[Analysis of DMD gene variants in a single center].

Objective: To investigate the DMD genetic variants of the Chinese population with Duchenne (DMD) and Becker muscular dystrophies (BMD). Methods: A cross-sectional study was conducted on 2 690 unrelated patients with DMD and BMD aged 0-18 who visited the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2005 to February 2022. The clinical data, such as gender, age, clinical manifestations, and address, were collected. Multiplex ligation-dependent probe amplification, next generation sequencing panel, Sanger sequencing, and PCR amplification were used to detect the variants of the DMD gene in the patients, whose clinical information and gene detection results were descriptively analyzed. Results: The 2 690 patients included 2 648 males and 42 females, with an age of 6.0 (4.0, 9.0) years. The serum creatine kinase increased in all patients. Pathogenic DMD gene variants were detected in the 2 618 patients, including 1 875 cases (71.6%) large deletions, 231 cases (8.8%) duplications, and 512 cases (19.6%) small variants. Among the deletion variants, the deletion of 3 exons was the most common, accounting for 15.4% (288/1 875); and hotspot deletion involved exons 45 to 50, accounting for 6.3% (119/1 875). Exon 2 was the most common type duplication region, accounting for 13.0% (30/231). Small variants were distributed in all 79 exons of the DMD gene, with no hotspots. In addition, the 46 small variants were previously unreported. Conclusion: Exon deletion is the most common type of DMD gene variant, followed by small variants and exon duplication.

Longitudinal perioperative patient-reported outcomes in open compared with minimally invasive hysterectomy.

BACKGROUND: There are few prospective studies in the gynecologic surgical literature that compared patient-reported outcomes between open and minimally invasive hysterectomies within enhanced recovery after surgery pathways. OBJECTIVE: This study aimed to compare prospectively collected perioperative patient-reported symptom burden and interference measures in open compared with minimally invasive hysterectomy cohorts within enhanced recovery after surgery pathways. STUDY DESIGN: We compared patient-reported symptom burden and functional interference in 646 patients who underwent a hysterectomy (254 underwent open surgery and 392 underwent minimally invasive surgery) for benign and malignant indications under enhanced recovery after surgery protocols. Outcomes were prospectively measured using the validated MD Anderson Symptom Inventory, which was administered perioperatively up to 8 weeks after surgery. Cohorts were compared using Fisher exact and chi-squared tests, adjusted longitudinal generalized linear mixed modeling, and Kaplan Meier curves to model return to no or mild symptoms. RESULTS: The open cohort had significantly worse preoperative physical functional interference (P=.001). At the time of hospital discharge postoperatively, the open cohort reported significantly higher mean symptom severity scores and more moderate or severe scores for overall (P<.001) and abdominal pain (P<.001), fatigue (P=.001), lack of appetite (P<.001), bloating (P=.041), and constipation (P<.001) when compared with the minimally invasive cohort. The open cohort also had significantly higher interference in physical functioning (score 5.0 vs 2.7; P<.001) than the minimally invasive cohort at the time of discharge with no differences in affective interference between the 2 groups. In mixed modeling analysis of the first 7 postoperative days, both cohorts reported improved symptom burden and functional interference over time with generally slower recovery in the open cohort. From 1 to 8 postoperative weeks, the open cohort had worse mean scores for all evaluated symptoms and interference measures except for pain with urination, although scores indicated mild symptomatic burden and interference in both cohorts. The time to return to no or mild symptoms was significantly longer in the open cohort for overall pain (14 vs 4 days; P<.001), fatigue (8 vs 4 days; P<.001), disturbed sleep (2 vs 2 days; P<.001), and appetite (1.5 vs 1 days; P<.001) but was significantly longer in the minimally invasive cohort for abdominal pain (42 vs 28 days; P<.001) and bloating (42 vs 8 days; P<.001). The median time to return to no or mild functional interference was longer in the open than in the minimally invasive hysterectomy cohort for physical functioning (36 vs 32 days; P<.001) with no difference in compositive affective functioning (5 vs 5 days; P=.07) between the groups. CONCLUSION: Open hysterectomy was associated with increased symptom burden in the immediate postoperative period and longer time to return to no or mild symptom burden and interference with physical functioning. However, all patient-reported measures improved within days to weeks of both open and minimally invasive surgery and differences were not always clinically significant.

