A real-world pharmacovigilance study of abaloparatide based on the FDA Adverse Event Reporting System (FAERS).

Abaloparatide (ABL) is a US Food and Drug Administration-approved parathyroid hormone-related peptide analog for treatment of osteoporosis in postmenopausal women at high risk of fracture. However, real-world data regarding its long-term safety and tolerability in large sample population are incomplete. We evaluated abaloparatide-associated safety signals by data mining of the FDA pharmacovigilance database. INTRODUCTION: We investigated 33,480(0.14%) ABL-related adverse events (AEs) through data mining of Food and Drug Administration Adverse Event Reporting System (FAERS) retrospectively. METHODS: Reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) were employed to quantify the signals of ABL-related AEs from 2017Quarter2 to 2022.Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (χ2) test. RESULTS: We collected 8,470,497 reports from the FAERS database, including 11,487 reports defined ABL as the primary suspected (PS) drug. Additionally, 36.16% of the reports were submitted by healthcare professionals (n=4154), compared to 62.26% reported by consumers (n=7140). A total 99 signals simultaneously conforming to four algorithms were detected, among which, 35 signals were identified as unexpected signals. Such as growing pains (n=13), waist circumference increased (n=21), sensory disturbance (n=103), tinnitus (n=65), visual acuity reduced (n=54), blood alkaline phosphatase increased (n=61), and hair growth abnormal (n=13). Patient age (p < 0.001) might be associated with an increased risk of AEs severity. The most common timeframe for AE occurrence was 0-7 days. CONCLUSION: Our study provided a deeper and broader understanding of abaloparatide's safety profiles, which would help healthcare professionals to mitigate the risk of AEs in clinical practice, a low number of unexpected AEs supporting ongoing additional pharmacovigilance.

Research and application of a new multilevel fuzzy comprehensive evaluation method for cold stress in dairy cows.

Effective and comprehensive evaluation of cold stress is critical for healthy dairy cow breeding in the winter. Previous studies on dairy cow cold stress have considered thermal environmental factors but not physiological factors or air quality. Therefore, this study aimed to propose a multilevel fuzzy comprehensive evaluation (FCE) method for cold stress in dairy cows based on the analytic hierarchy process (AHP) and a genetic algorithm (GA). First, the AHP was used to construct an evaluation index system for cold stress in dairy cows from 3 dimensions: thermal environment (temperature, relative humidity, wind speed, and illumination), physiological factors (respiratory rate, body surface temperature), and air quality [NH3, CO2, inhalable particulate matter (PM10)]. Second, the consistency test of the judgment matrix was transformed into a nonlinear constrained optimization problem and solved using the GA. Next, based on fuzzy set theory, the comment set and membership function were established to classify the degree of cold stress into 5 levels: none, mild, moderate, high, and extreme. Then, the degree of cold stress in cows was obtained using multilevel fuzzy comprehensive judgment. To investigate the effect of illumination indicators on cold stress in dairy cows, 24 prelactation cows from the south and north sides were selected for a 117-d comprehensive cold stress evaluation. The results showed that the mean mild cold stress durations were 605.3 h (25.22 d) and 725.5 h (30.23 d) and the moderate cold stress durations were 67.2 h (2.8 d) and 96 h (4.0 d) on the south and north sides, respectively. Simultaneously, generalized linear mixed model showed that there were significant correlations between the daily cold stress duration and milk yield, feeding time, lying time, and active steps in the cows on both sides. This method can reasonably indicate cow cold stress conditions and better guide cold protection practices in actual production.

[Ruxolitinib combined with liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase in treatment of relapsed/refractory pediatric hemophagocytic lymphohistiocytosis].

