl-tRNAs from the ribosomal machinery for cyclodipeptide formation. In this study, nine new CDPS genes from eight Streptomyces strains were cloned into pET28a vector and expressed in Escherichia coli. Structural elucidation of the isolated products led to the identification of one cyclo-L-Trp-L-Leu, two cyclo-L-Trp-L-Pro, and three cyclo-L-Trp-L-Trp synthases. Other three CDPSs produce cyclo-L-Trp-L-Ala or cyclo-L-Trp-L-Tyr as the major cyclodipeptide. Total product yields of 46 to 211 mg/L E. coli culture were obtained. Our findings represent rare examples of CDPS family derived from actinobacteria that form various tryptophan-containing cyclodipeptides. Furthermore, this study highlights the potential of the microbial machinery for tryptophan-containing cyclodipeptide biosynthesis and provides valid experimental basis for further combination of these CDPS genes with other modification genes in synthetic biology.

Identification of a heterologous cellulase and its N-terminus that can guide recombinant proteins out of Escherichia coli.

BACKGROUND: The Gram-negative bacterium Escherichia coli has been widely used as a cell factory for the production of proteins and specialty chemicals because it is the best characterized host with many available expression and regulation systems. However, recombinant proteins produced in Escherichia coli are generally intracellular and often found in the form of inclusion bodies. Extracellular production of proteins is advantageous compared with intracellular production because extracellular proteins can be purified more easily and can avoid protease attack, which results in higher product quality. In this study, we found a catalytic domain of a cellulase (Cel-CD) and its N-terminus can be employed as carriers for extracellular production of recombinant proteins. RESULTS: In this report, we identified the catalytic domain of a cellulase (Cel-CD) from Bacillus sp. that can be secreted into the medium from recombinant E. coli BL21 (DE3) in large quantities without its native signal peptide. By subcellular location analysis, we proved that the secretion was a two-step process and the N-terminal sequence of the full length Cel-CD played a crucial function in secretion. Both the Cel-CD and its N-terminal sequence can serve as carriers for efficient extracellular production of select target proteins. CONCLUSIONS: Fusion of heterologous proteins with N20 from Cel-CD can carry the target proteins out of the cells with a concentration from 101 to 691 mg/L in flask cultivation. The extracellular recombinant proteins with a relative high purity. The results suggested that this system has a potential application in plant biomass conversion and industrial production of enzymes and therapeutic proteins.

Tyrosine O-prenyltransferases TyrPT and SirD displaying similar behavior toward unnatural alkyl or benzyl diphosphate as their natural prenyl donor dimethylallyl diphosphate.

Prenyltransferases of the dimethylallyltryptophan synthase (DMATS) superfamily are involved in the biosynthesis of secondary metabolites and contribute as modification enzymes significantly to structural diversity of natural products. They show usually broad specificity toward their aromatic substrates with regiospecific prenylations on aromatic rings. However, most members of this superfamily exhibit a high specificity toward their prenyl donors and usually accept exclusively dimethylallyl diphosphate (DMAPP). Recently, several indole prenyltransferases from this family were also demonstrated to accept unnatural DMAPP analogs such as methylallyl, 2-pentenyl and benzyl diphosphate for alkylation, or benzylation of the indole ring. Partial or complete shift of the substitution position was observed for these enzymes. In this study, we report the acceptance of these DMAPP analogs by two tyrosine O-prenyltransferases TyrPT from Aspergillus niger and SirD from Leptosphaeria maculans for alkylation or benzylation of tyrosine and derivatives. NMR and mass spectrometry (MS) analyses of nine isolated enzyme products confirmed the regiospecific O- or N-alkylation or benzylation at position C-4 of the aromatic ring, which is the same prenylation position of these enzymes in the presence of DMAPP.

Protein engineering using mutability landscapes: Controlling site-selectivity of P450-catalyzed steroid hydroxylation.

Directed evolution and rational design have been used widely in engineering enzymes for their application in synthetic organic chemistry and biotechnology. With stereoselectivity playing a crucial role in catalysis for the synthesis of valuable chemical and pharmaceutical compounds, rational design has not achieved such wide success in this specific area compared to directed evolution. Nevertheless, one bottleneck of directed evolution is the laborious screening efforts and the observed trade-offs in catalytic profiles. This has motivated researchers to develop more efficient protein engineering methods. As a prime approach, mutability landscaping avoids such trade-offs by providing more information of sequence-function relationships. Here, we describe an application of this efficient protein engineering method to improve the regio-/stereoselectivity and activity of P450BM3 for steroid hydroxylation, while keeping the mutagenesis libraries small so that they will require only minimal screening.