Association between barium exposure and non-alcoholic fatty liver disease in U.S. adults.

Background and aims: There are very limited studies that have investigated the influence of environmental barium exposure on non-alcoholic fatty liver disease (NAFLD) in the general adult population. The purpose of the present paper was to examine any correlation between urinary barium levels (UBLs) and the risk of NAFLD. Patients and methods: A total of 4,556 participants aged ≥ 20 years were recruited from the National Health and Nutritional Survey. NAFLD was defined as the U.S. fatty liver index (USFLI) ≥ 30 in the absence of other chronic liver disease. Multivariate logistic regression was conducted to inspect the correlation between UBLs and the risk of NAFLD. Results: The outcome of adjusting covariates revealed a positive correlation between the natural log -transformed UBLs (Ln-UBLs) and the risk of NAFLD (OR: 1.24, 95%CI: 1.12-1.37, P<0.001). After dividing Ln-UBLs into quartiles, the participants in the highest quartile exhibited a 1.65-fold (95% CI: 1.26-2.15) increased likelihood of having NAFLD in contrast with the bottom quartile in the full model, and a distinct trend across the quartiles could be found (P for trend<0.001). Moreover, in the interaction analyses, it was further observed that the association between Ln-UBLs and NAFLD was modified by gender and was noticeably more pronounced in males (P for interaction =0.003). Conclusions: Our findings provided evidence of a positive correlation between UBLs and the prevalence of NAFLD. Furthermore, this association changed across gender and was more pronounced in males. Nevertheless, our finding requires further confirmation with prospective cohort studies in the future.

Comprehensive review of glucagon-like peptide 1 receptor agonist treatment on the risk of cardiovascular outcomes and retinopathy as diabetic complications.

Cardiovascular and microvascular disorders are serious complications of diabetes. Intensive glucose control is believed to hinder the pathological progression of these complications. In this review, we focus on the risk of diabetic retinopathy (DR) under intensive treatment with recently introduced glucose-lowering drugs, including glucagon-like peptide 1 receptor agonists (GLP-1RAs), sodium-glucose co-transporter-2 (SGLT2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. GLP-1RAs are more suitable for patients with diabetes at risk for, or established, cardiovascular complications, while SGLT2 inhibitors are more appropriate for complications of heart failure and chronic renal diseases. Accumulating evidence indicates that GLP-1RAs may provide a greater reduction in the risk of DR in patients with diabetes compared to DPP-4 inhibitors, sulfonylureas, or insulin. GLP-1RAs may be ideal antihyperglycemic drugs with direct benefits for the retina, since GLP-1R can be expressed in photoreceptors. Topical administration of GLP-1RAs induces direct retinal neuroprotection against DR by multiple mechanisms, such as preventing both neurodysfunction and retinal neurodegeneration; relieving the disruption of the blood-retinal barrier and associated vascular leakage, and inhibiting oxidative stress, inflammatory action, and neuronal apoptosis. Hence, it seems reasonable to utilize this strategy to treat patients with diabetes and early-stage DR, rather than exclusively using neuroprotective agents.

[ABC prognostic classification and MELD 3.0 and COSSH-ACLF â ¡ prognostic evaluation in acute-on-chronic liver failure].

Objective: To investigate the ABC prognostic classification and the updated version of Model for End-stage Liver Disease (MELD) score 3.0 and Chinese Group on the Study of Severe Hepatitis B ACLF Ⅱ score (COSSH-ACLF Ⅱ score) to evaluate the prognostic value in acute-on-chronic liver failure (ACLF). Methods: ABC classification was performed on a 1 409 follow-up cohorts. The area under the receiver operating characteristic curve (AUROC) was used to analyze MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ score after 3 days of hospitalization (COSSH-Ⅱ-3d). The prognostic predictive ability of patients were evaluated for 360 days, and the prediction differences of different classifications and different etiologies on the prognosis of ACLF were compared. Results: The survival curve of 1 409 cases with ACLF showed that the difference between class A, B, and C was statistically significant, Log Rank (Mantel-Cox) χ2=80.133, P<0.01. Compared with class A and C, χ2=76.198, P<0.01, the difference between class B and C, was not statistically significant χ2=3.717, P>0.05. AUROC [95% confidence interval (CI)] analyzed MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ-3d were 0.644, 0.655, 0.817 and 0.839, respectively (P<0.01). COSSH-Ⅱ had better prognostic predictive ability with class A ACLF and HBV-related ACLF (HBV-ACLF) for 360-days, and AUROC (95% CI) were 0.877 and 0.881, respectively (P<0.01), while MELD 3.0 prognostic predictive value was not better than MELD. Conclusion: ACLF prognosis is closely related to ABC classification. COSSH-Ⅱ score has a high predictive value for the prognostic evaluation of class A ACLF and HBV-ACLF. COSSH-Ⅱ score has a better prognostic evaluation value after 3 days of hospitalization, suggesting that attention should be paid to the treatment of ACLF in the early stage of admission.

