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Background: Before 1986, scrub typhus was only found endemic in southern China. Because human infections typically occur in the summer, it is called "summer type". During the autumn-winter period of 1986, a new type of scrub typhus was identified in Shandong and northern Jiangsu province of northern China. This newly recognized scrub typhus was subsequently reported in many areas of northern China and was then called "autumn-winter type". However, clinical characteristics of associated cases have not been reported.Methods: From 1995 to 2006, all suspected scrub typhus cases in five township hospitals of Feixian county, Shandong province were enrolled. Indirect immunofluorescent assay (IFA) was used as confirmatory serodiagnosis test. Polymerase chain reaction (PCR) connected with restriction fragment length polymorphism (RFLP) and sequence analyses were used for genotyping of O. tsutsugamushi DNAs. Clinical symptoms and demography of confirmed cases were analyzed.Results: A total of 480 scrub typhus cases were confirmed. The cases occurred every year exclusively between September and December with a peak occurrence in October. The case numbers were relatively higher in 1995, 1996, 1997, and 2000 than in other years. 57.9% of cases were in the group aged 21-50. More cases occurred in male (56%) than in female (44%). The predominant occupational group of the cases was farmers (85.0%). Farm work was reported the primary exposure to infection in 67.7% of cases. Fever, rash, and eschar were observed in 100.0%, 90.4%, and 88.5% of cases, respectively. Eschars formed frequently on or around umbilicus, abdomen areas, and front and back of waist (34.1%) in both genders. Normal results were observed in 88.7% (WBC counts), 84.5% (PLT counts), and 89.7% (RBC counts) of cases, respectively. Observations from the five hospitals were compared and no significant differences were found.Conclusion: The autumn-winter type scrub typhus in northern China occurred exclusively from September to December with a peak occurrence in October, which was different from the summer type in southern China. In comparison with the summer type, complications associated with autumn-winter type scrub typhus were less severe, and abnormalities of routine hematological parameters were less obvious. [ABSTRACT FROM AUTHOR]

Lack in understanding of the mechanism on brachial plexus avulsion (BPA)-induced neuropathic pain (NP) is the key factor restricting its treatment. In the current investigation, we focused on the nociceptor-localized K + -Cl - cotransporter 2 (KCC2) to investigate its role in BPA-induced NP and related pain sensitization. A novel mice model of BPA on the middle trunk (C7) was established, and BPA mice showed a significant reduction in mechanical withdrawal threshold of the affected fore- and hind- paws without affecting the motor function through CatWalk Gait analysis. Decreased expression of KCC2 in dorsal root ganglion (DRG) was detected through Western blot and FISH technology after BPA. Overexpression of KCC2 in DRG could reverse the hyperexcitability of DRG neurons and alleviate the pain of BPA mice synchronously. Meanwhile, the calcium response signal of the affected SDH could be significantly reduced through above method using spinal cord fiber photometry. The synthesis and release of brain-derived neurotrophic factor (BDNF) was also proved reduction through overexpression of KCC2 in DRG, which indicates BDNF can also act as the downstream role in this pain state. As in human-derived tissues, we found decreased expression of KCC2 and increased expression of BDNF and TrκB in avulsed roots of BPA patients compared with normal human DRGs. Our results indicate that nociceptor-localized KCC2 can suppress BPA-induced NP, and peripheral sensitization can be regulated to reverse central sensitization by targeting KCC2 in DRG at the peripheral level through BDNF signaling. The consistent results in both humanity and rodents endow great potential to future transformation of clinical practice., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the Animal Care and Use Committee of the Air Force Medical University ((IACUC No. 20220607) for animals and the Ethics Committee of Xijing Hospital, the Air Force Medical University (No. KY20222228-F-1) for human materials. Written consent for participation and publication has been obtained from all the participants in the current study. Competing interests: All authors declare no competing interests., (© 2025. The Author(s).)

Measurable residual disease (MRD) testing is an essential aspect of disease prognostication in acute lymphoblastic leukaemia (ALL) and informs clinical decisions. The depth of MRD clearance is highly relevant and requires assays with sufficient sensitivity. Austin Pathology is one of the few laboratories in Australia currently utilising a fully validated and National Association of Testing Authorities (NATA)-accredited ultrasensitive next-generation sequencing (NGS) platform for MRD monitoring in ALL. This technology is based on the detection of clonal rearrangement of immunoglobulin and T cell receptor genes in leukaemic cells, and is capable of achieving a limit of detection at least one to two logs below that of multiparametric flow cytometry (MFC). In this retrospective analysis, we report a clonotype detection rate of up to 85.7% at diagnosis, and a concordance rate of 78.7% in MRD results between NGS and MFC. Of the discordant samples, nearly all were NGS + /MFC - , highlighting the superior sensitivity of NGS. The enhanced sensitivity is clinically relevant, as discordant MRD results often heralded fulminant relapse, and therefore offer clinicians additional lead time and a window of opportunity to initiate pre-emptive therapy. Notwithstanding a small and heterogeneous cohort, our real-world survival data indicate an intermediate relapse risk for NGS + /MFC - patients. In light of recent approval of Medicare rebatable ALL MRD testing, we discuss how NGS can complement other techniques such as MFC in personalising management strategies. We recommend routine clonality testing by NGS at diagnosis and use a multi-modality approach for subsequent MRD monitoring., (Crown Copyright © 2024. Published by Elsevier B.V. All rights reserved.)

Patients with tissue inflammation or injury often experience aberrant mechanical pain hypersensitivity, one of leading symptoms in clinic. Despite this, the molecular mechanisms underlying mechanical distortion are poorly understood. Canonical transient receptor potential (TRPC) channels confer sensitivity to mechanical stimulation. TRPC3 and TRPC6 proteins, coassembling as heterotetrameric channels, are highly expressed in sensory neurons. However, how these channels mediate mechanical pain hypersensitivity has remained elusive. It is shown that in mice and human, TRPC3 and TRPC6 are upregulated in DRG and spinal dorsal horn under pathological states. Double knockout of TRPC3/6 blunts mechanical pain hypersensitivity, largely by decreasing nociceptor hyperexcitability and spinal synaptic potentiation via presynaptic mechanism. In corroboration with this, nociceptor-specific ablation of TRPC3/6 produces comparable pain relief. Mechanistic analysis reveals that upon peripheral inflammation, TRPC3/6 in primary sensory neurons get recruited via released bradykinin acting on B1/B2 receptors, facilitating BDNF secretion from spinal nociceptor terminals, which in turn potentiates synaptic transmission through TRPC3/6 and eventually results in mechanical pain hypersensitivity. Antagonizing TRPC3/6 in DRG relieves mechanical pain hypersensitivity in mice and nociceptor hyperexcitability in human. Thus, TRPC3/6 in nociceptors is crucially involved in pain plasticity and constitutes a promising therapeutic target against mechanical pain hypersensitivity with minor side effects., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

In the present research, the impacts of Ce additions at various concentrations (0, 1.0, 3.4, and 4.0 wt.%) on the evolution of the microstructure, mechanical properties, and thermal conductivity of as-cast and as-extruded Mg-3Sn alloys were investigated. The findings demonstrate that adding Ce caused the creation of a new ternary MgSnCe phase in the magnesium matrix. Some new Mg 17 Ce 2 phases are generated in the microstructure when Ce levels reach 4%. The thermal conductivity of the Mg-3Sn alloy is significantly improved due to Ce addition, and the Mg-3Sn-3.4Ce alloy exhibits the highest thermal conductivity, up to 133.8 W/(m·K) at 298 K. After extrusion, both the thermal conductivity and mechanical properties are further improved. The thermal conductivity perpendicular to the extrusion direction of Mg-3Sn-3.4Ce alloy could achieve 136.28 W/(m·K), and the tensile and yield strengths reach 264.3 MPa and 227.2 MPa, with an elongation of 7.9%. Adding Ce decreases the dissolved Sn atoms and breaks the eutectic α -Mg and Mg 2 Sn network organization, leading to a considerable increase in the thermal conductivity of as-cast Mg-3Sn alloys. Weakening the deformed grain texture contributed to the further enhancement of the thermal conductivity after extrusion.

