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Inflammatory pain hypersensitivity results partly from hyperexcitability of nociceptive (damage-sensing) dorsal root ganglion (DRG) neurons innervating inflamed tissue. However, most of the evidence for this is derived from experiments using acute inflammatory states. Herein, we used several approaches to examine the impact of chronic or persistent inflammation on the excitability of nociceptive DRG neurons and on their expression of I(h) and the underlying hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which regulate neuronal excitability. Using in vivo intracellular recordings of somatic action potentials from L4/L5 DRG neurons in normal rats and rats with hindlimb inflammation induced by complete Freund's adjuvant (CFA), we demonstrate increased excitability of C- but not Aδ-nociceptors, 5 to 7 days after CFA. This included an afterdischarge response to noxious pinch, which may contribute to inflammatory mechanohyperalgesia, and increased incidence of spontaneous activity (SA) and decreased electrical thresholds, which are likely to contribute to spontaneous pain and nociceptor sensitization, respectively. We also show, using voltage clamp in vivo, immunohistochemistry and behavioral assays that (1) the inflammation-induced nociceptor hyperexcitability is associated, in C- but not Aδ-nociceptors, with increases in the mean I(h) amplitude/density and in the proportion of I(h) expressing neurons, (2) increased proportion of small DRG neurons (mainly IB4-negative) expressing HCN2 but not HCN1 or HCN3 channel protein, (3) increased HCN2- immunoreactivity in the spinal dorsal horn, and (4) attenuation of inflammatory mechanoallodynia with the selective I(h) antagonist, ZD7288. Taken together, the findings suggest that C- but not Aδ-nociceptors sustain chronic inflammatory pain and that I(h)/HCN2 channels contribute to inflammation-induced C-nociceptor hyperexcitability. [ABSTRACT FROM AUTHOR]

Stanford type B aortic dissection involving the left subclavian artery (LSA) poses significant clinical challenges. The Castor single-branch stent graft and in situ fenestration are commonly used techniques, but the better endovascular treatment remains debated. This study evaluates the clinical effects of the Castor single-branched stent graft versus in situ fenestration in treating Stanford type B aortic dissection involving the LSA. We selected 75 patients with Stanford type B aortic dissection involving the LSA, admitted to the Second Affiliated Hospital of Nanchang University from January 2018 to May 2022. All patients underwent thoracic endovascular aortic repair; 34 received the Castor single-branched stent graft, while 41 underwent in situ fenestration. Clinical efficacy and perioperative complications were compared. The technical success rate of the Castor single-branch stent graft was significantly higher than that of in situ fenestration (97.06% vs 80.49%, P = .04). The Castor group exhibited significantly better outcomes in operative time (136.45 ± 25.53 min vs 157.08 ± 18.14 min), LSA blood flow recovery time (6.8 ± 2.3 min vs 20.1 ± 9.8 min), blood loss (29.03 ± 9.78 mL vs 35.69 ± 10.77 mL), contrast medium usage (288.71 ± 72.70 mL vs 352.78 ± 81.02 mL), and immediate postoperative endoleaks (1/34 vs 7/41) (P < .05). Stroke incidence (1/34 vs 2/41) and perioperative mortality (0/34 vs 1/41) were similar (P > .05). Hospital stays were comparable (15.71 ± 6.04 days vs 14.22 ± 5.01 days, P = .28). However, the cost of medical supplies (154,168.62 ± 28,288.44 CNY vs 119,589.72 ± 34,199.67 CNY) and total hospital expenses (192,665.88 ± 40,027.99 CNY vs 153,920.47 ± 42,670.87 CNY) were significantly higher in the Castor group (P < .05). The median follow-up time was 9 months (1-60 months). Follow-up showed similar 30-day postoperative mortality (1/41 vs 0/34, P = 1.00), stent patency (33/34 vs 39/41, P = .67), and stent migration rates (0/34 vs 1/41, P = 1.00). However, the endoleak rate was significantly higher in the in situ fenestration group (11/41 vs 1/34, P = .01). Both the Castor single-branch stent graft and the in situ fenestration technique effectively protect and reconstruct the LSA in Stanford type B aortic dissection, with the Castor single-branch stent graft showing higher technical success and fewer complications, indicating better clinical potential., Competing Interests: The authors have no conflict of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Several studies have reported that antioxidants exert both preventive and inhibitory effects against tumors. However, their causal effects on small-cell lung cancer (SCLC) remain controversial. Herein, we explored the causal effects of 6 antioxidants on SCLC by combining a genome-wide association study database and the Mendelian randomization (MR) approach. We obtained antioxidant genetic variance data for 6 exposure factors: carotene, vitamin A (retinol), selenium, zinc, vitamin C, and vitamin E, from the genome-wide association study database. The instrumental variables for exposure factors and SCLC outcomes were integrated by screening instrumental variables and merging data. Two-sample MR was used to analyze the causal relationship between exposure and outcomes. Finally, we examined the heterogeneity and horizontal pleiotropy of the MR analysis by performing multiple sensitivity analyses. We found a causal relationship between carotene and SCLC using two-sample MR analysis and sensitivity analysis (P = .02; odds ratio = 0.73; 95% confidence interval: 0.55-0.95). In contrast, there was no causal relationship between other examined antioxidants and SCLC. We found that diet-derived circulating antioxidants could afford protection against SCLC, and carotene is the causal protective factor against SCLC., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sex-specific differences in coronary phenotypes in response to stress have not been elucidated. This study investigated the sex-specific differences in the coronary computed tomography angiography-assessed coronary response to mental stress., Methods: This retrospective study included patients with coronary artery disease and without cancer who underwent resting 18 F-fluorodexoyglucose positron emission tomography/computed tomography and coronary computed tomography angiography within 3 months. 18 F-flourodeoxyglucose resting amygdalar uptake, an imaging biomarker of stress-related neural activity, coronary inflammation (fat attenuation index), and high-risk plaque characteristics were assessed by coronary computed tomography angiography. Their correlation and prognostic values were assessed according to sex., Results: A total of 364 participants (27.7% women and 72.3% men) were enrolled. Among those with heightened stress-related neural activity, women were more likely to have a higher fat attenuation index (43.0% versus 24.0%; P =0.004), while men had a higher frequency of high-risk plaques (53.7% versus 39.3%; P =0.036). High amygdalar 18 F-flourodeoxyglucose uptake (B-coefficient [SE], 3.62 [0.21]; P <0.001) was selected as the strongest predictor of fat attenuation index in a fully adjusted linear regression model in women, and the first-order interaction term consisting of sex and stress-related neural activity was significant ( P <0.001). Those with enhanced imaging biomarkers of stress-related neural activity showed increased risk of major adverse cardiovascular event both in women (24.5% versus 5.1%; adjusted hazard ratio, 3.62 [95% CI, 1.14-17.14]; P =0.039) and men (17.2% versus 6.9%; adjusted hazard ratio, 2.72 [95% CI, 1.10-6.69]; P =0.030)., Conclusions: Imaging-assessed stress-related neural activity carried prognostic values irrespective of sex; however, a sex-specific mechanism linking psychological stress to coronary plaque phenotypes existed in the current hypothesis-generating study., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05545618., Competing Interests: Disclosures None.

The normative regimens recommendations for treating metastatic uveal melanoma (mUM) are absent in the US. Recently, a phase III randomized clinical trial revealed that tebentafusp yielded a conspicuously longer overall survival than the control group. Based on the prominent efficacy, this study aimed to assess whether tebentafusp is cost-effective compared to the control group in patients with untreated mUM. A three-state partitioned survival model was developed to assess the costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER) from the perspective of US payers. Scenario analyses and sensitivity analyses were conducted to explore the conclusion uncertainty. Compared with control group, tebentafusp therapy yielded an additional 0.47 QALYs (1.19 vs. 0.72 QALYs) and an incremental cost of $444 280 ($633 822 vs. $189 542). The resultant ICER of $953 230/QALY far outweighed the willingness-to-pay threshold of $200 000/QALY. The ICER was always more than $750 000/QALY in all the univariable and probabilistic sensitivity analyses. Scenario analyses indicated that reducing the unit price of tebentafusp to $33.768/µg was associated with a favorable result of tebentafusp being cost-effective. For treatment-naive patients with mUM, the cost of tebentafusp therapy was not worth the improvement in survival benefits at the current price compared to the investigator's choice of therapy. The cost-effectiveness of tebentafusp could be promoted using value-based pricing., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: This study aimed to explore the effect of exercise and cold exposure on insulin sensitivity and the level of serum free fatty acids (FFA) in diet-induced obese rats., Methods: Sixty-four diet-induced obese rats were randomly assigned to eight groups: room temperature-sedentary, room temperature-exercise, acute cold exposure-sedentary, acute cold exposure-exercise, intermittent cold exposure-sedentary, intermittent cold exposure-exercise, sustained cold exposure-sedentary, and sustained cold exposure-exercise. After the interventions, the homeostatic model assessment for insulin resistance (HOMA-IR) values, the level of serum FFA, subcutaneous fat ratio (SFR) and visceral fat ratio, enzyme activities of adipose triglyceride lipase, and lipoprotein lipase (LPL) in inguinal adipose tissue, and protein expression of PGC1-α and p38 MAPK in skeletal muscle were investigated., Results: We found that exercise ( P = 0.0136) and cold exposure ( P < 0.0001) reduced HOMA-IR values independently. Exercise reduced serum FFA ( P = 0.0041), whereas cold exposure did not affect them. Moreover, the HOMA-IR values were positively correlated with the serum FFA levels ( r = 0.32, P = 0.01). SFR or visceral fat ratio was coordinately reduced by the interaction (for SFR, P = 0.0015) or opposing main effects between or of cold exposure and exercise, supporting the reduction of serum FFA. However, cold exposure or exercise increased the activity of adipose triglyceride lipase and LPL independently or interactively (for LPL, P = 0.0143), suggesting an increase in serum FFA. Finally, cold exposure and exercise enhanced protein expression of PGC1-α and p38 MAPK independently or interactively (for p38 MAPK, P = 0.0226), suggesting increased uptake and oxidation of serum FFA in muscle., Conclusions: These results suggest that the combination of exercise and cold exposure may result in more serum FFA utilization than production and thus lead to reduced serum FFA and increased insulin sensitivity., (Copyright © 2023 by the American College of Sports Medicine.)