Objective: To investigate the efficacy and safety of ruxolitinib, liposomal doxorubicin, etoposide, methylprednisolone+/-PEG-asparaginase (RU-DEP+/-L) in the treatment of relapsed/refractory (R/R) pediatric hemophagocytic lymphohistiocytosis (HLH). Methods: The clinical data of R/R pediatric HLH, who accepted the RU-DEP+/-L regimen at Beijing Children's Hospital from January 2018 to December 2019 was retrospectively analyzed. Results: A total of 16 patients were included in this study, including 13 males and 3 females, aged[M(Q1,Q3)] 1 (1, 2) years at diagnosis. Thirteen patients were diagnosed with Epstein-Barr virus (EBV)-HLH, 2 with EBV-induced primary HLH, and 1 with unclear etiology, among which 3 patients were co-infected with CMV. After the first-line treatment, 11 patients had no response, and 5 patients relapsed after complete response. Nine patients received the RU-L-DEP regimen, and 7 patients received the RU-DEP regimen. The overall response rate and complete response of RU-DEP+/-L treatment were 10/16 and 3/16, respectively. The negative conversion rate of plasma EBV-DNA was 7/15. The median follow-up time was 35.1 (2.4, 40.7) months, and 9/16 patients were survival. The 3-year overall survival rate after RU-DEP+/-L treatment in response and accepted hematopoietic stem cell transplantation (HSCT) was higher than that without response and did not receive HSCT (P=0.048). Among the 16 patients, 9 had varying degrees of myelosuppression, and 13 had an infection. Conclusions: RU-DEP+/-L can be used as a salvage treatment in R/R pediatric HLH, which can provide a bridge to HSCT and play an important role in the control of HLH. The main adverse reactions are myelosuppression and infection, which can be tolerated.

[The value of spleen density in predicting prognosis of patients with gastric cancer after curative gastrectomy].

Objective: To investigate the value of spleen density in predicting the prognosis of patients with gastric cancer after radical gastrectomy. Methods: A total of 415 patients with gastric cancer who underwent radical resection in the Department of General Surgery, Affiliated Cancer Hospital of Zhengzhou University from January 2012 to December 2015 were retrospectively analyzed. Of the patients, there were 295 males and 120 femles with a median age of 59 years (range 28-83 years). The patients were divided into diffuse decreased spleen density group (DROSD) (spleen density≤43.0 HU, n=118) and non-diffuse decreased spleen density group (N-DROSD) (spleen density>43.0 HU, n=297) according to the density of spleen detected by computed tomography (CT). The receiver operating characteristic (ROC) curve was used to identify the checkpoint of spleen density in predicting the recurrence of the gastric cancer in those patients. The relationship with clinicopathological factors and prognosis in the two groups were further analyzed. Results: The optimal critical value of spleen density for predicting postoperative recurrence of gastric cancer was 43.0 HU, the area under the curve of ROC was 0.608, and the sensitivity and specificity was 84.9% and 40.4%, respectively. Spleen density was related to albumin, hemoglobin, neutrophil lymphocyte ratio (NLR) and tumor diameter in patients with gastric cancer (all P<0.05). The 5-year disease-free survival rate and 5-year disease-specific survival rate of all the patients was 45.5% and 50.1%, respectively. Univariate survival analysis showed that age, NLR, PLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-free survival rate (all P<0.05); Age, NLR, tumor location, tumor diameter, Lauren classification, TNM stage, nerve invasion, vascular invasion, DROSD and adjuvant chemotherapy were all related to the 5-year disease-specific survival rate (all P<0.05). Multivariate survival analysis showed that high NLR level (HR=1.501, 95%CI: 1.136-1.984), late TNM stage (HR=2.559, 95%CI: 1.850-3.539), DROSD (HR=2.093, 95%CI: 1.571-2.788) and no adjuvant chemotherapy (HR=1.583, 95%CI: 1.204-2.083) were independent risk factor for the 5-year disease-free survival rate (all P<0.05). Late TNM stage (HR=1.938, 95%CI: 1.395-2.692), DROSD (HR=1.566, 95%CI: 1.180-2.078) and no adjuvant chemotherapy (HR=1.336, 95%CI: 1.016-1.758) were independent risk factors for the 5-year disease-free survival rate (all P<0.05). For stage Ⅰ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 78.6% and 83.7%, respectively; and the 5-year disease-specific survival rates was 85.7% and 89.8%, respectively (both P>0.05). For stage Ⅱ and Ⅲ patients, the 5-year disease-free survival rates of DROSD group and N-DROSD group was 15.4% and 48.8%, respectively, and the 5-year disease-specific survival rates was 17.3% and 54.0%, respectively (all P<0.001). Conclusion: As an imaging evaluation method, spleen density is a new tool, which can be used as a prognostic indicator for gastric cancer patients.

