Prediction of Subsequent Vertebral Fracture After Acute Osteoporotic Fractures from Clinical and Paraspinal Muscle Features.

To construct a nomogram based on clinical factors and paraspinal muscle features to predict vertebral fractures occurring after acute osteoporotic vertebral compression fracture (OVCF). We retrospectively enrolled 307 patients with acute OVCF between January 2013 and August 2022, and performed magnetic resonance imaging of the L3/4 and L4/5 intervertebral discs (IVDs) to estimate the cross-sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles. We also collected clinical and radiographic data. We used univariable and multivariable Cox proportional hazards models to identify factors that should be included in the predictive nomogram. Post-OVCF vertebral fracture occurred within 3, 12, and 24 months in 33, 69, and 98 out of the 307 patients (10.8%, 22.5%, and 31.9%, respectively). Multivariate analysis revealed that this event was associated with percutaneous vertebroplasty treatment, higher FI at the L3/4 IVD levels of the psoas muscle, and lower relative CSA of functional muscle at the L4/5 IVD levels of the multifidus muscle. Area under the curve values for subsequent vertebral fracture at 3, 12, and 24 months were 0.711, 0.724, and 0.737, respectively, indicating remarkable accuracy of the nomogram. We developed a model for predicting post-OVCF vertebral fracture from diagnostic information about prescribed treatment, FI at the L3/4 IVD levels of the psoas muscle, and relative CSA of functional muscle at the L4/5 IVD levels of the multifidus muscle. This model could facilitate personalized predictions and preventive strategies.

Indolent growth of low­grade myofibroblastic sarcoma of the knee with the resemblance of a benign lesion: A case report.

Low-grade myofibroblastic sarcoma (LGMS) is a rare soft-tissue malignant neoplasm originating from the stromal cells that is predominantly comprised of atypical myofibroblasts. The present study reports the case of a patient with low-grade myofibroblastic sarcoma in the soft tissue of the knee. The patient exhibited a soft, painless mass on the medial side of the left knee. During surgery, a yellow-white mass above the posterior margin of the sartorius muscle was identified. This mass, which was irregular and adherent to surrounding tissues, had a blurry boundary, indicative of invasive growth. The morphology of the mass significantly differed from conventional lipomas and was lacking typical features. Immunohistochemical staining confirmed the diagnosis of a malignant LGMS. The patient experienced no recurrence over 1 year of follow-up and reported complete recovery of knee range of motion. The present study suggests that an incisional biopsy may be performed if LGMS is suspected based on patient symptoms and imaging results. In addition, long-term follow-up is crucial for the timely detection and management of any recurrence, playing a key role in the patient's ongoing care and treatment.

Fatty Infiltration of Multifidus Muscles: An Easily Overlooked Risk Factor for the Severity of Osteoporotic Vertebral Fractures.

OBJECTIVES: Osteoporotic vertebral fractures (OVFs) are a critical public health concern requiring urgent attention, and severe OVFs impose substantial health and economic burdens on patients and society. Analysis of the risk factors for severe OVF is imperative to actively prevent the occurrence of this degenerative disorder. This study aimed to investigate the risk factors associated with the severity of OVF, with a specific focus on changes in the paraspinal muscles. METHODS: A total of 281 patients with a first-time single-level acute OVF between January 2016 and January 2023 were enrolled in the study. Clinical and radiological data were collected and analyzed. The cross-sectional area (CSA) and degree of fatty infiltration (FI) of the paraspinal muscles, including the multifidus muscles (MFMs), erector spinae muscles (ESMs), and psoas major muscles (PSMs), were measured by magnetic resonance imaging (MRI) of the L4/5 intervertebral discs. According to the classification system of osteoporotic fractures (OF classification) and recommended treatment plan, OVFs were divided into a low-grade OF group and a high-grade OF group. Univariate and multivariate logistic regression analyse s were performed to identify risk factors associated with the severity of OVF. RESULTS: Ninety-eight patients were included in the low-grade OF group, and 183 patients were included in the high-grade OF group. Univariate analysis revealed a significantly higher incidence of a high degree of FI of MFMs (OR = 1.71, p = 0.002) and ESMs (OR = 1.56, p = 0.021) in the high-grade OF group. Further multivariate logistic regression analysis demonstrated that a high degree of FI of the MFMs (OR = 1.71, p = 0.002) is an independent risk factor for the severity of OVF. CONCLUSION: A high degree of FI of the MFMs was identified as an independent risk factor for the severity of OVF. Decreasing the degree of FI in the MFMs might lower the incidence of the severity of OVF, potentially reducing the necessity for surgical intervention in OVF patients.