Imaging the Efficiency of Poly(3,4-ethylenedioxythiophene) Doped with Acid-Functionalized Carbon Nanotube and Iridium Oxide Electrode Coatings for Microstimulation.

Electrical microstimulation has shown promise in restoring neural deficits in humans. Electrodes coated with materials like the conducting polymer poly(3,4-ethylenedioxythiophene) doped with acid-functionalized carbon nanotubes (PEDOT/CNTs, or PC) exhibit superior charge injection than traditional metals like platinum. However, the stimulation performance of PC remains to be fully characterized. Advanced imaging techniques and transgenic tools allow for real-time observations of neural activity in vivo. Herein, microelectrodes coated with PC and iridium oxide (IrOx) (a commonly used high-charge-injection material) are implanted in GCaMP6s mice and electrical stimulation is applied while imaging neuronal calcium responses. Results show that PC-coated electrodes stimulate more intense and broader GCaMP responses than IrOx. Two-photon microscopy reveals that PC-coated electrodes activate significantly more neuronal soma and neuropil than IrOx-coated electrodes in constant-voltage stimulation and significantly more neuronal soma in constant-current stimulation. Furthermore, with the same injected charge, both materials activate more spatially confined neural elements with shorter pulses than longer pulses, providing a means to tune stimulation selectivity. Finite element analyses reveal that the PC coating creates a denser and nonuniform electric field, increasing the likelihood of activating nearby neural elements. PC coating can significantly improve energy efficiency for electrical stimulation applications.

[Efficacy and safety of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome treated with glycoprotein â ¡b/â ¢a receptor antagonist].

Objective: To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI). Methods: The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization. Results: A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI (OR=0.881, 95%CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group (OR=1.401, 95%CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group (OR=0.919, 95%CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group (OR=1.559, 95%CI 1.130-2.150; P=0.007). Conclusion: In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.

[Clinical analysis of 2 820 cases of drug-induced liver injury].

Objective: To investigate the clinical characteristics, incidence trend, underlying diseases, causative drug and prognosis of drug-induced liver injury (DILI), so as to provide basis for its prevention and treatment. Methods: A retrospective study was conducted on 2 820 DILI cases who were admitted to our hospital from January 2002 to December 2015, and their clinical characteristics, incidence trends, underlying related diseases, causative drug, treatment and outcome were analyzed. Results: Among 2 820 DILI cases, the ratio of male to female was 1:1.44, and the age was (44.00±16.32) years old. According to the clinical classification of DILI, there were 2 353 cases (83.43%) of hepatocyte injury, 353 cases (12.51%) of cholestatic type and 114 cases (4.04%) of mixed type. In the three clinical classification of DILI, there was no statistically significant difference in the ratio of male to female (χ(2) = 3.032, P > 0.05). However, the difference in the ratio of male to female between different age groups was statistically significant (χ(2) = 48.367, P < 0.001). Among the patients with liver disease and acute liver disease admitted to our hospital from January 2002 to December 2015, the proportion of DILI and acute DILI showed an overall upward trend. The main underlying related diseases of 2 820 DILI cases were fever (15.14%), skin diseases (11.84%), cardiovascular and cerebrovascular diseases (11.17%). Chinese herbal patent medicines (37.49%), antibiotics (15.85%), antipyretic-analgesics (14.37%), and so on were the main causative drugs involved, and the prognostic differences among the three clinical classifications of DILI in terms of cure, improvement, ineffectiveness, and death were statistically significant (H = 61.300, P < 0.001). Conclusion: In recent years, among the patients with liver disease in our hospital, the proportion of DILI has shown an obvious upward trend, involving a variety of underlying diseases and causative drugs, and thus it needs clinical attention.