Background: Doxorubicin is an effective chemotherapy drug for treating various types of cancer. However, lethal cardiotoxicity severely limits its clinical use. Recent evidence has indicated that aberrant activation of the cytosolic DNA-sensing cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-STING (stimulator of interferon genes) pathway plays a critical role in cardiovascular destruction. Here, we investigate the involvement of this mechanism in doxorubicin-induced cardiotoxicity (DIC)., Methods: Mice were treated with low-dose doxorubicin to induce chronic DIC. The role of the cGAS-STING pathway in DIC was evaluated in cGAS -deficiency (c GAS -/- ), Sting -deficiency ( Sting -/- ), and interferon regulatory factor 3 ( Irf3 )-deficiency ( Irf3 -/- ) mice. Endothelial cell (EC)-specific conditional Sting deficiency ( Sting flox/flox /Cdh5-Cre ERT ) mice were used to assess the importance of this pathway in ECs during DIC. We also examined the direct effects of the cGAS-STING pathway on nicotinamide adenine dinucleotide (NAD) homeostasis in vitro and in vivo., Results: In the chronic DIC model, we observed significant activation of the cGAS-STING pathway in cardiac ECs. Global cGAS , Sting , and Irf3 deficiency all markedly ameliorated DIC. EC-specific Sting deficiency significantly prevented DIC and endothelial dysfunction. Mechanistically, doxorubicin activated the cardiac EC cGAS-STING pathway and its target, IRF3, which directly induced CD38 expression. In cardiac ECs, the cGAS-STING pathway caused a reduction in NAD levels and subsequent mitochondrial dysfunction via the intracellular NAD glycohydrolase (NADase) activity of CD38. Furthermore, the cardiac EC cGAS-STING pathway also regulates NAD homeostasis and mitochondrial bioenergetics in cardiomyocytes through the ecto-NADase activity of CD38. We also demonstrated that pharmacological inhibition of TANK-binding kinase 1 or CD38 effectively ameliorated DIC without compromising the anticancer effects of doxorubicin., Conclusions: Our findings indicate a critical role of the cardiac EC cGAS-STING pathway in DIC. The cGAS-STING pathway may represent a novel therapeutic target for preventing DIC., Competing Interests: Disclosures None.

Rationale: Giant cell tumor of bone is a locally aggressive and rarely metastasizing neoplasm that typically affects the ends of long bones or the axial skeleton of young to middle-aged adults. As many as 69% to 100% of giant cell tumors harbor H3F3A gene mutations, while H3F3B gene mutations have rarely been reported., Patient Concerns: A 53-year-old male patient who underwent right distal femoral tumor resection., Diagnoses: Preoperative CT plain scan indicated giant cell tumor of bone with pathological fracture. Laboratory findings were as follows: serum calcium was 2.23 mmol/L (reference range: 2.1-2.55 mmol/L) and serum phosphorus was 1.35 mmol/L (reference range: 0.81-1.45 mmol/L)., Interventions: The histological morphology showed the typical features of a conventional GCT. The immunoprecipitation analysis results were as follows: H3.3G34W(-), H3.3G34R(-), H3.3G34V(-), and H3K36M(-). Sanger sequencing showed that the H3F3A and H3F3B gene mutations were wild type. The high-throughput gene sequencing results revealed the H3F3B gene mutations H3.3p.Gly35Trp and H3.3p.Val36Leu., Outcomes: The patient was stable with no recurrence in 12 months follow-up., Lessons: Giant cell tumor of bone with H3F3B gene mutations is extremely rare. In the pathological diagnosis of bone tumors, we need to analyze clinical presentation, imaging features, histology, immunophenotype, and cytogenetic/molecular alterations, in order to get a correct diagnosis., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Descending necrotizing mediastinitis is a serious complication of odontogenic infections. Incision and drainage of the maxillofacial infection with mediastinal drainage represent the principal management. However, chyle leakage after drainage in descending necrotizing mediastinitis is rare and has not been reported. Here the authors present a case of a 74-year-old man with chyle leakage after mediastinal drainage, which is successfully treated., Competing Interests: The authors report no conflicts of interest., (Copyright © 2022 by Mutaz B. Habal, MD.)

Background: The development of thoracic aortic dissection (TAD) is closely related to extracellular matrix degradation and vascular smooth muscle cell (VSMC) transformation from contractile to synthetic type. LGMN (legumain) degrades extracellular matrix components directly or by activating downstream signals. The role of LGMN in VSMC differentiation and the occurrence of TAD remains elusive., Methods: Microarray datasets concerning vascular dissection or aneurysm were downloaded from the Gene Expression Omnibus database to screen differentially expressed genes. Four-week-old male Lgmn knockout mice (Lgmn -/- ), macrophage-specific Lgmn knockout mice (Lgmn F/F ;LysM Cre ), and RR-11a-treated C57BL/6 mice were given BAPN (β-aminopropionitrile monofumarate; 1 g/kg/d) in drinking water for 4 weeks for TAD modeling. RNA sequencing analysis was performed to recapitulate transcriptome profile changes. Cell interaction was examined in macrophage and VSMC coculture system. The reciprocity of macrophage-derived LGMN with integrin αvβ3 in VSMCs was tested by coimmunoprecipitation assay and colocalization analyses., Results: Microarray datasets from the Gene Expression Omnibus database indicated upregulated LGMN in aorta from patients with TAD and mice with angiotensin II-induced AAA. Elevated LGMN was evidenced in aorta and sera from patients with TAD and mice with BAPN-induced TAD. BAPN-induced TAD progression was significantly ameliorated in Lgmn-deficient or inhibited mice. Macrophage-specific deletion of Lgmn alleviated BAPN-induced extracellular matrix degradation. Unbiased profiler polymerase chain reaction array and Gene Ontology analysis displayed that LGMN regulated VSMC phenotype transformation. Macrophage-specific deletion of Lgmn ameliorated VSMC phenotypic switch in BAPN-treated mice. Macrophage-derived LGMN inhibited VSMC differentiation in vitro as assessed by macrophages and the VSMC coculture system. Macrophage-derived LGMN bound to integrin αvβ3 in VSMCs and blocked integrin αvβ3, thereby attenuating Rho GTPase activation, downregulating VSMC differentiation markers and eventually exacerbating TAD development. ROCK (Rho kinase) inhibitor Y-27632 reversed the protective role of LGMN depletion in vascular dissection., Conclusions: LGMN signaling may be a novel target for the prevention and treatment of TAD.