The Impact of Arthroscopy on Surgical Decision-Making and Outcomes in Osteoarthritis Patients Undergoing Unicompartmental Knee Arthroplasty.

Background and objective Although unicompartmental knee arthroplasty (UKA) is a minimally invasive procedure, its application is limited due to strict criteria related to indications. In clinical practice, the aid of procedures such as arthroscopy is occasionally required to determine the surgical indication and thereby improve prognosis. In light of this, this study aimed to evaluate the impact of intraoperative arthroscopy on surgical decision-making in osteoarthritis (OA) patients and the prognosis of patients undergoing UKA. Methodology The clinical records of patients diagnosed with knee OA who underwent knee arthroplasty between January 2017 and January 2020 were retrospectively analyzed. The inclusion criteria were as follows: patients with radiographic evidence of single-compartmental Kellgren-Lawrence (KL) grade 3 or 4 knee OA but presenting symptoms of persistent multicompartmental knee pain or locking for at least six months, with a history of anterior cruciate ligament (ACL) injury or meniscus tear. They had undergone either UKA or total knee arthroplasty (TKA). Data on clinical characteristics and outcomes at baseline and during follow-up were collected. Results A total of 429 patients were included in the study. Patients who underwent arthroscopy were more likely to undergo UKA surgery than those who did not (p<0.05). Among patients who underwent UKA, no instances of blood transfusion during hospitalization or postoperative complications were reported, regardless of whether arthroscopy was performed or not. Although the overall Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores and Knee Society Functional Score (KSFS) did not differ between the two groups, the Knee Society Score (KSS) was significantly higher in patients who underwent arthroscopy (88.77 ±5.09) compared to those who did not (85.53 ±5.11). Similarly, the arthroscopy group had a higher overall Forgotten Joint Score (FJS) (44.6 ±4.20) than the UKA-only group (42.05 ±3.58). Conclusion Arthroscopy findings can assist in surgical decision-making for OA patients. Performing arthroscopy and UKA simultaneously is relatively safe and may be associated with favorable outcomes.

Highly Efficient Synthesis of Chlorogenic Acid Oleyl Alcohol Ester under Non-Catalytic and Solvent-Free Conditions.

As a natural polyphenolic compound, chlorogenic acid (CGA) has attracted increasing attention for its various biological activities, such as antioxidant, liver protection, intestinal barrier protection, and effective treatment of obesity and type II diabetes. However, the poor solubility of CGA in hydrophobic media limits its application in the food, drug and cosmetic industries. In order to obtain new hydrophobic derivatives, a highly efficient synthesis approach of CGA oleyl alcohol ester (CGOA) under non-catalytic and solvent-free conditions was developed in this study. The influences of reaction temperature, reaction time, substrate molar ratio, and stirring rate on the CGA conversion were investigated. The results showed that the optimal conditions were as follows: reaction temperature 200 °C, reaction time 3 h, molar ratio of CGA to oleyl alcohol 1:20, and stirring rate 200 rpm. Under these conditions, the CGA conversion could reach 93.59%. Then, the obtained crude product was purified by solvent extraction and column chromatography, and the purify of CGOA was improved to 98.72%. Finally, the structure of CGOA was identified by FT-IR, HPLC-MS and NMR. This study provides a simple and efficient strategy for the preparation of CGOA with the avoidance of catalysts and solvents.

A rare case of long-term joint swelling caused by pigmented villonodular synovitis in a 3-year-old girl: a case report.

The clinical symptoms of pigmented villonodular synovitis (PVNS) are usually insidious and non-specific; therefore, delays in diagnosis and treatment are common. Here, we describe a case of a 3-year-old patient presenting with long-term joint swelling to highlight the significance of considering PVNS as a differential diagnosis in children to prevent misdiagnosis and ensure early treatment. After arthroscopic debridement, our patient had a favorable clinical outcome and was free of recurrence.

Health-related quality of life in pediatric patients with ß-thalassemia major after hematopoietic stem cell transplantation.