Previous studies have shown that the C-C motif chemokine ligand 2 (CCL2) is widely expressed in the nervous system and involved in regulating the development of chronic pain and related anxiety-like behaviors, but its precise mechanism is still unclear. This paper provides an in-depth examination of the involvement of CCL2-CCR2 signaling in the anterior cingulate cortex (ACC) in intraplantar injection of complete Freund's adjuvant (CFA) leading to inflammatory pain and its concomitant anxiety-like behaviors by modulation of glutamatergic N-methyl-D-aspartate receptor (NMDAR). Our findings suggest that local bilateral injection of CCR2 antagonist in the ACC inhibits CFA-induced inflammatory pain and anxiety-like behavior. Meanwhile, the expression of CCR2 and CCL2 was significantly increased in ACC after 14 days of intraplantar injection of CFA, and CCR2 was mainly expressed in excitatory neurons. Whole-cell patch-clamp recordings showed that the CCR2 inhibitor RS504393 reduced the frequency of miniature excitatory postsynaptic currents (mEPSC) in ACC, and CCL2 was involved in the regulation of NMDAR-induced current in ACC neurons in the pathological state. In addition, local injection of the NR2B inhibitor of NMDAR subunits, Ro 25-6981, attenuated the effects of CCL2-induced hyperalgesia and anxiety-like behavior in the ACC. In summary, CCL2 acts on CCR2 in ACC excitatory neurons and participates in the regulation of CFA-induced pain and related anxiety-like behaviors through upregulation of NR2B. CCR2 in the ACC neuron may be a potential target for the treatment of chronic inflammatory pain and pain-related anxiety., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The matrix glycoprotein thrombospondin-1 (THBS1) modulates nitric oxide (NO) signaling in endothelial cells. A high-salt diet induces deficiencies of NO production and bioavailability, thereby leading to endothelial dysfunction. In this study we investigated the changes of THBS1 expression and its pathological role in the dysfunction of mesenteric artery endothelial cells (MAECs) induced by a high-salt diet. Wild-type rats, and wild-type and Thbs1 -/- mice were fed chow containing 8% w/w NaCl for 4 weeks. We showed that a high salt diet significantly increased THBS1 expression and secretion in plasma and MAECs, and damaged endothelium-dependent vasodilation of mesenteric resistance arteries in wild-type animals, but not in Thbs1 -/- mice. In rat MAECs, we demonstrated that a high salt environment (10-40 mM) dose-dependently increased THBS1 expression accompanied by suppressed endothelial nitric oxide synthase (eNOS) and phospho-eNOS S1177 production as well as NO release. Blockade of transforming growth factor-β1 (TGF-β1) activity by a TGF-β1 inhibitor SB 431542 reversed THBS1 up-regulation, rescued the eNOS decrease, enhanced phospho-eNOS S1177 expression, and inhibited Smad4 translocation to the nucleus. By conducting dual-luciferase reporter experiments in HEK293T cells, we demonstrated that Smad4, a transcription promoter, upregulated Thbs1 transcription. We conclude that THBS1 contributes to endothelial dysfunction in a high-salt environment and may be a potential target for treatment of high-salt-induced endothelium dysfunction., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Purpose: We attempted a technique for patients with congenital ring-little finger metacarpal synostosis involving simultaneous interpositional allograft bone after split osteotomy of the synostosis site and distraction lengthening of the fifth metacarpal along with correction of the metacarpal joint abduction contracture. The purpose of this study was to describe the surgical technique and its outcomes., Methods: We reviewed the medical records of children with congenital ring-little finger metacarpal synostosis treated surgically at our institute. Eight hands of six children with an average age of 5.0 (range, 1.7-9.3) years were treated by simultaneous interpositional allograft bone after split osteotomy, distraction lengthening, and tenotomy of abductor digiti minimi. We measured the metacarpal head-to-capitate area ratios from serial radiographs and analyzed them according to age. We also measured the change in the intermetacarpal angle (IMA) and metacarpal length ratio during an average of 8.1 (range, 1.4-16.8) years of follow-up. These changes were compared with changes in seven hands of five children with an average age of 8.1 (range, 1.5-15.6) years treated by the same method, but without a distraction lengthening of the fifth metacarpal and followed up for an of average 12.1 (range, 4.1-19.8) years, as a control group., Results: Abnormal metacarpal head-to-capitate area ratio before surgery was normalized in all patients within the first 2 years after surgery. The IMA change averaged 39.8°, and the metacarpal length ratio changed by 17%. The control group showed an average IMA change of 36.6° and metacarpal length ratio change of 6%., Conclusions: Simultaneous interpositional allograft bone after split osteotomy of the synostosis site and distraction lengthening of the fifth metacarpal with correction of metacarpal joint abduction contracture can restore the radiographic parameters in congenital ring-little finger metacarpal synostosis. The normalized ossification of the fifth metacarpal head indicates that the surgical procedure is probably safe., Type of Study/level of Evidence: Therapeutic V., (Copyright © 2023 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

Context: Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of 'thoracic obstruction'. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment., Objective: This work screens the active component acting on TRPC1 from Salvia miltiorrhizae ., Materials and Methods: TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski's rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells., Results: Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza . Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 μM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca 2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells., Discussion and Conclusions: We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae , and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.

The purpose of this study is to assess the clinical significance of the radiologic safe zone based on computed tomography and to compare the outcomes of three different implants for fixation of isolated radial head fractures. We retrospectively reviewed 367 patients who underwent internal fixation for isolated radial head fractures. We newly defined two subtypes of Mason type II fractures associated with the radiographic safe zone (IIA, two-part fracture allowing for safe fixation of plate; IIB, two-part fracture not allowing for safe fixation). 170 patients (CCS group, n = 82; HCS group, n = 31; plate group, n = 57) were investigated with no significant differences in demographics. The range of pronation and supination at 1 month postoperatively (P = 0.04 and P = 0.04) and the range of supination at 6 and 12 months postoperatively (P = 0.03 and P = 0.03) were significantly smaller in the plate group. In Mason type IIB fractures, the average MEPS was higher in the CCS and HSC groups than in the plate group (P = 0.01 and P = 0.02). And the average DASH score was lower in the CCS and HCS groups (P < 0.01 and P < 0.01). Evaluation of the radiologic safe zone is potentially helpful in selecting better surgical fixation option. For type III fractures, 2.3-mm cortical screws would be a better option than Acutrak screws. Plates would not be suitable for type IIB radial head fractures.

