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Lei Pan,1,2 Xu-Hao Wang,1 Fan-Qi Meng,1 Xin-Ming Su,1 Yue Li,1 Ming-Tao Xu,1 Feng-Yuan Su,3 De-Lei Kong,1 Wei Wang1 1Department of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, Shenyang, People’s Republic of China; 2Liaoning Provincial Centers for Disease Control and Prevention, Shenyang, People’s Republic of China; 3China Medical University, Shenyang, People’s Republic of ChinaCorrespondence: De-Lei KongDepartment of Respiratory and Critical Care Medicine, The First Hospital of China Medical University, 155 Nanjing North Street, Heping District, Shenyang, Liaoning, 110001, People’s Republic of ChinaEmail kongdelei@126.comAbstract: Disseminated infection caused by Nocardia farcinica with primary nephrotic syndrome is exceedingly rare. A 66-year-old female visited the outpatient department due to fever and fatigue who had been diagnosed as membranous nephropathy and with a long-term prednisone and immunosuppressive therapy. After lung biopsy for many times, culture from space-occupying lesion of the right lung and species identification by mass spectrometry-based methods (MALDI-TOF) revealed Nocardia farcinica. By imaging examination, space-occupying lesions from the lungs, brain, abdominal cavity and kidney were found. After 2 weeks of meropenem intravenous and up to 6 months of trimethoprim-sulfamethoxazole (TMP-SMX) therapy, our patient has remained relapse-free at that time of writing. Disseminated infection caused by Nocardia farcinica is usually subacute with complex clinical manifestations. In addition, it can be easily confused with diseases such as tumor and mycobacterial infection, and lead to fatal consequences. Therefore, we hope that we can remind clinicians considering by discussing common features of disseminated Nocardia farcinica infection.Keywords: disseminated nocardiosis, fever, space-occupying lesions, brain abscess, renal insufficiency

In Brief: Genes expressed in cumulus cells might be used as markers for competent oocytes/embryos. This study identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos., Abstract: Studies on the mechanisms behind cumulus expansion and cumulus cell (CC) apoptosis are essential for understanding the mechanisms for oocyte maturation. Genes expressed in CCs might be used as markers for competent oocytes and/or embryos. In this study, both in vitro (IVT) and in vivo (IVO) mouse oocyte models with significant difference in cumulus expansion and CC apoptosis were used to identify and validate new genes regulating cumulus expansion and CC apoptosis of mouse oocytes. We first performed mRNA sequencing and bioinformatic analysis using the IVT oocyte model to identify candidate genes. We then analyzed functions of the candidate genes by RNAi or gene overexpression to select the candidate cumulus expansion and CC apoptosis-regulating genes. Finally, we validated the cumulus expansion and CC apoptosis-regulating genes using the IVO oocyte model. The results showed that while Spp1, Sdc1, Ldlr, Ezr and Mmp2 promoted, Bmp2, Angpt2, Edn1, Itgb8, Cxcl10 and Agt inhibited cumulus expansion. Furthermore, Spp1, Sdc1 and Ldlr inhibited CC apoptosis. In conclusion, by using both IVT and IVO oocyte models, we have identified and validated a new group of cumulus expansion and/or apoptosis-regulating genes, which may be used for selection of quality oocytes/embryos and for elucidating the molecular mechanisms behind oocyte maturation.

Information on long-term effects of postovulatory oocyte aging (POA) on offspring is limited. Whether POA affects offspring by causing oxidative stress (OS) and mitochondrial damage is unknown. Here, in vivo-aged (IVA) mouse oocytes were collected 9 h after ovulation, while in vitro-aged (ITA) oocytes were obtained by culturing freshly ovulated oocytes for 9 h in media with low, moderate, or high antioxidant potential. Oocytes were fertilized in vitro and blastocysts transferred to produce F1 offspring. F1 mice were mated with naturally bred mice to generate F2 offspring. Both IVA and the ITA groups in low antioxidant medium showed significantly increased anxiety-like behavior and impaired spatial and fear learning/memory and hippocampal expression of anxiolytic and learning/memory-beneficial genes in both male and female F1 offspring. Furthermore, the aging in both groups increased OS and impaired mitochondrial function in oocytes, blastocysts, and hippocampus of F1 offspring; however, it did not affect the behavior of F2 offspring. It is concluded that POA caused OS and damaged mitochondria in aged oocytes, leading to defects in anxiety-like behavior and learning/memory of F1 offspring. Thus, POA is a crucial factor that causes psychological problems in offspring, and antioxidant measures may be taken to ameliorate the detrimental effects of POA on offspring.

Introduction: This study aims to analyze risk factors for ocular surface irritation symptoms in patients with non-corneal-damage inactive mild and moderate-to-severe Graves' orbitopathy (GO)., Methods: This retrospective study enrolled 307 patients with non-corneal-damage inactive GO admitted to Sun Yat-sen Memorial Hospital from April 2017 to September 2023. The activity and severity of GO were evaluated using the Clinical Activity Score (CAS) and the European Group on Graves' Orbitopathy (EUGOGO) classification, respectively. Multivariate logistic regression analysis was performed to analyze risk factors for ocular surface irritation symptoms., Results: Among patients with inactive GO, for mild cases, CAS (P < 0.001), upper eyelid lag (P = 0.049), and extraocular muscle involvement (P = 0.019) in the symptomatic group were greater than those in the asymptomatic group, and multivariate logistic regression analysis demonstrated that upper eyelid lag (P = 0.048), CAS 1 (P < 0.001), CAS 2 (P = 0.005), and extraocular muscle involvement (P = 0.029) were risk factors for ocular surface irritation symptoms; for moderate-to-severe cases, CAS (P = 0.004), extraocular muscle involvement (P < 0.001), marginal reflex distance 1 (MRD1) (P = 0.030), and thyroid-stimulating hormone (TSH) (P = 0.034) in the symptomatic group were greater than those in the asymptomatic group, while multivariate logistic regression analysis indicated that extraocular muscle involvement (P = 0.018) and MRD1 (P = 0.012) were risk factors for ocular surface irritation symptoms., Conclusion: In non-corneal-damage inactive mild and moderate-to-severe GO, eyelid malposition and periocular muscle inflammation are risk factors for ocular surface irritation symptoms., (© 2024. The Author(s).)

The mitochondrial calcium uniporter (MCU) is a major protein for the uptake of mitochondrial calcium to regulate intracellular energy metabolism, including processes such as mitophagy. The present study investigated the effect of the MCU on mitophagy in pancreatic ductal epithelial cells (PDECs) in acute pancreatitis (AP) in vitro . The normal human PDECs (HPDE6-C7) were treated with caerulein (CAE) to induce AP-like changes, with or without ruthenium red to inhibit the MCU. The mitochondrial membrane potentials (MMPs) and mitochondrial Ca 2+ levels were analyzed by fluorescence. The expression levels of MCU, LC3, p62, and translocase of the outer mitochondrial membrane complex subunit 20 (TOMM20), putative kinase 1 (PINK1), and Parkin were measured by western blotting and immunofluorescence. Mitophagy was observed by confocal fluorescence microscopy and transmission electron microscopy. The results showed that CAE increased the MCU protein expression, mitochondrial Ca 2+ levels, MMP depolarization and the protein expression of mitophagy markers including the LC3II/I ratio, PINK1, and Parkin. CAE decreased the protein expression of p62 and TOMM20, and promoted the formation of mitophagosomes in HPDE6-C7 cells. Notably, changes in these markers were reversed by inhibiting the MCU. In conclusion, an activated MCU may promote mitophagy by regulating the PINK1/Parkin pathway in PDECs in AP., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Lei et al.)

Background: Although studies suggest that maternal high glucose (HG) increases offspring susceptibility to type 2 diabetes mellitus (T2DM), the underlying mechanisms are largely unclear. We studied whether glucose levels in oviducts are elevated when pregestational diabetic females get pregnant and whether the oviductal HG (OVHG) would act directly on embryos to increase offspring's T2DM susceptibility., Methods: We established an in vivo model of OVHG by injecting female mice with streptozotocin (STZ) during the preimplantation period and an in vitro model of embryo culture with HG (ECHG) by culturing preimplantation embryos with HG, before examining glucose tolerance and insulin resistance (IR) in F1 and F2 offspring., Findings: Injection of female mice with STZ induced a lasting significant glucose elevation in blood and oviduct fluid during the preimplantation period. The glucose tolerance test showed that both the STZ-induced OVHG and the ECHG caused glucose intolerance in F1 male and F1-sired F2 male offspring but had no effect on female offspring. Insulin tolerance test and the analysis for IR-related gene expression and glycogen contents in liver and muscle revealed significant IR in these male offspring., Interpretation: This study provided evidence that HG can act directly on preimplantation embryos to increase offspring's T2DM susceptibility suggesting that the preimplantation period is a critical stage for transmission of mother's diabetes to offspring. FUND: This study was supported by grants from the China National Natural Science Foundation (Nos. 31772599, 32072738, 31702114, and 31902160), and the Natural Science Foundation of Shandong Province (Nos. ZR2022MC036, ZR2017BC025 and ZR2020QC102)., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The multidisciplinary treatment model led by surgery has become a comprehensive strategy and overall concept for the treatment of spinal metastatic tumors. But the surgical treatment of spinal metastatic tumors is different from primary malignant tumors of the spine. Surgery is only a part of the multidisciplinary comprehensive treatment. Therefore, the following aspects need to be evaluated comprehensively based on the survival assessment, evaluation of spinal stability damage, nerve dysfunction, and oncological characteristics of the metastatic tumors with a reasonable surgical intervention. The attention should be paid to the minimally invasive treatment of spinal metastases, progress of new radiotherapy technology, neoadjuvant chemotherapy, targeted drug therapy and other medical treatment to make a comprehensive and individualization decision which is benefit to relieve patients ' pain, reconstruct spinal stability and avoid paralysis. While improving patient survival, increasing local tumor control rate and possibly prolonging survival time, avoiding excessive surgery as much as possible.

