Clinical Analysis of Superficial Temporal Artery-Middle Cerebral Artery Bypass Combined with Brain-Temporal Muscle Sticking in the Treatment of Chronic Internal Carotid Artery Occlusion.

Objective: NHISS score, MMSE scale, craniocerebral CTA or DSA, and craniocerebral magnetic resonance 3D-ASL were used to evaluate the efficacy and safety of superficial temporal artery-middle cerebral artery (STA-MCA) shunt combined with cranial-muscular-merging (EMS) in the treatment of symptomatic chronic internal carotid artery occlusion. Methods: The purpose of this study was to retrospectively analyze the clinical data of 15 patients with symptomatic chronic internal carotid artery occlusion who received STA-MCA shunt combined with EMS treatment at Weifang Brain Hospital and Weifang Traditional Chinese Medicine Hospital from July 2016 to December 2020. The patients' neurological and cognitive functions were evaluated by NHISS score and MMSE examination before surgery and 6 months after surgery. Adverse reactions after surgery were observed, and preoperative and postoperative cerebral hemodynamics, the patency of the shunt anastomosis, and the compensation of collateral circulation were evaluated by cranial CTA or DSA and cranial MRI 3D-ASL. Results: All 15 patients underwent successful surgery. One patient experienced transient mild cerebral hyperperfusion syndrome postoperatively. Six months after surgery, the NHISS score was significantly improved compared with that before surgery (P = .0001), and the MMSE score was also significantly improved compared with before surgery (P = .0124). No adverse events of poor scalp healing, intracranial infection, subcutaneous fluid accumulation, subdural hematoma, or cerebral hemorrhage were observed postoperatively. Imaging examination showed that the shunt vessels were unobstructed, the middle cerebral artery was dilated, collateral circulation in the surgical area was increased, and cerebral blood flow increased. Conclusion: STA-MCA shunt combined with EMS treatment is safe and effective for symptomatic chronic internal carotid artery occlusion. It has the potential to improve cerebral blood flow and reduce clinical symptoms.

Alkaline Phosphatase and Parathyroid Hormone Levels: International Variation and Associations With Clinical Outcomes in the DOPPS.

Introduction: Secondary hyperparathyroidism (SHPT) increases the risk of fractures and cardiovascular (CV) disease in patients on hemodialysis (HD). The relationship between parathyroid hormone (PTH) and outcomes has been inconsistent, possibly due to variable bone responsiveness to PTH. The KDIGO guideline suggests monitoring total alkaline phosphatase (ALP), but the role of ALP versus PTH in the management of mineral and bone disorder (MBD) is not clear. Methods: The analysis included 28,888 patients on HD in 9 countries in Dialysis Outcomes and Practice Patterns Study (DOPPS) phase 3 to 7 (2005-2021). The primary exposures of interest were normalized ALP and PTH, which are raw values divided by facility upper normal limit, measured at study enrollment. Cox models were used to estimate hazard ratios of all-cause or CV mortality and any or hip fracture adjusted for potential confounders. Linear mixed models, adjusted for potential confounders, were employed to investigate the relationship between normalized ALP levels and patient characteristics. Results: Normalized PTH showed a J-shaped association with all-cause or CV mortality, and a weak linear association with fracture. In contrast, normalized ALP showed a strong association with all outcomes. Factors associated with higher ALP levels after controlling for PTH included Black race, longer dialysis vintage, diabetes mellitus, hypocalcemia, hypophosphatemia, elevated C-reactive protein (CRP), and the use of cinacalcet. Conclusion: Total ALP is a more robust exposure of adverse outcomes than PTH in patients on HD. PTH responsiveness is affected by race, primary renal disease, comorbidities, and mineral metabolism and therapy. Our results indicate that it may be useful to evaluate target organ response, rather than PTH alone when considering the consequences of (SHPT).

A study of triathletes' race strategies in different competition environments.