Objectives: The US Food and Drug Administration (FDA) approved nivolumab-ipilimumab and pembrolizumab-axitinib as first-line treatments for metastatic, clear-cell, renal cell carcinoma (mRCC) based on results from CheckMate 214 and KEYNOTE-426. Our objective was to compare the adjusted, lifetime cost-effectiveness between nivolumab-ipilimumab, pembrolizumab-axitinib, and sunitinib for patients with mRCC., Materials and Methods: A 3-state Markov model was developed comparing nivolumab-ipilimumab and pembrolizumab-axitinib to each other and sunitinib, over a 20-year lifetime horizon from a US medical center perspective. The clinical outcomes of nivolumab-ipilimumab and pembrolizumab-axitinib were compared using matching-adjusted indirect comparison. Costs of drug treatment, adverse events, and utilities associated with different health states and adverse events were determined using national sources and published literature. Our outcome was incremental cost-effectiveness ratio (ICER) using quality-adjusted life years (QALY). One-way and probabilistic sensitivity analyses were conducted., Results: Nivolumab-ipilimumab was the most cost-effective option in the base case analysis with an ICER of $34,190/QALY compared with sunitinib, while the pembrolizumab-axitinib ICER was dominated by nivolumab-ipilimumab and was not cost-effective (ICER=$12,630,828/QALY) compared with sunitinib. The mean total costs per patient for the nivolumab-ipilimumab and pembrolizumab-axitinib arms were $284,683 and $457,769, respectively, compared with sunitinib at $241,656. QALY was longer for nivolumab-ipilimumab (3.23 QALY) than for adjusted pembrolizumab-axitinib (1.99 QALY), which was longer than sunitinib's (1.98 QALY). These results were most sensitive to treatment cost in both groups, but plausible changes did not alter the conclusions., Conclusions: The base case scenario indicated that nivolumab-ipilimumab was the most cost-effective treatment option for mRCC compared with pembrolizumab-axitinib and sunitinib., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Mosaicism can be observed in karyotype analyses of amniotic fluid cells. Differentiating between true mosaicism and pseudomosaicism and determining mosaic proportions can help avoid misjudgments by doctors and effectively reduce mental and physical harm to pregnant women. However, the detection of mosaicism and mosaic proportions via karyotype analysis and fluorescence in situ hybridization (FISH) is extremely complex. We have developed a novel approach, "segmental duplication quantitative fluorescent PCR" (SD-QF-PCR), to detect mosaicism and mosaic proportions.In this study, twenty control samples and fourteen mosaic samples were tested by first-line karyotype analysis; by second-line karyotype analysis, SD-QF-PCR and FISH were used to reassess fetal sex chromosome mosaicism and mosaic proportions.Detection of the 20 control samples by second-line karyotype analysis via FISH and SD-QF-PCR showed normal and consistent results. Among the 14 mosaic samples, the numbers of samples showing true mosaicism and pseudomosaicism detected by the three methods were 6 and 8, respectively.Our study demonstrates that SD-QF-PCR can be used as a complementary method to traditional cytogenetic analysis of amniotic fluid mosaics and has clinical application value., Competing Interests: The authors report no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Progressive pseudorheumatoid dysplasia (PPD) is a rare disease that causes musculoskeletal deformities. There has been no detailed report on the outcome of PPD patients who undergo total hip arthroplasty (THA). The aim of this study was to investigate the clinical and radiological outcome of PPD patients undergoing THA after middle-term follow-up., Methods: This was a medical records review study. Patients with the diagnosis of PPD who underwent THA were enrolled. The PPD diagnosis was confirmed by genetic sequencing. Baseline clinical data were retrieved. The patients were followed for the Harris Hip Score, visual analogue score, range of hip motion, and postoperative complication. Life quality was evaluated with the Short Form 36. Plain x-ray films were used for radiographic evaluation., Results: Four cases were identified from the patient database in our institute. All the patients presented arthropathy of both hips and underwent 1-stage bilateral THA. All the patients had WISP3 mutation after genetic sequencing. The cases were followed at average 47.9 months (range, 18-93 months). Harris Hip Score increased from 39.67 ± 9.73 points preoperatively to 91.67 ± 4.32 points postoperatively (p < 0.05); Short Form 36 increased from 19.67 ± 1.53 points preoperatively to 71.33 ± 3.06 postoperatively (p < 0.05). The hip range of hip motion was significantly improved after operation. X-ray films showed no obvious radiolucent lines or aseptic loosening at the latest follow-up., Conclusions: This study indicated that THA was effective to treat the PPD patients complicated with hip arthropathy with satisfactory clinical and radiological outcome after mid-term follow-up., Competing Interests: Bin Feng is currently receiving a grant from the National Natural Science Foundation in China (grant number 81871740). The authors declare that they have no other conflict of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Postpartum hemorrhage (PPH) is a major obstetric complication, and the real-time measurement of blood loss is important in the management and treatment of PPH. We designed a new two-set liquid collection bag (TSLCB) for measuring postpartum blood loss in vaginal delivery. The aim of this study was to evaluate the effectiveness of the TSLCB in separating the blood from the amniotic fluid during vaginal delivery and in determining the accuracy of the measured postpartum blood loss., Methods: A prospective, randomized, case control study was conducted in the Women's Hospital, Zhejiang University School of Medicine, from March 2018 to April 2018. Sixty single pregnant women with spontaneous labor at 37-41 weeks without maternal complications were randomly divided into the experimental and control groups. The TSLCB was used to evaluate separately the amount of blood and amniotic fluid. For the control group, visual estimation and traditional plastic blood-collecting consumables were used to estimate the amount of postpartum blood loss. The measured blood loss between the two groups was compared, and the association of the measured blood loss with various clinical lab indices and vital signs was investigated., Results: The TSLCB (the experimental group) improved the detection of the measured blood loss compared with visual estimation and the traditional method (the control group) (P < .05). In the experimental group, correlation analysis showed that the measured blood loss at delivery and within 24 h of delivery was significantly associated with the decreased hemoglobin level, red blood cell count, and hematocrit level of patients (r = -0.574, -0.455, -0.437; r = 0.-595, -0.368, -0.374; P < .05). In the control group, only the measured blood loss within 24 h of delivery was associated with the decreased hemoglobin level (r = -0.395, P < .05). No blood transfusion and plasma expanders were required in the treatment of PPH for both groups., Conclusions: The TSLCB can be used to accurately measure the postpartum blood loss in vaginal delivery by medical personnel., Competing Interests: This study was supported by the Medical and Health Science and Technology Plan Project of Zhejiang Province (Grant No. 2017PY005 and Grant No. 2019PY040). The Department has no conflict of interests related to the trial., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Mechanical ventilation is a powerful tool for the treatment of various critical emergencies. However, surviving critically ill patients often have poor psychological and physiological outcomes. Prevention of various complications and adverse outcomes of mechanical ventilation is a priority and a challenge in the intensive care unit (ICU). Early intervention is the key to reducing complications and improving outcomes of mechanical ventilation in the ICU. As an auxiliary rehabilitation treatment, the improved sitting Wuqinxi intervention has recognized unique advantages. It has achieved beneficial therapeutic effects during early intervention in clinical practice. It can reduce the incidence of delirium, shorten the duration of mechanical ventilation, and prevent complications and secondary damages related to mechanical ventilation in the ICU. Therefore, the purpose of this study will be to explore the effect of improved sitting Wuqinxi on the clinical outcomes of mechanically ventilated ICU patients., Methods: This prospective, multicenter, randomized, single-blinded, parallel controlled clinical study will involve 160 patients who met the inclusion criteria. The patients will be randomly divided into the experimental and control groups. Both groups will be given standardized comprehensive western medicine treatment (including mechanical ventilation) and routine care in the ICU. Management of the experimental group will also include "improved sitting Wuqinxi," with the treatment objective to observe the effect of the improved sitting Wuqinxi intervention on the clinical outcomes in mechanically ventilated ICU patients. The outcome measures will include the incidence of complications, duration of mechanical ventilation, length of ICU stay, and cost of hospitalization. In addition, the effect of the improved sitting Wuqinxi intervention on the safety indexes of mechanically ventilated ICU patients will be assessed and the clinical effects of the improved sitting Wuqinxi intervention will be comprehensively evaluated., Discussion: The purpose of this study will be to evaluate the effect of the improved sitting Wuqinxi intervention on the incidence of complications, duration of mechanical ventilation, length of ICU stay, cost of hospitalization, and safety indicators. If successful, it will provide a reliable, simple, and feasible auxiliary rehabilitation treatment scheme for mechanically ventilated ICU patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Previous research has demonstrated that some false recognitions are accompanied by retrieval of contexts in which the corresponding semantic associates were presented during the study phase. What kind of neural processes support context retrieval in false recognition? Using functional MRI (fMRI), we tested the hypothesis that context retrieval in false recognition might be supported by brain areas in the core recollection network which also support context retrieval in true recognition. During the study, lists of semantically associated words were presented together with scene pictures that served as contexts. During test, participants judged whether the presented word was old or new. If old, they judged which scene picture was its context and rated memory strength for the context. The results revealed that several regions in the core recollection network, including the bilateral hippocampus, left angular gyrus, and left anterior cingulate cortex, showed greater activations for true recognitions with strong context memory than those with weak context memory. More importantly, these same regions also showed greater activations for false recognitions with strong context memory than those with weak context memory. These findings helped account for why some false recognitions are vivid and accompanied by retrieval of context.