Background: The emergence of immune checkpoint inhibitors (ICIs) has brought about a paradigm shift in the treatment landscape of non-small cell lung cancer (NSCLC). Despite the promising long-term survival outcomes and optimization of pathological complete response (cPR) demonstrated by various studies such as Impower010 and Checkmate-816, the effectiveness of neoadjuvant immunotherapy in advanced resectable NSCLC remains a subject of debate. Although previous research has explored the connection between the efficacy of neoadjuvant therapy and surgical-related safety, limited studies have specifically investigated the surgical-related safety of neoadjuvant immunotherapy. Therefore, our study aims to assess the efficacy and surgical-related safety of neoadjuvant immunotherapy in advanced resectable non-small cell lung cancer., Method: We conducted a retrospective study on a cohort of 93 patients with stage IIIA-IIIC NSCLC who underwent neoadjuvant therapy and surgical resection. Among them, 53 patients received neoadjuvant immunotherapy, 18 patients underwent neoadjuvant chemotherapy while the remaining 22 underwent neoadjuvant targeted therapy. The patients were separated into further groups according to their pathological type. Data analyses were performed using Mann-Whitney U test, chi-square test., Results: All patients were categorized into six distinct groups. Notably, the neoadjuvant immunotherapy squamous carcinoma group exhibited a favorable edge over the neoadjuvant targeted squamous carcinoma group concerning the duration of drainage tube indwelling and the extent of lymph node dissection. Furthermore, the neoadjuvant immunotherapy adenocarcinoma group outperformed neoadjuvant targeted therapy adenocarcinoma counterpart in terms of achieving complete pathological response (cPR). Simultaneously, the neoadjuvant immunotherapy adenocarcinoma group surpassed the neoadjuvant chemotherapy adenocarcinoma group in the incidence of hydrothorax. Nevertheless, no statistically significant disparities were noted between the neoadjuvant immunotherapy squamous carcinoma group and the neoadjuvant chemotherapy carcinoma group., Conclusion: Regarding surgical outcomes, neoadjuvant immunotherapy conferred notable advantages compared to conventional neoadjuvant chemotherapy and neoadjuvant targeted therapy for patients diagnosed with adenocarcinoma. In the case of squamous carcinoma, neoadjuvant immunotherapy exhibited superiority over neoadjuvant targeted therapy, although additional evidence is required to conclusively establish its precedence over neoadjuvant chemotherapy., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wang, Qi, Luo, Xu, Xu, Qiang, Zhang and Shen.)

Background: p-Aminobenzoic acid (pABA) is an environmentally friendly bioactive metabolite synthesized by Lysobacter antibioticus. This compound showed an unusual antifungal mode of action based on cytokinesis inhibition. However, the potential antibacterial properties of pABA remain unexplored., Results: In this study, pABA showed antibacterial activity against Gram-negative bacteria. This metabolite inhibited growth (EC 50  = 4.02 mM), and reduced swimming motility, extracellular protease activity, and biofilm formation in the soybean pathogen Xanthomonas axonopodis pv. glycines (Xag). Although pABA was previously reported to inhibit fungal cell division, no apparent effect was observed on Xag cell division genes. Instead, pABA reduced the expression of various membrane integrity-related genes, such as cirA, czcA, czcB, emrE, and tolC. Consistently, scanning electron microscopy observations revealed that pABA caused major alternations in Xag morphology and blocked the formation of bacterial consortiums. In addition, pABA reduced the content and profile of outer membrane proteins and lipopolysaccharides in Xag, which may explain the observed effects. Preventive and curative applications of 10 mM pABA reduced Xag symptoms in soybean plants by 52.1% and 75.2%, respectively., Conclusions: The antibacterial properties of pABA were studied for the first time, revealing new insights into its potential application for the management of bacterial pathogens. Although pABA was previously reported to show an antifungal mode of action based on cytokinesis inhibition, this compound inhibited Xag growth by altering the outer membrane's integrity. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

This study explored the prescription and medication rules of traditional Chinese medicine(TCM) in the prevention and treatment of diabetic microangiopathy based on literature mining. Relevant literature on TCM against diabetic microangiopathy was searched and prescriptions were collected. Microsoft Excel 2021 software was used to establish a prescription database, and an analysis was conducted on the frequency, properties, flavors, meridian tropism, and efficacy classifications of drugs. Association rule analysis, cluster analysis, and factor analysis were performed using SPSS Modeler 18.0 and SPSS Statistics 26.0 software. The characteristic active components and mechanisms of action of medium-high frequency drugs in the analysis of medication rules were explored through li-terature mining. A total of 1 327 prescriptions were included in this study, involving 411 drugs, with a total frequency reaching 19 154 times. The top five high-frequency drugs were Astragali Radix, Angelicae Sinensis Radix, Poria, Salviae Miltiorrhizae Radix et Rhizoma, and Rehmanniae Radix. The cold and warm drugs were used in combination. Drugs were mainly sweet, followed by bitter and pungent, and acted on the liver meridian. The majority of drugs were effective in tonifying deficiency, clearing heat, activating blood, and resolving stasis. Association rule analysis identified the highly supported drug pair of Astragali Radix-Angelicae Sinensis Radix and the highly confident drug combination of Poria-Alismatis Rhizoma-Corni Fructus. The strongest correlation was found among Astragali Radix, Angelicae Sinensis Radix, Poria, and Salviae Miltiorrhizae Radix et Rhizoma through the complex network analysis. Cluster analysis identified nine categories of drug combinations, while factor analysis identified 16 common factors. The analysis of active components in high-frequency drugs for the treatment of diabetic microangiopathy revealed that these effective components mainly exerted their effects by inhibiting oxidative stress and suppressing inflammatory reactions. The study found that the pathogenesis of diabetic microangiopathy was primarily characterized by deficiency in origin, with a combination of deficiency and excess. Deficiency was manifested as Qi deficiency and blood deficiency, while excess as phlegm-heat and blood stasis. The key organ involved in the pathological changes was the liver. The treatment mainly focused on supplementing Qi and nourishing blood, supplemented by clearing heat, coo-ling blood, activating blood, and dredging collaterals. Commonly used formulas included Danggui Buxue Decoction, Liuwei Dihuang Pills, Erzhi Pills, and Buyang Huanwu Decoction. The mechanisms of action of high-frequency drugs in the treatment of diabetic microangiopathy were often related to the inhibition of oxidative stress and suppression of inflammatory reactions. These findings can provide references for the clinical treatment of diabetic microangiopathy and the development of targeted drugs.

Although ethanol treatment is widely used to activate oocytes, the underlying mechanisms are largely unclear. Roles of intracellular calcium stores and extracellular calcium in ethanol-induced activation (EIA) of oocytes remain to be verified, and whether calcium-sensing receptor (CaSR) is involved in EIA is unknown. This study showed that calcium-free ageing (CFA) in vitro significantly decreased intracellular stored calcium (sCa) and CaSR expression, and impaired EIA, spindle/chromosome morphology and developmental potential of mouse oocytes. Although EIA in oocytes with full sCa after ageing with calcium does not require calcium influx, calcium influx is essential for EIA of oocytes with reduced sCa after CFA. Furthermore, the extremely low EIA rate in oocytes with CFA-downregulated CaSR expression and the fact that inhibiting CaSR significantly decreased the EIA of oocytes with a full complement of CaSR suggest that CaSR played a significant role in the EIA of ageing oocytes. In conclusion, CFA impaired EIA and the developmental potential of mouse oocytes by decreasing sCa and downregulating CaSR expression. Because mouse oocytes routinely treated for activation (18 h post hCG) are equipped with a full sCa complement and CaSR, the present results suggest that, while calcium influx is not essential, CaSR is required for the EIA of oocytes.