What is known, sports performance is impacted by a variety of factors. While most people understand the importance of training, proper nutrition, and adequate rest, not as many recognize the impact of environmental factors on athletic performance. This paper investigates the race strategies of Chinese triathletes in different competition environments, with a focus on the performance of professional triathletes during the Olympic Distance Triathlon held in China between 2015 and 2021. Data from 984 athletes who competed in 26 races were analyzed to evaluate the sensitivity of the three splits of swimming, cycling, and running to overall triathlon performance under different temperature (low, normal, and high), altitude (low, normal, and high), and waters (sea, river, and still waters) conditions. Results show that the effects of the three split times on overall time vary across different environments. Cycling has the greatest impact on overall performance when the temperature is suitable (at low temperature, at normal temperature) and the altitude is suitable (at low altitude, at normal altitude). While running has the greatest impact in high-temperature and high-altitude environments. For female athletes, in river waters, swimming has a greater effect on overall performance than cycling, but less than running. These findings provide practical suggestions for athletes, coaches, and competition organizers to optimize training and race strategies based on specific environmental conditions.

Using kin discrimination to construct synthetic microbial communities of Bacillus subtilis strains impacts the growth of black soldier fly larvae.

Using synthetic microbial communities to promote host growth is an effective approach. However, the construction of such communities lacks theoretical guidance. Kin discrimination is an effective means by which strains can recognize themselves from non-self, and construct competitive microbial communities to produce more secondary metabolites. However, the construction of cooperative communities benefits from the widespread use of beneficial microorganisms. We used kin discrimination to construct synthetic communities (SCs) comprising 13 Bacillus subtilis strains from the surface and gut of black soldier fly (BSF) larvae. We assessed larval growth promotion in a pigeon manure system and found that the synthetic community comprising 4 strains (SC 4) had the most profound effect. Genomic analyses of these 4 strains revealed that their complementary functional genes underpinned the robust functionality of the cooperative synthetic community, highlighting the importance of strain diversity. After analyzing the bacterial composition of BSF larvae and the pigeon manure substrate, we observed that SC 4 altered the bacterial abundance in both the larval gut and pigeon manure. This also influenced microbial metabolic functions and co-occurrence network complexity. Kin discrimination facilitates the rapid construction of synthetic communities. The positive effects of SC 4 on larval weight gain resulted from the functional redundancy and complementarity among the strains. Furthermore, SC 4 may enhance larval growth by inducing shifts in the bacterial composition of the larval gut and pigeon manure. This elucidated how the SC promoted larval growth by regulating bacterial composition and provided theoretical guidance for the construction of SCs.

IRON MAN interacts with Cu-DEFICIENCY INDUCED TRANSCRIPTION FACTOR 1 to maintain copper homeostasis.

Copper (Cu) is essential for plant growth and development. IRON MAN (IMA) is a family of small peptides that can bind both iron (Fe) and Cu ions. It was reported that IMAs mediate Fe homeostasis in Arabidopsis thaliana. However, it remains unclear whether IMAs are involved in Cu homeostasis. The transcript abundance of IMA genes decreased in response to Cu deficiency. The combined disruption of all IMA genes caused enhanced tolerance to Cu deficiency and resulted in an increase in the transcript abundance of Cu uptake genes, whereas the overexpression of IMA1 or IMA3 led to the opposite results. Protein interaction assays indicated that IMAs interact with Cu-DEFICIENCY INDUCED TRANSCRIPTION FACTOR1 (CITF1), which is a positive regulator of the Cu uptake genes. Further studies showed that IMAs not only interfere with the DNA binding of CITF1 but also repress the transcriptional activation activity of CITF1, hence resulting in downregulation of the Cu uptake genes. Genetic analyses indicated that IMAs modulate Cu homeostasis in a CITF1-dependent manner. Our findings indicate that IMAs inhibit the functions of CITF1 in regulating Cu deficiency responses, thereby providing a conceptual framework for comprehending the regulation of Cu homeostasis.

Sintilimab Plus Chemotherapy for Unresectable Gastric or Gastroesophageal Junction Cancer: The ORIENT-16 Randomized Clinical Trial.