Background: Rapid on-site evaluation (ROSE) is a kind of rapid evaluation of specimen satisfaction, preliminary diagnosis and priority strategy, the diagnostic accuracy of ROSE in the field of pulmonary intervention shows wide variation. The aim of the study was to further clarify the accuracy and diagnostic efficacy of ROSE in interventional pulmonology., Methods: This review summarizes and meta-analyzes studies of ROSE in interventional pulmonology, the ROSE diagnoses would be compared with the final pathologic diagnoses. The following electronic databases have been searched: PubMed, Cochrane Library, Embase, Web of science, CNKI, and WANFANG DATA. The methodologic quality of studies has been assessed using the Quality of Diagnostic Studies (QUADAS-2) instrument. This review is conducted using standard methods for systematic reviews of diagnostic accuracy studies. STATA SE 12.0 is used for data synthesis and analysis., Results: This review evaluates the accuracy and diagnostic efficacy of ROSE in interventional pulmonology, and the process factors that may influence the ROSE diagnosis are analyzed, such as Smear method, profession of smear technician, staining method, Profession of stain technician, Profession of reading slides, invasive procedure, Anesthesia method and etc. CONCLUSION:: This review will stimulate proper evaluation of ROSE and provide assistance for clinical practice.

Background: The use of antibiotics in the acute exacerbations of chronic obstructive pulmonary disease (COPD) remains controversial. Serum C-reactive protein (CRP), a sensitive biomarker for systemic inflammation and tissue damage, is a good indicator of lower respiratory tract bacterial infection. However, due to the small sample size of the existing studies, the clinical value of CRP in guiding the use of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) antibiotics is insufficient. The aim of this study was to evaluate the value of CRP-guided treatment strategies for AECOPD patients., Methods: This review summarizes and meta-analyses randomized controlled trials (RCTs) of CRP guiding antibiotic prescribing for COPD exacerbations. RCTs compare either usual-care or the GOLD strategy have been included. The following electronic databases have been searched: PubMed, Cochrane Library, Embase, CNKI, CBM, VIP, and Wanfang Data. The methodologic quality of RCTs has been assessed using the Cochrane risk assessment tool. All trials included are analyzed according to the criteria of the Cochrane Handbook. Review Manager 5.3, R-3.5.1 software, and GRADE pro GDT web solution are used for data synthesis and analysis., Results: This review evaluates the effects of CRP testing on the antibiotic use, CCQ, EQ-5D utility scores and adverse events in patients with COPD exacerbations., Conclusion: This review provides clear evidence that CRP testing can reduce the use of antibiotics in patients with AECOPD without causing harm.

Objective: The authors conducted a cost-effectiveness analysis incorporating recent phase III clinical trial (IMpassion130) data to evaluate the cost-effectiveness of atezolizumab in combination with nab-paclitaxel (AnP) against nab-paclitaxel alone as the first-line treatment for advanced triple-negative breast cancer in developed and developing countries., Materials and Methods: A decision-analytic Markov model was developed using IMpassion130 data to evaluate the cost-effectiveness of AnP over a lifetime from the US health care payer and Chinese health care system perspective. Model inputs were derived from IMpassion130 and published literature. The primary outcomes of the model were quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Uncertainty was addressed using univariate and probabilistic sensitivity analyses., Results: For the intention-to-treat (ITT) population, the projected mean outcome was better with AnP (1.41 QALYs) than with nab-paclitaxel alone (0.99 QALYs). Similar results were obtained for the programmed death ligand 1 (PD-L1)-positive population, with the obtained mean outcomes of 1.66 and 0.88 QALYs, respectively. For the Unites States, the ICER values comparing AnP with nab-paclitaxel were US$331,996.89 and US$229,359.88 per QALY gained for the ITT and PD-L1-positive populations, respectively. For China, the ICER values were US$106,339.26 and US$72,971.88 per QALY gained for the ITT and PD-L1-positive populations, respectively. The univariate sensitivity analysis indicated that the price of atezolizumab was the most influential factor in our study. AnP had 0% cost-effectiveness at the willingness-to-pay thresholds of US$150,000/QALY in the United States and US$29,383/QALY in China., Conclusion: AnP is not a cost-effective choice as the first-line treatment for advanced triple-negative breast cancer in the United States and China.

The study aims to evaluate the clinical outcomes and surgery survivorship for over 10 years following patellar resurfacing or nonresurfacing in total knee arthroplasty (TKA) in a cohort of Chinese patients.From 1998 to 2003, 355 patients underwent primary TKA in our institute. The survivorship of TKA between the patellar resurfacing and nonresurfacing groups and the clinical outcome of Hospital for Special Surgery knee score, Western Ontario and McMaster Universities index score, patellar score, patellar related complications, and radiological results were studied at latest follow-up.There was no statistically significant difference for the Hospital for Special Surgery score, Western Ontario and McMaster Universities score, and the patellar score between the 2 groups after an average 12.4-year follow-up. Nonresurfacing group had higher anterior knee pain than the resurfacing group (13.2% vs 5.6%). The patients with rheumatoid arthritis had a 2.9-fold higher rate of patellar-related complications than did the patients with osteoarthritis. The 10-year survival rate was not significantly different between the 2 groups both for revision surgery (P = .505) and for patellar-related complication (P = .194).There was no significant difference in the long-term clinical outcome and survivorship between patellar resurfacing and nonresurfacing. Patellar nonresurfacing could be advisable during primary TKA for osteoarthritis patients. Selective patellar resurfacing for RA patients could achieve lower patellar-related complications.

Background: A low first-pass success rate of radial artery cannulation was obtained when using the conventional palpation technique (C-PT) or conventional ultrasound-guided techniques, we; therefore, evaluate the effect of a modified long-axis in-plane ultrasound technique (M-LAINUT) in guiding radial artery cannulation in adults., Methods: We conducted a prospective, randomized and controlled clinical trial of 288 patients undergoing radial artery cannulation. Patients were randomized 1:1 to M-LAINUT or C-PT group at Fujian Medical University Union Hospital between 2017 and 2018. Radial artery cannulation was performed by 3 anesthesiologists with different experience. The outcome was the first and total radial artery cannulation success rates, the number of attempts and the cannulation time, and incidence of complications., Results: Two hundred eighty-five patients were statistically analyzed. The success rate of first attempt was 91.6% in the M-LAINUT group (n = 143) and 57.7% in the C-PT group (n = 142; P < .001) (odds ratio, 7.9; 95% confidence interval, 4.0-15.7). The total success rate (≤5 minutes and ≤3 attempts) in the M-LAINUT group was 97.9%, compared to 84.5% in the palpation group (P < .001) (odds ratio, 8.5; 95% confidence interval, 2.5-29.2). The total cannulation time was shorter and the number of attempts was fewer in the M-LAINUT group than that in the C-PT group (P < .05). The incidence of hematoma in the C-PT group was 19.7%, which was significantly higher than the 2.8% in the M-LAINUT group (P < .001)., Conclusions: Modified long-axis in-plane ultrasound-guided radial artery cannulation can increase the first and total radial artery cannulation success rates, reduce the number of attempts, and shorten the total cannulation time in adults.

Background: To evaluate the safety and efficacy of dexmedetomidine in patients undergoing total knee and hip arthroplasty for postoperative pain control., Methods: An updated systematic review and meta-analysis of randomized controlled trials (RCTs) identified in systematic searches of MEDLINE, EMBASE, Google Scholar, the Cochrane Database and the Chinese SinoMed Database., Results: Fourteen RCTs with a total of 1220 patients were included. Overall, dexmedetomidine therapy was associated with significantly decreased pain scores 24 hours after surgery (WMD, -0.36; 95% CI, -0.49 to -0.22; I = 90.0%, P < .001) compared with scores in the control group after total hip arthroplasty (THA) and total knee arthroplasty (TKA). Furthermore, the rate of postoperative delirium was also markedly decreased with dexmedetomidine therapy (RR, 0.38; 95% CI, 0.24 to 0.59; I = 0.0%, P < .001). Moreover, compared with the control group, dexmedetomidine treatment was associated with a decreased risk of postoperative nausea and vomiting in patients undergoing TKA (RR, 0.34; 95% CI, 0.15 to 0.79; I = 0.0%, P = .012), and there was a similar risk of hypotension (RR, 1.03; 95% CI, 0.72 to 1.49; I = 24.4%, P = .87) regardless of whether patients underwent TKA or THA. However, the rate of bradycardia was significantly increased with dexmedetomidine treatment in those undergoing TKA (RR, 6.11; 95% CI, 2.35 to 15.91; I = 0.0%, P < .001)., Conclusions: Dexmedetomidine therapy seems to be an effective treatment for pain control and postoperative delirium in patients undergoing TKA/THA. However, the incidence of bradycardia is markedly increased in patients undergoing TKA. Hence, much larger prospective clinical studies are warranted to confirm these findings.