Background: The intestinal microcirculation functions in food absorption and metabolic substance exchanges. Accumulating evidence indicates that intestinal microcirculatory dysfunction is a significant source of multiple gastrointestinal diseases. To date, there has not been a scientometric analysis of intestinal microcirculatory research., Aim: To investigate the current status, development trends, and frontiers of intestinal microcirculatory research based on bibliometric analysis., Methods: VOSviewer and CiteSpace 6.1.R2 were used to identify the overall characteristics and knowledge map of intestinal microcirculatory research based on the core literature published from 2000 to 2021 in the Web of Science database. The characteristics of each article, country of origin, institution, journal, cocitations, and other information were analyzed and visualized., Results: There were 1364 publications enrolled in the bibliometric analysis, exhibiting an upward trend from 2000 to 2021 with increased participation worldwide. The United States and Dalhousie University took the lead among countries and institutions, respectively. Shock was the most prolific journal, and Nature Reviews Microbiology Clinical had the most citations. The topical hotspots and frontiers in intestinal microcirculatory research were centered on the pathological processes of functional impairment of intestinal microvessels, diverse intestinal illnesses, and clinical treatment., Conclusion: Our study highlights insights into trends of the published research on the intestinal microcirculation and offers serviceable guidance to researchers by summarizing the prolific areas in intestinal disease research to date., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Purpose: To assess the outcomes of balanced orbital decompression for chorioretinal folds (CRFs) with and without optic disc edema (ODE) in dysthyroid optic neuropathy (DON)., Method: A retrospective, interventional study was performed at Sun Yat-sen Memorial Hospital from April 2018 to November 2021. We collected the medical records of 13 patients (24 eyes) with DON and CRFs. Then, we divided them into the ODE group (15 eyes, 62.5%) and the non-ODE group (NODE group, 9 eyes, 37.5%). The valid ophthalmic examination parameters of 8 eyes in each group after balanced orbital decompression were compared at the 6-month follow-up., Results: The mean best corrected visual acuity (BCVA, 0.29 ± 0.27) and visual field-mean deviation (VF-MD, -6.55 ± 3.71 dB) in the ODE group were significantly worse than those in the NODE group (0.06 ± 0.15 and -3.49 ± 1.56 dB; all p < 0.01). Six months after orbital decompression, all parameters were found to have significantly improved in both groups, including BCVA and VF-MD (all p < 0.05). Moreover, the improvement amplitude of BCVA ( p = 0.020) in the ODE group was significantly greater than that in the NODE group. There was no difference in BCVA between the ODE group (0.13 ± 0.19) and the NODE group (0.10 ± 0.13). The disc edema of all eyes (8/8 eyes, 100%) in the ODE group was completely mitigated after orbital decompression. The CRF resolution of 2 eyes (2/8 eyes, 25%) in the ODE group and no eyes in the NODE group was mitigated., Conclusions: Balanced orbital decompression can significantly improve visual functions and eliminate optic disc edema in DON patients, whether CRF relieves or not., Competing Interests: There is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported., (Copyright © 2023 Peng Zeng et al.)

Purpose: To evaluate the clinical outcomes of arthroscopically assisted double-bundle medial patellofemoral complex reconstruction (MPFC-R)., Methods: A retrospective review was carried out among adult patients who experienced at least 2 patellar dislocations and underwent primary arthroscopically assisted MPFC-R between January 2014 and November 2019. Dejour classification, tibial tubercle-trochlear groove (TT-TG) distance, and patellar height (with Insall-Salvati index) were measured. Pre- and postoperative patellar tilt were compared. Information on outcome scores, ability to return to sports, postoperative recurrent dislocations, and complications was recorded., Results: A total of 42 MPFC-Rs in 39 patients were included. Mean age at surgery was 22.2 ± 7.6 years; 69.2% of patients were female. Mean follow-up was 47.3 ± 20.2 months. Seventy-four percent of cases had Dejour B (19.0%), C (33.3%), and D (21.4%) trochlear dysplasia; mean TT-TG distance was 19.6 ± 3.5 mm, and mean Insall-Salvati index was 1.21 ± 0.17. Mean patellar tilt decreased from 27.6 ± 11.6° to 9.4 ± 6.5° (P < .001). All patients had statistically significant (P < .001) improvement in mean International Knee Documentation Committee (IKDC) (44.9 ± 18.2 to 87.5 ± 6.9), Lysholm (61.4 ± 16.6 to 94.1 ± 6.4), Kujala (56.0 ± 16.8 to 92.9 ± 5.3), and Tegner score (2.7 ± 1.3 to 4.6 ± 1.4). The majority of patients (96.9%) returned to sports, with 90.3% returning to the same or greater level of activity. No postoperative dislocations or subluxations were reported., Conclusions: Arthroscopically assisted double-bundle MPFC-R is a promising procedure to treat recurrent patellar instability at 2- to 7-year mid-term follow-up, despite the presence of trochlear dysplasia, elevated TT-TG distance and patellar alta. The improvement of IKDC score exceeded the minimal clinically important difference in 95.2% patients, and 66.7% surpassed the patient acceptable symptomatic state based on postoperative IKDC score with no redislocations being reported at latest follow-up., Level of Evidence: Level IV, case series, retrospective., (Copyright © 2022 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.)

Soybean plants are highly susceptible to Fusarium species, which significantly reduce soybean production and quality. Several Fusarium species have been reported to synthesize mycotoxins, such as trichothecene, which have been related to major human diseases. In November 2021, soybean pods in Nantong municipality, China, showed black necrotic lesions during the harvest stage. The disease incidence reached 69%. The pathogen was identified as Fusarium sulawense via morphological analysis and sequencing of ITS , EF1-α and RPB2 genes. A PCR assay with primers targeting the trichothecene biosynthesis genes suggested that the three isolates could synthesize trichothecenes. The effectiveness of fungicide carbendazim and natural metabolites dipicolinic acid and kojic acid was screened for the management of F. sulawense on postharvest soybean pods. The highest efficacy was obtained when combining 3.8 mg/mL carbendazim and 0.84 mg/mL dipicolinic acid (curative efficacy: 49.1% lesion length inhibition; preventive efficacy: 82.7% lesion length inhibition), or 1.9 mg/mL carbendazim and 0.71 mg/mL kojic acid (preventive efficacy: 84.9% lesion length inhibition). Collectively, this report will lead to a better understanding of the safety hazards found in soybean products in China and reveals the application of dipicolinic and kojic acids to reduce the use of carbendazim.

Antrodia camphorata (A. camphorata) is an edible fungus containing various bioactive compounds generally used for health benefits. This study aimed to explore the potential neuroprotective activities of solid-state-cultured mycelium of A. camphorata (SCMAC) against Parkinson's disease (PD), as well as the underlying mechanism using an in vitro 6-hydroxydopamine (6-OHDA)-induced PC12 cell model. The results showed that SCMAC extracts alleviated cell toxicity induced by 6-OHDA and the loss of dopaminergic neurons, which was confirmed by the increase of cell viabilities, inhibition of cell apoptosis, the upregulation of tyrosine hydroxylase (TH) and dopamine transporter (DAT) levels and the downregulation of α-Synuclein level. After purification, 11 compounds were identified by the NMR technique, including a quinone, four phenolic acid derivatives, three ubiquinone derivatives, two alkaloids, and a triterpenoid. The present study suggests that SCMAC could be an attractive candidate for the prevention or treatment of PD. PRACTICAL APPLICATIONS: Parkinson's disease seriously affects the lifetime and quality of the elder population for a long history. Long-term consumption of L-DOPA will result in side effects, such as developing abnormal involuntary movements called dyskinesia. This study showed that natural SCMAC extracts could be a potential therapeutic agent for the treatment of neurodegenerative disorder., (© 2022 Wiley Periodicals LLC.)

Since Mentha haplocalyx leaves are rich in bioactive constitutes, particularly volatile compounds, there are higher demands for high-quality dried medicinal and aromatic peppermint products. This study aimed to assess the drying kinetics of hot air thin layer drying Mentha haplocalyx leaves and exploring the effects of hot air-drying temperatures on the textural properties and sensory quality. According to our results, the Midilli model is the best model representing the hot air-drying process. The effective moisture diffusivity (Deff) and activation energy (Ea) of the hot air-drying process were determined as 7.51 × 10 -9 -3.03 × 10 -8 m 2 /s and 57.98 KJ/moL, respectively. The changes of textural and aromatic profiles of dried Mentha haplocalyx leaves were subsequently evaluated by the SEM, GC-MS and E-nose technology. Changes in leaf cellular membrane structures were observed in this study, indicating that the loss of moisture content induced the shrinkage of leaf cells during the hot air-drying process. Moreover, the altered profile of volatile compounds was identified at the different drying temperatures. As a result of the GC-MS analysis, increasing the content of D-carvone from 61.89%, 69.25% and 78.2% resulted in drying temperatures of 35 °C, 45 °C and 55 °C, respectively; while a decreasing trend of other volatile compounds, including D-Limonene, cineole and l-caryophyllene was detected as drying temperature elevated. Finally, the aromatic profile was evaluated by E-nose, and results of the flavor radar fingerprint and PCA showed that aromatic profiles were significantly altered by the drying process. The overall results elucidated that the hot air thin layer drying at 35 °C efficiently improved the final quality of dried Mentha haplocalyx leaves by maintaining flavor properties.