[Expression of LIAS and NRF2 in PBMCs from patients with silicosis and their correlation with silicosis].

Objective: To investigate the expression of lipoic acid synthase gene (LIAS) and nuclear factor-erythroid 2-related factor 2 gene (NRF2) in peripheral blood mononuclear cells (PBMCs) from patients with silicosis and their correlation with silicosis. Methods: A total of 45 healthy controls and 107 patients with silicosis were randomly selected in this study in May 2019. PBMCs were isolated from peripheral blood and NRF2 protein expression was detected by immunofluorescence. The mRNA levels of LIAS and NRF2 in PBMCs were determined by real-time PCR. The dose-response relationship beween LIAS and NRF2 mRNA expression levels and their association with silicosis were analyzed by restricted cubic spline (RCS) and logistic regression. Results: Compared with the control group, the number of monocytes in the case group was significantly increased, and the forced expiratory volume in the first second (FEV(1.0)) decreased, the difference was statistically significant (P<0.05) . The positive expression rate of NRF2 in PBMCs of silicosis patients in stage Ⅰ group was significantly higher than that in the control group, and the positive expression rate of NRF2 in silicosis patients in stageⅡ and Ⅲ groups was lower than that in silicosis patients in control group and stage Ⅰ group (P<0.01) . Results of RCS showed that there was a linear dose-response relationship between LIAS and NRF2 mRNA expression (overall correlation test, χ(2)=213.710, P<0.01; non-linear test, χ(2)=1.340, P=0.511) . There was a positive correlation between mRNA expression of LIAS and that of NRF2 (r=0.651, P<0.01) . The results of multivariate analysis showed that LIAS and NRF2 were increased the risk of incidence in silicosis patients with stageⅠ (OR=11.184, 4.332, P<0.05) and NRF2 was the protective factor in silicosis patients with stage Ⅱ and Ⅲ (OR=0.225, 0.208, P<0.05) after adjusting for potential confounding factors including age, education level, BMI and smoking. Conclusion: There is a linear dose-response relationship between the expression of LIAS and NRF2 mRNA in PBMCs of silicosis patients, LIAS and NRF2 are involved in the pathogenesis of silicosis.

[Application of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy].

Objective: To explore the application value of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy. Methods: The retrospective cohort study was conducted. The clinicopathological data of 82 patients with gastric cancer who were admitted to Henan Tumor Hospital from April 2016 to April 2019 were collected. 38 patients who used carbon nanoparticles labeled node staining were in the observation group, while other 44 patients were in the control group. Data analysis including the operation and results of harvested of lymph nodes. Results: All patients successfully completed the operation.Thirty-eight patients successfully completed the injection of carbon nanoparticles. Surgery: observation group operating time was (150±28) min, intraoperative blood loss was (207±121) ml, group operating time was (140±23) min, intraoperative blood loss was (256±182) ml. There was no statistically significant difference between the two groups. Detection of Lymph node: A total of 1 260 lymph nodes were detected in the observation group and 981 in the control group. In the observation group, the mean lymph node sorting time was (17.2±3.3) min, the average number of harvested lymph node was 33.2±10.4, the number of the first station of lymph node was 19.8±5.3, the second station of lymph node was 13.4±6.4, the number of harvested small node(<5 mm) was 673, the positive lymph nodes was 13(range,1-31). They were all higher than those in the control group, which were (20.6±4.4)min,22.3±6.6, 12.6±4.1, 9.7±3.2,432,6 (range,1-13) , respectively. The difference between the two groups was statistically significant (P<0.05). The metastasis rate was 19.1% (241/1 260) in observation group and 16.5%(162/981) in the control group. The difference was no statistical(P>0.05). The rate of black -dyed harvested lymph node was 54.4%(686/1 260) in carbon nanoparticles group. Conclusions: The application of carbon nanoparticles labeled node staining in D2 radical resection of gastric cancer with neoadjuvant chemotherapy is feasible and safe. It can increase the number of lymph nodes detected, which is beneficial to the evaluation of chemotherapy effect and prognosis of patients.