[Advances in early warning and treatment of pre-hepatic failure].

Liver function of patients with pre-hepatic failure deteriorates rapidly, and with this there exists a risk of liver failure and high rates of mortality. This paper summarizes the concept of pre-hepatic failure, particularly the advances in early warning and treatment of pre-hepatic failure developing into hepatic failure, with a view to enhance clinicians' concerns to pre-hepatic failure for promoting the advancement of liver failure prevention and treatment, and improving the success rate of liver failure treatment.

[Establishment of clinical features and prognostic scoring model in early-stage hepatitis B-related acute-on-chronic liver failure].

Objective: To explore the clinical characteristics and establish a corresponding prognostic scoring model in patients with early-stage clinical features of hepatitis B-induced acute-on-chronic liver failure (HBV-ACLF). Methods: Clinical characteristics of 725 cases with hepatitis B-related acute-on-chronic hepatic dysfunction (HBV-ACHD) were retrospectively analyzed using Chinese group on the study of severe hepatitis B (COSSH). The independent risk factors associated with 90-day prognosis to establish a prognostic scoring model was analyzed by multivariate Cox regression, and was validated by 500 internal and 390 external HBV-ACHD patients. Results: Among 725 cases with HBV-ACHD, 76.8% were male, 96.8% had cirrhosis base,66.5% had complications of ascites, 4.1% had coagulation failure in respect to organ failure, and 9.2% had 90-day mortality rate. Multivariate Cox regression analysis showed that TBil, WBC and ALP were the best predictors of 90-day mortality rate in HBV-ACHD patients. The established scoring model was COSS-HACHADs = 0.75 × ln(WBC) + 0.57 × ln(TBil)-0.94 × ln(ALP) +10. The area under the receiver operating characteristic curve (AUROC) of subjects was significantly higher than MELD, MELD-Na, CTP and CLIF-C ADs(P < 0.05). An analysis of 500 and 390 cases of internal random selection group and external group had similar verified results. Conclusion: HBV-ACHD patients are a group of people with decompensated cirrhosis combined with small number of organ failure, and the 90-day mortality rate is 9.2%. COSSH-ACHDs have a higher predictive effect on HBV-ACHD patients' 90-day prognosis, and thus provide evidence-based medicine for early clinical diagnosis and treatment.

[Clinical observation of drug-coated balloon in the treatment of lower extremity arterial long segment lesions].

Objective: To observe the efficacy of drug -coated balloon (DCB) in the treatment of long -segment arterial stenosis in lower extremity. Methods: Were retrospectively analyzed in February 2017 to January 2018,the First Hospital Affiliated to China Medical University of vascular surgical treated 80 patients with lower limb sclerosis of arterial congee appearance (lesion length>10 cm), accept the DCB and stents (BMS) treatment, compared two groups of patients with preoperative and postoperative issue patency rate of target lesion, ABI, Rutherford, amputation rate and the change of clinical symptoms and quality of life. Results: There were 60 cases in DCB group,20 cases in BMS group and 80 cases in BMS group. The patency rate of DCB group was 83.33% and 75.00% at 6 and 12 months after operation. The patency rate was 85.00% and 65.00% in the BMS group at 6 and 12 months after surgery. ABI, walking distance, Rutherford grade and clinical symptoms were significantly improved in the two groups compared with those before surgery. During the operation, 1 patient in the DCB group presented flow limiting interlayer and 1 patient still had>50% stenosis after predilation, and then underwent stent implantation for remediation. Conclusion: The treatment of lower limb arterial stenosis with DCB can obtain better near -and medium-term clinical efficacy.

Tenuivirus utilizes its glycoprotein as a helper component to overcome insect midgut barriers for its circulative and propagative transmission.