The present study explored the kinetics and variation of volatile components of Atractylodis Macrocephalae Rhizoma during the hot-air drying process to obtain the optimal process parameters under multiple goals such as drying efficiency and drying quality. The dry basis moisture content and drying rate curves along with the change of drying time of Atractylodis Macrocephalae Rhizoma were investigated at five levels of drying air temperatures(30, 40, 50, 60, and 70 ℃). The relationship between moisture ratio and time in the drying process of Atractylodis Macrocephalae Rhizoma was fitted and verified by Midilli model, Page model, Overhults model, Modified Page model, Logaritmic model, Two terms Exponential model, and Newton model. Meanwhile, the effective diffusion coefficient of moisture(D&#95;(eff)) and activation energy(E&#95;a) in Atractylodis Macrocephalae Rhizoma were calculated under different drying air temperatures. GC-MS was used to determine the volatile components and content changes of the fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures. The dry basis moisture content and drying rate of Atractylodis Macrocephalae Rhizoma were closely related to the temperature of the drying medium, and the moisture of the Atractylodis Macrocephalae Rhizoma decreased with the prolonged drying time. As revealed by the drying rate curve, the drying rate increased with the increase in hot air temperature, and the migration of moisture was accelerated. The comparison of the correlation coefficient(R~2), chi-square(χ~2), and root mean standard error(RMSE) of each model indicated that the parameter average of the Midilli model had the highest degree of fit, with R~2=0.999 2, χ~2=8.78×10~(-5), and RMSE=8.20×10~(-3). Besides, the D&#95;(eff) at 30-70 ℃ was in the range of 1.04×10~(-9)-6.28×10~(-9) m~2·s~(-1), and E&#95;a was 37.47 kJ·mol~(-1). The volatile components of fresh Atractylodis Macrocephalae Rhizoma and dried products at different temperatures were determined by GC-MS, and 18, 18, 18, 17, 17, and 18 compounds were identified respectively, which accounted for more than 84.76% of the volatile components. In conclusion, the hot-air drying of Atractylodis Macrocephalae Rhizoma can be model-fitted and verified and the variation law of the moisture and volatile components of Atractylodis Macrocephalae Rhizoma with temperature is obtained. This study is expected to provide new ideas for exploring the drying characteristics and quality of aromatic Chinese medicine.

Although it is known that stresses on females damage oocytes with increased production of stress hormones, whether corticotrophin-releasing hormone (CRH) or adrenocorticotropic hormone (ACTH) harm oocytes directly are largely unknown. We demonstrated that CRH exposure during in vitro maturation impaired competence of both pig and mouse cumulus-oocyte-complexes (COCs), and it impaired competence and induced apoptosis in pig cumulus-denuded oocytes (DOs) but not in mouse DOs. CRH receptor 1 was expressed in pig DOs and in cumulus cells (CCs) of both species but not in mouse DOs. In the presence of CRH, whereas mouse CCs underwent apoptosis, pig CCs did not. While pig CCs did, mouse CCs did not express CRH-binding protein. ACTH did not affect competence of either pig or mouse COCs or DOs although they all expressed ACTH receptor. Both pig and mouse CCs expressed steroidogenic acute regulatory protein (StAR), and ACTH enhanced their progesterone production while alleviating their apoptosis. Neither pig nor mouse DOs expressed StAR, but ACTH inhibited maturation-promoting factor and decelerated meiotic progression of DOs suggesting activation of protein kinase A (PKA). In conclusion, CRH impaired pig and mouse oocyte competence by interacting with CRH receptor and inducing CCs apoptosis, respectively. ACTH activated PKA in both DOs and CCs although it showed no effect on oocyte competence., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Idiopathic necrosis of the femoral head (INFH) is a common disease with unknown cause. Its successful treatment relies on the repair of the necrotic bone. The application of autologous mesenchymal stem cells (MSCs) has shown great promise in saving the patients from undergoing total hip arthroplasty. Leucine-rich repeat-containing 17 ( LRRC17 ) is less expressed in patients with femoral head necrosis and LRRC17 can inhibit bone degradation. However, it remains unknown whether LRRC17 plays a role in the pathogenesis of INFH. The present study aimed to investigate the potential role and mechanism of LRRC17 in the pathogenesis and treatment of INFH. It was found that despite the similar cell morphology and MSC surface marker expressions of human bone marrow MSCs (BMSCs) isolated from patients with INFH (INFH-hBMSC) and femoral neck fracture (FNF) (FNF-hBMSC), INFH-hBMSC had higher percentage of apoptosis (P<0.05), as well as lower osteogenic potential and higher adipogenic potential (both P<0.05). However, there was no difference in cell proliferation between FNF-hBMSC and INFH-hBMSC (P>0.05). It was also confirmed that the expression of LRRC17 was lower in the bone tissue and hBMSCs from patients with INFH compared with patients with FNF (P<0.05). Overexpression of LRRC17 promoted osteogenesis and inhibited the adipogenesis in hBMSCs, accompanied with the increase of Wnt3a and β-catenin expressions, and the decrease of Wnt5a and receptor activator of nuclear factor κ-B ligand (Rankl) expressions (all, P<0.05). Furthermore, knockout of LRRC17 in hBMSCs inhibited the expression levels of osteogenic and promoted adipogenic markers, while decreasing Wnt3a and β-catenin expressions, and increasing Wnt5a and Rankl expressions (all, P<0.05). The present preliminary study suggested that imbalanced bone metabolism may be involved in the pathogenesis of INFH. The modulation of the LRRC17 gene may delay or even restore the balance of osteogenic and adipogenic differentiation in autologous BMSCs derived from patients with INFH, providing a new target for the treatment of INFH., Competing Interests: All authors declare that they have no competing interests., (Copyright: © Song et al.)

Guangsangon E (GSE) is a novel Diels-Alder adduct isolated from leaves of Morus alba L, a traditional Chinese medicine widely applied in respiratory diseases. It is reported that GSE has cytotoxic effect on cancer cells. In our research, we investigated its anticancer effect on respiratory cancer and revealed that GSE induces autophagy and apoptosis in lung and nasopharyngeal cancer cells. We first observed that GSE inhibits cell proliferation and induces apoptosis in A549 and CNE1 cells. Meanwhile, the upregulation of autophagosome marker LC3 and increased formation of GFP-LC3 puncta demonstrates the induction of autophagy in GSE-treated cells. Moreover, GSE increases the autophagy flux by enhancing lysosomal activity and the fusion of autophagosomes and lysosomes. Next, we investigated that endoplasmic reticulum (ER) stress is involved in autophagy induction by GSE. GSE activates the ER stress through reactive oxygen species (ROS) accumulation, which can be blocked by ROS scavenger NAC. Finally, inhibition of autophagy attenuates GSE-caused cell death, termed as "autophagy-mediated cell death." Taken together, we revealed the molecular mechanism of GSE against respiratory cancer, which demonstrates great potential of GSE in the treatment of representative cancer.

Sirtuin 3 (SIRT3) is a potential therapeutic target for cardiovascular, metabolic, and other aging-related diseases. In this study, we investigated the role of SIRT3 in diabetic cardiomyopathy (DCM). Mice were injected with streptozotocin (STZ, 60 mg/kg, ip) to induce diabetes mellitus. Our proteomics analysis revealed that SIRT3 expression in the myocardium of diabetic mice was lower than that of control mice, as subsequently confirmed by real-time PCR and Western blotting. To explore the role of SIRT3 in DCM, SIRT3-knockout mice and 129S1/SvImJ wild-type mice were injected with STZ. We found that diabetic mice with SIRT3 deficiency exhibited aggravated cardiac dysfunction, increased lactate dehydrogenase (LDH) level in the serum, decreased adenosine triphosphate (ATP) level in the myocardium, exacerbated myocardial injury, and promoted myocardial reactive oxygen species (ROS) accumulation. Neonatal rat cardiomyocytes were transfected with SIRT3 siRNA, then exposed to high glucose (HG, 25.5 mM). We found that downregulation of SIRT3 further increased LDH release, decreased ATP level, suppressed the mitochondrial membrane potential, and elevated oxidative stress in HG-treated cardiomyocytes. SIRT3 deficiency further raised expression of necroptosis-related proteins including receptor-interacting protein kinase 1 (RIPK1), RIPK3, and cleaved caspase 3, and upregulated the expression of inflammation-related proteins including NLR family pyrin domain-containing protein 3 (NLRP3), caspase 1 p20, and interleukin-1β both in vitro and in vivo. Collectively, SIRT3 deficiency aggravated hyperglycemia-induced mitochondrial damage, increased ROS accumulation, promoted necroptosis, possibly activated the NLRP3 inflammasome, and ultimately exacerbated DCM in the mice. These results suggest that SIRT3 can be a molecular intervention target for the prevention and treatment of DCM.

Background: To investigate the clinical characteristics of Graves' orbitopathy (GO) with elevated intraocular pressure (IOP) using the European Group of Graves' Orbitopathy (EUGOGO) system., Methods: In this retrospective study, the clinical data of GO patients with elevated IOP (≥21 mmHg) were collected in Sun Yat-sen Memorial Hospital from January 2010 to June 2016. The demographic characteristics, clinical history of thyroid disease and GO, and ocular examination data were evaluated, and the activity and severity of GO were classified., Results: Data were collected from 58 eyes of 39 patients. The durations of thyroid disease and GO were 15.9 ± 18.9 months and 7.5 ± 6.2 months, respectively. The average IOP was 24.8 ± 5.3 mmHg (range: 21-55 mmHg). No significant difference in IOP was observed between active and inactive eyes. Eight eyes (13.8%), 29 eyes (50.0%), and 21 eyes (36.2%) were graded as mild, moderate-severe, and sight-threatening disease, respectively, according to the EUGOGO classification. The IOP was not significantly different among the three EUGOGO grades. No glaucomatous optic nerve damage or visual field defects were found., Conclusion: Increased IOP was evident for every grade of GO severity and activity of the EUGOGO system. IOP, glaucomatous optic nerve damage, and visual fields must be evaluated regularly during follow-up evaluations, regardless of the degree of activity and severity of GO., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2021 Shu-Xian Fan et al.)