Importance: Gastric and gastroesophageal junction cancers are diagnosed in more than 1 million people worldwide annually, and few effective treatments are available. Sintilimab, a recombinant human IgG4 monoclonal antibody that binds to programmed cell death 1 (PD-1), in combination with chemotherapy, has demonstrated promising efficacy. Objective: To compare overall survival of patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction cancers who were treated with sintilimab with chemotherapy vs placebo with chemotherapy. Also compared were a subset of patients with a PD ligand 1 (PD-L1) combined positive score (CPS) of 5 or more (range, 1-100). Design, Setting, and Participants: Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 62 hospitals in China that enrolled 650 patients with unresectable locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma between January 3, 2019, and August 5, 2020. Final follow-up occurred on June 20, 2021. Interventions: Patients were randomized 1:1 to either sintilimab (n = 327) or placebo (n = 323) combined with capecitabine and oxaliplatin (the XELOX regimen) every 3 weeks for a maximum of 6 cycles. Maintenance therapy with sintilimab or placebo plus capecitabine continued for up to 2 years. Main Outcomes and Measures: The primary end point was overall survival time from randomization. Results: Of the 650 patients (mean age, 59 years; 483 [74.3%] men), 327 were randomized to sintilimab plus chemotherapy and 323 to placebo plus chemotherapy. Among the randomized patients, 397 (61.1%) had tumors with a PD-L1 CPS of 5 or more; 563 (86.6%) discontinued study treatment and 388 (59.7%) died; 1 patient (<0.1%) was lost to follow-up. Among all randomized patients, sintilimab improved overall survival compared with placebo (median, 15.2 vs 12.3 months; stratified hazard ratio [HR], 0.77 [95% CI, 0.63-0.94]; P = .009). Among patients with a CPS of 5 or more, sintilimab improved overall survival compared with placebo (median, 18.4 vs 12.9 months; HR, 0.66 [95% CI, 0.50-0.86]; P = .002). The most common grade 3 or higher treatment-related adverse events were decreased platelet count (sintilimab, 24.7% vs placebo, 21.3%), decreased neutrophil count (sintilimab, 20.1% vs placebo, 18.8%), and anemia (sintilimab, 12.5% vs placebo, 8.8%). Conclusions and Relevance: Among patients with unresectable locally advanced or metastatic gastric and gastroesophageal junction adenocarcinoma treated with first-line chemotherapy, sintilimab significantly improved overall survival for all patients and for patients with a CPS of 5 or more compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03745170.

Pruritus in Hemodialysis Patients: Longitudinal Associations With Clinical and Patient-Reported Outcomes.

RATIONALE & OBJECTIVE: Cross-sectional studies have reported an association of chronic kidney disease-associated pruritus (CKD-aP) with adverse clinical events and patient-reported outcomes (PROs). We studied the longitudinal associations between changes in CKD-aP and clinical outcomes among patients receiving maintenance hemodialysis. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: 7,976 hemodialysis recipients across 21 countries in phases 4-6 (2009-2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS) who had 2 CKD-aP assessments approximately 12 months apart. EXPOSURES: Exposure status was based on the assessment of pruritis initially and again approximately 1 year later. Four groups were identified, including those with moderate or more severe pruritis only at the initial assessment (resolved), only at the second assessment (incident), at neither assessment (absent), or at both assessments (persistent). OUTCOMES: Laboratory values and PROs ascertained at the initial assessment of pruritis and 1 year later. ANALYTICAL APPROACH: Linear mixed model to investigate changes in laboratory values and PROs over the 1-year study period across the 4 exposure groups. RESULTS: 51% of patients had moderate to severe CKD-aP symptoms at either assessment (22% at both). The prevalences of depression, restless sleep, and feeling drained increased over the study period (+13%,+10%, and+14%, respectively) among patients with incident pruritus and decreased (-5%, -8%, and -12%, respectively) among patients with resolved pruritus. Minimal changes in PROs over time were observed for the absent and persistent groups. Changes over time in laboratory values (phosphorus, Kt/V) were not detected for either of these groups. Compared with patients with absent CKD-aP, the adjusted HRs for patients with persistent CKD-aP were 1.29 (95% CI, 1.09-1.53) for all-cause mortality, 1.17 (1.07-1.28) for all-cause hospitalization, and 1.48 (1.26-1.74) for cardiovascular events. LIMITATIONS: No interim evaluation of CKD-aP symptoms between the 2 assessments; potential selection bias from patients who died or were otherwise lost to follow-up before the second assessment. CONCLUSIONS: CKD-aP symptoms are chronic, and these findings highlight the potential value of repeated assessment of this symptom using standardized approaches. Future research should systematically investigate potential causes of CKD-aP and options for its effective treatment. PLAIN-LANGUAGE SUMMARY: Previous research has studied itching and its consequences in hemodialysis recipients only at a single time point. We surveyed 7,976 patients receiving maintenance hemodialysis to assess itching over a period of 1 year. We found that, among those experiencing itching at the initial assessment, more than half had persistent symptoms 1 year later. Those in whom itching developed during follow-up were more likely to experience depression, poor sleep, long recovery times after dialysis, and feeling faint or drained. These patients also rated their quality of life as poorer than those who did not experience itching. These findings emphasize the potential value of clinical detection of itching and the pursuit of effective treatments for patients receiving dialysis experiencing these symptoms.

