Prevalence and Risk Factors of Frailty in Stroke Patients: A Meta-Analysis and Systematic Review.

OBJECTIVES: Summarize the existing evidence regarding the prevalence and risk factors of frailty in stroke patients. DESIGN: A meta-analysis and systematic review. PARTICIPANTS: Stroke patients in hospitals or communities. METHODS: We undertook a systematic review and meta-analysis using articles available in 8 databases, including PubMed, The Cochrane Library, Web of Science, Embase, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Weipu Database (VIP) from January 1990 to April 2022. Studies were quality rated using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality tool. RESULTS: A total of 24 studies involving 30,423 participants were identified. The prevalence of frailty and pre-frailty in stroke patients was 27% (95%CI: 0.23-0.31) and 47.9% (95%CI: 0.43-0.53). Female gender (OR = 1.76, 95%CI: 1.63-1.91), advanced age (MD = 6.73, 95%CI: 3.55-9.91), diabetes (OR = 1.34, 95%CI: 1.06-1.69), hyperlipidemia (OR = 1.46, 95%CI: 1.04-2.04), atrial fibrillation (OR = 1.36, 95%CI: 1.01-1.82), National Institutes of Stroke Scale (NIHSS) admission scores (MD = 2.27, 95%CI: 1.72-2.81) were risk factors of frailty in stroke patients. CONCLUSIONS: Frailty was more prevalent in stroke patients. Female gender, advanced age, diabetes, hyperlipidemia, atrial fibrillation, and National Institutes of Stroke Scale (NIHSS) admission scores were identified as risk factors for frailty in stroke patients. In the future, medical staff should pay attention to the early screening of frailty in high-risk groups and provide information on its prevention.

[Application of robot-assisted laparoscopic sentinel lymph node tracing in treating endometrial carcinoma].

Objective: To investigate the value of robot-assisted laparoscopic indocyanine green sentinel lymph node (SLN) tracing in treating endometrial carcinoma. Methods: Thirty-two patients with early-staging endometrial carcinoma were operated with laparoscopic comprehensive staging laparotomy from January 2019 to December 2021. At the same time, the SLN detection was performed by near-infrared fluorescence imaging tracer technology, in which the tracer was indocyanine green. Sixteen cases were injected with indocyanine green before laparoscopic surgery, and 16 cases were injected with indocyanine green before robot-assisted laparoscopic surgery. The operation index, postoperative complications, prognosis, and lymph node dissection were compared between the two groups. Results: (1) The mean age of patients in the robot group was (54.7±8.1) years old, and was (54.9±8.8) years old in the laparoscopic group. There were no significant difference between the two groups (t=0.06, P=0.951). (2) Intraoperative blood loss [(131±40) vs (169±57) ml], hemoglobin difference before and after surgery [(11.2±5.4) vs (15.5±5.7) g/L], the length of stay after operation [(6.2±1.3) vs (8.6±1.4) days] between the robot group and the laparoscopic group were compared, and the differences were statistically significant (all P<0.05). (3) SLNs were detected in all 16 patients in the robotic group, and a total of 41 SLNs were detected. SLNs were detected in 15 of the 16 patients in the laparoscopy group, and a total of 40 SLNs were detected. Compared with the laparoscopic group (15/16), the total detection rate of SLN in the robotic group (16/16), there were no statistical significance (χ2=1.03, P=0.310). Compared with the laparoscopic group (7/15), the SLN bilateral detection rate in the robotic group (10/16), there were also no significant difference (χ2=0.78, P=0.376). The number of lymph nodes detected in surgery group (16.6±4.1) were lower than those in the laparoscopy surgery group (21.0±7.1), while there were no statistically difference between the two groups (χ2=2.01, P=0.054). There was no tumor metastasis in the resected lymph nodes and SLN between the two groups. The false negative rate of SLN in diagnosing endometrial cancer postoperative lymph node metastasis was 0, and the negative predictive value was 100%. (4) The pelvic and retroperitoneal lymph nodes were divided into five regions, which were the left pelvis, the right pelvis, the presacral region, the deep inguinal region, and the abdominal aorta. The numbers of SLN of unilateral detection and bilateral pelvic detection between two groups showed no significant differences (all P>0.05). The left pelvis had the most SLN imaging in both groups, followed by the right pelvis, para-aortic, and deep groin. (5) There was one patient in both robotic group and laparoscopic group with postoperative complications, which were urinary retention and pelvic lymph node cyst respectively. There were no significant differences in the incidence of complications between the two groups (χ2=0.97, P=1.000). The median follow-up time after operation was 14 months (range 6-24 months). During the follow-up period, no local recurrence or distant metastasis was found between the two groups of endometrial cancer patients. Conclusions: Compared with the laparoscopic group, the robot group has less intraoperative blood loss and shorter postoperative hospital stay. The bilateral detection rate of SLN in the group was better than that of laparoscopy.