[Association between dust exposure and the risk of hypertension of male coal miners in Henan Province].

Objective: To explore the association between dust exposure and the incidence of hypertension in male coal miners. Methods: Using the method of retrospective cohort study,a hypertension cohort of colliery in Henan Province was established in January 2006. From 2006 to 2017,all the male coal miners in a colliery who were exposed to dust were selected into the exposure group including tunneling, mining,auxiliary and combining workers, and workers from administrative logistics departments who were not exposed to dust were selected into the control group. The eligible participants should satisfy following conditions: working more than one year, with clear and complete record of occupation change, and with complete archives and reliable diagnosis of occupational health surveillance. The exclusion criteria of participants were with hypertension at the baseline of study or with heart,liver,kidney diseases and malignant tumors. A total of 12 647 participants were enrolled in this study (11 663 in the exposure group and 984 in the control group). The follow-up period was from January 2006 to December 2017,with a total follow-up of 89 259.75 person-years. Questionnaires and physical measurements were used to collect general demographic characteristics, occupational exposure history and occupational health surveillance data of all participants. The Cox proportional hazards regression model was used to estimate the association between the dust exposure and the incidence of hypertension. Results: During the follow-up period, 2 549 new-onset hypertension patients were identified with an incidence density of hypertension about 2 855.71 per 100 000 person-years. The incidence density of hypertension was 2 967.58 per 100 000 person-years in the exposure group, and 1 643.85 per 100 000 person-years in the control group. The results of multivariate Cox proportional hazards regression model showed that after the adjustment of marriage, age, smoking, alcohol drinking and body mass index,the risk of hypertension was higher in the exposure group compared with the control group (HR=1.692, 95%CI: 1.410-2.032). Further analysis showed that compared with workers from administrative logistics departments,the risk of hypertension in tunneling,mining and auxiliary working was 1.629(1.345-1.973),1.677(1.374-2.046) and 1.782(1.475-2.151),respectively. Conclusion: Dust exposure may increase the risk of hypertension in male coal miners.

[Study on the effects of total flavonoids from litchi nucleus on nuclear translocation of nuclear factor-kappa B and related protein expression in rat hepatic stellate cell].

Objective: The effect of total flavonoids of litchi (TFL) on nuclear translocation of nuclear factor-kappa B (NF- kappa B) in rat hepatic stellate cell line (HSC-T6) induced by transforming growth factor - beta 1 (TGF- beta 1) in vitro was studied to explore the mechanism of action of anti-hepatic fibrosis drugs. Methods: HSC-T6 was cultured in vitro, induced by TGFß1 for 24 h, and then treated with TFL at 125, 250 and 500 µg/ml for 48 h. The effect of TFL on NF-κB nuclear translocation in HSC-T6 was observed by confocal laser microscopy. The effects of TFL on the expression of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and Collagen I protein were detected by western blot. The expressions of TLR4 and p-NF-κB p65 were detected by immunofluorescence. Data were presented as mean±SEM. Homogeneity test of variance was performed and then followed by one-way analysis of variance (ANOVA). The multiple comparisons between groups were performed by LSD test. P < 0.05 was considered statistically significant. Results: Confocal laser scanning microscopy showed TFL inhibited the nuclear translocation of NF-κB in activated HSC-T6 in a concentration-dependent manner and TFL down regulated the protein expression levels of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and collagen I protein in HSC-T6 in a concentration-dependent manner. Conclusion: The mechanism of TFL against hepatic fibrosis may be related to the inhibition of nuclear translocation of NF-κb in the activated HSC-T6 and the expression of TLR4, P-iκbɑ, P-nf-κb p65, NF-κb and collagen I protein in HSC-T6.

[CT typing and surgical approach for adenocarcinoma of the esophagogastric junction].