Clinical Outcomes in Patients on Hemodialysis with Congestive Heart Failure.

Introduction: Congestive heart failure (CHF) is one of the common complications in patients with end-stage kidney disease. In the general population, CHF increases the risk of the death. However, there is no well-designed relevant study in the Chinese hemodialysis (HD) population addressing the risks associated with CHF. The aim of this study was to explore the impact of CHF on clinical outcomes in HD patients. Methods: Data from a prospective cohort study, the China Dialysis Outcomes and Practice Patterns Study (DOPPS) 5 (2012-2015), were analyzed. Demographic data, comorbidities, lab data, and death records were extracted. CHF was defined by the diagnosis records upon study inclusion. Our primary outcome was all-cause and cardiovascular (CV) mortality; secondary outcomes were all-cause and cause-specific hospitalization risk. Associations between CHF and outcomes were evaluated using Cox regression models. Stepwise multivariate logistic regression was used to identify the related risk factors, and subgroup analyses were carried out. Results: Of 1,411 patients without missing CHF history information, 24.1% (340) had CHF diagnosis at enrollment. The overall mortality rates were 21.8% versus 12.0% (p < 0.001) in patients with and without CHF during follow-up, respectively. CHF was associated with higher all-cause mortality (adjusted HR: 1.72, 95% confidence interval [CI]: 1.17-2.53, p = 0.006), and the association with CV death was of similar magnitude (HR: 1.60, 95% CI: 0.91-2.81, p = 0.105). CHF patients had more episodes of hospitalization due to heart failure (HR: 2.93, 95% CI: 1.49-5.76, p < 0.01). However, compared with patients without CHF, the all-cause hospitalization risk was not much higher in CHF patients (HR: 1.09, 95% CI: 0.90-1.33, p = 0.39). Subgroup analysis found that the effect of CHF on all-cause mortality was stronger for male patients, patients with residual renal function, the elderly (≥60 years of age), patients with arteriovenous fistulae vascular accesses, nondiabetic patients, low-flux dialyzer users, and inadequately dialyzed patients (standardized Kt/V <2). Conclusion: In HD patients, CHF was found to be associated with a higher risk of all-cause mortality and cause-specific hospitalization risk. Further research is needed to identify opportunities to improve care for HD patients combined with CHF.

Morphological and radiological features of congenital muscular hypertrophy of the upper limb: experience from a tertiary institution.

Congenital muscular hypertrophy is a rare overgrowth disorder in the phosphatidylinositol-3-kinase related spectrum. In the past 3 years, ten patients with 11 limbs involved were treated in our centre. The aim of the study was to describe the clinical and radiological deformities of these patients. We documented the characteristic clinical morphological changes, such as hypertrophy, loss of wrist flexion, thumb hyperabduction, finger deviation and skin crease changes in the palm. Radiologically, the mean first metacarpal radial deviation angle of the affected side measured 55° (range 34 to 67) compared to the normal contralateral side 42° (range 32 to 53). The mean intermetacarpal space ratio was 1.2 (range 1.1 to 1.4) and the mean palm width ratio was 1.2 (range 1.1 to 1.3). In this study, we were able to further characterize the radiological and morphological changes of congenital muscular hypertrophy of upper limbs, which would be helpful for establishing the diagnosis and monitor treatment of this rare condition.Level of evidence: IV.

Willingness to use acupuncture: Knowledge, attitudes, beliefs, and practices among allergic rhinitis patients.