Many persistent transmitted plant viruses, including rice stripe virus (RSV), cause serious damage to crop production worldwide. Although many reports have indicated that a successful insect-mediated virus transmission depends on a proper interaction between the virus and its insect vector, the mechanism(s) controlling this interaction remained poorly understood. In this study, we used RSV and its small brown planthopper (SBPH) vector as a working model to elucidate the molecular mechanisms underlying the entrance of RSV virions into SBPH midgut cells for virus circulative and propagative transmission. We have determined that this non-enveloped tenuivirus uses its non-structural glycoprotein NSvc2 as a helper component to overcome the midgut barrier(s) for RSV replication and transmission. In the absence of this glycoprotein, purified RSV virions were unable to enter SBPH midgut cells. In the RSV-infected cells, this glycoprotein was processed into two mature proteins: an amino-terminal protein (NSvc2-N) and a carboxyl-terminal protein (NSvc2-C). Both NSvc2-N and NSvc2-C interact with RSV virions. Our results showed that the NSvc2-N could bind directly to the surface of midgut lumen via its N-glycosylation sites. Upon recognition, the midgut cells underwent endocytosis followed by compartmentalization of RSV virions and NSvc2 into early and then late endosomes. The NSvc2-C triggered cell membrane fusion via its highly conserved fusion loop motifs under the acidic condition inside the late endosomes, leading to the release of RSV virions from endosomes into cytosol. In summary, our results showed for the first time that a rice tenuivirus utilized its glycoprotein NSvc2 as a helper component to ensure a proper interaction between its virions and SBPH midgut cells for its circulative and propagative transmission.

A brainstem mass of Müllerian type Epithelial Origin without any primary cancer source.

Brainstem tumors are rare, even rarer is a brainstem tumor containing tissues of an embryologic gynecologic origin. We report a very rare case of presence of a calcified heterogeneously contrast enhancing brainstem mass of Müllerian origin in a patient in a 38 year old female with no female genital tract cancer and past surgical history of ventriculoperitoneal (VP) shunt placement for congenital hydrocephalus. To our knowledge this is the very first and unusual case of a mass of gynecologic origin in the brainstem region especially in the setting of no history of gynecological tumor. The authors also reviewed the literature for all tumors reported for anterograde and retrograde dissemination of tumor cells through VP shunt. This case is a reaffirmation of the importance of brain tumor location and tissue diagnosis for the purpose of adjuvant treatment of neurosurgical lesions in the neurocritical care setting. It also highlights the role of catheters as potential routes of iatrogenic transmission not just in anterograde but also in a retrograde manner to the CNS, which is very unusual. This is the only second case to report retrograde flow of tumor cells from an extraneural source up the VP catheters. The authors suggest that intraperitoneal chemotherapy should be considered in the cases of known extraneural abdominal malignancies of high malignant potential with or without the presence of peritoneal infiltration in order to avoid dissemination through VP shunts.

LncRNA-NEF inhibits proliferation, migration and invasion of esophageal squamous-cell carcinoma cells by inactivating wnt/ß-catenin pathway.

OBJECTIVE: Our study aimed to investigate the role of lncRNA-Neighboring Enhancer of FOXA2 (NEF) in esophageal squamous-cell carcinoma. PATIENTS AND METHODS: Tumor tissues and adjacent tissues were obtained from esophageal squamous-cell carcinoma patients, and blood samples were extracted from both patients with esophageal squamous-cell carcinoma and healthy volunteers. The expression of NEF was detected by quantitative Real-Time Polymerase Chain Reaction (qRT-PCR). All patients were followed-up for 5 years and ROC curve analysis and survival analysis were performed to evaluate the diagnostic and prognostic values of serum NEF for esophageal squamous-cell carcinoma. NEF expression vector was transfected into cells of esophageal squamous-cell carcinoma cell lines. Cell proliferation, migration and invasion were detected by CCK-8 assay, transwell migration assay, and transwell invasion assay, respectively. The interaction between NEF and wnt/ß-catenin pathway were explored by Western blot and qRT-PCR. RESULTS: Expression of NEF was significantly downregulated in tumor tissues than in adjacent tissues in most patients. Serum level of NEF was higher in esophageal squamous-cell carcinoma patients than in healthy controls, and was significantly correlated with tumor size and tumor distant tumor metastasis. Serum NEF is a promising diagnostic and prognostic marker for esophageal squamous-cell carcinoma. NEF overexpression inhibited cancer cell proliferation, migration and invasion. NEF overexpression decreased the expression levels of wnt/ß-catenin pathway-related proteins, while Wnt activator showed no significant effects on NEF. However, Wnt inhibitor reduced the effects of NEF overexpression on cell proliferation, migration and invasion. CONCLUSIONS: LncRNA NEF may inhibit the proliferation, migration and invasion of esophageal squamous-cell carcinoma cells by inactivating with wnt/ß-catenin pathway.