Objective: To investigate the feasibility, safety and efficacy of preoperative CT in the classification of adenocarcinoma of the esophagogastric junction. Methods: A total of 517 consecutive patients from May 2012 to June 2016 with esophagogastric junction carcinoma in the department of general surgery of Henan Cancer Hospital was retrospectively analyzed, according to the clinical pathological data of three type four layer method and statistics of various types of surgery in patients with preoperative enhanced CT. Results: 517 patients were successfully received surgery, including 152 cases of type Ⅰ(131 cases of complete abdominal surgery, 21 cases of abdominal incision diaphragm in thoracic surgery), 239 cases of type Ⅱ (177 cases of complete abdominal surgery, 62 cases of abdominal incision diaphragm in thoracic surgery), Ⅲ/Ⅳ type choice of chest abdominal surgery in 126 cases. The operation time was (102±17) min, the amount of hemorrhage was (136±18) ml, the dominant anastomotic fistula happened in 16 cases, 5 cases of pancreatic fistula, 7 cases of intestinal obstruction, anastomotic stenosis in 3 cases, thoracic and abdominal sensation in 12 cases, all the complications were cured by conservative treatment. The average value of esophageal resection margin was(5.1±0.6)cm, 2 cases with positive residual tumor margin and average length of stay was (8.9±1.6)d. Conclusion: Using preoperative enhanced CT in the adenocarcinoma of the esophagogastric junction to choose surgical approach can ensure the safety margin. What's more, unnecessary thoracotomy is reduced which is expected to be a new classification method for the operation of esophagogastric junction cancer.

[The advantage of artery approach in lymph node sorting of rectal cancer].

Objective: To explore the technical advantages of artery approach in lymph node sortingofrectal cancer. Methods: Sixty patients with rectal cancer who treated in general surgery department of Henan provincial tumor hospitalfrom July 2015 to January 2016 were enrolled. Patientswere divided into two groupsrandomly.Lymph node sorting methods of control group andobservation group were the traditional method and the artery approach method respectively. The total number of lymph nodes, the average inspection number, the patients number of lymph nodes less than 12, the number of positive lymph nodes, the metastasis rate of the patients, the number of average diameter less than 5 mm, the number of the positive lymph nodes which average diameter less than 5 mm, the sorting time of lymph nodes, the total number of every stationand other indicators were collected and compared. Results: There wasa significant difference between the observation group and the control groupin the total number(553 vs 395, P<0.05), the number of positive ones(96 vs 54, P<0.05), average inspection number(18.43±5.93 vs 13.27±1.96, P=0.000), the sorting time (min) (14.1±2.5 vs 17.4±3.2, P=0.000), the average diameter less than 5 mm number(4.73±1.31 vs 1.23±1.14, P=0.000), the number of positive ones average diameter less than 5 mm(0.97±1.03 vs 0.20±0.55, P=0.010), the first(8.17±4.58 vs 5.07±1.96, P=0.000) and second station(6.57±1.87 vs 4.90±1.69, P=0.001)inspection number.The inspection number less than 12, the positive rate of lymph node, the metastatic rate of the patient and the inspection number of third station have no significant differences (all P≥0.05). Conclusion: Theartery approach method inrectal cancer lymph node inspectionhas many advantages such as simple operation, obtaining more lymph nodes and more accurate pathological staging.

[Observation of clinical and electrophysiological features in patients with distal myasthenia gravis].

Objective: To explore the clinical and electrophysiological features and prognosis of distal myasthenia gravis (MG). Methods: Data of MG patients in Beijing Tiantan Hospital from October 2016 to March 2017 were reviewed, including thorough neurological examinations, nerve conduction studies, repetitive nerve stimulations (RNS) and needle electromyographies. Distal MG patients were included and were analyzed as to their clinical and electrophysiological features and response to treatments. Results: Four patients (7.7%) could be classified as distal type among 52 definitely diagnosed MG patients. They had initial symptoms at age 36 to 64 and developed distal limb muscle weakness in the first month to 6 years after the onset of this disease. Hand muscles were preferentially involved in a non-uniform way. And one patient also had leg weakness on his tibialis anterior muscles. RNS showed a more significant decrement at slow rates in distal muscles, compared with proximal muscles. The baseline compound muscle action potentials (CMAP) of the distal affected muscles presented with slightly decreased or fluctuating amplitudes. Their weakness of ocular, bulbar, proximal and distal limb muscles improved generally after administration of acetylcholinesterase inhibitors or steroids plus acetylcholinesterase inhibitors. Electrophysiological reexaminations revealed increased baseline CMAPs, reduced decrement on RNS, and relief of myogenic changes on needle electromyography. Conclusions: Relatively prominent distal limb muscle weakness can be found in a minority of MG patients. Besides profound decrement on slow rate RNS, the involved distal muscles may have a characteristic decreased baseline CMAP, sometimes with a diurnal fluctuation. Distal MG responds well to regular treatments. Its short-term prognosis seems similar to that of common MG with proximal predominance.