Background: The dried bark of Ailanthus altissima (Mill.) Swingle is widely used in traditional Chinese medicine for the treatment of ulcerative colitis. The objective of this study was to explore the therapeutic basis of the dried bark of Ailanthus altissima (Mill.) Swingle for the treatment of ulcerative colitis based on Virtual Screening-Molecular Docking-Activity Evaluation technology., Methods: By searching the Traditional Chinese Medicine Systems Pharmacology TCMSP Database and Analysis Platform, 89 compounds were obtained from the chemical components of the dried bark of Ailanthus altissima (Mill.) Swingle. Then, after preliminarily screening the compounds based on Lipinski's rule of five and other relevant conditions, the AutoDock Vina molecular docking software was used to evaluate the affinity of the compounds to ulcerative colitis-related target proteins and their binding modes through use of the scoring function to identify the best candidate compounds. Further verification of the compound's properties was achieved through in vitro experiments., Results: Twenty-two compounds obtained from the secondary screening were molecularly docked with ulcerative colitis-related target proteins (IL-1R, TLR, EGFR, TGFR, and Wnt) using AutoDock Vina. The free energies of the highest scoring compounds binding to the active cavity of human IL-1R, TLR, EGFR, TGFR, and Wnt proteins were - 8.7, - 8.0, - 9.2, - 7.7, and - 8.5 kcal/mol, respectively. The potential compounds, dehydrocrebanine, ailanthone, and kaempferol, were obtained through scoring function and docking mode analysis. Furthermore, the potential compound ailanthone (1, 3, and 10 µM) was found to have no significant effect on cell proliferation, though at 10 µM it reduced the level of pro-inflammatory factors caused by lipopolysaccharide., Conclusion: Among the active components of the dried bark of Ailanthus altissima (Mill.) Swingle, ailanthone plays a major role in its anti-inflammatory properties. The present study shows that ailanthone has advantages in cell proliferation and in inhibiting of inflammation, but further animal research is needed to confirm its pharmaceutical potential., (© 2023. The Author(s).)

Lampriform fishes (Lampriformes), which primarily inhabit deep-sea environments, are large marine fishes varying from the whole-body endothermic opah to the world's longest bony fish-giant oarfish, with species morphologies varying from long and thin to deep and compressed, making them an ideal model for studying the adaptive radiation of teleost fishes. Moreover, this group is important from a phylogenetic perspective owing to their ancient origins among teleosts. However, knowledge about the group is limited, which is, at least partially, due to the dearth of recorded molecular data. This study is the first to analyze the mitochondrial genomes of three lampriform species ( Lampris incognitus, Trachipterus ishikawae, and Regalecus russelii ) and infer a time-calibrated phylogeny, including 68 species among 29 orders. Our phylomitogenomic analyses support the classification of Lampriformes as monophyletic and sister to Acanthopterygii; hence, addressing the longstanding controversy regarding the phylogenetic status of Lampriformes among teleosts. Comparative mitogenomic analyses indicate that tRNA losses existed in at least five Lampriformes species, which may reveal the mitogenomic structure variation associated with adaptive radiation. However, codon usage in Lampriformes did not change significantly, and it is hypothesized that the nucleus transported the corresponding tRNA, which led to function substitutions. The positive selection analysis revealed that atp8 and cox3 were positively selected in opah, which might have co-evolved with the endothermic trait. This study provides important insights into the systematic taxonomy and adaptive evolution studies of Lampriformes species.

Objective: This study aims to comprehensively assess the direct, severe harms of screening colonoscopy in the United States. Whereas other investigators have completed systematic reviews estimating the harms of all types of colonoscopy, this analysis focuses on screening colonoscopies that had adequate follow up to avoid undercounting delayed harms., Data Sources: PubMed and Embase were queried for relevant studies on screening colonoscopy harms published between January 1, 2002, and April 1, 2022., Study Selection: English-language studies of screening colonoscopy for average risk patients were included. Studies must have followed patients for adequate time post procedure, defined as 30 days after colonoscopy., Main Outcomes: The primary outcome was the number of severe bleeding events and gastrointestinal (GI) perforations within 30 days of screening colonoscopy., Results: A total of 1951 studies were reviewed for inclusion; 94 were reviewed in full text. Of those reviewed in full, 6 studies, including a total of 467,139 colonoscopies, met our inclusion criteria and were included in our analysis of harms related to screening colonoscopies. The rate of severe bleeding ranged credibly from 16.4 to 36.18 per 10,000 colonoscopies; the rate of perforation ranged credibly from 7.62 to 8.50 per 10,000 colonoscopies., Conclusions: This study is the first to estimate direct harms from screening colonoscopy, including harms that occur up to 30 days after the procedure. The risk of harm subsequent to screening colonoscopy is higher than previously reported and should be discussed with patients when engaging in shared decision making., Competing Interests: Conflict of interest: None., (© Copyright by the American Board of Family Medicine.)

Background: Recent studies have demonstrated that the distal forearm dual-energy X-ray absorptiometry (DEXA) scan might be a better method for screening bone mineral density (BMD) and the risk of a distal forearm fracture, compared with a central DEXA scan. Therefore, the purpose of this study was to determine the effectiveness of a distal forearm DEXA scan for predicting the occurrence of a distal radius fracture (DRF) in elderly females who were not initially diagnosed with osteoporosis after a central DEXA scan., Methods: Among the female patients who visited our institutes and who were over 50 years old and underwent DEXA scans at 3 sites (lumbar spine, proximal femur, and distal forearm), 228 patients with DRF (group 1) and 228 propensity score-matched patients without fractures (group 2) were included in this study. The patients' general characteristics, BMD, and T-scores were compared. The odds ratios (OR) of each measurement and correlation ratio among BMD values of the different sites were evaluated., Results: The distal forearm T-score of the elderly females with DRF (group 1) was significantly lower than that of the control group (group 2) (p < 0.001 for the one-third radius and ultradistal radius measurements). BMD measured during the distal forearm DEXA scan was a better predictor of DRF risk than BMD measured during the central DEXA (OR = 2.33; p = 0.031 for the one-third radius, and OR = 3.98; p < 0.001 for the ultradistal radius). The distal one-third radius BMD was correlated with hip BMD, rather than lumbar BMD (p < 0.05 in each group)., Conclusion: Performing a distal forearm DEXA scan in addition to a central DEXA scan appears to be clinically significant for detecting the low BMD in the distal radius, which is associated with osteoporotic DRF in elderly females., Level of Evidence: III; case-control study., (© 2023. The Author(s).)

Inlet flow direction significantly affects the hydraulic performance of an axial-flow pump. Usually, the research papers ignore this phenomenon, resulting in discrepancies between simulation and experimental results. This study examines the influence of inflow direction in five cases (0%, 5%, 10%, 15%, and 30% pre-swirl intensities) to determine the relationship between the pre-swirl intensity and the hydraulic performance of the axial-flow pump. Based on this, changing the setting angle of the inlet guide vane (IGV) is proposed and thoroughly investigated to reduce the effect of inflow direction. In this study, the influence of clearances in IGV blades on hydraulic performance is also investigated in detail. Numerical simulations are performed using ANSYS-CFX and a shear stress transport reattachment modification (SST k-[Formula: see text]) turbulence model with small y+ values at all walls. Specifically, the hydraulic performance curves and internal flow characteristics, including contours and streamlines, are assessed and analyzed. The inflow direction significantly impacts the hydraulic efficiency of the axial-flow pump. Increased pre-swirl intensity causes more loss in the IGV passage. The internal flow field and performance are not affected by the clearance at the hub and shroud of the IGV. However, the tip clearance of the impeller causes a decrease in hydraulic efficiency due to the tip leakage vortex. By adjusting the setting angle of the IGV, the efficiency and head gradually increase from a negative to a positive setting angle. Additionally, 30° is considered the critical setting angle for IGV., (© 2023. The Author(s).)