[Biological characteristics of sheep peripheral blood mesenchymal stem cell].

OBJECTIVE: To obtain eripheral blood mesenchymal stem cells (PBMSCs) from sheep and rabbits by continuous mobilization of granulocyte colony-stimulating factor (G-CSF), and by comparing the success rates, cell yields and biological characteristics of the two sources of PBMSCs, and to provide the experimental basis for the preclinical study of PBMSCs transplantation to repair articular cartilage injury and cartilage tissue engineering. METHODS: Through morphological characteristics, flow cytometry analysis of its surface markers, and induction of trilineage differentiation of the two cells in vitro (ie: adipogenic differentiation, osteogenic differentiation, chondrogenic differentiation), the obtained cells were finally confirmed to be PBMSCs. The colony-forming units (CFUs) and the acquisition success rates of the two PBMSCs were counted and compared, and the production of the second generation of the two PBMSCs was counted and compared by hemocytometer, and the cell counting kit-8 was used to detect the doubling time of the two PBMSCs, and the results of trilineage differentiation were quantitatively analyzed by image processing. RESULTS: Microscopically, the PBMSCs of fusiform sheep and rabbits were arranged in fish group, and the second generation of sheep and rabbit PBMSCs expressed CD44 and CD90, but not CD34 and CD45. The induction of trilineage differentiation of the two cells in vitro were successful. The CFUs of primary sheep and rabbits PBMSCs were: 7.27±1.56, 5.73±1.62, and the success rate of acquisition of sheep and rabbits PBMSCs were 78.57% and 36.67%. The number of the second-generation sheep and rabbits PBMSCs that obtained per milliliter of peripheral blood were: 29 582±2 138, 26 732±2 286, and the cell doubling times (h) of the third-generation sheep and rabbits PBMSCs were: 22.32±0.28, 33.21±0.64, the cell doubling time (h) of the fourth generation sheep and rabbits PBMSCs were: 23.62±0.56, 35.30±0.38, and the quantitative lipid ratio of sheep and rabbit PBMSCs were: 7.77%±3.81%, 17.05%±1.52%, sheep and rabbit PBMSCs chondroglobus acid mucopolysaccharide positive ratios were: 11.67%±0.53%, 8.14%±0.57%. There were statistical differences among the above groups (P < 0.05). CONCLUSION: The continuous mobilization of G-CSF to obtain sheep PBMSCs is more efficient. Sheep PBMSCs have more abundant yield and stronger proliferation ability.Sheep PBMSCs can produce more acidic mucopolysaccharides and have lower adipogenic abi-lity under appropriate conditions. Sheep PBMSCs have good research prospects in repair of articular cartilage injury with autologous stem cell transplantation and preclinical animal in vivo experiment of cartilage tissue engineering.This experiment provides further experimental basis for this kind of research.

Penetration of inferior alveolar nerve canal increased by bicortical fixation after bilateral sagittal split osteotomy in mandibular prognathism.