This study aims to assess knowledge, attitudes, beliefs, and practices (KABP) among China mainland allergic rhinitis (AR) participants regarding their willingness to use acupuncture. Little is known about the understanding, attitudes, beliefs and practices of people with AR in China. A questionnaire was designed and administered to AR participants in mainland China to gather information about KABP regarding acupuncture use. A total of 324 valid questionnaires were collected from 30 provinces on the Chinese mainland. We recorded basic information and data about AR. The questionnaire designed according to KABP theory and with excellent reliability (Cronbach α coefficient: 0.725) and validity (KMO: 0.819). Knowledge: Fifty-five percent (179) of respondents reported knowing about acupuncture. The majority (172) knew that acupuncture was used for AR; 119 had received acupuncture for AR, and about 66% were aware of acupuncture. Attitudes and beliefs: Seventy percent of patients were willing to recommend acupuncture for AR to family and friends. Practice: Approximately 75% of respondents were willing to undergo acupuncture if they knew it was effective for AR. Approximately 25% of the respondents answered "Do it a few times and see how it works," "Do several treatments depending on how much they can afford," or "It is up to the doctor to decide". Correlation analysis: Those who identified with traditional Chinese medicine showed a robust willingness to recommend acupuncture for treating other diseases to family and friends (R = 0.718, P < .01) and a robust willingness to recommend acupuncture for AR to their families and friends (R = 0.564, P < .01). Acupuncture for AR has shown excellent awareness, recommendation and acceptance in mainland China. Efficacy, affordability, and trust in doctors were the 3 key factors that led respondents to choose acupuncture for their AR. Identification with traditional Chinese medicine culture significantly influenced attitudes, leading to AR recommendations and acceptance of acupuncture.

Active Vitamin D Use and Fractures in Hemodialysis Patients: Results from the International DOPPS.

Active vitamin D is commonly used to control secondary hyperparathyroidism in dialysis patients, but it is unknown whether active vitamin D directly improves bone strength, independently of its ability to suppress parathyroid hormone (PTH). We analyzed the association between the prescription of active vitamin D and incidence of any fracture and hip fracture in 41,677 in-center hemodialysis patients from 21 countries in phases 3 to 6 (2005 to 2018) of the Dialysis Outcomes and Practice Patterns Study (DOPPS). We used Cox regression, adjusted for PTH and other potential confounders, and used a per-protocol approach to censor patients at treatment switch during follow-up. We also used a facility preference approach to minimize confounding by indication. Overall, 55% of patients were prescribed active vitamin D at study enrollment. Event rates (per patient-year) were 0.024 for any fracture and 0.010 for hip fracture. The adjusted hazard ratio (95% confidence interval) comparing patients prescribed versus not prescribed active vitamin D was 1.02 (0.90 to 1.17) for any fracture and 1.00 (0.81 to 1.23) for hip fracture. In the facility preference approach, there was no difference in fracture rate between facilities with higher versus lower active vitamin D prescriptions. Thus, our results do not suggest a PTH-independent benefit of active vitamin D in fracture prevention and support the current KDIGO guideline suggesting the use of active vitamin D only in subjects with elevated or rising PTH. Further research is needed to determine the role of active vitamin D beyond PTH control. © 2023 American Society for Bone and Mineral Research (ASBMR).

TGF-ß1/SMAD3 Regulates Programmed Cell Death 5 That Suppresses Cardiac Fibrosis Post-Myocardial Infarction by Inhibiting HDAC3.

BACKGROUND: Progressive cardiac fibrosis leads to ventricular wall stiffness, cardiac dysfunction, and eventually heart failure, but the underlying mechanism remains unexplored. PDCD5 (programmed cell death 5) ubiquitously expresses in tissues, including the heart; however, the role of PDCD5 in cardiac fibrosis is largely unknown. Therefore, this study aims at exploring the possible role and underlying mechanisms of PDCD5 in the pathogenesis of cardiac fibrosis. METHODS AND RESULTS: PDCD5 levels were found to be elevated in the serum obtained from patients with cardiac fibrosis, in fibrotic mice heart tissues after myocardial infarction, and in cardiac fibroblasts stimulated by Ang II (angiotensin II)- or TGF-ß1 (transforming growth factor-ß1). Overexpression of PDCD5 in cardiac fibroblasts or treatment with PDCD5 protein reduced the expression of profibrogenic proteins in response to TGF-ß1 stimulation, while knockdown of PDCD5 increased fibrotic responses. It has been demonstrated that SMAD3, a protein that is also known as mothers against decapentaplegic homolog 3, directly upregulated PDCD5 during cardiac fibrosis. Subsequently, the increased PDCD5 promoted HDAC3 (histone deacetylase 3) ubiquitination, thus, inhibiting HDAC3 to reduce fibrotic responses. Fibroblast-specific knock-in of PDCD5 in mice ameliorated cardiac fibrosis after myocardial infarction and enhanced cardiac function, and these protective effects were eliminated by AAV9-mediated HDAC3 overexpression. CONCLUSIONS: The findings of this study demonstrated that PDCD5 is upregulated by SMAD3 during cardiac fibrosis, which subsequently ameliorated progressive fibrosis and cardiac dysfunction through HDAC3 inhibition. Thus, this study suggests that PDCD5 functions as a negative feedback factor on fibrotic signaling pathways and might serve as a potential therapeutic target to suppress the progression of fibrotic responses.