[Influence of postoperative pelvic floor function on different surgical procedures of hysterectomy].

Objective: To compare the influence of postoperative pelvic floor function after different surgical procedures of hysterectomy. Methods: A total of 260 patients who underwent hysterectomy in Renmin hospital of Wuhan University from January 2012 to January 2014 were enrolled in the study, and divided into 5 groups by different surgical procedures, which were total abdominal hysterectomy (A-TH; 46 cases), total laparoscopic hysterectomy (L-TH; 59 cases), total vaginal hysterectomy (V-TH; 42 cases), abdominal intrafascial hysterectomy (A-CISH; 78 cases), laparoscopic intrafascial hysterectomy (L-CISH; 35 cases). Pelvic examination, pelvic organ prolapse quantitation (POP-Q), test of pelvic muscle strength, pelvic floor distress inventory-short form 20 (PFDI-20) and the female sexual function index (FSFI) questionnaire were measured after 6 months and 12 months. Results: The differences of pelvic organ prolapse incidence after 6 months, A-TH and A-CISH [7% (3/46) versus 3% (2/78)], A-TH and L-CISH [7% (3/46) versus 3% (1/35)] were statistically significance (all P<0.05).POP-Q grade after 6 months between A-TH and A-CISH was statistically different in degree (P<0.05). The differences of incidence of abnormal pelvic floor muscle fatigue after 6 months of A-TH and A-CISH [59% (27/46) versus 29% (23/78)], A-TH and L-CISH [59% (27/46) versus 26% (9/35)] were statistically significant (all P<0.05), after 12 months the difference of L-TH and A-CISH [61% (36/59) versus 29%(23/78)] was statistically different (P<0.05). The differences of incidence of abnormal pelvic floor muscle strength after 6 months of L-TH and A-CISH [53% (31/59) verus 24% (19/78)], V-TH and A-CISH [60% (25/42) verus 24% (19/78)], V-TH and L-CISH [60% (25/42) verus 23% (8/35)] were statistically significant (all P<0.05); after 12 months the difference of V-TH and A-CISH [57% (24/42) versus 26%(20/78)] was statistically significant (P<0.05). Stress urinary incontinence, abnormal bowel movements after 6 months and 12 months were no significant difference between groups (all P>0.05), PFDI-20 total score was not statistically significant (P>0.05). FSFI total score after 6 months and 12 months in A-TH and A-CISH, L-TH and A-CISH, A-CISH and L-CISH were statistically significant (all P<0.05). Conclusion: The influences of different surgical procedures to pelvic floor function are no statistical difference; as to the surgical resection of hysterectomy, intrafascia hysterectomy compared with extrafascia hysterectomy, the former is more helpful to the protection of the structure and function of the pelvic floor.

[Therapeutic effect of combined use of FGF1-loaded nano-liposomes and ultrasound-targeted microbubble destruction technique on treating rats with experimental diabetic cardiomyopathy].