Study Design: Retrospective comparative study., Objective: This study aimed to compare the clinical effects and imaging features of polymethyl methacrylate (PMMA) bone cement with and without mineralized collagen (MC) in percutaneous kyphoplasty (PKP) for osteoporotic vertebral compression fractures (OVCFs)., Summary of Background Data: PKP with PMMA is widely performed for OVCF. However, numerous complications have also been reported about the PMMA bone cement. Moreover, PMMA bone cement with and without MC have not been compared with respect to their postoperative efficacy and long-term follow-up., Methods: From July 2016 to July 2017, 105 OVCF patients were randomly divided into two groups based on their PKP treatment: MC-PMMA group and PMMA group. Clinical operation, cement leakage, Oswestry Disability Index, visual analog scale, height of the fractured vertebrae, Cobb angle, refracture of the adjacent vertebra, recompression, and computed tomography values of the injured vertebra were compared between the two groups postoperatively and after 1-year follow-up., Results: Clinical operation showed no differences between the two groups. Visual analog scale scores, Oswestry Disability Index scores, and Cobb angles showed statistically significant differences between the two groups after 1-year follow-up. The height of the vertebral body showed significant difference at 3 days postoperatively and preoperatively in each group and significant difference after 1 year between the two groups. The rate of refracture and leakage of the MC-PMMA group was lower than that of the PMMA group. The computed tomography value of the MC-PMMA group was obviously higher than that of the PMMA group after 1-year follow-up., Conclusion: MC-modified PMMA did not change the beneficial properties of PMMA. This new bone cement has better biocompatibility, can form a stable structure in the vertebral body, and improve the prognosis of patients by reducing pain and reoperation., Level of Evidence: 3.

Rationale: Targeting inflammation has been shown to provide clinical benefit in the field of cardiovascular diseases. Although manipulating regulatory T-cell function is an important goal of immunotherapy, the molecules that mediate their suppressive activity remain largely unknown. IL (interleukin)-35, an immunosuppressive cytokine mainly produced by regulatory T cells, is a novel member of the IL-12 family and is composed of an EBI3 (Epstein-Barr virus-induced gene 3) subunit and a p35 subunit. However, the role of IL-35 in infarct healing remains elusive., Objective: This study aimed to determine whether IL-35 signaling is involved in healing and cardiac remodeling after myocardial infarction (MI) and, if so, to elucidate the underlying molecular mechanisms., Methods and Results: IL-35 subunits (EBI3 and p35), which are mainly expressed in regulatory T cells, were upregulated in mice after MI. After IL-35 inhibition, mice showed impaired infarct healing and aggravated cardiac remodeling, as demonstrated by a significant increase in mortality because of cardiac rupture, decreased wall thickness, and worse cardiac function compared with wild-type MI mice. IL-35 inhibition also led to decreased expression of α-SMA (α-smooth muscle actin) and collagen I/III in the hearts of mice after MI. Pharmacological inhibition of IL-35 suppressed the accumulation of Ly6C low and major histocompatibility complex II low /C-C motif chemokine receptor type 2 - (MHC II low CCR2 - ) macrophages in infarcted hearts. IL-35 activated transcription of CX3CR1 (C-X3-C motif chemokine receptor 1) and TGF (transforming growth factor) β1 in macrophages by inducing GP130 signaling, via IL12Rβ2 and phosphorylation of STAT1 (signal transducer and activator of transcription family) and STAT4 and subsequently promoted Ly6C low macrophage survival and extracellular matrix deposition. Moreover, compared with control MI mice, IL-35-treated MI mice showed increased expression of α-SMA and collagen within scars, correlating with decreased left ventricular rupture rates., Conclusions: IL-35 reduces cardiac rupture, improves wound healing, and attenuates cardiac remodeling after MI by promoting reparative CX3CR1 + Ly6C low macrophage survival.

Background: Excessive accumulation of reactive oxygen species (ROS), catalyzed by the NADPH oxidases (NOX), is involved in the pathogenesis of ischemia-reperfusion (IR) injury. The underlying epigenetic mechanism remains elusive., Methods: We evaluated the potential role of megakaryocytic leukemia 1 (MKL1), as a bridge linking epigenetic activation of NOX to ROS production and cardiac ischemia-reperfusion injury., Results: Following IR injury, MKL1-deficient (knockout) mice exhibited smaller myocardial infarction along with improved heart function compared with wild-type littermates. Similarly, pharmaceutical inhibition of MKL1 with CCG-1423 also attenuated myocardial infarction and improved heart function in mice. Amelioration of IR injury as a result of MKL1 deletion or inhibition was accompanied by reduced ROS in vivo and in vitro. In response to IR, MKL1 levels were specifically elevated in macrophages, but not in cardiomyocytes, in the heart. Of note, macrophage-specific deletion (MϕcKO), instead of cardiomyocyte-restricted ablation (CMcKO), of MKL1 in mice led to similar improvements of infarct size, heart function, and myocardial ROS generation. Reporter assay and chromatin immunoprecipitation assay revealed that MKL1 directly bound to the promoters of NOX genes to activate NOX transcription. Mechanistically, MKL1 recruited the histone acetyltransferase MOF (male absent on the first) to modify the chromatin structure surrounding the NOX promoters. Knockdown of MOF in macrophages blocked hypoxia/reoxygenation-induced NOX transactivation and ROS accumulation. Of importance, pharmaceutical inhibition of MOF with MG149 significantly downregulated NOX1/NOX4 expression, dampened ROS production, and normalized myocardial function in mice exposed to IR injury. Finally, administration of a specific NOX1/4 inhibitor GKT137831 dampened ROS generation and rescued heart function after IR in mice., Conclusions: Our data delineate an MKL1-MOF-NOX axis in macrophages that contributes to IR injury, and as such we have provided novel therapeutic targets in the treatment of ischemic heart disease.

Rationale: Progressive pseudorheumatoid dysplasia (PPD) is a rare autosomal recessive inherited disease that causes severe systemic joint deformity and articular dysfunction in young patients., Patient Concerns: Ilizarov technique treatment in PPD patients has never been reported before., Diagnoses: A 17-year-old male patient presented with a 10-year history of polyarthritis and 4-year history of progressive hip and knee pain and stiffness. Genetic testing for the WISP3 gene was done and showed compound heterozygous mutations: NM&#95;198239.1 (WISP3):c.1064&#95;1065dupGT (p.Gln356ValfsTer33) and NM&#95;198239.1 (WISP3):c.643+2T > C., Interventions: Taking his young age into consideration, the Ilizarov external fixation technique was adopted for the treatment of the deformity in knees., Outcomes: One year after the operation, the improvement of joint deformity was satisfactory., Lessons: The Ilizarov technique is economical and less invasive, and most importantly, it can delay the possible arthroplasty. It gives young PPD patients with arthropathy an alternative treatment.

Plasma brain natriuretic peptide (BNP), a diagnostic marker of cardiovascular diseases, has been previously linked to cerebrovascular diseases. Our goal was to determine whether plasma BNP level is helpful for identifying high-risk individuals who are likely to present with the 3 main subtypes of cerebral small vessel diseases (CSVDs), namely, white matter lesions, lacunar infarcts, and cerebral microbleeds, on magnetic resonance imaging (MRI) in patients with hypertension.Three hundred forty-six consecutive hypertensive patients presenting at our cardiology or neurology clinic were investigated. Plasma BNP level was measured by chemiluminescent microparticle immunoassay. The presence of CSVD was assessed by 1.5-T brain MRI. Multivariate linear regression was used to determine whether individual or combined MRI-defined CSVD subtypes were associated with BNP level, after adjustment for several covariates.The mean age of patients was 69.1 ± 9.8 years, and 44.2% were female. The highest quartile BNP group was positively associated with advanced age, female sex, clinically manifesting cardiac diseases, and ischemic CSVD (white matter lesions and lacunar infarcts) and no association with cerebral microbleeds. According to multivariate linear regression, white matter lesions [β = 0.722; 95% confidence interval (95% CI), 0.624-0.819] and lacunar infarcts (β = 0.635; 95% CI, 0.508-0.762) were independently associated with BNP level, even after controlling for vascular risk factors and clinically manifesting cardiac diseases. Combined white matter lesions and lacunar infarcts were more strongly associated with BNP level than each subtype alone. With the cutoff value of 106.4 pg/mL, BNP level had a sensitivity, a specificity, and an area under the curve of 95.2%, 64.9%, and 0.799, respectively, for white matter lesions, whereas the values were 143.0 pg/mL, 81.6%, 73.5%, and 0.848, respectively, for lacunar infarcts.Plasma BNP level, which is independently correlated with individual or combined white matter lesions and lacunar infarcts, is a useful molecular marker for identifying ischemic CSVD in patients with hypertension.