Differences in Microbial Communities Stimulated by Malic Acid Have the Potential to Improve Nutrient Absorption and Fruit Quality of Grapes.

Malic acid is a component of the rhizosphere exudate and is vital for crop growth. However, little information is available about the effects of external applications of malic acid on the nutrient absorption and quality of grape fruit, and few studies have been performed on the relationship between the changes in the rhizosphere microbial community and nutrient absorption and fruit quality of grapes after adding malic acid. Here, the LM (low concentration of malic acid) and HM (high concentration of malic acid) treatments comprised 5% and 10% malic acid (the ratio of acid to the total weight of the fertilizer) combined with NPK fertilizer, respectively. Applying malic acid changed the grape rhizosphere microbial community structure and community-level physiological profile (CLPP) significantly, and HM had a positive effect on the utilization of substrates. The microbial community structure in the rhizosphere of the grapes with added malic acid was closely related to the CLPP. The N and P content in the leaves and fruits increased after applying malic acid compared to the control, while K content in the fruits increased significantly. In addition, malic acid significantly reduced the weight per fruit, significantly increased soluble sugar content (SSC) and vitamin C content of the fruit, and significantly improved the fruit sugar-acid ratio and grape tasting score. Moreover, the principal component analysis and grape nutrient and fruit quality scores showed that grape nutrients and fruit quality were significantly affected by malic acid and ranked as 5% malic acid > 10% malic acid > control. Pearson's correlation heatmap of microbial composition, nutrient absorption and fruit quality of the grapes showed that the grape microbial community was closely related to grape nutrients and fruit quality. Adding malic acid was positively correlated to Planococcaceae, Bacillaceae, Woeseiaceae and Rhodobacteraceae. Furthermore, Planococcaceae, Bacillaceae, Woeseiaceae and Rhodobacteraceae were closely related to grape nutrient absorption and fruit quality. Bacillaceae and Woeseiaceae were positively correlated with total soluble sugar, while Planococcaceae and Rhodobacteraceae were positively correlated with titratable acid. Hence, Bacillaceae and Woeseiaceae were the key bacteria that played a major role in grape fruit quality and nutrient absorption after applying malic acid water-soluble fertilizer.

Rare Case of Cystic Lymphangioma Transforming Into Lymphangiosarcoma: A Case Report.

Cystic lymphangioma (CL) is a rare benign tumor that mainly occurs in the neck and axilla and usually occurs in children, whereas lymphangiosarcoma (LAS) is a rare invasive tumor, usually secondary to chronic lymphedema caused by various causes, with a rare malignant transformation from CL. We presented the case of a 63-year-old woman who underwent four surgical excisions for multiple recurrence of CL in the right groin. The changes of imaging and pathological examination revealed the unusual process of its gradual malignant transformation into LAS. We followed up the patient for 16 years, and she eventually died of LAS complications.

Case Report: Hemophagocytic Lymphocytosis in a Patient With Glutaric Aciduria Type IIC.

Hemophagocytic lymphocytosis (HLH) is a rare disease caused by inborn errors of immunity (IEI), secondary to infection, lymphoma or autoimmune disorders, but we often overlook the fact that HLH can be secondary to inborn errors of metabolism (IEM). Here, we describe a patient who was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. The diagnosis of glutaric aciduria type IIC, a IEM, was confirmed by whole exome sequencing. The patient was treated with coenzyme Q10 and riboflavin which effectively improved her liver function. During treatment, the patient developed severe anemia and thrombocytopenia. Persistent fever, splenomegaly, cytopenias, increased ferritin, hypertriglyceridemia, hypofibrinogenemia, and hemophagocytosis in the bone marrow pointed to the diagnosis of HLH; however, the patient eventually died of gastrointestinal bleeding. After other potential causes were ruled out, the patient was diagnosed with glutaric aciduria type IIC complicated by features suggestive of possible HLH. When cytopenias occurs in IEM patients, HLH is a possible complication that cannot be ignored. This case suggests a possible relationship between IEM and risk for immune dysregulation.