To improve the coding performance of depth maps, 3D-HEVC includes several new depth intra coding tools at the expense of increased complexity due to a flexible quadtree Coding Unit/Prediction Unit (CU/PU) partitioning structure and a huge number of intra mode candidates. Compared to natural images, depth maps contain large plain regions surrounded by sharp edges at the object boundaries. Our observation finds that the features proposed in the literature either speed up the CU/PU size decision or intra mode decision and they are also difficult to make proper predictions for CUs/PUs with the multi-directional edges in depth maps. In this work, we reveal that the CUs with multi-directional edges are highly correlated with the distribution of corner points (CPs) in the depth map. CP is proposed as a good feature that can guide to split the CUs with multi-directional edges into smaller units until only single directional edge remains. This smaller unit can then be well predicted by the conventional intra mode. Besides, a fast intra mode decision is also proposed for non-CP PUs, which prunes the conventional HEVC intra modes, skips the depth modeling mode decision, and early determines segment-wise depth coding. Furthermore, a two-step adaptive corner point selection technique is designed to make the proposed algorithm adaptive to frame content and quantization parameters, with the capability of providing the flexible tradeoff between the synthesized view quality and complexity. Simulation results show that the proposed algorithm can provide about 66% time reduction of the 3D-HEVC intra encoder without incurring noticeable performance degradation for synthesized views and it also outperforms the previous state-of-the-art algorithms in term of time reduction and ∆ BDBR.

Studies suggested that postovulatory oocyte aging might be prevented by maintaining a high maturation-promoting factor (MPF) activity. Whether AMP-activated protein kinase (AMPK) plays any role in postovulatory oocyte aging is unknown. Furthermore, while activation of AMPK stimulates meiotic resumption in mouse oocytes, it inhibits meiotic resumption in pig and bovine oocytes. Thus, the species difference in AMPK regulation of oocyte MPF activities is worth in-depth studies. This study showed that AMPK activation with metformin or 5-aminoimidazole- 4-carboxamide- 1-beta-d- ribofuranoside and inactivation with compound C significantly increased and decreased, respectively, the activation susceptibility (AS) and other aging parameters in aging mouse oocytes. While AMPK activity increased, MPF activity and cyclic adenosine monophosphate (cAMP) decreased significantly with time post ovulation. In vitro activation and inactivation of AMPK significantly decreased and increased the MPF activity, respectively. MPF upregulation with MG132 or downregulation with roscovitine completely abolished the effects of AMPK activation or inactivation on AS of aging oocytes, respectively. AMPK facilitated oocyte aging with increased reactive oxygen species (ROS) and cytoplasmic calcium. Furthermore, treatment with Ca2+/calmodulin-dependent protein kinase (CaMK) inhibitors significantly decreased AS and AMPK activation. Taken together, the results suggested that AMPK facilitated oocyte aging through inhibiting MPF activities, and postovulatory oocyte aging activated AMPK with decreased cAMP by activating CaMKs via increasing ROS and cytoplasmic calcium., (© The Author(s) 2020. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Three new indole alkaloids, flueindolines A-C (1-3), along with nine known alkaloids (4-12), were isolated from the fruits of Flueggea virosa (Roxb. ex Willd.) Voigt. Compounds 1 and 2 are two new fused tricyclic indole alkaloids possessing an unusual pyrido[1, 2-a]indole framework, and 3 presents a rare spiro (pyrrolizidinyl-oxindole) backbone. Their structures with absolute configurations were elucidated by means of comprehensive spectroscopic analysis, chemical calculation, as well as X-ray crystallography. Chiral resolution and absolute configuration determination of the known compounds 4, 10, and 11 were reported for the first time. The hypothetical biogenetical pathways of 1-3 were herein also proposed., (Copyright © 2020 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.)

Objective: To analyze the correlation between intracranial air and electrode displacement after deep brain stimulation. Compared the accuracy of the electrodes on both sides while bilateral intracranial air. Methods: A total of 133 patients with bilateral DBS from February 2017 to February 2019 in neurosurgery department of the General Hospital of Northern Theater Command were included. A total of 266 electrodes were implanted, including 160 sides of subthalamic nucleus, 2 sides of ventromedial nucleus of thalamus and 104 sides of Globus pallidus interior. All patients underwent three-dimensional reconstruction of the head 2 hours after operation and 1 week after operation, which was fused with the preoperative surgical plan.The volume of the intracranial air is obtained by summing up the CT layer-by-layer measurements after surgery. The distance between the implanted electrode and the preoperative target on the X and Y axes in the target plane is measured.Values were expressed as means±SEM,and the t test was performed. Bivariate correlation analysis using linear correlation analysis. P< 0.05 was considered statistically significant. Results: There was no statistically significant difference in the fusion error of the electrode between 2 hours and 1 week after surgery on the X-axis. But there was significant difference on the Y-axis. The difference between intracranial air volume and two fusion errors was not linearly correlated on X axis, but linearly positively correlated on Y axis. Conclusion: Intracranial air volume is an important factor affecting the accuracy of DBS surgery. The larger intracranial air volume, the larger the displacement of electrodes on Y axis.

Objective: To investigate the effects of human leukocyte-associated antigen-G (HLA-G) expression in silencing trophoblast cell line JEG-3 under normal and hypoxic conditions on invasion and proliferation of JEG-3 cells. Methods: Inhibition of HLA-G expression in JEG-3 cells by transfection of small interfering RNA (siRNA),the transfected JEG-3 cells were divided into 4 groups: normoxia control group, hypoxia control group, normoxia inhibition group and hypoxia inhibition group. The levels of HLA-G mRNA and protein in 4 groups of cells were detected by real-time quantitive PCR and western blot. The proliferation activity and invasion ability of 4 groups of cells were determined by methylthiazolyl tetrazolium (MTT) assay and invasion assay. Results: (1) Real-time quantitive PCR technology showed: the level of HLA-G mRNA in the hypoxic inhibition group (0.220±0.050) was significantly different ( P< 0.05), when compared with that in the hypoxic control group (0.630±0.030) and normoxic inhibition group (0.400±0.020). (2) Western blot analysis showed: the expression level of HLA-G protein in the hypoxic inhibition group was 0.260±0.010, statistically different from that in the hypoxic control group (0.850±0.100) and the normoxic inhibition group (0.560±0.020; P< 0.05).(3) MTT showed: proliferative activity of JEG-3 cells in the normoxic inhibition group was 0.490±0.070, the ability of cell proliferation was reduced. When compared with that in the normoxic control group (0.850±0.050), the differences was statistically significant ( P< 0.05). The proliferative activity of JEG-3 cells in the hypoxic inhibition group (0.330±0.070) was lower than that in the normoxic inhibition group (0.490±0.070), and there was a significant difference ( P< 0.05). (4) Invasion assay showed: compared with the normoxic control group (98±7), the invasive ability of JEG-3 cells in the normoxic inhibition group (73±7) was weakened, and the difference was statistically significant ( P< 0.05). The number of transmembrane cells (52±11) of JEG-3 cells in the hypoxic inhibition group was lower than that in the hypoxic control group (72±7), and the difference was statistically significant ( P< 0.05). Compared with the normoxic inhibition group, the invasion ability of JEG-3 cells in the hypoxic inhibition group decreased, and the difference was statistically significant ( P< 0.05). Conclusion: Under hypoxia, using siRNA technology to down-regulate the expression of HLA-G may affect the proliferation and invasion ability of trophoblast cells, which may be involved in the occurrence of hypertensive disorder of pregnancy.

Purpose: To study the clinical significance of the Graves' orbitopathy-specific quality of life (GO-QOL) questionnaire in mainland Chinese patients., Methods: A cross-sectional study was performed at the Ophthalmology Department of the Sun Yat-sen Memorial Hospital from April 2017 to April 2018. Eighty-eight consecutive Graves' orbitopathy (GO) patients completed the two subscales of the GO-QOL questionnaire: visual functioning and appearance. The disease severity of GO was measured by the European Group on Graves' Orbitopathy (EUGOGO) classification, and clinical activity was evaluated by the clinical activity score (CAS)., Results: The mean scores of GO-QOL questionnaire for the visual functioning and appearance subscales were 68.4 ± 31.2 and 62.0 ± 27.4, respectively. Lower QOL scores for the visual functioning subscale were significantly correlated with disease severity, the CAS and diplopia (all p < 0.05). Lower QOL scores for appearance were significantly correlated with the CAS ( p < 0.05). Although no correlation was found between the appearance subscale scores and disease severity ( p =0.407), a downward trend in the appearance subscale scores as the severity of GO increased from mild to sight-threatening GO was found., Conclusion: A strong correlation between disease severity and clinical activity has been shown in the GO-QOL questionnaire, suggested by the EUGOGO. The GO-QOL questionnaire is a simple and effective appraisal instrument in the evaluation of health-related QOL in the mainland Chinese patients with GO.

Flueggeacosines A-C (1-3), three dimeric securinine-type alkaloid analogues with unprecedented skeletons, were isolated from Flueggea suffruticosa. Compounds 1 and 2 are the first examples of C-3-C-15' connected dimeric securinine-type alkaloids. Compound 3 is an unprecedented heterodimer of securinine-type and benzoquinolizidine alkaloids. Biosynthetic pathways for 1-3 were proposed on the basis of the coexisting alkaloid monomers as the precursors. Compound 2 exhibited significant activity in promoting neuronal differentiation of Neuro-2a cells.