Our main purpose was to evaluate health-related quality of life (HRQOL) in ß-thalassemia major patients who underwent transplantation from September 2012 to November 2019. The PedsQL 4.0 scale proxy version was administered to 221 transplant patients aged 5-18 years. Their HRQOL results in the proxy-report were compared with those in the proxy-report of 429 matched healthy peers and 198 matched nontransplant patients. Compared with their healthy peers, the transplant patients exhibited worse HRQOL in the physical health domain (P < 0.001), school domain (P < 0.001) and overall scores (P = 0.006). Patients within 4 years after transplantation exhibited physical functioning (P < 0.001), school functioning (P < 0.001) and overall HRQOL damage (P = 0.001); the scores across all domains for patients more than 4 years after transplantation were not significantly different from those for the healthy controls. The transplant patients rated their HRQOL for all domains better than the nontransplant patients (P < 0.001). The HRQOL of patients after human leukocyte antigen (HLA)-matched related and HLA-matched unrelated donor transplantation were not significantly different. Chronic graft-versus-host disease and two or more comorbidities were independently negatively associated with overall HRQOL outcomes (P = 0.032 and P < 0.001, respectively). In conclusion, patients more than 4 years after transplantation achieve an HRQOL equal to that of their healthy peers.

Protective effects of tetramethylpyrazine on dysfunction of the locus coeruleus in rats exposed to single prolonged stress by anti-ER stress mechanism.

Post-traumatic stress disorder (PTSD) is a serious stress-related neuropsychiatric disorder caused by major traumatic events. Abnormal activity of the locus coeruleus (LC)-noradrenergic system is related to the development of PTSD-like symptoms. Our previous studies have indicated that endoplasmic reticulum (ER) stress induced neuronal apoptosis of LC in rats with PTSD. The purpose of this study was to further investigate the role of ER stress pathways in LC neuronal dysfunction and elucidate the effect of the bioactive component tetramethylpyrazine (TMP) against ER stress response. We used an acute exposure to single prolonged stress (SPS) to model PTSD in rats. There were higher norepinephrine (NE) levels in the brain, increased tyrosine hydroxylase expression in LC, and enhanced anxiety-like behaviors in rats exposed to SPS, which were observed by enzyme-linked immunosorbent assay, western blot analysis and elevated plus maze test, respectively. In addition, the three major pathways of ER stress were activated by SPS exposure, which may be involved in the dysregulation of the LC-noradrenergic system of rats with PTSD. Furthermore, we found that TMP administration significantly suppressed the increased responsiveness of LC-noradrenergic system, effectively reduced the anxiety response of SPS rats, and selectively attenuated the activation of pro-apoptotic ER stress pathways. The results suggest that TMP was efficient in improving the LC-NE dysfunction induced by excessive ER stress. TMP exhibited a significant neuroprotective effect and potential therapeutics on PTSD-like symptoms.

Two-stage Enzymatic Hydrolysis of Soybean Concentrated Phospholipid to Prepare Glycerylphosphorylcholine: Optimized by Response Surface Methodology.

A two-stage enzymatic hydrolysis method, in which phospholipase A1 (PLA1) was added after phospholipase A2 (PLA2) was added for a certain time, was successfully carried out to prepare glycerylphosphorylcholine (GPC) from soybean concentrated phospholipid. Effects of reaction variables on hydrolysis reaction were optimized using response surface methodology, and the optimal conditions were as follows: PLA2 load of 1.25%, PLA1 load of 0.70%, substrate concentration of 13%, reaction temperature of 41°C, and stirring rate of 680 rpm. Under the optimal conditions, the GPC yield reached 83.07%, which is close to the predicted value by the fitted model. This paper not only provides an efficient and low-cost method to prepare GPC, but also improves the high-value utilization of soybean concentrated phospholipid.

Prognostic prediction and gene regulation network of EIF2S2 in hepatocellular carcinoma based on data mining.