Dynamic changes on chest CT of COVID-19 patients with solitary pulmonary lesion in initial CT.

PURPOSE: To investigate the dynamic evolution of image features of COVID-19 patients appearing as a solitary lesion at initial chest CT scan. MATERIALS AND METHODS: Twenty-two COVID-19 patients with solitary pulmonary lesion from three hospitals in China were enrolled from January 18, 2020 to March 18, 2020. The clinical feature and laboratory findings at first visit, as well as characteristics and dynamic evolution of chest CT images were analyzed. Among them, the CT score evaluation was the sum of the lung involvement in five lobes (0-5 points for each lobe, with a total score ranging from 0 to 25). RESULTS: 22 COVID-19 patients (11 males and 11 females, with an average age of 40.7 ± 10.3) developed a solitary pulmonary lesion within 4 days after the onset of symptoms, the peak time of CT score was about 11 days (with a median CT score of 6), and was discharged about 19 days. The peak of CT score was positively correlated with the peak time and the discharge time (p < 0.001, r = 0.793; p < 0.001, r = 0.715). Scan-1 (first visit): 22 cases (100%) showed GGO and one lobe was involved, CT score was 1.0/1.0 (median/IQR). Scan-2 (peak): 15 cases (68%) showed crazy-paving pattern, 19 cases (86%) showed consolidation, and 2.5 lobes were involved, CT score was 6.0/12.0. Scan-3 (before discharge): ten cases (45%) showed linear opacities, none had crazy-paving pattern, and 2.5 lobes were involved, CT score was 6.0/11.0. Scan-4 (after discharge): three cases (19%) showed linear opacities and one lobe was involved, CT score was 2.0/5.0. CONCLUSION: The chest CT features are related to the course of COVID-19 disease, and dynamic chest CT scan are helpful to monitor disease progress and patients' condition. In recovered patients with COVID-19, the positive CT manifestations were found within 4 days, lung involvement peaking at approximately 11 days, and discharged at about 19 days. The patients with more severe the lung injury was, the later the peak time appeared and the longer the recovery time was. Although the lesion was resolved over time, isolation and reexamination were required after discharge.

Encephalomyelitis Caused by Balamuthia mandrillaris in a Woman With Breast Cancer: A Case Report and Review of the Literature.

Balamuthia mandrillaris is one cause of a rare and severe brain infection called granulomatous amoebic encephalitis (GAE), which has a mortality rate of >90%. Diagnosis of Balamuthia GAE is difficult because symptoms are non-specific. Here, we report a case of Balamuthia amoebic encephalomyelitis (encephalitis and myelitis) in a woman with breast cancer. She sustained trauma near a garbage dump 2 years ago and subsequently developed a skin lesion with a Mycobacterium abscessus infection. She experienced dizziness, lethargy, nausea and vomiting, inability to walk, and deterioration of consciousness. Next-generation sequencing of cerebrospinal fluid (CSF) samples revealed B. mandrillaris, and MRI of both brain and spinal cord showed abnormal signals. T-cell receptor (TCR) sequencing of the CSF identified the Top1 TCR. A combination of amphotericin B, flucytosine, fluconazole, sulfamethoxazole, trimethoprim, clarithromycin, pentamidine, and miltefosine was administrated, but she deteriorated gradually and died on day 27 post-admission.

Influence of Skull Fracture on Traumatic Brain Injury Risk Induced by Blunt Impact.

This study is aimed at investigating the influence of skull fractures on traumatic brain injury induced by blunt impact via numerous studies of head-ground impacts. First, finite element (FE) damage modeling was implemented in the skull of the Total HUman Model for Safety (THUMS), and the skull fracture prediction performance was validated against a head-ground impact experiment. Then, the original head model of the THUMS was assigned as the control model without skull element damage modeling. Eighteen (18) head-ground impact models were established using these two FE head models, with three head impact locations (frontal, parietal, and occipital regions) and three impact velocities (25, 35, and 45 km/h). The predicted maximum principal strain and cumulative strain damage measure of the brain tissue were employed to evaluate the effect of skull fracture on the cerebral contusion and diffuse brain injury risks, respectively. Simulation results showed that the skull fracture could reduce the risk of diffuse brain injury risk under medium and high velocities significantly, while it could increase the risk of brain contusion under high-impact velocity.