Surgical Management of Giant Retrocerebellar Arachnoid Cysts with a Cystoventricular Stent After Long-Term, Independent, and Simultaneous Intracystic and Intraventricular Pressure Monitoring.

BACKGROUND: Outcomes of surgical treated patients with giant retrocerebellar arachnoid cysts with the available typically preferred techniques frequently are unsatisfactory. OBJECTIVES: We hypothesized that a pressure gradient may exist between the cyst and the ventricular system that may be responsible for the posterior fossa-related symptoms and headaches, and, if so, that connecting both cavities by means of a shunt catheter (i.e., cystoventricular stent), the pressure differences would equilibrate and the symptoms resolve. To prove our hypothesis, we decided to simultaneously monitor the intracyst pressure and the intraventricular pressure. METHODS: This was a retrospective chart review analysis of 5 consecutive patients with giant retrocerebellar arachnoid cysts treated between 2014 and 2016. RESULTS: Four patients underwent 3 days of continuous intracranial pressure monitoring, and 1 patient was monitored in the surgical suit. Cyst and ventricular pressures tended to be within normal accepted values in all patients, and a pressure gradient was noticed only in the 2 patients with previous cyst surgeries. All patients were treated with a cystoventricular stent, and overall, had long-term sustained good outcomes, with resolution of symptoms in 3 and significant improvement in 2. CONCLUSIONS: Patients with symptomatic large retrocerebellar arachnoid cysts do not seem to have increased intracranial pressure, and regardless of the presence or absence of a pressure gradient between the cyst and the ventricles, a cystoventricular stent seems to be effective and the best first surgical option to offer.

Study the relevance between inflammatory factors and estradiol and their association with knee osteoarthritis in postmenopausal women.

OBJECTIVE: To investigate whether serum levels of inflammatory factors and estradiol (E2) are involved in the pathogenesis of postmenopausal women with knee osteoarthritis (OA). PATIENTS AND METHODS: 58 randomly patients diagnosed with postmenopausal knee OA that underwent orthopedic surgery from October 2013 to October 2016 in our hospital were selected. These patients, considered as the experimental group, according to the degree of cartilage damage, were divided into light, medium and heavy groups. 58 patients with menstrual disorders without knee OA were in the control group. 35 cases without osteoarthritis were included in the normal control group. Serum levels of interleukin-1 (IL-1), interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), erythrocyte sedimentation rate (ESR), high sensitive C- reactive protein (CRP), estradiol (E2) and IL-1, IL-6 and TNF-α levels in the synovial fluid of the experimental group were measured. RESULTS: The serum levels of IL-1, IL-6, TNF-α, and CRP in the normal control group, the control group and the experimental group were gradually increasing, the difference was statistically significant (p<0.05). The level of serum E2 was gradually decreasing (p<0.05); the difference of ESR between normal control group and control group had no significant difference (p>0.05), but the level of ESR in experimental group was higher than the normal control group and the control group (p<0.05). The serum levels of IL-1, TNF-α in experimental group of mild, moderate and severe sub-group were gradually increasing, the difference was statistically significant (p<0.05); while the level of IL-6 in the early, middle stage of OA increased significantly, and the late was reduced (p<0.05). The level of E2 was gradually decreased in the mild, moderate and severe sub-group of the experimental group, which had statistically significant difference (p<0.05). The level of serum E2 in the experimental group was positively correlated with the levels of IL-1, IL-6 and TNF-α in synovial fluid (p<0.05). CONCLUSIONS: The lack of estradiol is associated with the pathogenesis of OA in postmenopausal women, the inflammatory factors of IL-1, IL-6, TNF-α in postmenopausal increased in serum and synovial fluid may promote and aggravate the OA.

Acupuncture for reduction of symptom burden in multiple myeloma patients undergoing autologous hematopoietic stem cell transplantation: a randomized sham-controlled trial.