The purpose of this three-dimensional cone beam computed tomography (CBCT) study was to identify the difference between monocortical fixation (MCF) and bicortical fixation (BCF) in mandibular canal penetration after bilateral sagittal split osteotomy (BSSO) to correct mandibular prognathism, where interosseous fixation was done by BCF or MCF. CBCT was performed 1 week postoperatively and Dolphin 3D software was used to assess direct penetration of the mandibular canal by either type of screw. The primary outcome variable was the presence or absence of mandibular canal penetration and was categorized as a binary coded variable. The BCF and MCF groups were compared by χ2 test, and the odds ratio for canal penetration was estimated. Multiple logistic regression was performed to identify factors related to canal penetration. A total of 118 patients were included. The MCF group had only 6% canal penetrations (3/50 patients) and the BCF group had 58.8% canal penetrations (40/68 patients). The regression model showed that BCF was the only factor causing mandibular canal penetration, with an adjusted odds ratio of 52.5. Awareness of the increased risk of canal penetration with BCF and potential nerve injury might influence case selection.

[Analysing pathogenic bacterial spectrum and drug resistance of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation].

Objective: To elucidate the clinical characteristics of bloodstream infection in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT) in our hospital and improves the survival of transplant patients with bloodstream infection. Methods: Two hundred and ten patients with allo-HSCT from the Department of Hematology were retrospectively analyzed between October 2014 and September 2019. Pathogen distribution, drug resistance, risk factors, and outcomes were investigated in 49 allo-HSCT patients with bloodstream infections. Results: Forty-nine of 210 patients with allo-HSCT had bloodstream infection, and 59 pathogenic microorganisms were identified, mainly Gram-negative bacteria (67.8%) , of which E. coli had the highest incidence (23.7%) , CRO accounted for 42.5%, and Grampositive bacteria accounted for 23.7% (without vancomycin or linezolid-resistant strain) . Additionally, fungi accounted for 8.5%. Univariate analysis suggested that the risk factors of bloodstream infection were gender, pretransplant disease status, and conditioning regimen. In contrast, multivariate analysis showed that bloodstream infection was mainly related to conditioning regimens. Further grouping results showed that 77.6% of patients with neutropenia had bloodstream infections, and 22.4% of patients with non-neutropenia had bloodstream infections; 81.0% of patients with active infections before transplantation had bloodstream infections, while bloodstream infection occurred in 16.9% of patients without active infection. Survival analysis showed that long-term survival of patients with bloodstream infection is shorter than that of patients without bloodstream infection and long-term survival of patients with CRO infection is shorter than that of patients without CRO infection. The survival of patients with neutropenia longer than 14 d is shorter than that of patients with neutropenia shorter than 14 d. Furthermore, there is no correlation between whether there is an active infection before transplantation and whether they are in a neutropenic state at the time of infection and survival. Conclusion: Our results suggest that effective prevention of bloodstream infections from drug-resistant bacteria, particularly CRO, shortening the duration of neutropenia, eradication of potential infections before transplantation, and patient-adaptive conditioning could reduce transplant-related mortality and improve prognosis.

[Association between pulse pressure and new-onset diabetes in hypertensive patients].

Objective: To determine the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Methods: In this prospective cohort study, hypertensive patients from the Kailuan Study, who were diagnosed in 2006-2007 check-up, were screened for enrollment. Participants who finished the biennial follow-up until December 31, 2017 were finally included in this analysis. The primary outcome was incident diabetes development. The pulse pressure variables were divided into quartiles (Q1-Q4), and the Kaplan-Meier curve was used to examine and estimate the cumulative incidence of new-onset diabetes among quartiles. Cox proportional hazards regression model was performed to explore the association between pulse pressure and the risk of new-onset diabetes in hypertensive patients. Results: During an average follow-up of 8.17 years, 6 617 new-onset diabetes were identified out of the 32 917 hypertensive patients with no history or evidence of diabetes in 2006-2007 check-up. Participants were classified into quartiles according to pulse pressure levels as follows: Q1 group(<41 mmHg (1mmHg=0.133kPa))(n=7 995); Q2 group(41-<51 mmHg) (n=8 196); Q3 group (51-<61 mmHg) (n= 8 270); Q4 group (≥61 mmHg) (n=8 456). The cumulative incidences of new-onset diabetes across the quartiles were 16.94%, 19.61%, 21.07%, and 22.33%, respectively, with the incidence density was 20.27, 23.20, 24.92, and 26.10 per 1 000 person-years, respectively. The cumulative incidence of new-onset diabetes increased in proportion with increasing pulse pressure levels (P<0.01 by the Log-rank test). After multivariate adjustment, compared with the first quartile, the hazard ratios for new-onset diabetes in the third and fourth quartiles were 1.13 (95%CI 1.04-1.22, P<0.01) and 1.14 (95%CI 1.05-1.24, P<0.01), respectively. The risk of new-onset diabetes increased 5%(HR=1.05, 95%CI 1.02-1.08, P<0.01) with the fractional pulse pressure increased per 1 SD (0.13). Findings from the three sensitivity analyses were consistent with the main results in this cohort. Conclusions: Pulse pressure at baseline is positively associated with the incidence of new-onset diabetes among hypertensive individuals, and pulse pressure is an independent risk factor for the development of diabetes in hypertensive patients.