Study Aim: Little is known about preceptors' comfort and readiness to teach clinical students about the care of patients with substance and opioid use disorder (SUD/OUD). This study explores preceptors' views about caring for such patients, and their preparedness to teach about SUD/OUD management, to improve graduate competencies., Methods: Participants were recruited by convenience and snowball sampling. Semi-structured interviews were conducted with physician, physician assistant, and nurse practitioner preceptors who taught medical and physician assistant students. Interviews were conducted via Zoom® videoconferencing. Transcripts were generated and independently analyzed for themes by 4 experienced coders using constant comparison and a grounded theory approach., Results: Fifteen interviews were conducted to theme saturation. We identified 3 major themes and 10 subthemes supported by exemplar quotes. The major themes were: education about SUD/OUD in primary care (subthemes include need for longitudinal curriculum, redefining 'success' in treatment, and precepting challenges), treatment of SUD/OUD in primary care (need for systemic support and care continuity), and medication-assisted therapy (MAT) training as a tool for teaching (preceptors' own training, and need for clinical students to be trained)., Conclusions: Preceptors agreed that treatment of SUD/OUD belongs in primary care and students should learn about SUD/OUD from the start of their medical education. Data analysis enabled the construction of an emerging conceptual framework reflecting a diversity of experiences and opinions of preceptor comfort and preparedness to teach about SUD/OUD, associated with various barriers and motivators. This framework can guide future strategies to address facilitators and obstacles to advance and promote preceptor preparedness to teach students about the care and management of patients with SUD/OUD., (© 2022. The Author(s).)

Purpose: Physician assistant (PA) graduates should be prepared to care for patients with substance use disorders. Medication-assisted therapy (MAT) allows PA graduates to provide that care by becoming licensed to prescribe buprenorphine. However, it is unclear how feasible and effective it is to implement online MAT waiver training during PA school. This study examined student knowledge and attitudes after training to assess its impact and perceived value., Methods: We conducted a 15-question survey after one class of students completed training during clinical rotations. Students self-reported pre/post change in awareness, knowledge, interest, comfort and confidence, perceived usefulness to practice, and assessed quality using 5-point Likert scale (higher scores = more positive) and narrative responses. Data analysis was performed using the Wilcoxon signed rank test and descriptive statistics. Free text comments were analyzed for themes using constant comparison., Results: Fifty-five (100%) students completed training within 6 weeks. The survey response rate was 49/55 (89%). Pre-to-post score changes were significant (p < .05) from +0.39 to +1.35 with the greatest changes seen in knowledge (+1.35), comfort (+1.14), awareness (+1.06), and confidence (+1.08); the lowest change was in interest (score change +0.39). Students reported being satisfied with content organization and quality (mean 3.82) and recommended training to colleagues (3.98); 82% reported they would have preferred 3 months to complete training; 46% would have preferred training prior to the start of clinical rotations. Major themes indicated a desire for better preparation and flexibility of platform, with ambivalence about relevance to practice., Conclusion: Online MAT waiver training is feasible and effective. However, students may not be convinced of its relevance to future practice. Faculty should offer adequate preparation and optimize integration into existing curricula., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Physician Assistant Education Association.)

Purpose: To demonstrate the differences between outcomes and complications after reverse total shoulder arthroplasty (rTSA), according to the types of lateralized prosthesis designs: glenoid-based lateralization (LG) and humerus-based lateralization (LH)., Methods: PubMed, Embase, and the Cochrane Library databases were systematically searched for studies published before 1 April 2021, using the PRISMA guidelines. A network meta-analysis was applied for indirect comparison, incorporating studies including medialized or conventional Grammont prosthesis and each lateralized prosthesis (LG vs control and LH vs control). Out of 1,989 screened studies, 11 studies were included to compare functional scores, range of motion (ROM), radiologic outcomes, and revision rates. In addition, six articles from the included studies, which had repaired subscapularis after rTSA were analyzed to exclude the potential influence of subscapularis repair on the outcomes. The data were pooled using a random-effects model. The pooled estimates of the mean differences (MDs) and 95% confidence intervals (CIs) were calculated for continuous data, while dichotomous data were analyzed using the pooled relative risk (RR) and their 95% CIs., Results: The ROM, complications, and functional scores were similar between the two groups. In subgroup analysis of 6 studies involving concomitant subscapularis repair, the LH group showed higher American Shoulder and Elbow Surgeons (ASES) scores and Constant scores than the control group. Regarding the ROM, LH group showed better forward elevation than the LG group (LH vs LG: MD 10.07, 95% CI -9.05-29.19)., Conclusion: Overall, the outcomes and occurrence of complications were not significantly different between the two lateralized prosthesis groups. However, when the subscapularis was repaired, LH prosthesis seems to be more suitable to obtain a better ASES score and ROM., Level of Evidence: Level III, network meta-analysis.

The development of a cathode for solid-state lithium-oxygen batteries has been hindered in practice by a low capacity and limited cycle life despite their potential for high energy density. Here, a previously unexplored strategy is proposed wherein the cathode delivers a specific capacity of 200 milliampere hour per gram over 665 discharge/charge cycles, while existing cathodes achieve only ~50 milliampere hour per gram and ~100 cycles. A highly conductive ruthenium-based composite is designed as a carbon-free cathode by first-principles calculations to avoid the degradation associated with carbonaceous materials, implying an improvement in stability during the electrochemical cycling. In addition, water vapor is added into the main oxygen gas as an additive to change the discharge product from growth-restricted lithium peroxide to easily grown lithium hydroxide, resulting in a notable increase in capacity. Thus, the proposed strategy is effective for developing reversible solid-state lithium-oxygen batteries with high energy density.

Study Design: A retrospective case control study., Purpose: This study aimed to assess the clinical significance of sagittal balance for predicting and managing the recollapse of cemented vertebra following percutaneous vertebroplasty (PVP) in patients with thoracolumbar osteoporotic vertebral fracture (OVF)., Overview of Literature: Recently, the recollapse of cemented vertebra following PVP for OVF has been reported. Although the risk factors for recollapse have been determined, the association between sagittal spinopelvic parameters and sagittal imbalance with recollapse has not been established., Methods: Ambulatory patients who underwent single-level PVP for thoracolumbar OVF with a follow-up of at least 24 months were retrospectively reviewed. The patients were divided into two groups depending on the presence of symptomatic recollapse at the cemented vertebra: (1) recollapsed (RC) group and (2) noncollapsed (NC) group. The patient characteristics and radiographic measurements associated with sagittal imbalance were analyzed at each follow-up visit., Results: Overall, 134 patients (RC group, n=28; NC group, n=106) were enrolled. The mean fracture-free interval was 3.2 months (range, 1.2-25.1 months). The multivariate binary logistic regression analysis identified low bone mineral density (p =0.047), degree of dynamic mobility within the vertebra (p =0.025), and sagittal imbalance as significant risk factors for recollapse (p =0.013; odds ratio, 5.405). The progression of sagittal imbalance and thoracolumbar kyphosis (T10-L2) was more significant in the RC and sagittal imbalance groups than in the NC group (both p =0.000)., Conclusions: Sagittal imbalance, lower bone mineral density, and dynamic mobility within the vertebra are associated with the recollapse of cemented vertebrae following PVP. Sagittal imbalance, rather than local kyphosis or thoracolumbar kyphosis, is particularly significant in that it results in more progressive collapse and sagittal deformity and is accompanied by substantial back pain and neurological deficits. Therefore, a stricter and more active management, including anti-osteoporosis medication, is required for the treatment of OVF with sagittal imbalance of the spine.