Peripheral neuropathic pain associated with partial nerve injury is believed to be driven partly by aberrant spontaneous activity (SA) in both injured and uninjured dorsal root ganglion (DRG) neurons. The underlying ionic mechanisms are not fully understood, but hyperpolarization-activated cyclic nucleotide-gated (HCN) channels which underlie the excitatory Ih current have been implicated in SA generation in axotomized A-fiber neurons after L5-spinal nerve ligation/axotomy (SNL/SNA). Here, using a modified model of SNA (mSNA) which involves, in addition to L5-SNA, loose ligation of the L4-spinal nerve with neuroinflammation-inducing chromic gut, we examined whether HCN channels also contribute to SA in the adjacent L4-neurons. Intracellular recordings from L4-DRG neurons in control rats, and L4-DRG neurons in mSNA rats were made using in vivo voltage- and current-clamp techniques. Compared with control, L4 C-nociceptors and Aβ-low-threshold mechanoreceptors (LTMs) exhibited SA 7 days after mSNA. This was accompanied, in C-nociceptors, by a significant increase in Ih amplitude, the percentage of Ih-expressing neurons, and Ih activation rate. Hyperpolarization-activated cyclic nucleotide-gated channel blockade with ZD7288 (10 mg/kg, intravenously) suppressed SA in C-nociceptors, but not Aβ-LTMs, and caused in C-nociceptors, membrane hyperpolarization and a decrease in Ih activation rate. Furthermore, intraplantar injection of ZD7288 (100 μM) was found to be as effective as gabapentin (positive control) in attenuating cold hypersensitivity in mSNA rats. These findings suggest that HCN channels contribute to nerve injury-induced SA in L4 C-nociceptors, but not Aβ-LTMs, and that ZD7288 exerts its analgesic effects by altering Ih activation properties and/or causing membrane hyperpolarization in L4 C-nociceptors.

Rationale: Hemophilic arthropathy (HA) is a crucial morbidity and a major cause of joint pain and disability in patients with hemophilia A. Surgical methods, such as total joint arthroplasty, are of vital importance for end-stage HA treatment, but the feasibility and effects of multi-joint replacement surgery remain debatable., Patient Concerns: A 24-year-old patient with advanced HA presented multiple joint pain. Physical examination revealed joint tenderness, swelling, and limited activity. Radiographs revealed bilateral knee joints and left elbow joint damage with joint space narrowing, articular facet erosion, and bone deformation., Diagnoses: The patient was diagnosed with hemophilic arthropathy with multi-joint lesions., Interventions: The key points of this case include arthropathy in multiple joints and the management of simultaneous total multi-joint arthroplasty. We performed bilateral total knee arthroplasty and total left elbow arthroplasty simultaneously after adequate preparations. Special attention was paid to factor VIII infusion, hemorrhage control, and other safety precautions perioperatively., Outcomes: After the surgery, no complications, such as infection or aseptic loosening, occurred, and the joints functioned well at follow-up., Lessons: The surgical outcome and safety of multi-joint replacement for HA are attested. Simultaneous multi-joint arthroplasty can ameliorate the quality of life for patients with hemophilia A.

Background: Intrafascial nerve-sparing prostatectomy has been currently applied based on the updated anatomic understanding of periprostatic cavernous nerves, in order to provide patients better postoperative recovery of continence and potency. The aim of our study is to perform a pooled analysis of available literatures regarding the functional outcomes following intrafascial nerve-sparing technique., Methods: The authors performed database searches of articles published till October 2017 on PubMed using following keywords across the "title" and "abstract" field of the records: intrafascial, veil, curtain dissection, high anterior release, incremental nerve sparing, and radical prostatectomy. Fulfilled papers were screened and data were extracted independently by 3 reviewers. Main outcome was the postoperative continence and potency rate stratified by follow-up durations. Both 1-arm and comparative meta-analyses were performed and meta-regression models were conducted to evaluate the confounding factors., Results: Using the electronic search strategy, a total of 71 records were retrieved and 20 studies were finally included, of which 6 were surgical series and 14 were controlled studies. Our 1-arm meta-analysis summarized the pooled continence rates after intrafascial prostatectomy were 59.4%, 76.2%, 89.9%, and 92.2% at postoperative follow-up of 1, 3, 6, and 12 months, respectively. Regardless of the variance in potency definition, the pooled potency rates after intrafascial prostatectomy were 42.2%, 54.2%, and 72.2% at 3, 6, and 12 months, respectively. Comparative analysis showed that the intrafascial group offered better continence rates at 1, 3, and 6 months with an odds ratio (OR) of 2.38 (95% confidence interval [CI]: 1.73-3.26), 1.82 (95% CI: 1.18-2.82), and 2.19 (95% CI: 1.43-3.34) as compared with the interfascial group. Moreover, potency rate in the intrafascial group was higher at 12 months than in the interfascial group, with an OR of 2.44 (95% CI: 1.35-4.42)., Conclusion: Based on the limited evidence, our study demonstrated that intrafascial nerve-sparing prostatectomy could provide patients with earlier recovery of continence and better erectile function compared with conventional interfascial approach, but physiological mechanisms about this technique still need further study.

Dot-blot hybridization and high-resolution melting curve methods are used to detect G6PD gene mutations; however, the performance and throughput limitations of these methods hinder their use for screening large populations. For simple screening, we developed a novel approach called "Amplification Refractory Mutation System combined with Melting Curve Analysis (ARMS-MC)," which enables rapid and batch-based detection of the 6 most common G6PD mutations.In this method, we established 4 PCR reaction systems that can be used to detect the 6 most common G6PD mutations (c.95A>G, c.392G>T, c.871G>A, c.1024C>T, c.1376G>T, and c.1388G>A) in the Chinese population.The ARMS-MC method was evaluated with 174 cases of clinical G6PD-deficient samples, and the results were verified by direct sequencing at G6PD gene exons. The results showed that 170 samples had ≥1 of the 6 mutations, which accounted for 97.70% of all mutations. These results were consistent with the results of direct sequencing with 100% accuracy and specificity. Sequencing validation revealed other mutations in the 4 samples in which no mutation was detected by the ARMS-MC method.ARMS-MC provides a rapid, simple, inexpensive, and accurate screening method for detecting the most common G6PD mutations in Chinese people.

Recently, clinical application of 3D printed model was increasing. However, there was no systemic study for confirming the precision and reliability of 3D printed model. Some senior clinical doctors mistrusted its reliability in clinical application. The purpose of this study was to evaluate the precision and reliability of stereolithography appearance (SLA) 3D printed model.Some related parameters were selected to research the reliability of SLA 3D printed model. The computed tomography (CT) data of bone/prosthesis and model were collected and 3D reconstructed. Some anatomical parameters were measured and statistical analysis was performed; the intraclass correlation coefficient (ICC) was used to was used to evaluate the similarity between the model and real bone/prosthesis. the absolute difference (mm) and relative difference (%) were conducted. For prosthesis model, the 3-dimensional error was measured.There was no significant difference in the anatomical parameters except max height (MH) of long bone. All the ICCs were greater than 0.990. The maximum absolute and relative difference were 0.45 mm and 1.10%; The 3-dimensional error analysis showed that positive/minus distance were 0.273 mm/0.237 mm.The application of SLA 3D printed model in diagnosis and treatment process of complex orthopedic disease was reliable and precise.

MINI: Posterior hemivertebra resection with anterior structural reconstruction and short segmental fusion may be a reliable procedure for selected patients with scoliokyphosis due to a hemivertebra, providing good correction both on the coronal and sagittal planes, saving mobile segments with lower risk of implants failures., Study Design: Perspective study., Objectives: To evaluate indications and preliminary results of posterior hemivertebra resection with anterior structural reconstruction with titanium mesh cage and short segmental fusion., Summary of Background Data: There exist a lot of reports on posterior hemivertebra resection for the early surgical intervention of congenital scoliosis because of hemivertebra. However, a few reports describe the procedure of the anterior structural reconstruction after posterior hemivertebra resection., Methods: In this study, 18 selected children of mean age 5.4 years (range, 2-12 yrs) with scoliokyphosis because of hemivertebra were treated with posterior hemivertebra resection with anterior structural reconstruction and short segmental fusion. They were followed for an average of 37.1 (24-85) months. Radiograghs, operative reports, and patient charts were studied to evaluate the correction and complications., Results: Average fused segments were 1.67 (1-3). The segmental scoliosis was 40.1° before surgery, 4.1° postsurgery, and 5.7° at the latest the follow up. Moreover, the segmental kyphosis (difference to normal segmental alignment) was improved from 27.6° to 3.9°. The correction of the compensatory cranial and caudal curve was 74.7% and 82.4%. The trunk shift improved from 17.7 mm to 5.3 mm. No complications occurred until the latest follow up., Conclusion: Posterior hemivertebra resection with anterior structural reconstruction and short segmental fusion is a reliable procedure for selected patients with scoliokyphosis because of hemivertebra. A structural reconstruction is essential to the avoidance of overcorrection of the segmental scoliosis and resultant postoperative coronal imbalance with limited fused levels in some patients, increasing chances of short segmental fusion and saving mobile segments. As a fulcrum, anterior reconstruction with a titanium mesh cage could help to improve the correction of segmental kyphosis. Furthermore, the cage may help to stabilize the level of hemivertebra resection like a structural autograft, enhancing the postoperative stability and decreasing the stress of the pedicle and implants., Level of Evidence: 4.