BACKGROUND: Hepatocellular carcinoma (HCC) is a malignant tumor with a high fatality rate, predicting poor prognosis and therapeutic effect. Screening potential prognostic genes in HCC could be a creative way to advance clinical treatment. Eukaryotic translation initiation factor 2 subunit beta (EIF2S2) has reportedly been linked to several tumors, including liver cancer, but the prognostic predictions remain unknown. Therefore, we aimed to clarify the prognostic role and interaction network of EIF2S2 in HCC using bioinformatics data. METHODS: We screened EIF2S2 using the Oncomine, Ualcan, and TCGA databases. R software was used to analyze the mRNA level and clinicopathological characteristics of hepatocellular carcinoma. Evaluation of the correlations between EIF2S2 and patients' survival was made using the Kaplan-Meier curves and Cox proportional hazards regression model. Then, the influence of EIF2S2 gene mutations on the prognosis of patients was explored by cBioPortal. The protein-protein interaction network of 50 similar genes related to EIF2S2 was implemented by GEPIA2 and Metascape. The LinkedOmics database allowed us to carry out Gene Set Enrichment Analysis. Finally, we constructed the EIF2S2 kinase, miRNA, and transcription factor target networks using GeneMANIA. RESULTS: EIF2S2 mRNA was overexpressed in HCC and was closely associated with clinicopathological features, including gender, age, race, tumor grade, and stage. There was no correlation between EIF2S2 genetic mutations and prognostic survival. Combining Cox proportional hazards regression model analyses, high-expressed EIF2S2 predicted poor prognosis in HCC patients. Additionally, we screened the top three EIF2S2-related genes (PFDN4, HM13, and SNRPD1), the 50 similar genes, and then constructed a 50-similar-gene protein-protein interaction network identified by the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways using Metascape. EIF2S2 target networks in HCC were identified in kinase, miRNA, and transcription factor networks, including the mitogen-activated protein kinase 1 (MAPK1), miRNAs (Mir-144), and transcription factors (GGAANCGGAANY_UNKNOWN) using GeneMANIA. CONCLUSIONS: EIF2S2 plays a crucial role in the gene-regulating network of HCC and may be a potential prognostic marker or therapeutic target for HCC patients.

Cross-Linked Versus Conventional Polyethylene for Long-Term Clinical Outcomes After Total Hip Arthroplasty: A Systematic Review and Meta-Analysis.

Background: Cross-linked polyethylene (HXLPE) liners have been used for total hip arthroplasty (THA) to address the problem of osteolysis and revision surgery associated with conventional polyethylene (CPE) liners. This systematic review and meta-analysis investigated the long-term efficacy of HXLPE in preventing revision surgery and radiological osteolysis in comparison to CPE. Materials and Methods: A comprehensive search of PubMed, Embase, and the Cochrane Library from their respective inception to September 2018 was conducted to identify potential candidate articles. Data were pooled using Stata software 14.0. The quality of randomized controlled trials (RCTs) and observational studies was assessed by two different authors using the Cochrane risk-of-bias tool and the Newcastle-Ottawa scale (NOS), respectively. Results: Eight RCTs and six observational studies were included in this review. The pooled results significantly favored HXLPE over CPE in terms of total number of revisions and radiological osteolysis, with a risk reduction of 78% (95% confidence interval [CI] 0.13-0.36; p < 0.001) and 80% (95% CI 0.13-0.29; p < 0.001), respectively. Additionally, subgroup analyses of pooled data from RCTs and observational studies both showed the efficacy of HXLPE in the prevention of revision and osteolysis. Polyethylene wear in the HXLPE group was significantly less than that in the CPE group in terms of linear wear rates and head penetration rates (both p < 0.001). No significant differences were observed with regard to functional outcomes. Conclusions: The current evidence shows that HXLPE significantly improved the clinical and radiographic outcomes, but not the functional outcomes, in comparison to CPE in long-term follow-up.

A Neural Circuit from Thalamic Paraventricular Nucleus to Central Amygdala for the Facilitation of Neuropathic Pain.