This work reports the first synthesis and characterization of a ferroelectric perovskite oxide-based heterostructure as well as its application for photoelectrochemical (PEC) bioanalytical purposes. Specifically, exemplified by [KNbO 3 ] 1- x [BaNi 1/2 Nb 1/2 O 3-δ ] x (KBNNO), the ferroelectric perovskite oxides were prepared by solid-state synthesis, while the TiO 2 nanorod (NR) arrays were obtained via a hydrothermal method. Using the technique of pulsed laser deposition (PLD), KBNNO were then deposited on TiO 2 NRs to form KBNNO@TiO 2 NR heterostructures. Various characterization techniques were applied to reveal compositional and structural information on the as-fabricated sample, and favorable alignment existed between the two components as displayed by the PEC test. In the detection of l-cysteine, the as-fabricated KBNNO@TiO 2 NRs demonstrated good performance in terms of sensitivity and selectivity. This work revealed the potential of ferroelectric perovskite oxide and its heterostructures for innovative PEC bioanalytical applications, and we hope it will generate more interest in the development of various ferroelectrics-based heterostructures for advanced PEC bioanalysis.

Dihydromyricetin (DMY), one of the flavonoids in vine tea, exerts several pharmacological actions. However, it is not clear whether DMY has a protective effect on pressure overload-induced myocardial hypertrophy. In the present study, male C57BL/6 mice aging 8⁻10 weeks were subjected to transverse aortic constriction (TAC) surgery after 2 weeks of DMY (250 mg/kg/day) intragastric administration. DMY was given for another 2 weeks after surgery. Blood pressure, myocardial structure, cardiomyocyte cross-sectional area, cardiac function, and cardiac index were observed. The level of oxidative stress in the myocardium was assessed with dihydroethidium staining. Our results showed that DMY had no significant effect on the blood pressure. DMY decreased inter ventricular septum and left ventricular posterior wall thickness, relative wall thickness, cardiomyocyte cross-sectional areas, as well as cardiac index after TAC. DMY pretreatment also significantly reduced arterial natriuretic peptide (ANP), brain natriuretic peptide (BNP) mRNA and protein expressions, decreased reactive oxygen species production and malondialdehyde (MDA) level, while increased total antioxidant capacity (T-AOC), activity of superoxide dismutase (SOD), expression of sirtuin 3 (SIRT3), forkhead-box-protein 3a (FOXO3a) and SOD2, and SIRT3 activity in the myocardium of mice after TAC. Taken together, DMY ameliorated TAC induced myocardial hypertrophy in mice related to oxidative stress inhibition and SIRT3 pathway enhancement.

Background: Magnetic resonance (MR) imaging provides a unique, noninvasive diagnostic platform to quantify the physiological and biochemical variables of skeletal muscle at rest. This study was to investigate the difference in thigh skeletal muscles between snowboarding halfpipe athletes and healthy volunteers via multiparametric MR imaging., Methods: A comparative study was conducted between 12 healthy volunteers and 14 snowboarding halfpipe athletes. MR scanning targeted the left leg at the level of the proximal thigh on a 3.0T MR system. The measured parameters compared between the two groups included T1, T2, T2* relaxation times, fat fraction (FF), and cross-sectional area (CSA) of the quadriceps femoris and the hamstring muscles. Statistical analysis was carried out using independent sample t-test. Interrater reliability was also assessed with intraclass correlation coefficients (ICCs)., Results: It was statistically equivalent between two groups in age, body mass index, thigh circumference, calf circumference, systolic blood pressure, and resting heart rate (all P > 0.05). However, the T1 and T2 values of the hamstring muscles in the athlete group were found to be significantly shorter than those in control group (T1: 1063.3 ± 24.1 ms vs. 1112.0 ± 38.2 ms in biceps femoris, 1050.4 ± 31.2 ms vs. 1095.0 ± 39.5 ms in semitendinosus, 1053.1 ± 31.7 ms vs. 1118.4 ± 40.0 ms in semimembranosus, respectively; T2: 33.4 ± 0.7 ms vs. 36.1 ± 1.9 ms in biceps femoris, 34.6 ± 2.0 ms vs. 37.0 ± 1.9 ms in semitendinosus, 36.9 ± 1.5 ms vs. 38.9 ± 2.4 ms in semimembranosus, respectively; all P < 0.05) although T2* relaxation time was detected with no significant difference. The FF of the hamstring muscles was obviously less than the control group (5.5 ± 1.9% vs. 10.7 ± 4.7%, P < 0.001). In addition, the quadriceps' CSA in the athlete group was substantially larger than the control group (8039.0 ± 1072.3 vs. 6258.2 ± 852.0 mm 2 , P < 0.001). Interrater reliability was excellent (ICC: 0.758-0.994)., Conclusion: Multiple MR imaging parameters indicated significant differences between snowboarding halfpipe athletes and healthy volunteers in the thigh skeletal muscles., Competing Interests: There are no conflicts of interest

Reconstruction of the defect following limb-sparing resection of malignant bone tumors is controversial and extremely challenging. Extracorporeal irradiation (ECI) and re-implantation have been used for limb salvage surgery for patients, with major advantages, including biological reconstruction, ready availability and preservation of bone stock, over replacement with a megaprosthesis. The purpose of the present study was to present our experience and details of all patients treated with this surgery. Between June 2005 and December 2014, we followed-up 23 patients with limb malignancies who were treated with en bloc excision followed by 50-Gy single dose ECI and re-implantation of involved bone segments. All cases were evaluated based on clinical and radiological examinations, complications and Musculoskeletal Tumor Society (MSTS) score. Mean follow-up period was 77.6 months (range, 17-116 months). A total of 17 patients (73.9%) demonstrated no evidence of disease, 5 (21.7%) patients succumbed to the disease and 1 (4.3%) patient was alive with the disease at the final follow-up. Local recurrence occurred in 3 patients (recurrence rate, 13.0%) in the bed outside of the irradiated graft, and 4 of the 5 patients that lost their lives did so due to associated metastatic disease. The mean value of the MSTS score was 78.8% (50-93.3%). The majority of patients demonstrated solid bony union; however, 3 patients had non-union (13.0%) and 1 had a delayed union (4.3%). Early or late complications occurred in 11 patients (47.8%). Although the complication rate (47.8%) and re-operation rate (39.1%) were high, ECI and re-implantation may be a useful and cheap technique following en bloc resection for limb salvage in appropriately selected patients.

Objective: To investigate the protective effect of thalidomide on acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats and its possible mechanism., Methods: Sixty SPF Wistar rats were randomly divided into six groups with 10 rats in each group. The rat model of PQ poisoning was reproduced by intraperitoneal injection of PQ solution 20 mg/kg (PQ model group), and the rats were treated by intraperitoneal injection of gradient thalidomide (50, 100, 200 mg/kg treatment groups) 30 minutes later continuously for 3 days. The normal saline (NS) control group and thalidomide control group (thalidomide 200 mg/kg) were established. After 3 days, the abdominal aorta blood was collected, and the superoxide dismutase (SOD) activity was determined by hydroxylamine method, serum malondialdehyde (MDA) content was determined by thiobarbituric acid method. The rats were sacrificed for lung tissue, the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). The phosphorylation levels of p65 and inhibitor-α of nuclear factor-κB (NF-κB) (IκB-α), which were the NF-κB signaling pathway proteins, were determined by Western Blot. The pathological changes in lung tissue were observed under light microscope by hematoxylin-eosin (HE) staining., Results: Under microscope, obvious congestion of pulmonary interstitial and alveolar septum, a large number of inflammatory cells infiltration and thickened alveolar wall were observed after 3 days of PQ poisoning, and the congestion of pulmonary interstitial and alveolar septum, edema and inflammatory cells infiltration in the lung tissue were significantly reduced after treatment of 50, 100, 200 mg/kg thalidomide, but compared with NS control group, there was still a small amount of edema fluid, inflammatory cells and erythrocytes in the lungs tissue. Compared with the NS control group, serum MDA content and the levels of TNF-α and IL-6, and the phosphorylation of p65 and IκB-α in lung tissue were significantly increased after PQ exposure, and the activity of serum SOD was significantly decreased. Treatment with 50, 100, 200 mg/kg thalidomide could significantly reduce the levels of MDA, TNF-α, IL-6, and phosphorylation of IκB-α and p65, and increase SOD activity, in a dose-dependent manner, and the levels were significantly different from PQ model group [MDA (mmol/L): 8.26±1.20, 6.72±1.18, 5.51±1.44 vs. 9.02±1.03, TNF-α (ng/mg): 3.00±0.14, 1.84±0.18, 1.58±0.11 vs. 3.30±0.14, IL-6 (ng/mg): 1.26±0.04, 1.06±0.04, 0.97±0.08 vs. 1.97±0.07, p-p65/p65: 6.01±0.35, 3.64±0.15, 2.89±0.18 vs. 6.34±0.23, p-IκB-α/IκB-α: 2.27±0.13, 2.14±0.22, 1.52±0.14 vs. 2.96±0.20, SOD (kU/L): 195.7±19.3, 207.1±25.6, 225.8±23.1 vs. 188.2±26.6, all P < 0.05]. There was no significant effect on lung by 200 mg/kg thalidomide alone., Conclusions: Thalidomide has a protective effect on ALI induced by PQ poisoning in rats in a dose-dependent manner, the mechanism may be achieved by reducing the level of oxygen free radicals, reducing the inflammatory factor and inhibiting the IκB-α/NF-κB signal pathway activation.