A New Predictive Nomogram for the Risk of Delayed Incision Healing After Open Posterior Lumbar Surgery: A Retrospective Study.

STUDY DESIGN: This was a primary research study. OBJECTIVE: A risk nomogram was established and externally validated by exploring the related risk factors for delayed incision healing in patients undergoing open posterior lumbar surgery. SUMMARY OF BACKGROUND DATA: The use of a nomogram model to predict prognosis in patients with delayed incision healing is an evolving field given the complex presentation of patients with this condition. PATIENTS AND METHODS: This study reviewed 954 patients with data collected from January 2017 to December 2021 who were randomized into a training set and a validation set (7:3). We built a prediction model based on a training set of 616 patients. The "least absolute shrinkage and selection operator" regression model was applied to screen out the optimal prediction features, and binary logistic regression was used to develop a prediction model. The discrimination, calibration, and clinical applicability of the prediction model were assessed by using the area under the curve, C -index, calibration curve, and decision curve analysis. RESULTS: Postoperative delayed incision healing occurred in 214 (24.4%) patients. The least absolute shrinkage and selection operator regression model showed that smoking, white blood cell count, infection, diabetes, and obesity were involved in delayed incision healing ( P ≠ 0). A binary logistic regression model confirmed that smoking [odds ratio (OR) = 3.854, 95% CI: 1.578~9.674, P = 0.003], infection (OR = 119.524, 95% CI: 59.430~263.921, P < 0.001), diabetes (OR = 3.935, 95% CI: 1.628~9.703, P = 0.003), and obesity (OR = 9.906, 95% CI: 4.435~23.266, P < 0.001) were predictors of delayed incision healing, and a nomogram model was established. The area under the curve was 0.917 (95% CI: 0.876-0.959). The calibration curve showed good consistency. Decision curve analysis showed that when the risk threshold of delayed incision healing was >5%, the use of this nomogram was more clinically valuable. CONCLUSIONS: Smoking, infection, diabetes, and obesity are risk factors for delayed incision healing. The nomogram model could be used to predict the risk of delayed incision healing and could provide a reference for early clinical intervention.

CMTM3 deficiency induces cardiac hypertrophy by regulating MAPK/ERK signaling.

OBJECTIVES: Cardiac hypertrophy is the heart's compensatory response stimulated by various pathophysiological factors. However, prolonged cardiac hypertrophy poses a significant risk of progression to heart failure, lethal arrhythmias, and even sudden cardiac death. For this reason, it is crucial to effectively prevent the occurrence and development of cardiac hypertrophy. CMTM is a superfamily of human chemotaxis, which is involved in immune response and tumorigenesis. CMTM3 expressed widely in tissues, including the heart, but its cardiac function remains unclear. This research aims to explore the effect and mechanism of CMTM3 in the development of cardiac hypertrophy. METHODS AND RESULTS: We generated a Cmtm3 knockout mouse model (Cmtm3-/-) as the loss-of-function approach. CMTM3 deficiency induced cardiac hypertrophy and further exacerbated hypertrophy and cardiac dysfunction stimulated by Angiotensin Ⅱ infusion. In Ang Ⅱ-infusion stimulated hypertrophic hearts and phenylephrine-induced hypertrophic neonatal cardiomyocytes, CMTM3 expression significantly increased. However, adenovirus-mediated overexpression of CMTM3 inhibited the hypertrophy of rat neonatal cardiomyocytes induced by PE stimulation. In terms of mechanism, RNA-seq data revealed that Cmtm3 knockout-induced cardiac hypertrophy was related to MAPK/ERK activation. In vitro, CMTM3 overexpression significantly inhibited the increased phosphorylation of p38 and ERK induced by PE stimulation. CONCLUSIONS: CMTM3 deficiency induces cardiac hypertrophy and aggravates hypertrophy and impaired cardiac function stimulated by angiotensin Ⅱ infusion. The expression of CMTM3 increases during cardiac hypertrophy, and the increased CMTM3 can inhibit further hypertrophy of cardiomyocytes by inhibiting MAPK signaling. Thus, CMTM3 plays a negative regulatory effect in the occurrence and development of cardiac hypertrophy.