As one of the thalamic midline nuclei, the thalamic paraventricular nucleus (PVT) is considered to be an important signal integration site for many descending and ascending pathways that modulate a variety of behaviors, including feeding, emotions, and drug-seeking. A recent study has demonstrated that the PVT is implicated in the acute visceral pain response, but it is unclear whether the PVT plays a critical role in the central processing of chronic pain. Here, we report that the neurons in the posterior portion of the PVT (pPVT) and their downstream pathway are involved in descending nociceptive facilitation regarding the development of neuropathic pain conditions in male rats. Lesions or inhibition of pPVT neurons alleviated mechanical allodynia induced by spared nerve injury (SNI). The excitability of pPVT-central amygdala (CeA) projection neurons was significantly increased in SNI rats. Importantly, selective optogenetic activation of the pPVT-CeA pathway induced obvious mechanical hypersensitivity in naive rats. In addition, we used rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques to define a novel neuronal circuit in which glutamatergic neurons in the vlPAG were the target of the pPVT-CeA descending facilitation pathway. Our data suggest that this pPVTGlu+-CeA-vlPAGGlu+ circuit mediates central mechanisms of descending pain facilitation underlying persistent pain conditions.SIGNIFICANCE STATEMENT Studies have shown that the interactions between the posterior portion of the thalamic paraventricular nucleus (pPVT) and central amygdala (CeA) play a critical role in pain-related emotional regulation. However, most reports have associated this circuit with fear and anxiety behaviors. Here, an integrative approach of behavioral tests, electrophysiology, and immunohistochemistry was used to advance the novel concept that the pPVT-CeA pathway activation facilitates neuropathic pain processing. Using rabies virus (RV)-based and cell-type-specific retrograde transsynaptic tracing techniques, we found that glutamatergic neurons in the vlPAG were the target of the pPVT-CeA pathway. Thus, this study indicates the involvement of a pPVTGlu+-CeA-vlPAGGlu+ pathway in a descending facilitatory mechanism underlying neuropathic pain.

Involvement of the Ventrolateral Periaqueductal Gray Matter-Central Medial Thalamic Nucleus-Basolateral Amygdala Pathway in Neuropathic Pain Regulation of Rats.

The central medial nucleus (CM), a prominent cell group of the intralaminar nuclei (ILN) of the thalamus, and the ventrolateral periaqueductal gray matter (vlPAG) are two major components of the medial pain system. Whether vlPAG and CM are input sources of nociceptive information to the basolateral amygdala (BLA) and whether they are involved in neuropathic pain regulation remain unclear. Clarifying the hierarchical organization of these subcortical nuclei (vlPAG, CM, and BLA) can enhance our understanding on the neural circuits for pain regulation. Behavioral test results showed that a CM lesion made by kainic acid (KA) injection could effectively alleviate mechanical hyperalgesia 4, 6, and 8 days after spared nerve injury (SNI) surgery, with the symptoms returning after 10 days. Morphological studies revealed that: (1) the CM received afferents from vlPAG and sent efferents to BLA, indicating that an indirect vlPAG-CM-BLA pathway exists; (2) such CM-BLA projections were primarily excitatory glutamatergic neurons as revealed by fluorescence in situ hybridization; (3) the fibers originated from the CM-formed close contacts with both excitatory and inhibitory neurons in the BLA; and (4) BLA-projecting CM neurons expressed Fos induced by SNI and formed close contacts with fibers from vlPAG, suggesting that the vlPAG-CM-BLA indirect pathway was activated in neuropathic pain conditions. Finally, the vlPAG-CM-BLA indirect pathway was further confirmed using anterograde and monosynaptic virus tracing investigation. In summary, our present results provide behavioral and morphological evidence that the indirect vlPAG-CM-BLA pathway might be a novel pain pathway involved in neuropathic pain regulation.

dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors.

The dorsal medial prefrontal cortex (dmPFC) has been recognized as a key cortical area for nociceptive modulation. However, the underlying neural pathway and the function of specific cell types remain largely unclear. Here, we show that lesions in the dmPFC induced an algesic and anxious state. Using multiple tracing methods including a rabies-based transsynaptic tracing method, we outlined an excitatory descending neural pathway from the dmPFC to the ventrolateral periaqueductal gray (vlPAG). Specific activation of the dmPFC/vlPAG neural pathway by optogenetic manipulation produced analgesic and antianxiety effects in a mouse model of chronic pain. Inhibitory neurons in the dmPFC were specifically activated using a chemogenetic approach, which logically produced an algesic and anxious state under both normal and chronic pain conditions. Antagonists of the GABAA receptor (GABAAR) or mGluR1 were applied to the dmPFC, which produced analgesic and antianxiety effects. In summary, the results of our study suggest that the dmPFC/vlPAG neural pathway might participate in the maintenance of pain thresholds and antianxiety behaviors under normal conditions, while silencing or suppressing the dmPFC/vlPAG pathway might be involved in the initial stages and maintenance of chronic pain and the emergence of anxiety-like behaviors.