PURPOSE: Hematopoietic stem cell transplantation (HCT) is potentially curative for a number of hematologic malignancies, but is associated with high symptom burden. We conducted a randomized sham-controlled trial (RCT) to evaluate efficacy and safety of acupuncture as an integrative treatment for managing common symptoms during HCT. METHODS: Adult patients with multiple myeloma undergoing high-dose melphalan followed by autologous HCT (AHCT) were randomized to receive either true or sham acupuncture once daily for 5 days starting the day after chemotherapy. Patients and clinical evaluators, but not acupuncturists, were blinded to group assignment. Symptom burden, the primary outcome was assessed with the MD Anderson Symptom Inventory (MDASI) at baseline, during transplantation, and at 15 and 30 days post transplantation. RESULTS: Among 60 participants, true acupuncture produced nonsignificant reductions in overall MDASI core symptom scores and symptom interference scores during transplantation (P = .4 and .3, respectively), at 15 days (P = .10 and .3), and at 30 days posttransplantation (P = .2 and .4) relative to sham. However, true acupuncture was significantly more efficacious in reducing nausea, lack of appetite, and drowsiness at 15 days (P = .042, .025, and .010, respectively). Patients receiving sham acupuncture were more likely to increase pain medication use posttransplantation (odds ratio 5.31, P = .017). CONCLUSIONS: Acupuncture was well tolerated with few attributable adverse events. True acupuncture may prevent escalation of symptoms including nausea, lack of appetite, and drowsiness experienced by patients undergoing AHCT, and reduce the use of pain medications. These findings need to be confirmed in a future definitive study. TRIAL REGISTRATION: NCT01811862.

Imatinib-induced ophthalmological side-effects in GIST patients are associated with the variations of EGFR, SLC22A1, SLC22A5 and ABCB1.

Imatinib-induced ophthalmological side-effects, including conjunctiva hemorrhage and periorbital oedema, although very common and still remain relatively little understood. The present study investigated the effects of genetic polymorphisms of drug targets and membrane transporters on these side effects. We found that the minor allele of EGFR rs10258429 and SLC22A1 rs683369 were significant risk determinants of conjunctival hemorrhage with OR of 7.061 (95%CI=1.791-27.837, P=0.005 for EGFR rs10258429 CT+TT vs CC), and 4.809 (95%CI=1.267-18.431, P=0.021 for SLC22A1 rs683369 GG+CG vs CC). The minor allele of SLC22A5 rs274558 and ABCB1 rs2235040 were protective factors to periorbital oedema with OR of 0.313 (95%CI=0.149-0.656, P=0.002 for SLC22A5 rs274558 AA+AG vs GG), and 0.253 (95%CI=0.079-0.805, P=0.020 for ABCB1 rs2235040 CT vs CC). These results indicated that variants in EGFR, SLC22A1, SLC22A5 and ABCB1 influenced the incidence of Imatinib-induced ophthalmological toxicities, and polymorphism analyses in associated genes might be beneficial to optimize Imatinib treatment.

Cadherin 6 is activated by Epstein-Barr virus LMP1 to mediate EMT and metastasis as an interplay node of multiple pathways in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is an epithelial malignancy, which is notorious among head-and-neck cancers with its metastatic feature. Epstein-Barr virus (EBV) infection plays a fundamental role in NPC development with the mechanism is not well understood. Here we demonstrate that EBV oncoprotein LMP1 drives EMT and metastasis of NPC by reactivating the adhesion molecule, cadherin 6 (CDH6), which normally occurs in embryogenesis with unknown role in NPC. CDH6 was found to be upregulated in LMP1-positive NPC tissues, and was identified as a target of the epithelium-specific miR-203. LMP1-activated NF-κB transcriptionally repressed the miR-203 expression by binding to the promoter region of miR-203 gene. CDH6 activation in turn induced EMT and promoted metastasis in NPC. CDH6 depletion, NF-κB inhibitor and miR-203 overexpression were able to impair the EMT effects. The miR-203 downregulation in NPC tissues was strongly associated with metastasis clinically. The CDH6 activator, Runt-related transcription factor 2 (RUNX2), was also activated by EBV in the event. For both CDH6 and RUNX2 are components at TGF-ß downstream, CDH6 became a node protein for the interplay of multiple signalings including NF-κB and TGF-ß. Therefore, the switch-on of miR-203 was important for nasopharyngeal epithelial cells to maintain normal phenotype. This study demonstrates that EBV has evolved sophisticated strategies by driving epithelial cells to obtain malignant features, particularly in NPC metastasis, providing novel biomarkers for the therapy and prognosis of EBV-associated NPC.