Rationale: Arterial injuries during total knee arthroplasty (TKA) though rare may occur. Hemophilia may further challenge the management of such injury., Patient Concerns: A 48-year-old male patient with severe hemophilia type A and stiff knee arthropathy underwent bilateral TKAs. Left popliteal artery injury was detected at the end of the left TKA., Diagnoses: Urgent angiography confirmed the diagnosis of the left popliteal artery transection., Interventions: With clotting factor VIII replacement treatment, open repair was performed by end-to-end vascular bypass with the autograft of the large saphenous vein. No anticoagulant and antiplatelet treatment was administered postoperatively. Doses of the factor VIII were decreased step by step postoperatively., Outcomes: Left lower limb was reperfused 4 hours after the onset of the ischemia. The patient recovered uneventfully. Postoperative Doppler examination showed the left popliteal artery remained patent., Lessons: The hemophilia may endanger the patients to higher risk of arterial injury during TKA because of the severe deformity and fibrosis around knee joint. For the hemophilia patients, with rational coagulation factor replacement therapy, open repair with autograft was an effective revascularization procedure for artery injury.

Study Design: A case-control association study was performed to investigate the relationship between ladybird homeobox (LBX1) and adolescent idiopathic scoliosis (AIS) in northern Chinese Han population., Objective: To explore the prevalence and functional importance of LBX1 polymorphisms in patients with AIS within the northern Chinese Han population., Summary of Background Data: AIS is the most common subtype of idiopathic scoliosis. Genetic factors such as LBX1 polymorphisms have been recently proved to be associated with AIS in some populations. In this study we explored the prevalence and functional importance of the polymorphisms around LBX1 in patients with AIS within the northern Chinese Han population., Methods: Five tag single nucleotide polymorphisms (SNPs) around or in LBX1 were genotyped in 180 patients with AIS and 182 controls. And the luciferase assay was performed to explore the functional importance of the most significant SNPs., Results: We replicated that rs11190870, previously reported as the most significantly associated SNP, was enriched in our AIS cohort. In addition, we found that the T allele of rs1322331 was associated with a novel risk allele (odds ratio = 3.349, 95% confidence interval 1.742-6.436). In the following luciferase assay, the TT-type promoter showed significantly reduced transcription activity in vitro., Conclusion: Two SNPs around LBX1, rs11190870 and rs1322331 are associated with AIS in northern Chinese Han population. The T allele of rs1322331 is a novel risk allele. We hypothesize that rs1322331 might increase patients' susceptibility to AIS by reducing LBX1-AS1 transcription and thus upregulating the function of LBX1., Level of Evidence: 3.

Introduction: Because allogeneic blood transfusion carries a risk of serious complications, erythropoietin (EPO) has been used in patients scheduled for total hip or knee arthroplasty in an effort to reduce the need for allogeneic blood transfusion; however, its efficacy, cost-effectiveness, and safety are still controversial. The purpose of this review was to determine the hematopoiesis-promoting effect and potential complications, as well as the cost-effectiveness, of preoperative use of EPO in patients scheduled for total hip or knee arthroplasty., Methods: We searched MEDLINE, EMBASE, Cochrane, and ClinicalTrials.gov databases for relevant literature from 2000 to 2015. Risk of bias was assessed for all included studies and data were extracted and analyzed., Results: Preoperative use of EPO was associated with lower exposure to allogeneic blood transfusion (odds ratio = 0.41) and higher hemoglobin concentration after surgery (standardized mean difference = 0.86, P < 0.001). Complications were not generally reported, but there was no significant difference between the group with and without EPO based on given data. Cost-effectiveness was also summarized but was not conclusive., Conclusion: Preoperative administration of EPO reduces the requirement for allogeneic blood transfusion and increases hemoglobin level after surgery. The studies of cost-effectiveness were not conclusive. Further studies and guidelines specific to blood management in the perioperative stage of total knee and hip arthroplasty are expected., Competing Interests: The authors report no conflicts of interest.

The American Heart Association aims to improve cardiovascular health by encouraging the general population to meet 7 cardiovascular health behaviors and factors. The atherogenic index of plasma (AIP) is an important index. Our aim is to evaluate the relationship between ideal cardiovascular health and the atherogenic index of plasma (AIP) in middle-aged Chinese men.A cross-sectional study was performed. A total of 27,824 middle-aged Chinese men were enrolled. The association between ideal cardiovascular health behaviors and factors and AIP was determined. The 7 cardiovascular health metrics were scored as follows: 0, poor; 1, general; and 2, ideal. The cardiovascular health status was classified according to the total score, as follows: 0 to 4, inadequate; 5 to 9, average; and 10 to 14, optimum. Analyses assessed the prevalence of 7 cardiovascular health metrics, its association with AIP. Logistic regression models were used to calculate odds ratios (ORs), adjusting for age.All 7 cardiovascular health metrics were shown to correlate with AIP (all P values < 0.05), and the strongest correlation existed between body mass and AIP, followed by total cholesterol and AIP. The mean AIP level increased with the decrease in the score of each of the 7 cardiovascular health metrics (all P values < 0.05). The subjects with poor cardiovascular health status had a 4.982-fold increase in the high risk of developing atherosclerosis, whereas a 1-point increase in the cardiovascular health score resulted a 0.046 reduction in AIP and a 22.3% reduction in the high-risk of developing atherosclerosis (OR = 0.777, 95% CI: 0.768-0.787).The ideal cardiovascular health score correlated significantly with AIP, and a 1-point increase in the cardiovascular health score led to a 0.046 reduction in AIP and a 22.3% reduction in the high risk of developing atherosclerosis. These validated the value of ideal cardiovascular health behaviors and factors in the prediction of high risk of developing cardiovascular diseases. Ideal cardiovascular health metrics are of great realistic significance for the prevention and control of atherosclerosis and cardiovascular diseases., Competing Interests: The authors have no conflicts of interest to disclose.

Cryptococcus neoformans causes opportunistic infections in immunocompromised patients, with vertebral osteomyelitis being a very rare involvement.This study is to present a case of thoracolumbar scoliosis occurring in the setting of cryptococcal osteomyelitis.Pharmacological intervention with anticryptococcal medicine and medical management of immune hemolytic anemia were administered. After initial acute stabilization, she underwent spinal debridement and fusion on October 29, 2008. She eventually recovered fully from this episode with no subsequent mechanical instability or neurological deficits on subsequent clinic follow-ups.To the best of our knowledge, there have been no reports describing the onset of spinal cryptococcal osteomyelitis along with immune hemolytic anemia. We suggest a comprehensive algorithm for the diagnosis of vertebral cryptococcal osteomyelitis.

Study Design: A case of arytenoid dislocation after anterior cervical corpectomy and fusion (ACCF) is reported., Objective: To emphasize that arytenoid dislocation could be a possible cause of prolonged hoarseness in patients after ACCF., Summary of Background: Prolonged hoarseness is a common postoperative complication of cervical surgeries, especially in the anterior approach. Postoperative hoarseness is usually associated with paresis of the recurrent laryngeal nerve (RLN). However, other causes such as arytenoids dislocation, which is often misdiagnosed as RLN palsy, should not be ignored either., Methods: We reported one case of arytenoid dislocation after ACCF and reviewed the related literatures., Results: One patient treated with ACCF experienced prolonged postoperative hoarseness. Arytenoid dislocation was confirmed by laryngoscopy examination and three-dimensional computed tomography (CT) scan. To deal with the problem, a closed reduction of cricoarytenoid joint was performed under general anesthesia. Fortunately, the motion of vocal fold became nearly back to normal after surgery and the patient recovered uneventfully. He was satisfied with the clinical outcome at the final follow-up., Conclusion: Arytenoid dislocation should never be ignored in the differential diagnosis of prolonged postoperative hoarseness after ACCF. This situation can be confirmed by CT scan, vocal cord electromyography (EMG), fiberoptic laryngoscopy, or strobovideolaryngoscopy. Once the diagnosis is established, appropriate treatment should be considered immediately., Level of Evidence: 3.

Objective: Endothelin-1 is a potent vasoconstrictor derived from vascular endothelium. Elevated endothelin-1 levels are observed in a host of cardiovascular pathologies including cardiomyopathy. The epigenetic mechanism responsible for endothelin-1 induction in these pathological processes remains elusive., Approach and Results: We report here that induction of endothelin-1 expression in endothelial cells by angiotensin II (Ang II) was accompanied by the accumulation of histone H3K4 trimethylation, a preeminent histone modification for transcriptional activation, on the endothelin-1 promoter. In the meantime, Ang II stimulated the expression and the occupancy of Suv, Ez, and Trithorax domain 1 (SET1), a mammalian histone H3K4 trimethyltransferase, on the endothelin-1 promoter, both in vitro and in vivo. SET1 was recruited to the endothelin-1 promoter by activating protein 1 (c-Jun/c-Fos) and synergized with activating protein 1 to activate endothelin-1 transcription in response to Ang II treatment. Knockdown of SET1 in endothelial cells blocked Ang II-induced endothelin-1 synthesis and abrogated hypertrophy of cultured cardiomyocyte. Finally, endothelial-specific depletion of SET1 in mice attenuated Ang II-induced pathological hypertrophy and cardiac fibrosis., Conclusions: Our data suggest that SET1 epigenetically activates endothelin-1 transcription in endothelial cells, thereby contributing to Ang II-induced cardiac hypertrophy. As such, screening of small-molecule compound that inhibits SET1 activity will likely offer a new therapeutic solution to the treatment of cardiomyopathy., (© 2015 American Heart Association, Inc.)