Enzymatic preparation of glycerophosphatilcholine catalyzed by combinational phospholipases: a comparative study of concerted versus stepwise catalysis.

Glycerophosphatilcholine (GPC) is widely applied in medical, pharmaceutical, food and cosmetic industries. Due to the lack of natural resources, enzymatic preparation of GPC has been explored in recent years. This study aimed to investigate and compare the effects of different addition methods of combinational phospholipases (PLA1 and PLA2) and various process parameters (time, temperature, pH, substrate concentrate, enzyme load, and stirring rate) on the preparation of GPC. The results showed that compared with concerted catalysis, the catalytic efficiency of adding PLA2 and then PLA1 (PLA2 → A1) was higher, whereas that of adding PLA1 and then PLA2 was lower. The main reason might be that the method of PLA2 → A1 could reduce acyl migration and the competition between PLA1 and PLA2, which was beneficial to improve the GPC yield and shorten the reaction time. This paper could provide a novel approach for the future preparation of GPC catalyzed by combinational phospholipases.

Preparation of Structured Lipid Enriched with Medium Chain Triacylglycerol by Chemical Catalyzed Acidolysis of Coconut Oil: Optimized by Response Surface Methodology.

Medium chain triacylglycerols (MCTs) have gained wide attention due to its ability to induce the residual glyceride lipolysis and improve fat absorption. In this study, structured lipid enriched with MCTs was synthesized by chemical catalyzed acidolysis of coconut oil with the mixture of caprylic acid (Cy) and capric acid (Ca) in a solvent-free system. Three catalysts were compared for their efficiency in the production of MCTs yield. The results indicated that the highest yield of MCTs was achieved by H2SO4. Effects of reaction variables on the acidolysis reaction were optimized using response surface methodology, and the optimum conditions were as follows: molar ratio of Cy to Ca 1:1, reaction time 4 h, molar ratio of MCFAs to coconut oil 12:1, catalyst loading 12 wt%, reaction temperature 110℃. Under these conditions, the obtained structured lipid contained 89.5% of MCFAs and at least 82.0% of MCTs. This paper provides a simple and low-cost method for preparing structured lipid enriched with MCTs.

Repair of Peripheral Nerve Sensory Impairments via the Transplantation of Bone Marrow Neural Tissue-Committed Stem Cell-Derived Sensory Neurons.

The present study aimed to investigate the efficacy of transplantation of bone marrow neural tissue-committed stem cell-derived sensory neuron-like cells for the repair of peripheral nerve sensory impairments in rats. Bone marrow was isolated and cultured to obtain the neural tissue-committed stem cells (NTCSCs), and the differentiation of these cells into sensory neuron-like cells was induced. Bone marrow mesenchymal stem cells (BMSCs), bone marrow NTCSCs, and bone marrow NTCSC-derived sensory neurons (NTCSC-SNs) were transplanted by microinjection into the L4 and L5 dorsal root ganglions (DRGs) in an animal model of sensory defect. On the 2nd, 4th, 8th, and 12th week after the transplantation, the effects of the three types of stem cells on the repair of the sensory functional defect were analyzed via behavioral observation, sensory function evaluation, electrophysiological examination of the sciatic nerve, and morphological observation of the DRGs. The results revealed that the transplanted BMSCs, NTCSCs, and NTCSC-SNs were all able to repair the sensory nerves. In addition, the effect of the NTCSC-SNs was significantly better than that of the other two types of stem cells. The general posture and gait of the animals in the sensory defect model exhibited evident improvement over time. Plantar temperature sensitivity and pain sensitivity gradually recovered, and the sensation latency was reduced, with faster sensory nerve conduction velocity. Transplantation of NTCSC-SNs can improve the repair of peripheral nerve sensory defects in rats.

Speckle-type POZ protein suppresses hepatocellular carcinoma cell migration and invasion via ubiquitin-dependent proteolysis of SUMO1/sentrin specific peptidase 7.