The inflammatory response following spinal cord injury (SCI) involves the activation of resident microglia and the infiltration of macrophages. Activated microglia/macrophages have either detrimental or beneficial effects on neural regeneration based on their functional polarized M1/M2 subsets. Aldose reductase (AR) has recently been shown to be a key component of the innate immune response. However, the mechanisms involved in AR and innate immune response remain unclear. In this study, wild-type (WT) or AR-deficiency (KO) mice were subjected to SCI by a spinal crush injury model. AR KO mice showed better locomotor recovery and smaller injury lesion areas after spinal cord crushing compared with WT mice. Here, we first demonstrated that AR deficiency repressed the expression level of inducible nitric oxide synthase (iNOS) induced by lipopolysaccharide (LPS) in vitro via the activation of autophagy. AR deficiency caused 4-hydroxy-2-(E)-nonenal (4-HNE) accumulation in LPS-induced macrophages. We also found that exogenous addition of low concentrations of 4-HNE in LPS-induced macrophages had the effect of promoting further activation of NF-κB pathway, whereas high concentrations of 4-HNE had inhibitory effects. Together, these results indicated that autophagy as a mechanism underlying AR and 4-HNE in LPS-induced macrophages., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Postsynaptic NMDARs at spinal synapses are required for postsynaptic long-term potentiation and chronic pain. However, how presynaptic NMDARs (PreNMDARs) in spinal nociceptor terminals control presynaptic plasticity and pain hypersensitivity has remained unclear. Here we report that PreNMDARs in spinal nociceptor terminals modulate synaptic transmission in a nociceptive tone-dependent manner. PreNMDARs depresses presynaptic transmission in basal state, while paradoxically causing presynaptic potentiation upon injury. This state-dependent modulation is dependent on Ca 2+ influx via PreNMDARs. Small conductance Ca 2+ -activated K + (SK) channels are responsible for PreNMDARs-mediated synaptic depression. Rather, tissue inflammation induces PreNMDARs-PKG-I-dependent BDNF secretion from spinal nociceptor terminals, leading to SK channels downregulation, which in turn converts presynaptic depression to potentiation. Our findings shed light on the state-dependent characteristics of PreNMDARs in spinal nociceptor terminals on modulating nociceptive transmission and revealed a mechanism underlying state-dependent transition. Moreover, we identify PreNMDARs in spinal nociceptor terminals as key constituents of activity-dependent pain sensitization., (© 2022. The Author(s).)

We find all polyhedral graphs such that their complements are still polyhedral. These turn out to be all self-complementary., (© The Author(s) 2022.)

As one of the most challenging inflammatory diseases, the incidence of ulcerative colitis (UC) is increasing year by year, but the existing therapeutic drugs are not effective and lack of targeting. Nanomaterials are expected to become promising delivery system due to their good targeting effects. Here, we designed a nanomaterial sensitive to reactive oxygen species, which can be used to treat IBD, especially UC. It is a self-assembled polyether micelle that can be oxidized at the inflammation site where the concentration of reactive oxygen increases, and effectively release the encapsulated budesonide (Bud). Experiments have proved that for DSS-induced colitis, the synthetic drug-loaded nanoparticles have excellent therapeutic effects, can effectively repair intestinal barrier, and significantly improve the damaged colon tissue. At the same time, it has a beneficial regulatory effect on inflammatory factors. Molecular mechanism studies have shown that it achieves its therapeutic effects by activating the peroxisome proliferators-activated receptors- γ (PPAR- γ ) pathway and inhibiting the nuclear factor (NF)- κ B pathway. This study proves that oral nano-micelles have an important impact on improving the efficacy of UC treatment drugs and have far-reaching significance for the targeted treatment of gastrointestinal diseases.

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

Background: For treating displaced patella fractures, tension band wiring is the most widely used technique. However, implant removal surgery is often necessary to alleviate discomfort caused by fixation materials. On the contrary, fixation using nonabsorbable suture materials is anticipated to result in comparable outcomes without need for further implant removal surgery. However, there is a lack of clinical studies comparing the two fixation techniques (wire and nonabsorbable suture materials) for acute patella fractures., Methods: From 2014 to 2018, we retrospectively reviewed 60 patients who underwent open reduction with internal fixation for acute patella fracture. Thirty patients (group 1) who received surgery using tension band wiring and 30 patients (group 2) who received surgery using nonabsorbable suture materials were enrolled. The average follow-up period was more than 1 year after operation. Operation time, postoperative bone union time, range of motion (ROM) of the knee joint, postoperative clinical results, and complications were compared between the two groups., Result: Operation time, clinical bone union, and radiologic bone union were not statistically different between groups 1 and 2. At 3 months postoperatively, flexion was 120.3 ± 9.4° in group 1 and 110.5 ± 7.7° in group 2, showing statistically significant difference (p = 0.037). At 6 and 12 months postoperatively, the ROM was similar in both groups. Hospital for special surgery score at 3 months postoperatively was 78.4 ± 8.2 in group 1 and 83.7 ± 8.7 in group 2, showing statistically significant differences (p = 0.032). However, at 6 and 12 months postoperatively, there were no statistical differences. Lysholm score at 3 months postoperatively was 73.5 ± 8.1 in group 1 and 80.4 ± 8.2 in group 2, showing statistically significant difference (p = 0.016), but at 6 and 12 months postoperatively, there were no statistical differences., Conclusion: Fixation using multiple nonabsorbable suture materials can be an alternative surgical method in managing patella fractures, along with tension band wiring., (© 2021. The Author(s).)

Introduction: Evidence suggests that clinicians may view or label patients as nonadherent in a biased manner. Therefore, we performed a retrospective cohort analysis exploring associations between patient demographics and zip code-level income with the International Classification of Diseases, Tenth Version (ICD-10) diagnoses for nonadherence among type 2 diabetes mellitus (T2DM) patients, comparing primary and specialty care settings. Providers in the primary care group included internal medicine and family medicine physicians. In the specialty care group, providers included endocrinologists and diabetologists only., Methods: Participants were identified from 5 primary care and 4 endocrinology sites in the University of Pennsylvania Health System between January 1, 2015, and January 1, 2019. Demographics, hemoglobin A1c (HbA1c), and ICD-10 codes for T2DM and nonadherence were extracted from the electronic health record and analyzed in October 2019. Log-binomial regression models were used to estimate patients' risk of nonadherence labeling by race, insurance, and zip code-level median household income, controlling for patient characteristics and HbA1c as a proxy for diabetes self-management. Results were compared between primary and specialty care sites., Results: A total of 6072 patients aged 18-70 years were included in this study. Black race, Medicare, and Medicaid were associated with increased nonadherence labeling while controlling for patient characteristics ([ARR = 2.48, 95% CI: 2.01, 3.04], [ARR = 1.82, 95% CI: 1.50, 2.18], [ARR = 1.61, 95% CI: 1.32, 1.93], respectively). The results remained significant on adjustment with zip code-level income and showed no differences between primary and specialty sites. Lower-income zip codes showed a significant association with increased rates of nonadherence labeling., Conclusions: Black race, non-private insurance, and lower-income zip codes were associated with disproportionately high rates of nonadherence labeling in both primary and specialty management of T2DM, possibly suggestive of racial or class bias., Competing Interests: Conflict of interest: None., (© Copyright 2021 by the American Board of Family Medicine.)

Patients with neuropathic pain often experience comorbid psychiatric disorders. Cellular plasticity in the anterior cingulate cortex (ACC) is assumed to be a critical interface for pain perception and emotion. However, substantial efforts have thus far been focused on the intracellular mechanisms of plasticity rather than the extracellular alterations that might trigger and facilitate intracellular changes. Laminin, a key element of the extracellular matrix (ECM), consists of one α-, one β-, and one γ-chain and is implicated in several pathophysiological processes. Here, we showed in mice that laminin β1 (LAMB1) in the ACC was significantly downregulated upon peripheral neuropathy. Knockdown of LAMB1 in the ACC exacerbated pain sensitivity and induced anxiety and depression. Mechanistic analysis revealed that loss of LAMB1 caused actin dysregulation via interaction with integrin β1 and the subsequent Src-dependent RhoA/LIMK/cofilin pathway, leading to increased presynaptic transmitter release probability and abnormal postsynaptic spine remodeling, which in turn orchestrated the structural and functional plasticity of pyramidal neurons and eventually resulted in pain hypersensitivity and anxiodepression. This study sheds new light on the functional capability of ECM LAMB1 in modulating pain plasticity and identifies a mechanism that conveys extracellular alterations to intracellular plasticity. Moreover, we identified cingulate LAMB1/integrin β1 signaling as a promising therapeutic target for the treatment of neuropathic pain and associated anxiodepression.