Study Design: A retrospective study of 1162 consecutive patients who underwent spinal deformity surgical procedures at our spine center from January 2010 to December 2013., Objective: To develop and evaluate a protocol of intraoperative motor evoked potential (MEP) monitoring with the warning criteria we had established on the basis of our clinical experiences and the review of previous literature., Summary of Background Data: Though MEPs monitoring have become widely used in spinal deformity surgery, different alarm criteria and response protocol used in different studies compromised their comparability; Furthermore, high false-positive rate of MEP reported by previous studies has become an increasingly prominent problem that will limit its clinical use and development., Methods: The intraoperative monitoring data of 1162 consecutive patients who underwent spinal deformity surgical procedures at our spine center were retrospectively analyzed. Age, sex, diagnosis, preoperative neurological status, intraspinal anomalies, baseline MEP, and MEP change were collected. The protocol with the warning criteria we had established was used. The false-positive rate, false-negative rate, and positive predictive value were calculated., Results: Significant intraoperative changes were seen in the MEP data in 52 (4.4%) of all the cases. In 25 cases among which, significant MEP changes were synchronously and logically associated with high-risk surgical maneuver (pedicle screw insertion, osteotomy, correction, etc.). The false-positive rate of MEP monitoring was 0.26% (3/1140), whereas the sensitivity and specificity of MEP for detection of clinically significant intraoperative cord injury were 100% and 99.7%, respectively. The positive predictive value of a MEP alert in terms of a new postoperative neurological deficit was 83.3%., Conclusion: Our study indicates that the appropriate use of MEP monitoring based on our protocol is able to obtain satisfying sensitivity and specificity and thus provide important information for intraoperative decision making.

Study Design: Retrospective study., Objective: To evaluate the clinical outcomes of the hybrid technique of 1-stage posterior osteotomy with short segmental fusion and dual growing rod (GR) technique for severe rigid congenital scoliosis., Summary of Background Data: As some types of congenital scoliosis consist of long curve including sharp deformities producing enormous asymmetric growth at apex, they cannot be well corrected with osteotomy and short segmental fusion. GR technique may be the best option. However, enormous asymmetric growth potential due to the sharp deformities at the apex will increase risk of complications, especially implant failures., Methods: Seven patients (2 males, 5 females) undergoing this hybrid technique for severe rigid congenital scoliosis were retrospectively reviewed. The patients' charts were reviewed. The analysis included age at initial surgery and the latest follow-up, number and frequency of lengthening, and complications. Radiographical evaluation included measured changes in scoliosis Cobb angle, thoracic kyphosis, lumbar lordosis, trunk shift, length of T1-S1, and instrumentation., Results: The mean follow-up was 53.3 (30-77) months. The mean age at the initial surgery is 5.9 (2-10) years. The averaged lengthenings were of 5.3 per patient. The mean scoliosis improved from 81.4° to 40.1° after initial surgery and was 41.0° at the latest follow-up. The average T1-S1 length was of 1.23 cm per year. The space available for lung ratio increased from 0.86 to 0.96., Conclusion: Osteotomy with short fusion could help to improve the correction of the GR and eliminate the large asymmetric growth potential around the apex, with little influence to the length of the spine. Dual GR technique could maintain correction achieved at initial surgery while allowing spinal growth to continue. This hybrid technique may be an option for young patients who present sharp deformities with large asymmetric growth potential in a long congenital spinal deformity., Level of Evidence: 4.

Study Design: Retrospective review., Objective: To identify the incidence and characteristics of rib anomalies in patients with congenital scoliosis (CS) in a Chinese population., Summary of Background Data: Rib deformities and intraspinal anomalies often coexist in individuals with CS. Rib deformities may assist in diagnosing occult anomalies in these patients. The incidence of rib anomalies and the relationship between rib and vertebral abnormalities in Chinese patients with CS have not been reported., Methods: A total of 382 patients operated on at Peking Union Medical College Hospital during January 2010 to October 2012 were identified from a single institutional database. The demographic distribution, clinical and radiographical data were collected to investigate the incidence of rib anomalies, and the vertebral and intraspinal abnormalities associated with it., Results: A total of 192 patients (50.3%) were documented with rib anomalies including numerical variation (46.4%) and structural changes (72.4%). Missing ribs was the most commonly seen anomaly in these patients, accounting for 43.8% of the rib anomalies. Of the patients with rib anomalies, a slightly higher proportion of patients had simple anomalies, 106 (55.2%) versus 86 (44.8%). Rib changes were most common in patients with thoracic or thoracolumbar vertebral anomalies, and occurred most frequently on the concave side (65.5%) or in the lower thoracic spine (36.5%). The overall incidence rate of intraspinal anomalies was 40.1% (153/382), and these were most commonly seen in patients with thoracic vertebral anomalies or with upper and middle thoracic rib anomalies., Conclusion: The incidence of rib anomalies was 50.3% in surgical patients with CS. The rib anomalies vary with the location and type of vertebral anomalies. The incidence of intraspinal anomalies was significantly higher in patients with rib anomalies than in those without rib anomalies., Level of Evidence: 4.

Rationale: Endothelial dysfunction inflicted by inflammation is found in a host of cardiovascular pathologies. One hallmark event in this process is the aggregation and adhesion of leukocyte to the vessel wall mediated by the upregulation of adhesion molecules (CAM) in endothelial cells at the transcriptional level. The epigenetic modulator(s) of CAM transactivation and its underlying pathophysiological relevance remain poorly defined., Objective: Our goal was to determine the involvement of Brahma related gene 1 (Brg1) and Brahma (Brm) in CAM transactivation and its relevance in the pathogenesis of atherosclerosis., Methods and Results: In the present study, we report that proinflammatory stimuli augmented the expression of Brg1 and Brm in vitro in cultured endothelial cells and in vivo in arteries isolated from rodents. Overexpression of Brg1 and Brm promoted while knockdown of Brg1 and Brm abrogated transactivation of adhesion molecules and leukocyte adhesion induced by inflammatory signals. Brg1 and Brm interacted with and were recruited to the CAM promoters by nuclear factor κB/p65. Conversely, depletion of Brg1 and Brm disrupted the kinetics of p65 binding on CAM promoters and crippled CAM activation. Silencing of Brg1 and Brm also altered key epigenetic changes associated with CAM transactivation. Of intrigue, 17β-estradiol antagonized both the expression and activity of Brg1/Brm. Most importantly, endothelial-targeted elimination of Brg1/Brm conferred atheroprotective effects to Apoe(-/-) mice on a Western diet., Conclusions: Our data suggest that Brg1 and Brm integrate various proinflammatory cues into CAM transactivation and endothelial malfunction and, as such, may serve as potential therapeutic targets in treating inflammation-related cardiovascular diseases.

As a common disease, osteonecrosis attracts more and more attention. In this paper, we investigated the relationship between the alterations of endothelial-derived and platelet-derived microparticles and the changes of coagulation and inflammation in the steroid-induced avascular osteonecrosis of femoral head using the rabbit model. We also explored the possible mechanism of the membrane particles associated with the development of the rabbit femoral head ischemic necrosis. With a 28-day continuous observation, the level of membrane microparticles was significantly heightened after methylprednisolone treatment. The coagulating and inflammatory factors also tended to increase. The data demonstrated that the levels of membrane microparticles had significantly individual differences, which meant the increased levels of membrane microparticles may be related to hypercoagulability, thrombosis, and inflammation in microcirculation and played an important role in steroid-induced osteonecrosis. It will be very useful and helpful to guide clinical trials.

Background: Human leukocyte antigen (HLA)-G, a nonclassical HLA class I molecule, induces a wide range of tolerogenic immunological effects by means of interaction with its inhibitory receptors. However, recent studies show that HLA-G dimer formation is essential to bind to its receptors and exhibit its effects., Methods: In this study, a soluble divalent HLA-G/IgG molecule (sHLA-G dimer) was constructed. Its inhibitory effect on T-cell alloresponse was studied with mixed lymphocyte reaction in vitro, which was set up by mixing inactivated T1 cells with HLA-mismatched peripheral blood lymphocytes in the presence or absence of the sHLA-G dimer., Results: The results show that sHLA-G dimer inhibits T-cell alloresponse by reducing proliferation of both CD4+ and CD8+ T cells and suppressing generation of alloreactive cytotoxic T lymphocytes at nanomole concentration. The inhibition of the sHLA-G dimer is observed to be more effective than that of sHLA-G monomer. Our results also indicate that sHLA-G dimer up-regulates inhibitory receptor ILT2 on alloreactive CD8+ T cells, which contributes to the significant inhibition on T-cell alloresponse., Conclusion: The sHLA-G dimer formed by IgG-Fc fragment shows more inhibitory effects on alloreactive T cells, which may have implications for allotransplantation.