Effects of Exercise Alone or in Combination with High-Protein Diet on Muscle Function, Aerobic Capacity, and Physical Function in Middle-Aged Obese Adults: A Randomized Controlled Trial.

BACKGROUND: Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults. MATERIALS AND METHODS: Sixty-nine middle-aged (50-64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a high-protein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention. RESULTS: After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test). CONCLUSIONS: For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.

The impact of a surgery-first approach on oral health-related quality of life.

Orthognathic surgery using a surgery-first approach (SFA) has been shown to result in better quality of life (QoL) throughout the treatment duration; however, the effects of gender, age and type of dentofacial deformity on SFA-related QoL remain unknown. In total, 228 consecutive patients underwent SFA for correction of dentofacial deformities (skeletal class III, bimaxillary protrusion and facial asymmetry). We assessed their QoL before surgery and at 1, 6 and 12 months after surgery using the Orthognathic Quality of Life Questionnaire (OQLQ). The results indicated a significant decrease in the total OQLQ, facial aesthetics and social aspect domain scores 1, 6 and 12 months after surgery. Among all domains, the greatest improvement was noted in the facial aesthetics domain. The oral function scores declined significantly immediately after surgery, but improved significantly 6 and 12 months after surgery; however, the awareness scores remained relatively stable. At each time point, women and the bimaxillary protrusion group exhibited a significantly higher total and specific domain scores. Patients aged 18-22 years exhibited lower total and four specific domain scores than older patients. Thus, QoL improves in all aspects, except awareness domain, by 12 months after SFA, but gender, age, and type of dentofacial deformity affect this improvement.

[Study of PA-HSOS severity grading to predict the prognosis of patients with PA-HSOS treated by transjugular intrahepatic portosystemic shunt].

Objective: To explore pyrrolizidine alkaloid-induced hepatic sinusoidal obstruction syndrome (PA-HSOS) severity grading to predict the prognostic value for PA-HSOS patients treated with transjugular intrahepatic portosystemic shunt (TIPS). Methods: Clinical data of patients with PA-HSOS who were critically ill or had ineffective drug treatment and underwent TIPS treatment from December 2013 to September 2019 were retrospectively analyzed. PA-HSOS severity grading criteria in adult was quoted, revised and defined from the European Group for Blood and Marrow Transplantation (EBMT). The survival time, the rate of shunt dysfunction and the incidence of postoperative hepatic encephalopathy in different severity groups after TIPS were compared. Univariate Cox or Binomial Logistic regression analysis was used to evaluate the impact of each variable. Variables with P < 0.1 were regarded as statistically significant variables for the prognosis, and were introduced into Cox or Binomial Logistic regression hierarchical regression analysis as controlled covariates. PA-HSOS severity grading was analyzed as dummy variables. Results: A total of 102 patient data were collected, and the median follow-up time was 14.52 months. The difference in survival time of patients with different severity levels was statistically significant (P = 0.023). The mortality risk in moderate patients was 1.575 times higher than that of mild patients (95%CI: 0.216-11.457, P = 0.654). The mortality risk of severe and very severe patients was 7.424 times higher than that of mild patients (95% CI: 1.612-34.197, P = 0.010). There was no statistically significant difference in postoperative hepatic encephalopathy recurrence rate and shunt dysfunction rate (P > 0.05). Conclusion: PA-HSOS severity grading has prognostic value for PA-HSOS patients receiving TIPS treatment, and can be used as an important reference for guiding the timing of TIPS intervention.