Objective: To compare the safety and efficacy of insulin degludec (IDeg) with those of insulin glargine (IGlar) in insulin-naive subjects with type 2 diabetes (T2DM). Methods: This was a 26-week, randomized, open-label, parallel-group, treat-to-target trial in 560 Chinese subjects with T2DM (men/women: 274/263, mean age 56 years, mean diabetes duration 7 years) inadequately controlled on oral antidiabetic drugs (OADs). Subjects were randomized 2∶1 to once-daily IDeg (373 subjects) or IGlar(187 subjects), both in combination with metformin. The primary endpoint was changes from baseline in glycosylated hemoglobin(HbA1c) after 26 weeks. Results: Mean HbA1c decreased from 8.2% in both groups to 6.9% in IDeg and 7.0% in IGlar, respectively. Estimated treatment difference (ETD) of IDeg-IGlar in change from baseline was -0.10% points (95% CI -0.25-0.05). The proportion of subjects achieving HbA1c<7.0% was 56.3%and 49.7% with IDeg and IGlar, respectively [estimated odds ratio of IDeg/IGlar: 1.26(95% CI 0.88-1.82)]. Numerically lower rateof overall confirmed hypoglycaemia and statistically significantly lower nocturnal confirmed hypoglycemia were associated with IDeg compared with IGlar, respectively [estimated rateratio of IDeg/IGlar 0.69(95% CI 0.46-1.03), and 0.43(95% CI 0.19-0.97)]. No differences in other safety parameters were found between the two groups. Conclusions: IDeg was non-inferior to IGlar in terms of glycaemic control, and was associated with a statistically significantly lower rate of nocturnal confirmed hypoglycaemia. IDeg is considered to be suitable for initiating insulin therapy in Chinese T2DM patients on OADs requiring intensified treatment. Clinical trail registration: Clinicaltrials.gov, NCT01849289.

The aim of the study was to explore the effect and its clinical relevance of short-term intensive insulin treatment on plasma concentrations of lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) and secretory phospholipase A(2) (sPLA(2)) in newly diagnosed type 2 diabetes mellitus (T2DM). Ninety newly diagnosed T2DM patients were recruited and received continuous subcutaneous insulin infusion (CSII) for about 2 weeks. After CSII, sPLA(2) levels [173.78 (80.95, 278.09) μg/L] were significantly decreased compared with the levels before [219.33 (130.03, 337.30) μg/L], P <0.01, while no statistic significant changes could be viewed in Lp-PLA(2) levels. Correlation analysis showed that the changes of Lp-PLA(2) and sPLA(2) were both positively correlated with the changes of homeostasis model assessment of insulin resistance(HOMA-IR)after CSII ( r =0.537, 0.493 respectively, all P <0.05). The Lp-PLA(2) and sPLA(2) level reduction after CSII might help to protect the patients from diabetic macroangiopathy. Trial registration Chinese Clinical Trial Registry, ChiCTR-TRC-10001618.

Background: China has the highest absolute disease burden of diabetes worldwide. For diabetic patients, diabetes-related vascular complications are major causes of morbidity and mortality. The roles of lipoprotein-associated phospholipase A 2 (Lp-PLA 2 ) and secretory phospholipase A 2 (sPLA 2 ) as inflammatory markers have been recently evaluated in the pathogenesis of both diabetes and atherosclerosis. We aimed to determine the mechanism through which patients with newly diagnosed type 2 diabetes gain long-term vascular benefit from intensive insulin therapy by evaluating the change in Lp-PLA 2 and sPLA 2 levels after early intensive insulin treatment and its relevance with insulin resistance and pancreatic β-cell function., Methods: In total, 90 patients with newly diagnosed type 2 diabetes mellitus were enrolled. All patients received continuous subcutaneous insulin infusion (CSII) for approximately 2 weeks. Intravenous glucose-tolerance test (IVGTT) and oral glucose-tolerance test (OGTT) were performed, and plasma concentrations of Lp-PLA 2 and sPLA 2 were measured before and after CSII., Results: Levels of Lp-PLA 2 and sPLA 2 were significantly higher in diabetic patients with macroangiopathy than in those without (P < 0.05). After CSII, the sPLA 2 level decreased significantly in all diabetic patients (P < 0.05), while the Lp-PLA2 level changed only in those with macroangiopathy (P < 0.05). The area under the curve of insulin in IVGTT and OGTT, the acute insulin response (AIR 3-5 ), early phase of insulin secretion (ΔIns30/ΔG30), modified β-cell function index, and homeostatic model assessment for β-cell function (HOMA-β) increased after treatment even when adjusted for the influence of insulin resistance (IR; P < 0.001). The HOMA-IR was lower after treatment, and the three other indicators adopted to estimate insulin sensitivity (ISI ced , IAI, and QUICKI) were higher after treatment (P < 0.05). Correlation analysis showed that the decrease in the Lp-PLA 2 and sPLA 2 levels was positively correlated with a reduction in HOMA-IR after CSII (P < 0.05). Additionally, multiple linear regression analysis showed that Lp-PLA 2 and sPLA 2 independently correlated with HOMA-IR (P < 0.05)., Conclusions: Lp-PLA 2 and sPLA 2 are closely related to insulin resistance and macroangiopathy in diabetic patients. Intensive insulin therapy might help improve IR and protect against diabetic macroangiopathy by influencing the Lp-PLA 2 and sPLA 2 levels., Trial Registration: ChiCTR-TRC-10001618 2010 September 16.

Background: Doxorubicin (DOX) is an antitumor antibiotics used against malignancies. But its toxicity limits the therapy of DOX., Objective: The purpose of this study was to evaluate DOX toxicity and the alteration of energy metabolism after short term and long term treatment., Methods: Male Sprague-Dawley rats were randomly assigned to four groups: Short term control group, short term DOX treatment group, long term control group and long term DOX treatment group. In short term treated group, rats were injected with DOX i.p. at a dose of 2.5 mg/kg every 48 h for six equal injections. In long term, treated group, rats were tail-intravenously injected with DOX at a dose of 3 mg/kg once a week for four weeks. At the end of the experiment, histopathological changes, general blood biomarkers, endogenous antioxidant enzymes, cardiac energy metabolism and related mRNA expression of AMPK signal pathway were determined., Results: DOX induced prominent oxidative stress, a higher mortality rate, histological and ECG changes, obvious cardiac hypertrophy, acute cardiac damage and cardiac energy impairment in short term treatment rats. In long term treatment rats, DOX caused serious nephropathy and systolic dysfunction, terrible cardiac energy impairment, clear alteration of substrate utilization and AMPK signal pathway., Conclusion: DOX treatment can induce different damages after short term and long term treatment. In short term treatment group, rats experienced a terrible mortality rate about 40%, the acute cardiac damage, cardiac energy impairment and an early heart failure which are potential connected with reduction of glucose utilization. In the long term treatment group, serious nephropathy and obvious changes of mRNA expressions of AMPK signal pathway were observed. Meanwhile, the serious cardiac energy impairment and substrate utilization alteration denote an obviously heart failure. This study could be helpful to develop therapy strategies of DOX complications for clinical application., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Transforming growth factor beta 1 (TGF-β1) and bone morphogenetic protein-2 (BMP-2) are important regulators of bone repair and regeneration. In this study, we examined whether TGF-β1 and BMP-2 expressions were delayed during bone healing in type 1 diabetes mellitus. Tibial fractures were created in 95 diabetic and 95 control adult male Wistar rats of 10 weeks of age. At 1, 2, 3, 4, and 5 weeks after fracture induction, five rats were sacrificed from each group. The expressions of TGF-β1 and BMP2 in the fractured tibias were measured by immunohistochemistry and quantitative reverse-transcription polymerase chain reaction, weekly for the first 5 weeks post-fracture. Mechanical parameters (bending rigidity, torsional rigidity, destruction torque) of the healing bones were also assessed at 3, 4, and 5 weeks post-fracture, after the rats were sacrificed. The bending rigidity, torsional rigidity and destruction torque of the two groups increased continuously during the healing process. The diabetes group had lower mean values for bending rigidity, torsional rigidity and destruction torque compared with the control group (P<0.05). TGF-β1 and BMP-2 expression were significantly lower (P<0.05) in the control group than in the diabetes group at postoperative weeks 1, 2, and 3. Peak levels of TGF-β1 and BMP-2 expression were delayed by 1 week in the diabetes group compared with the control group. Our results demonstrate that there was a delayed recovery in the biomechanical function of the fractured bones in diabetic rats. This delay may be associated with a delayed expression of the growth factors TGF-β1 and BMP-2.