Phytase plays an important role in crop seed germination and plant growth. In order to fully understand the plant growth-promoting mechanism by Rahnella &nbsp; aquatilis JZ-GX1, the effect of this strain on germination of maize seeds was determined in vitro, and the colonization of maize root by R. aquatilis JZ-GX1 was observed by scanning electron microscope. Different inoculum concentrations and Phytate-related soil properties were applied to investigate the effect of R. aquatilis JZ-GX1 on the growth of maize seedlings. The results showed that R. aquatilis JZ-GX1 could effectively secrete indole acetic acid and had significantly promoted seed germination and root length of maize. A large number of R. aquatilis JZ-GX1 cells colonized on the root surface, root hair and the root interior of maize. When the inoculation concentration was 10 7 cfu/mL and the insoluble organophosphorus compound phytate existed in the soil, the net photosynthetic rate, chlorophyll content, phytase activity secreted by roots, total phosphorus concentration and biomass accumulation of maize seedlings were the highest. In contrast, no significant effect of inoculation was found when the total P content was low or when inorganic P was sufficient in the soil. R. aquatilis JZ-GX1 promotes the growth of maize directly by secreting IAA and indirectly by secreting phytase. This work provides beneficial information for the development and application of R. aquatilis JZ-GX1 as a microbial fertilizer in the future.

Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.

Purpose: Although the pronator quadratus (PQ) preservation approach for volar plating of distal radius fracture has been commonly used recently, its superiority to the conventional PQ dissection approach, especially for comminuted intra-articular distal radius fractures, has not been well established. The purpose of this study was to assess the efficacy of PQ preservation for comminuted intra-articular fractures and to evaluate the healed PQ during hardware removal surgery., Materials and Methods: From January 2014 to March 2019, 86 patients who underwent both volar plating for AO Foundation/Orthopedic Trauma Association classification type C2 or C3 distal radius fractures and subsequent hardware removal were assessed in this study. Radiographic measurements, clinical outcomes at each follow-up, and the integrity of healed PQ during hardware removal were compared between the PQ dissection (group D) and PQ preservation (group P) groups., Results: Complete union with acceptable reduction on radiographic measurements was achieved in both groups. Group P showed a statistically significant earlier recovery of clinical outcomes at 2 weeks and 1 month postoperatively and improved anatomical restoration of PQ muscle covering the plate, which was identified during hardware removal surgery. Flexor tendon rupture was identified in 2 patients (5%) and tenosynovitis in 6 patients (14%) in group D; no patient had flexor tendon rupture (0%), and 2 patients (5%) had tenosynovitis in group P., Conclusions: Pronator quadratus preservation approach for volar plating is easily applicable and useful even for comminuted intra-articular distal radius fractures and is helpful for earlier restoration of wrist function and in preventing flexor tendon problems in the latter postoperative period., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: In this paper, based on the age, sex, disease type, and consultation time of dental emergency during COVID-19 epidemic, a comprehensive analysis of dental emergency management and prevention and control of COVID-19 was conducted., Methods: A total of 739 emergency dental cases were collected from January 29 2020 to February 28 2020. They were divided into 3 groups，including adolescents (≤18 years), young adults (18 ~ 60 years), and elderly ( ≥60 years old). The data was analyzed using SPSS 21.0 software package., Results: The ratio of male to female was 1.24∶1. There were 655 emergency cases during the day and 84 cases during the night. The types of diseases included pericoronitis (15.83%), apical periodontitis (14.21%), pulpitis (13.40%), periodontitis (12.31%), oral mucosal disease (12.18%), Oral and maxillofacial trauma (10.55%), oral and maxillofacial space infection (8.39%), dental disease in children (5.41%), oral and maxillofacial tumors (2.84%), temporomandibular joint dislocations and disorders (1.76%), and others (3.11%)., Conclusions: Under the epidemic situation of the new coronavirus, as one of the high-risk departments, it is of great significance to enhance the clinical emergency skills and ability of emergency treatment, improve patients' oral health awareness, address the diagnosis and treatment of essential diseases, for the improvement the quality of dental medical care and the prevention and control of COVID-19 epidemic.

Patients with neuropathic pain often experience exaggerated pain and anxiety. Central sensitization has been linked with the maintenance of neuropathic pain and may become an autonomous pain generator. Conversely, emerging evidence accumulated that central sensitization is initiated and maintained by ongoing nociceptive primary afferent inputs. However, it remains elusive what mechanisms underlie this phenomenon and which peripheral candidate contributes to central sensitization that accounts for pain hypersensitivity and pain-related anxiety. Previous studies have implicated peripherally localized cGMP-dependent protein kinase I (PKG-I) in plasticity of nociceptors and spinal synaptic transmission as well as inflammatory hyperalgesia. However, whether peripheral PKG-I contributes to cortical plasticity and hence maintains nerve injury-induced pain hypersensitivity and anxiety is unknown. Here, we demonstrated significant upregulation of PKG-I in ipsilateral L3 dorsal root ganglia (DRG), no change in L4 DRG, and downregulation in L5 DRG upon spared nerve injury. Genetic ablation of PKG-I specifically in nociceptors or post-treatment with intervertebral foramen injection of PKG-I antagonist, KT5823, attenuated the development and maintenance of spared nerve injury-induced bilateral pain hypersensitivity and anxiety. Mechanistic analysis revealed that activation of PKG-I in nociceptors is responsible for synaptic potentiation in the anterior cingulate cortex upon peripheral neuropathy through presynaptic mechanisms involving brain-derived neurotropic factor signaling. Our results revealed that PKG-I expressed in nociceptors is a key determinant for cingulate synaptic plasticity after nerve injury, which contributes to the maintenance of pain hypersensitivity and anxiety. Thereby, this study presents a strong basis for opening up a novel therapeutic target, PKG-I, in nociceptors for treatment of comorbidity of neuropathic pain and anxiety with least side effects.

Previous studies have shown that CCL2 may cause chronic pain, but the exact mechanism of central sensitization is unclear. In this article, we further explore the presynaptic role of CCL2. Behavioral experiments show that intervertebral foramen injection CCR2 antagonists into dorsal root ganglion (DRG) can inhibit the inflammatory pain caused by CCL2 in spinal cord. We raised the question of the role of presynaptic CCR2 in the spinal dorsal horn. Subsequent electron microscopy experiments showed that CCR2 was expressed in the presynaptic CGRP terminal in the spinal dorsal horn. CCL2 can enhance presynaptic calcium signal. Whole-cell patch-clamp recordings showed that CCL2 can enhance NMDAR-eEPSCs through presynaptic effects, and further application of glutamate sensor method proved that CCL2 can act on presynaptic CCR2 to increase the release of presynaptic glutamate. In conclusion, we suggest that CCL2 can directly act on the CCR2 on presynaptic terminals of sensory neurons in the spinal dorsal horn, leading to an increase in the release of presynaptic glutamate and participate in the formation of central sensitization.