Upregulation of lncRNA DANCR functions as an oncogenic role in non-small lung cancer by regulating miR-214-5p/CIZ1 axis.

OBJECTIVE: Lung cancer has an unfavorable prognosis due to the lack of efficient diagnostic and therapeutic strategies. Therefore, this study sought to figure out the effect of long non-coding RNA (lncRNA) DANCR on lung cancer progression. PATIENTS AND METHODS: LncRNA DANCR and miR-214-5p expressions in non-small cell lung cancer (NSCLC) were detected by Real Time-quantitative Polymerase Chain Reaction (RT-qPCR). Function assays, including Cell Counting Kit-8 (CCK-8) and flow cytometric analysis were conducted to clarify the role of DANCR and miR-214-5p in the progression of NSCLC. Western blot, Dual-Luciferase reporter assay, and RNA immunoprecipitation assay (RIP) were performed to elucidate the underlying mechanism. RESULTS: LncRNA DANCR was upregulated in NSCLC. The knockdown of lncRNA DANCR inhibited cell proliferation and accelerated cell apoptosis in NSCLC. LncRNA DANCR interacted with miR-214-5p. MiR-214-5p over-expression partially reversed the regulatory effects of DANCR on proliferation and apoptosis in NSCLC. In addition, CIZ1 was the downstream gene binding miR-214-5p. LncRNA DANCR could regulate the miR-214-5p/CIZ1 axis. CONCLUSIONS: Downregulation of lncRNA DANCR inhibited cell proliferation and induced cell apoptosis in NSCLC by regulating the miR-214-5p/CIZ1 axis. LncRNA DANCR may act as an oncogene and promote the progression of NSCLC.

Long-term comparison study of philtral ridge morphology with two different techniques of philtral reconstruction.

Cleft lip and/or cleft palate are the most common congenital craniofacial anomalies. Philtral ridge morphology is an important aesthetic component of unilateral cleft lip (UCL) repair. To this end, we have developed two techniques of philtral ridge reconstruction: (1) asymmetric mattress muscle sutures, and (2) overlapping mattress muscle sutures. The objective of this retrospective cohort study was to compare their outcomes in UCL repairs. Group I patients (n=30) underwent UCL repair before August 2003, including philtral ridge reconstruction by asymmetric mattress muscle sutures. Group II patients (n=30) underwent UCL repair after August 2003, including philtral ridge reconstruction by overlapping mattress muscle sutures. Philtral morphology was evaluated by ultrasonographic and three-dimensional photographic measurements, examining cleft side philtral projection and philtral ridge symmetry. These demonstrated that group II patients had better philtral column symmetry and projection on the cleft side when compared to group I. Overlapping mattress muscle sutures produced better philtral morphology in UCL repairs than asymmetric mattress muscle sutures.

Is skeletal stability after bimaxillary surgery for skeletal class III deformity related to surgical occlusal contact?

A stable occlusion at the time of surgery is considered important for post-surgical stability after orthognathic surgery. The aim of this study was to determine whether skeletal stability after bimaxillary surgery using a surgery-first approach for skeletal class III deformity is related to the surgical occlusal contact or surgical change. Forty-two adult patients with a skeletal class III deformity corrected by Le Fort I osteotomy and bilateral sagittal split osteotomy with a surgery-first approach were studied. Dental models were set and used to measure the surgical occlusal contact, including contact distribution, contact number, and contact area. Cone beam computed tomography was used to measure the surgical change (amount and rotation) and post-surgical skeletal stability. The relationship between skeletal stability and surgical occlusal contact or surgical change was evaluated. No relationship was found between maxillary or mandibular stability and surgical occlusal contact. However, a significant relationship was found between maxillary and mandibular stability and the amount and rotation of surgical change. The results suggest that in the surgical-orthodontic correction of skeletal class III deformity with a surgery-first approach, the post-surgical skeletal stability is not related to the surgical occlusal contact but is related to the surgical change.

Isolation of Desulfovibrio spp. from human gut microbiota using a next-generation sequencing directed culture method.