Identification of susceptibility loci for cognitive impairment in a cohort of Han Chinese patients with Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Identifying PD cognitive impairment (PDCI) in the early stage will help slow or prevent PD dementia. Susceptibility loci for PDCI are inconsistent in different studies. The aim of this study is to determine susceptibility loci for PDCI in the Han Chinese population. A total of 24 single nucleotide polymorphisms (SNPs) associated with PDCI were genotyped by Massarray system and Sanger sequencing in 158 PD patients and 275 healthy controls. Two SNPs (rs34778348 in LRRK2, rs78973108 in GBA) had different genotype distribution between PD and controls. None of risk SNPs was identified between PDCI and PD with normal cognition (PDNC). Aging and high Unified Parkinson's Disease Rating Scale (UPDRS) score were the independent risk factors for PDCI, rather than sex and SNPs. Our study showed that none of risk SNPs was identified to be significantly associated with cognitive decline of PD patients, indicating the effect of susceptibility loci on PDCI is subtle in the Han Chinese population.

Two Cytochrome P450 Enzymes from Streptomyces sp. NRRL S-1868 Catalyze Distinct Dimerization of Tryptophan-Containing Cyclodipeptides.

Heterologous expression in Streptomyces coelicolor and in vitro enzyme characterization proved that two P450 enzymes, AspB and NasB, from Streptomyces sp. NRRL S-1868 catalyze two new dimerization patterns of tryptophan-containing cyclodipeptides. Structure elucidation of the metabolites revealed an N1-C7' dimer of two cWP molecules as the predominant product of AspB and C3-C7' connected cWP with cWA as that of NasB.

Coupling of cyclo-l-Trp-l-Trp with Hypoxanthine Increases the Structure Diversity of Guanitrypmycins.

The cyclo-l-Trp-l-Trp (cWW, 1) tailoring P450 GutD2774 from Streptomyces lavendulae was characterized by expression in Streptomyces coelicolor, precursor feeding and enzyme assays. GutD2774 catalyzes mainly the transfer of hypoxanthine to C2 and C3 of the indole ring of 1. cWW adducts with guanine were detected as minor products. An orthologous cluster was identified in Streptomyces xanthophaeus. These results expand the spectrum of cyclodipeptide derivatives by involvement of an additional nucleobase and identification of new coupling patterns.

Bending Performance and Reinforcement of Rocker Panel Components with Unidirectional Carbon Fiber Composite.

Unidirectional carbon fiber composite material is one of the most common types of composites employed in vehicles, and its bending performance plays an important role in crash safety, especially in side pole impact. This study aimed to redesign one of the most important components of the side structure of a vehicle, the rocker panel, with unidirectional carbon fiber composite material. Our results show that it is not easy to acquire the same bending performance as that of a steel rocker panel by merely replacing it with carbon fiber material and increasing the wall thickness. Therefore, reinforcements were employed to improve the bending performance of the carbon fiber rocker panel, and a polypropylene reinforcement method achieved a weight reduction of 40.7% compared with high-strength steel.

Effect of Graphene Carbon Nitride on Ultraviolet-Curing Coatings.

Graphene carbon nitride (g-C3N4) was successfully prepared by semi-closed pyrolysis and then incorporated into the ultraviolet (UV)-curing system to synthesize different specimens of g-C3N4-hybridized UV-curing (g-C3N4/UV) coatings. The apparent appearance and dispersity g-C3N4 were characterized through X-ray diffraction (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (FTIR). The influence of the curing speed and mechanical properties was also tested. The dispersion level of g-C3N4 can be kept less than 1 µm by mechanical mixing. The pencil hardness of composite coatings could be 6H while the adhesion based on glass could be 1 level. The degree of curing of the coating could be obviously improved by the addition of g-C3N4, leading to a 7 percent increase of the gel content. Additionally, the decomposition of hard segments of polyurethane acrylate could be avoided by the use of g-C3N4 resulting in an increasing stability to heat. We found the gel content in an aerobic environment was lower than that in an anaerobic environment. On this basis, the function and mechanism of g-C3N4 was investigated in detail and methods to eliminate the O2 were proposed.