Previous studies have shown that CCL2 (C-C motif chemokine ligand 2) induces chronic pain, but the exact mechanisms are still unknown. Here, we established models to explore the potential mechanisms. Behavioral experiments revealed that an antagonist of extracellular signal-regulated kinase (ERK) inhibited not only CCL2-induced inflammatory pain, but also pain responses induced by complete Freund's adjuvant. We posed the question of the intracellular signaling cascade involved. Subsequent experiments showed that CCL2 up-regulated the expression of phosphorylated ERK (pERK) and N-methyl D-aspartate receptor [NMDAR] subtype 2B (GluN2B); meanwhile, antagonists of CCR2 and ERK effectively reversed these phenomena. Whole-cell patch-clamp recordings revealed that CCL2 enhanced the NMDAR-induced currents via activating the pERK pathway, which was blocked by antagonists of GluN2B and ERK. In summary, we demonstrate that CCL2 directly interacts with CCR2 to enhance NMDAR-induced currents, eventually leading to inflammatory pain mainly through the CCL2-CCR2-pERK-GluN2B pathway.

Opioid analgesics remain the mainstay for managing intractable chronic pain, but their use is limited by detrimental side effects such as analgesic tolerance and hyperalgesia. Calcium-dependent synaptic plasticity is a key determinant in opiates tolerance and hyperalgesia. However, the exact substrates for this calcium-dependent synaptic plasticity in mediating these maladaptive processes are largely unknown. Canonical transient receptor potential 1, 4, and 5 (TRPC1, 4, 5) proteins assemble into heteromultimeric nonselective cation channels with high Ca 2+ permeability and influence various neuronal functions. However, whether and how TRPC1/4/5 channels contribute to the development of opiates tolerance and hyperalgesia remains elusive. Here, we show that TRPC1/4/5 channels contribute to the generation of morphine tolerance and hyperalgesia. Chronic morphine exposure leads to upregulation of TRPC1/4/5 channels in the spinal cord. Spinally expressed TRPC1, TPRC4, and TRPC5 are required for chronic morphine-induced synaptic long-term potentiation (LTP) as well as remodeling of synaptic spines in the dorsal horn, thereby orchestrating functional and structural plasticity during the course of morphine-induced hyperalgesia and tolerance. These effects are attributed to TRPC1/4/5-mediated Ca 2+ elevation in the spinal dorsal horn induced by chronic morphine treatment. This study identifies TRPC1/4/5 channels as a promising novel target to prevent the unwanted morphine tolerance and hyperalgesia., (© 2020 Federation of American Societies for Experimental Biology.)

Chronic pathological pain is one of the most intractable clinical problems faced by clinicians and can be devastating for patients. Despite much progress we have made in understanding chronic pain in the last decades, its underlying mechanisms remain elusive. It is assumed that abnormal increase of calcium levels in the cells is a key determinant in the transition from acute to chronic pain. Exploring molecular players mediating Ca 2+ entry into cells and molecular mechanisms underlying activity-dependent changes in Ca 2+ signaling in the somatosensory pain pathway is therefore helpful towards understanding the development of chronic, pathological pain. Canonical transient receptor potential (TRPC) channels form a subfamily of nonselective cation channels, which permit the permeability of Ca 2+ and Na+ into the cells. Initiation of Ca 2+ entry pathways by these channels triggers the development of many physiological and pathological functions. In this review, we will focus on the functional implication of TRPC channels in nociception with the elucidation of their role in the detection of external stimuli and nociceptive hypersensitivity., Competing Interests: The authors declare no completing financial interests., (Copyright © 2020 Zhi-Chuan Sun et al.)

Purpose: Current operative treatment for advanced thumb carpometacarpal (CMC) joint arthritis mainly constitutes complete trapeziectomy with or without additional stabilizing procedures. However, it is unclear whether the additional procedures influence overall clinical outcomes. Therefore, the purpose of this study was to evaluate the effectiveness of our posttrapeziectomy suture suspensionplasty technique, performed using the abductor pollicis longus and flexor carpi radialis tendons, in patients with advanced thumb CMC arthritis., Materials and Methods: We evaluated 36 thumbs of 35 patients with advanced thumb CMC arthritis treated with combined operative excision of trapezium followed by a suture suspensionplasty using flexor carpi radialis and abductor pollicis longus tendons. We used a minimal volar approach to create a sling construct with a nonabsorbable suture material, which could support the thumb metacarpal base without pin fixation or tendon transfer. For radiographic evaluation, we used the ratio of the radial metacarpal subluxation to metacarpal articular width, estimated from the bilateral stress-view radiographic images of the thumb, and calculated the trapezial space ratio by dividing the trapezial space height by the proximal phalangeal length. The clinical outcomes were evaluated using the visual analog scale and disabilities of the arm, shoulder, and hand scores, along with evaluation of the improvement in both postoperative range of motion and strength recovery., Results: The mean duration of follow-up was 26 months (range, 18-60 months). The average visual analog scale and disabilities of the arm, shoulder, and hand scores decreased from 5.9 to 0.4 and from 51.6 to 27.0, respectively. The range of motion during palmar abduction and opposition of the metacarpophalangeal joint improved with an increase in mean value from 49.1 degrees to 54.1 degrees, and from 7.8 to 9.3 Kapandji score, respectively. The grip and key pinch strengths showed no significant changes from mean preoperative values of 13.3 kg and 3.8 kg to 13.2 kg and 3.2 kg, respectively, as measured at the 18-month follow-up., Conclusions: Our suture suspensionplasty technique has several advantages including minimal invasive approach, short operative time, cost-effectiveness, and early mobilization. We suggest that it can be used as an effective, alternative stabilization method after a complete trapeziectomy.

Brachial plexus avulsion (BPA) represents the most devastating nerve injury in the upper extremity and is always considered as a sophisticated problem due to its resistance to most standard pain relief medications or neurosurgical interventions. There is also a lack of understanding on the underlying mechanisms. Our study aimed to investigate whether spinal CCL2-CCR2 signaling contributed to the development of neuropathic pain following BPA via modulating glutamate N-methyl-d-aspartate receptor (NMDAR). A rat model of BPA on lower trunk (C8-T1) was established, and the sham- and BPA-operated animals were intrathecally injected with saline, C-C chemokine receptor type 2 (CCR2) inhibitor INCB3344 and NMDAR antagonist DL-AP5 one week postoperatively, the behavioral performance of the treated animals and expressions of C-C motif ligand 2 (CCL2), CCR2, and N-methyl-D-aspartic acid receptor 2B (NR2B) in spinal cord sections of each group were examined. It was shown that BPA injury significantly reduced mechanic withdrawal thresholds the next day after surgery until the end of the observation. Both CCL2 and CCR2 expressions increased in BPA rats compared to those in sham rats. CCL2 was mainly localized in astrocytes, and CCR2 was preferably expressed on astrocytes and neurons. Besides, NMDAR subunit NR2B increased in BPA-operated rats, which was reversed in response to CCR2 and NR2B inhibition. However, these inhibitors didn't change the spinal NMDAR level in sham rats. CCR2 and NMDAR inhibition efficiently alleviated mechanical allodynia caused by BPA either at early or late phase of neuropathic pain. Collectively, CCL2-CCR2 axis is associated with mechanical pain after BPA by elevating NMDAR signaling., (Copyright © 2019 IBRO. Published by Elsevier Ltd. All rights reserved.)

The three-dimensional geometry of a micromixer with an asymmetrical split-and-recombine mechanism was optimized to enhance the fluid-mixing capability at a Reynolds number of 20. Single and multi-objective optimizations were carried out by using particle swarm optimization and a genetic algorithm on a modeled surrogate surface. Surrogate modeling was performed using the computational results for the mixing. Mixing and flow analyses were carried out by solving the convection-diffusion equation in combination with the three-dimensional continuity and momentum equations. The optimization was carried out with two design variables related to dimensionless geometric parameters. The mixing effectiveness was chosen as the objective function for the single-objective optimization, and the pressure drop and mixing index at the outlet were chosen for the multi-objective optimization. The sampling points in the design space were determined using a design of experiment technique called Latin hypercube sampling. The surrogates for the objective functions were developed using a Kriging model. The single-objective optimization resulted in 58.9% enhancement of the mixing effectiveness compared to the reference design. The multi-objective optimization provided Pareto-optimal solutions that showed a maximum increase of 48.5% in the mixing index and a maximum decrease of 55.0% in the pressure drop in comparison to the reference design.