Desulfovibrio spp. is predominant member of sulphate-reducing bacteria in human gut microbiota. Previous studies indicated that the isolation of Desulfovibrio strains from human faecal samples is very important to study the roles of human intestinal Desulfovibrio spp. in maintaining healthy states or causing diseases, as well as defining their biological characteristics. However, there are very few reports describing the isolation of Desulfovibrio spp. from human faecal samples. In this study, faecal samples were inoculated into various media containing different components. The enriched culture communities were identified using 16S rRNA gene high-throughput sequencing analysis, enabling us to identify the specific components that enable the enrichment of Desulfovibrio. Using this information, we developed five specific media and identified an effective enrichment medium that produced the highest relative abundance of Desulfovibrio in communities cultured from four faecal samples (26·5, 73·5, 44·7 and 77·6% respectively). In addition, the major non-Desulfovibrio genera were identified. Finally, three species of Desulfovibrio, D. desulfuricans, D. piger and D. legallii were isolated, representing the first time that has D. legallii been isolated from a human gastrointestinal source. SIGNIFICANCE AND IMPACT OF THE STUDY: ost of the human intestinal bacteria have not been cultured because of lack of appropriate culture method and appropriate media. Desulfovibrio spp. is associated with several clinical conditions like inflammatory bowel disease, but until now there are very few reports describing the isolation of Desulfovibrio spp. from human faecal samples. In this study, 16S rRNA gene high-throughput sequencing analysis was applied to screen appropriate enrichment media and selective cultivation of Desulfovibrio. This sequencing-based directed culture method described here can be used for the selective cultivation of gut bacteria of interest.

HCCS1 inhibits the stemness of human pancreatic cancer stem-like cells.

OBJECTIVE: SW1990-spheroid enrichment (SW1990-SE) cells were isolated using a new type of consecutive spheroid enrichment in this study. Cell surface markers were determined by flow cytometry for identification. In vivo tumorigenicity was applied by subcutaneous transplantation in nude mice for verifying the stemness characteristics of SW1990-SE cells. MATERIALS AND METHODS: SW1990-SE cells were subjected to lentivirus infection for establishing the SW1990-SE cell line stably low-expressing HCCS1 (SW1990-SE-shHCCS1) and negative control cell line (SW1990-SE-LV3NC). The stemness regulatory effects of HCCS1 on SW1990-SE cells were evaluated by cell counting kit-8 (CCK-8) assay and 96-wells plate single cell cloning assay in vitro. Subcutaneous transplantation in nude mice was conducted for evaluating the in vivo stemness regulation of HCCS1 on SW1990-SE cells.. RESULTS: HCCS1 knockdown in SW1990-SE cells did not markedly change the cell proliferation and doubling time, whereas the in vitro spheroid diameter and single cell cloning efficacy remarkably increased. In vivo experiments showed that HCCS1 knockdown greatly enhanced the tumorigenicity of SW1990-SE cells in nude mice. CONCLUSIONS: This study first obtains the human pancreatic cancer stem-like cells SW1990-SE through consecutive spheroid enrichment. Both in vivo and in vitro experiments verified that HCCS1 knockdown largely enhanced the stemness of SW1990-SE cells. Our study provides an important reference for the research of tumor stem cells.

[Diagnostic value of combination of US and MRI in preoperative prediction for the extrathyroidal extension of papillary thyroid carcinoma].

Objective: The purpose of the present study was to evaluate the diagnostic performance of preoperative ultrasonography(US), magnetic resonance imaging(MRI) and US combined with MRI in the prediction of extrathyroidal extension(ETE) in patients with papillary thyroid carcinoma(PTC). Methods: Between January 2013 and December 2016, a total of 83 consecutive patients underwent surgery for pathologically confirmed PTCs with ETE. We analyzed all patients with PTC with ETE who received preoperative combination of US and MRI scan to evaluate ETE. Results: For minimal ETE, the accuracy was 92.2%(47/51) of US, 74.5%(38/51) of MRI, and their combination was 98.0%(50/51). The differences of the three methods for minimal ETE were statistically significantly different(P=0.000). For extensive ETE, the accuracy was 62.5%(20/32) of US, 87.5%(28/32) of MRI, and their combination was 93.8%(30/32). The different of the three methods for extensive ETE was statistically significantly different(P=0.000). For the total accuracy of ETE, US was 80.7%(67/83), MRI was 79.5% (66/83), and their combination was 96.4%(80/83). The difference of the three methods for ETE was statistically significantly different(P=0.001). Conclusion: The combination of US and MRI can improve the preoperative diagnostic accuracy of ETE for PTC.