Hepatocellular carcinoma (HCC) is associated with high metastatic potential and high mortality. Accumulating evidence has demonstrated that speckle-type POZ protein (SPOP) is a key adaptor molecule of ubiquitination. However, the molecular mechanism of SPOP-mediated ubiquitination in HCC metastasis remains obscure. In the present study, our results indicated that SPOP expression was significantly downregulated in HCC and was associated with tumor size, differentiation and metastasis. Cox regression model showed that low SPOP expression was a risk factor related to the prognosis of HCC patients. Loss- and gain-of-function assays demonstrated that SPOP inhibited HCC cell migration and invasion in vitro. Mechanisitically, co-immunoprecipitation and ubiquitination assays revealed that SPOP recognized and bound SENP7 and promoted its degradation via ubiquitin-dependent proteolysis. Analysis of immunohistochemistry showed that vimentin expression was correlated negatively with SPOP and positively with SENP7. These results implied that increased degradation of SENP7 by overexpression of SPOP decreased vimentin levels, which in turn attenuated HCC cell metastasis. Moreover, in vivo assays showed that SPOP overexpression also significantly suppressed liver and lung metastases. In summary, SPOP inhibits HCC cell metastasis via ubiquitin-dependent SENP7 proteolysis and may thus serve as a new opinion for the prevention of HCC metastasis.

Interaction of ACE genotype and salt intake on hypertension among Chinese Kazakhs: results from a population-based cross-sectional study.

OBJECTIVES: To explore the effect of interaction between ACE genotype and salt intake on hypertension among Chinese Kazakhs, and to compare applications of interactions between logistic model and generalised partially linear tree-based regression (GPLTR) model. DESIGN: Population-based cross-sectional study. SETTING: Hong Dun, North Xinjiang, China. PARTICIPANTS: Non-consanguineous Chinese Kazakh participants (n=916, 342 men and 574 women) aged ≥30 years. MAIN OUTCOME MEASURES: Association between ACE genotype and hypertension, association between salt intake and hypertension, and interaction of ACE genotype and salt intake on hypertension in two models. RESULTS: Associations between salt intake and hypertension were different in ACE genotype of II and ID+DD. Under the logistic models, main and interaction effects were not observed for men, but effects were present in opposite directions for women (main effect of ACE: OR=0.20, p=0.003; interaction effect: OR=1.07, p=0.027). Under the GPLTR model, Bayesian information criterion trees included both salt intake and ACE genotype as split variables. Individuals with a salt intake ≥19.5 g/day and ID+DD genotypes had a 3.99-fold (p=0.004) higher risk of hypertension compared with the II genotype for men, whereas salt intake <20.1 g/day and ID+DD genotypes had an OR=0.55 (p=0.014) compared with the II genotype for women. CONCLUSIONS: An interaction of ACE genotype and salt intake on hypertension was observed among Chinese Kazakhs but in different ways according to sex. The GPLTR model appears to be more suitable for an exploration of interactions in complex diseases.

Prevalence, Awareness, Treatment, and Control of Hypertension among Kazakhs with high Salt Intake in Xinjiang, China: A Community-based Cross-sectional Study.

Hypertension is a leading cause of death worldwide; data on hypertension among ethnic minorities in China are sparse. This study aimed to estimate hypertension prevalence, awareness, treatment, and control in a Kazakh population, and to assess the association between salt intake and the above measures. A cross-sectional survey was conducted among Kazakh adults (≥30 years old) in the town of Hongdun, Altay, Xinjiang. Survey procedures included a questionnaire, physical measurement, and laboratory tests. Of 1805 eligible individuals, 1668 (92.4%) were included in the analysis. After adjustment for gender, age, and occupation, prevalence of hypertension was 45.5%. The proportions with awareness, treatment, control, or medication-control were 61.0%, 28.8%, 2.9% and 10.1%, respectively. Higher prevalence was seen among nomads and farmers (50.7% and 44.6%, respectively). However, the proportions with treatment or control were lower than seen among urban citizens. Hypertension prevalence was higher in those with higher salt intake (p = 0.0008). In contrast, the proportions with awareness (p = 0.0389), treatment (p = 0.0010), control (p = 0.0503), and medication-control (p = 0.2012) reduced as salt intake increased. In conclusion, hypertension prevalence is high in this population, but the proportions with awareness, treatment, or control are sub-optimal. Public health interventions that improve hypertension prevention and control, particularly among nomads, is needed.