Background: (-)-Gallocatechin gallate (GCG) shows multi-bioactivities. Its stability, however, has not been investigated systematically yet. Therefore, the objective of this study was to characterize the stability of GCG and to find ways to stabilize it in biological assays. Furthermore, the epimerization of the compound, its auto-oxidation and degradation were also analyzed by liquid chromatography mass spectrometry (LC-MS)., Results: The stability of GCG was concentration-dependent and was sensitive to pH, temperature, bivalent cations, and dissolved oxygen level. The results also showed that GCG was not stable in common buffers (50 mmol L -1 , pH 7.4, 37 °C) or in cell culture medium DMEM/F12 under physiological conditions (pH 7.4, 37 °C). Our experiments indicated that nitrogen-saturation and the addition of ascorbic acid (VC) could stabilize GCG in biological assays. In addition, LC-MS determination indicated that GCG was able to be epimerized to its epimer (-)-epigallocatechin gallate (EGCG). Meanwhile it was also able to be auto-oxidized to theasinensin and compound P2 and degraded to gallocatechin and gallic acid in pure water at 100 °C., Conclusion: The stability of GCG should be seriously considered in research on the bioactivity of it to avoid possible artifacts. Nitrogen-saturation and use of VC are good ways to make GCG stable in biological assays. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

Previously study has proved the non-erythropoietic mutant erythropoietin (MEPO) exerted neuroprotective effects against ischemic cerebral injury, with an efficacy similar to that of wild-type EPO. This study investigates its effects on neurogenesis, angiogenesis, and gliogenesis in cerebral ischemic mice. Male C57BL/6 mice were subjected to middle cerebral artery occlusion (MCAO) and reperfusion. EPO (5000 U/kg), MEPO (5000 U/kg) or equal volume of normal saline was injected intraperitoneally. Neurological function was evaluated by Rota-rod test, Neurological severity scores (NSS) and Adhesive removal test. After ischemia and reperfusion (I/R), the survival rate, brain tissue loss, neurogenesis, angiogenesis and gliogenesis were detected by Nissl staining, Immunofluorescence and Western blot, respectively. The results shown that MEPO significantly increased survival rate, reduced brain tissue loss, and improved neurological function after MCAO (P < 0.05). Furthermore, MEPO obviously enhanced the proliferation of neuronal precursors (DCX) and promoted its differentiation into mature neurons (NeuN) (P < 0.05). In addition, compared to normal saline treatment mice, MEPO increased the number of BrdU-positive cells in the cerebral vasculature (P < 0.05). Whereas, MEPO treatment also reduced the numbers of newly generated astrocytes (GFAP) and microglia (Iba1) (P < 0.05). Among all the tests in this study, there was no significant difference between EPO group and MEPO group. Taken together, MEPO promoted the regeneration of neurons and blood vessels in peripheral area of infarction, and suppressed the gliogenesis, thus promoting neurogenesis, improving neurological function and survival rate. Our findings suggest that the MEPO may be a therapeutic drug for ischemic stroke intervention., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The presence of α‑dicarbonyl compounds (α-DCs) in vivo has been associated with the development of complications of diabetes mellitus (DM) and also with other chronic diseases. Therefore, quantitative analysis of α-DCs in body fluids is crucial to understand their roles in the formation of these chronic diseases. We established in this study a practical HPLC-UV method to measure 3‑deoxyglucosone (3-DG), glyoxal (GO), methylglyoxal (MGO), diacetyl (DA), and pentane‑2,3‑dione (PD) in blood plasma using 4‑(2,3‑dimethyl‑6‑quinoxalinyl)‑1,2‑benzenediamine (DQB) as a derivatizing reagent. The derivatizing reaction could be carried out quickly under mild conditions and the HPLC determination is simple, sensitive, and easy to operate. The recoveries of the α-DCs are between 85.26% and 110.20% (intra-day) and 87.25% and 103.18% (inter-day); the RSDs are between 1.28% and 5.69% (intra-day) and 2.26% and 6.34% (inter-day). We found the plasma levels of 3-DG, GO, and MGO in the diabetic patients are all significantly higher than those in healthy subjects. The results also show that the contents of GO and MGO in diabetic nephropathy (DN) patients are both significantly higher than those in simple T2DM patients. Moreover, it is found for the first time that the plasma level of GO might be a potential predictor of DN. The developed method would be useful for the measurements of the plasma α-DCs and the data acquired could be informative in the diagnosis of DM complications., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: To investigate MiRNA-126 amounts in serum exosomes from allergic asthma patients as well as lung tissues of asthmatic mice, evaluating the expression of its target gene DNMT1 in mouse specimens., Methods: MiRNA-126 amounts in serum exosomes from asthmatic patients were detected by real-time PCR. The mouse model of allergic asthma was established by OVA-sensitization, and allergic symptoms were recorded; serum IL-4 and sIgE level evaluation (ELISA), broncho alveolar lavage fluid (BALF) cell count and H&E staining were performed to assess airway inflammation. MiRNA-126 and DNMT1 levels in the lung of asthmatic and control mice were detected by real-time PCR; DNMT1 protein levels were detected by immunoblot., Results: MiRNA-126 amounts in peripheral blood exosomes from patients with allergic asthma were significantly higher than that of healthy volunteers (P<0.05). The frequencies of scratching of both sides of the nose and sneezing were elevated within 10 min of excitation in asthmatic rats compared with controls. Meanwhile, OVA-sIgE and IL-4 levels were significantly higher in asthmatic animals than controls (P<0.05). In the asthma group, narrowed bronchial lumen and thickened wall were observed, and bronchial and peripheral vessels showed overt inflammatory cell infiltration. Eosinophil, neutrophil and mast cell amounts in the BALF of asthmatic mice were significantly higher than control values. Furthermore, lung miRNA-126 expression in asthmatic mice was significantly higher than that of controls. Finally, DNMT1 mRNA and protein levels were significantly lower in asthmatic animals compared with controls (P < 0.01)., Conclusion: MiRNA-126 is highly expressed in serum exosomes from allergic asthma patients and lung tissues of asthmatic mice, suggesting that it may be involved in the pathogenesis of bronchial asthma., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

In order to maximize the mixing performance of a micromixer with an integrated three-dimensional serpentine and split-and-recombination configuration, multi-objective optimizations were performed at two different Reynolds numbers, 1 and 120, based on numerical simulation. Numerical analyses of fluid flow and mixing in the micromixer were performed using three-dimensional Navier-Stokes equations and convection-diffusion equation. Three dimensionless design variables that were related to the geometry of the micromixer were selected as design variables for optimization. Mixing index at the exit and pressure drop through the micromixer were employed as two objective functions. A parametric study was carried out to explore the effects of the design variables on the objective functions. Latin hypercube sampling method as a design-of-experiment technique has been used to select design points in the design space. Surrogate modeling of the objective functions was performed by using radial basis neural network. Concave Pareto-optimal curves comprising of Pareto-optimal solutions that represents the trade-off between the objective functions were obtained using a multi-objective genetic algorithm at Re = 1 and 120. Through the optimizations, maximum enhancements of 18.8% and 6.0% in mixing index were achieved at Re = 1 and 120, respectively., Competing Interests: The authors declare there is no conflict of interest.