An αIIb ß3 antagonist prevents thrombosis without causing Fc receptor γ-chain IIa-mediated thrombocytopenia.

Essentials FcγRIIa-mediated thrombocytopenia is associated with drug-dependent antibodies (DDAbs). We investigated the correlation between αIIb ß3 binding epitopes and induction of DDAbs. An FcγRIIa-transgenic mouse model was used to evaluate thrombocytopenia among anti-thrombotics. An antithrombotic with binding motif toward αIIb ß-propeller domain has less bleeding tendency. SUMMARY: Background Thrombocytopenia, a common side effect of Arg-Gly-Asp-mimetic antiplatelet drugs, is associated with drug-dependent antibodies (DDAbs) that recognize conformation-altered integrin αIIb ß3 . Objective To explore the correlation between αIIb ß3 binding epitopes and induction of DDAb binding to conformation-altered αIIb ß3 , we examined whether two purified disintegrins, TMV-2 and TMV-7, with distinct binding motifs have different effects on induction of αIIb ß3 conformational change and platelet aggregation in the presence of AP2, an IgG1 inhibitory mAb raised against αIIb ß3 . Methods We investigated the possible mechanisms of intrinsic platelet activation of TMV-2 and TMV-7 in the presence of AP2 by examining the signal cascade, tail bleeding time and immune thrombocytopenia in Fc receptor γ-chain IIa (FcγRIIa) transgenic mice. Results TMV-7 has a binding motif that recognizes the αIIb ß-propeller domain of αIIb ß3 , unlike that of TMV-2. TMV-7 neither primed the platelets to bind ligand, nor caused a conformational change of αIIb ß3 as identified with the ligand-induced binding site mAb AP5. In contrast to eptifibatide and TMV-2, cotreatment of TMV-7 with AP2 did not induce FcγRIIa-mediated platelet aggregation and the downstream activation cascade. Both TMV-2 and TMV-7 efficaciously prevented occlusive thrombosis in vivo. Notably, both eptifibatide and TMV-2 caused severe thrombocytopenia mediated by FcγRIIa, prolonged tail bleeding time in vivo, and repressed human whole blood coagulation indexes, whereas TMV-7 did not impair hemostatic capacity. Conclusions TMV-7 shows antiplatelet and antithrombotic activities resulting from a mechanism different from that of all other tested αIIb ß3 antagonists, and may offer advantages as a therapeutic agent with a better safety profile.

Deficiency in VHR/DUSP3, a suppressor of focal adhesion kinase, reveals its role in regulating cell adhesion and migration.

Vaccinia H1-related phosphatase (VHR/DUSP3) is a member of the dual-specificity phosphatase family. Deregulation of VHR is observed in various malignant diseases. We identified focal adhesion kinase (FAK) as a VHR-interacting molecule. Over-expression of VHR decreased tyrosine phosphorylation of FAK and decreasing VHR promoted FAK tyrosine phosphorylation. In vitro assays proved that recombinant VHR directly dephosphorylated FAK and paxillin. VHR-knockout mice did not have obvious abnormality; however, VHR-knockout cells showed decreased expression of integrins and FAK but stronger FAK and paxillin phosphorylation upon attachment to fibronectin. Additionally, VHR-knockout fibroblast and lung epithelial cells had elevated ligand-induced epidermal growth factor receptor (EGFR) phosphorylation. Inducible expression of VHR suppressed directional cell migration, and VHR deficiency resulted in a higher cell migratory ability. VHR-knockout cells have stronger FAK phosphorylation in cell adhesions, long-lasting trailing ends and slower turnover of focal adhesions. These collective data indicate that VHR is a FAK phosphatase and participates in regulating the formation and disassembly of focal adhesions.

[Anatomic study and clinical practice of mesopancreas and total mesopancreatic excision].