Objective: The aim of this study was to assess the levels of serum lipid and awareness, treatment, and control of dyslipidemia in type 2 diabetes mellitus (T2DM) patients from top-ranked endocrinology clinics in large cities of China., Materials and Methods: A cross-sectional study in a representative sample of 4807 Chinese adults 40 to 75 years of age was conducted during 2010 to 2011 at 20 endocrinology clinics in top-ranked hospitals covering most of the major cities of China. Serum lipid levels were measured, and treatment of dyslipidemia was recorded and assessed., Results: In the present study, the prevalence of dyslipidemia was 67.1% in T2DM subjects. Among those with dyslipidemia, the proportion of awareness and treatment was 68.7% and 55.9%. Among participants with lipid-lowering therapy, 686 subjects achieved the low-density lipoprotein cholesterol (LDL-C) control less than 2.60 mmol/L, with the rate being 39.4%. In those patients with previous cardiovascular disease, the percentage of participants who achieved LDL-C goal (1.80 mmol/L) was 15.3%., Conclusion: The prevalence of dyslipidemia is high, and the awareness, treatment, and control of dyslipidemia are relatively low in Chinese T2DM patients. This calls for the awareness and intervention of dyslipidemia in these patients., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Giant cell tumors (GCT) of the distal radius at Campanacci grade II/III are particularly challenging to treat. Wide excision is the management of choice, but this creates a defect at the distal end of radius. We treated 11 cases of GCT of the distal radius by en bloc excision and custom prosthetic replacement. The purpose of this study was to present our experience and assess the functional outcomes of all patients treated with this surgery., Materials and Methods: Between 2005 and 2014, we followed up 11 patients with GCT of the distal radius who were treated with en bloc excision and custom prosthetic replacement. All cases were evaluated based on clinical and radiological examinations, passive range of motion (ROM) of the wrist joint, complications, and Musculoskeletal Tumor Society (MSTS) score., Results: Mean follow-up period was 55.5 months (24-83 months); mean resected length of the radius was 7.9 cm. One patient had tumor recurrence in the soft tissues after 15 months (recurrence rate 9.09 %). No patient had fracture, recurrence in the bone, metastases, or immune rejection. No complications were seen, such as loosening, rupture, or dislocation of the custom prosthesis. One patient developed superficial infection at the operative site which resolved after a course of antibiotics for 4 weeks. One patient experienced pain, which could be endured without the need for analgesics. Average ROM was 40.9° of dorsiflexion, 30.0° of volar flexion, 46.4° of supination, and 38.2° of pronation. Mean grip strength was 71 % (42-86 %). Overall revised MSTS score averaged 80.3 % (63.3-93.3 %) with one being excellent, five good, and five satisfactory., Conclusion: En bloc excision and custom prosthetic replacement for a Campanacci grade II/III GCT of the distal radius results in reasonable functional outcome at intermediate follow-up evaluation. Although average ROM of the ipsilateral wrist is poorer than some studies with other techniques, this method can be considered a reasonable option.

Background: The best preoperative examination in Graves' disease with thyroid cancer still remains uncertain. The objectives of the present study were to investigate the prevalence of thyroid cancer in Graves' disease patients, and to identify the predictive factors and ultrasonographic features of thyroid cancer that may aid the preoperative diagnosis in Graves' disease., Methods: This retrospective study included 423 patients with Graves' disease who underwent surgical treatment from 2002 to 2012 at our institution. The clinical features and ultrasonographic findings of thyroid nodules were recorded. The diagnosis of thyroid cancer was determined according to the pathological results., Results: Thyroid cancer was discovered in 58 of the 423 (13.7 %) surgically treated Graves' disease patients; 46 of those 58 patients had thyroid nodules, and the other 12 patients were diagnosed with incidentally discovered thyroid carcinomas without thyroid nodules. Among the 58 patients with thyroid cancer, papillary microcarcinomas were discovered in 50 patients, and multifocality and lymph node involvement were detected in the other 8 patients. Multivariate regression analysis showed younger age was the only significant factor predictive of metastatic thyroid cancer. Ultrasonographic findings of calcification and intranodular blood flow in thyroid nodules indicate that they are more likely to harbor thyroid cancers., Conclusions: Because the influencing factor of metastatic thyroid cancers in Graves' disease is young age, every suspicious nodule in Graves' disease patients should be evaluated and treated carefully, especially in younger patients because of the potential for metastasis.

A direct electrochemical DNA biosensor based on zero current potentiometry was fabricated by immobilization of ssDNA onto gold nanoparticles (AuNPs) coated pencil graphite electrode (PGE). One ssDNA/AuNPs/PGE was connected in series between clips of working and counter electrodes of a potentiostat, and then immersed into the solution together with a reference electrode, establishing a novel DNA biosensor for specific DNA detection. The variation of zero current potential difference (ΔE(zcp)) before and after hybridization of the self-assembled probe DNA with the target DNA was used as a signal to characterize and quantify the target DNA sequence. The whole DNA biosensor fabrication process was characterized by cyclic voltammetry and electrochemical impedance spectroscopy with the use of ferricyanide as an electrochemical redox indicator. Under the optimized conditions, ΔE(zcp) was linear with the concentrations of the complementary target DNA in the range from 10nM to 1μM, with a detection limit of 6.9nM. The DNA biosensor showed a good reproducibility and selectivity. Prepared DNA biosensor is facile and sensitive, and it eliminates the need of using exogenous reagents to monitor the oligonucleotides hybridization., (Copyright © 2012 Elsevier B.V. All rights reserved.)

In this paper, gold nanoparticle-thionine-reduced graphene oxide (GNP-THi-GR) nanocomposites were prepared to design a label-free immunosensor for the sensitive detection of carcinoembryonic antigen (CEA). The nanocomposites with good biocompatibility, excellent redox electrochemical activity and large surface area were coated onto the glassy carbon electrode (GCE) surface and then CEA antibody (anti-CEA) was immobilized on the electrode to construct the immunosensor. The morphologies and electrochemistry of the formed nanocomposites were investigated by using scanning electron microscopy (SEM), ultraviolet-visible (UV-vis) spectrometry, electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). CV and differential pulse voltammetry (DPV) studies demonstrated that the formation of antibody-antigen complexes decreased the peak current of THi in the GNP-THi-GR nanocomposites. The decreased currents were proportional to the CEA concentration in the range of 10-500 pg/mL with a detection limit of 4 pg/mL. The proposed method was simple, fast and inexpensive for the determination of CEA at very low levels., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Density functional theory calculations have been carried out to investigate α-, β-, γ-, α*-, β*-, and γ*-[(PO(4))(2)W(18)O(54)](6-) Wells-Dawson isomers, which exhibited stability in the order of α > β > γ > γ* > β* > α*, reproduced the experimental observations (α > β > γ), and confirmed the hypothesis of Contant and Thouvenot (γ* > β* > α*). Energy decomposition analysis reveals that both the spatial arrangement of the host W(18)O(54) cage (eclipsed or staggered) and its structural distortion induced by the encapsulated guest anions are two dominant factors in control of the stability order, while the influences of host-guest interaction and distortion of the guest anions are very small. A building block decomposition approach is designed and provides an effective means to clarify the detailed relationship between the local distortion and energy. By using this method, it is found that the eclipsed belt, and in particular the staggered belt, significantly distort the two caps inside the Wells-Dawson structure. Notably, there is a direct relationship between the overall stability and distortion in the belts, which is proven to be partly originating from the dominance in the quantity of the belt building blocks over that of the caps (12:6). Besides, half-unit {XW(9)} decomposition confirms that [(XO(4))(2)W(18)O(54)](n-) (X = Si, Ge, Al, and Ga) are thermodynamically instable because of the notable electrostatic repulsion between two {XW(9)} units induced by the highly charged guest anions., (© 2011 American Chemical Society)

Objective: To identify the differences in maxillary growth vector with different vertical skeletal patterns of skeletal class I before and after growth spurts., Methods: One hundred and ninety four cases with different vertical skeletal patterns of skeletal class I were selected and categorized into six groups according to their vertical skeletal patterns and cervical vertebral stages: cervical vertebral maturation stage (CVMS)1,2-horizontal pattern (n=30); CVMS1,2-average pattern (n=32); CVMS1, 2-vertical pattern (n=33); CVMS5, 6-horizontal pattern (n=34); CVMS5, 6-average pattern (n=29); and CVMS5, 6-vertical pattern (n=36). Lateral cephalograms were taken on all of the cases. The angle SN-C axis (theta) and angel PP-C axis (alpha) were measured., Results: (1) The skeletal class I with a vertical growth pattern had larger angle SN-C axis than those with a horizontal or average growth pattern before growth spurts (P(average-vertical) < 0.05, P(horizontal-vertical) < 0.001). (2) The skeletal class I with a vertical growth pattern had the largest angle SN-C axis after growth spurts, followed by those with an average growth pattern. Those with a horizontal growth pattern had the smallest angle SN-C axis. The differences were statistically significant (P(horizontal-average) < 0.05, P(horizontal-vertical) < 0.001, P(average-vertical) < 0.001). (3) The skeletal class I with the same vertical growth pattern had slightly larger angle SN-C axis after growth spurts than before growth spurts, but without statistical significance. (4) The skeletal class I had relatively stable angle PP-C axis and no significant differences were found before and after growth spurts or among those with various vertical skeletal facial types., Conclusion: The magnitude of angle SN-C axis is closely associated with vertical growth patterns and is weakly influenced by maxillofacial growth and development.