Triplication and tetraplication of the thumb: a modification of the Rotterdam classification.

We proposed a modification of the Rotterdam classification for thumb triplication and tetraplication. Twenty-one patients were included (24 cases of thumb triplication and four cases of tetraplication). These were analysed and classified according to a modification of the Rotterdam classification involving three steps; from the radial to ulnar side, we first identified each thumb on radiographs and gross appearance to divide into triplication or tetraplication. Second, we define the levels of duplication and established the nomenclature. Third, the aberrant features and their location were assigned for each thumb, again from radial to ulnar side. A surgical algorithm was also proposed. This modified classification may be helpful for characterizing the rare conditions of thumb triplication and tetraplication for use in patient and management and communication between surgeons.Level of evidence: III.

Emergence of OXA-484-Producing Klebsiella variicola in China.

Purpose: The frequent and inappropriate use of antibiotics has caused a dramatic rise in the number, species, and degree of multi-drug resistant bacteria, making them more prevalent and difficult to treat. In this context, the aim of the present study was to characterize the OXA-484-producing strains isolated from a perianal swab of a patient by using whole-genome analysis. Patients and Methods: In this study, carbapenemase-producing Klebsiella variicola was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), average nucleotide identity (ANI) and PCR. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting were utilized to characterize the plasmid profiles of K. variicola 4717. In particular, WGS was performed to obtain genomic information on this clinical isolate, and assemble all the plasmids of the bla OXA-484-harboring strain. Results: The antimicrobial susceptibility pattern of K. variicola 4717 revealed that it was resistant to a range of antibiotics, including aztreonam, imipenem, meropenem, ceftriaxone, cefotaxime, ceftazidime, levofloxacin, ciprofloxacin, piperacillin-tazobactam, methylene-sulfamer oxazole, amoxicillin-clavulanic acid, cefepime, and tigecycline. Its susceptibility to chloromycin was intermediate, while it was still susceptible to amikacin, gentamicin, fosfomycin, and polymyxin B. The presence of two companion plasmids, p4717_1 and p4717_2, together with a plasmid carrying the bla OXA-484 gene was observed. An in-depth investigation of p4717-OXA-484 uncovered that it is an IncX3-type plasmid and shares a similar segment encoded by IS26. Given the similar genetic background, it was conceivable that bla OXA-484 could have developed from bla OXA-181 through a series of mutations. Conclusion: Herein, we described the first genome sequence of K. variicola strain harbouring the class D ß-actamase bla OXA-484 in an Inc-X3-type plasmid. Our work also uncovered the genetic characterization of K. variicola 4717 and the importance of initiating antimicrobial detection promptly.

Emergence and clonal dissemination of KPC-3-producing Pseudomonas aeruginosa in China with an IncP-2 megaplasmid.

BACKGROUND: Despite the global prevalence of Klebsiella pneumoniae Carbapenemase (KPC)-type class A ß-lactamases, occurrences of KPC-3-producing isolates in China remain infrequent. This study aims to explore the emergence, antibiotic resistance profiles, and plasmid characteristics of blaKPC-3-carrying Pseudomonas aeruginosa. METHODS: Species identification was performed by MALDI-TOF-MS, and antimicrobial resistance genes (ARGs) were identified by polymerase chain reaction (PCR). The characteristics of the target strain were detected by whole-genome sequencing (WGS) and antimicrobial susceptibility testing (AST). Plasmids were analyzed by S1-nuclease pulsed-field gel electrophoresis(S1-PFGE), Southern blotting and transconjugation experiment. RESULTS: Five P. aeruginosa strains carrying blaKPC-3 were isolated from two Chinese patients without a history of travelling to endemic areas. All strains belonged to the novel sequence type ST1076. The blaKPC-3 was carried on a 395-kb IncP-2 megaplasmid with a conserved structure (IS6100-ISKpn27-blaKPC-3-ISKpn6-korC-klcA), and this genetic sequence was identical to many plasmid-encoded KPC of Pseudomonas species. By further analyzing the genetic context, it was supposed that the original of blaKPC-3 in our work was a series of mutation of blaKPC-2. CONCLUSIONS: The emergence of a multidrug resistance IncP-2 megaplasmid and clonal transmission of blaKPC-3-producing P. aeruginosa in China underlined the crucial need for continuous monitoring of blaKPC-3 for prevention and control of its further dissemination in China.