Objective: To explore the anatomical characteristics of the mesopancreas, to define the range of the total mesopancreas excision and to evaluate the feasibility, safety and effectiveness in the treatment of pancreatic cancer. Methods: A regional anatomical and pathological study was performed on 14 cadavers with large slices and paraffin sections. The clinical and pathological data of 58 consecutive patients underwent total mesopancreas excision for pancreatic head carcinoma from January 2013 to December 2015 were prospectively collected and analysed. The perioperative morbidity, mortality and clinical outcomes of patients underwent total mesopancreas excision were compared with the patients underwent conventional pancreaticoduodenectomy from January 2010 to December 2012. Results: The mesopancreas located in the retropancreatic area, extending from the head, neck, and uncinated process of pancreas to the aorto-caval groove, in which there were loose areolar tissue, adipose tissue, nerve plexus, lymphatic and capillaries. Although no fibrous sheath or fascia like mesocolorectum was found around the structures, a relatively fixed extent could be defined according to its embryologic and anatomic characters. In clinical practice, total mesopancreas excision was classified into two levels according to the extent of resection in this series: level Ⅰ was a"standard total mesopancreas excision" or"total mesopancreas excision in a narrow sense" , which was similar to the extent of standard resection from consensus statement of ISGPS. Level Ⅱ was defined as any procedure extending the range of level Ⅰ, called the"extended total mesopancreas excision" or"total mesopancreas excision in a broad sense". In TMpE group, the intraoperative blood loss( (461.4±184.5)ml vs. (532.2±319.8)ml, P=0.301), operation time( (368.6±92.5)minutes vs. (397.1±112.7)minutes, P=0.559), total complication rate (39.7% vs. 51.2%, P=0.250), fistula mortality (25.9% vs. 30.2%, P=0.628) were all reduced. There were significantly higher R0 rate (91.4% vs.76.7%, P=0.041) and more harvested lymph nodes (16.2 vs. 11.4, P=0.000) and lower total and local recurrence: rate (half-year local recurrence rate: 7.8% vs. 23.7%, P=0.036; one-year local recurrence rate: 18.2% vs. 39.5%, P=0.018) and longer disease-free survival (16.9 months vs. 13.4 months, P=0.044) and overall survival(22.5 months vs. 19.9 months, P>0.05) were also found in the study group. Conclusions: Mesopancreas is different from mesorectum since it has no fascial envelop, which should be regarded as a surgical concept, rather than an anatomical structure. Total mesopancreas excision is safe and feasible for pancreatic head cancer and probably helps to increase the R0 resection rate and improve the clinical outcomes.

Protein disulfide isomerase a4 acts as a novel regulator of cancer growth through the procaspase pathway.

Protein disulfide isomerase a4 (PDIA4) is implicated in the growth and death of tumor cells; however, its molecular mechanism and therapeutic potential in cancer are unclear. Here, we found that PDIA4 expression was upregulated in a variety of tumor cell lines and human lung adenocarcinoma tissues. Knockdown and overexpression of PDIA4 in tumor cells showed that PDIA4 facilitated cell growth via the reduction of caspases 3 and 7 activity. Consistently, Lewis lung carcinoma cells overexpressing PDIA4 grew faster than did parental cells in tumor-bearing mice, as shown by a reduced survival rate, increased tumor size and metastasis, and decreased cell death and caspases 3 and 7 activity. PDIA4 knockdown resulted in opposite outcomes. Moreover, results obtained in mice with spontaneous hepatoma indicated that PDIA4 deficiency significantly reduced hepatic tumorigenesis and cyst formation and increased mouse survival, tumor death, and caspases 3 and 7 activity. Mechanistic studies illustrated that PDIA4 negatively regulated tumor cell death by inhibiting degradation and activation of procaspases 3 and 7 via their mutual interaction in a CGHC-dependent manner. Finally, we found that 1,2-dihydroxytrideca-5,7,9,11-tetrayne, a PDIA4 inhibitor, reduced tumor development via enhancement of caspase-mediated cell death in TSA tumor-bearing mice. These findings characterize PDIA4 as a negative regulator of cancer cell apoptosis and suggest that PDIA4 is a potential therapeutic target for cancer.