Objective: The therapeutic effect of acid fibroblast growth factor 1(FGF1) on rats with diabetic cardiomyopathy (DCM) was evaluated by using nano-liposomes combined with ultrasound-targeted microbubble destruction technique (UTMD). Methods: The FGF1-loaded nano-liposomes were prepared by water-in-water emulsion method combined with lyophilization technique.TypeⅠdiabetes model was induced by intraperitoneal injection of streptozotocin (STZ, 70 mg/kg) in 60 male SD rats.Sixteen weeks later, diabetic rats were randomly divided into: placebo group (saline treatment), FGF1 group, FGF1-loaded nano-liposomes group, and FGF1-loaded nano-liposomes plus UTMD group (n=15 each). After two weeks of intervention followed by 2 weeks intervention stop, all rats underwent cardiac catheterization, and the left ventricular end-systolic pressure (LVESP), left ventricular end-diastolic pressure (LVEDP) and the maximal increase/decrease rate of left ventricular pressure (LV±dp/dtmax) were measured.Then, the rats were sacrificed and myocardial tissue were obtained for Masson trichrome staining, TUNEL apoptotic staining and CD31 immunohistochemistry staining to quantify myocardial collagen fraction (CVF), cardiac myocyte apoptotic index and myocardial microvascular density (MVD). Results: (1)Scanning electron microscope results revealed good morphology and FGF1 encapsulation efficiency (84.3±2.8)% with high stability and dispensability of FGF1 loaded nano-liposomes.(2)The hemodynamic evaluation showed that LVESP, LV + dp/dt(max) and LV -dp/dt(max) were all significantly higher, while LVEDP was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group(all P<0.05). (3)The Masson trichrome staining demonstrated that CVF was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (4)The CD31 immunohistochemical staining results showed that MVD was significantly lower in all DCM groups than in control group and was significantly higher in the FGF1-loaded nano-liposome+ UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). (5)The TUNEL results showed that apoptotic index was significantly higher in all DCM groups than in control group and was significantly lower in the FGF1-loaded nano-liposome + UTMD group than in DCM group, FGF1 solution group, and FGF1 nano-liposome group (all P<0.05). Conclusion: FGF1 nano-liposomes combining with UTMD technique can significantly improve cardiac functions and attenuate myocardial CVF and apoptosis and enhance myocardial MVD in DCM rats.

[Treatment of advanced Siewert type â ¡ esophagogastric junction adenocarcinoma by thoracoabdominal radical gastrectomy and D2 lymphadenectomy].

OBJECTIVE: To investigate the advantages of thoracoabdominal radical gastrectomy for advanced Siewert type Ⅱ adenocarcinoma of the esophagogastric junction. METHODS: Clinical data of 86 patients with Siewert type Ⅱ adennocarcinoma of the esophagogastric junction who received surgical treatment at the Henan Provincial Tumor Hospital from January 2015 to January 2016 were retrospectively analyzed. Among them, 44 patients underwent abdominal operation (abdominal group), and 42 patients underwent thoracoabdominal radical gastrectomy (thoraco-abdominal group). The operation time, lymph node number, distance between the tumor and cutting edge, amount of intraoperational blood loss, postoperative pulmonary complications, and postoperative hospital stay in the two groups were compared. RESULTS: Comparing the thoracoabdominal group with the abdominal group, the number of removed lymph nodes was 41.57±9.22 vs. 35.09±10.61 (P<0.01), the number of removed mediastinal lymph nodes was 6.38±1.50 vs. 3.52±1.42 (P<0.01), the distance between the tumor and cut edge was (5.62±0.73) cm vs. (3.30±0.85) cm (P<0.01), whereas the operation time, intraoperative blood loss, postoperative pulmonary complications, occurrence of anastomotic leakage and hospital stay were statistically not significantly different (P>0.05 for all). CONCLUSIONS: For patients with advanced Siewert type Ⅱ adenocarcinoma of the esophagogastric junction, radical gastrectomy through thoracoabdominal approach can resect a longer segment of the esophagus, dissect more mediastinal lymph nodes, and does not increase post-operative complications and extend hospital stay, thus, exhibits obvious advantages in the surgical treatment of Siewert Ⅱ adenocarcinoma of the esophagogastric junction.

Molecular cloning, characterization, and expression of Rab5B, Rab6A, and Rab7 from Litopenaeus vannamei (Penaeidae).

The Rab protein family belongs to a superfamily of ras-like GTP-binding proteins. Rab proteins regulate many steps of membrane trafficking. In this study, three Rab family members, Rab5B, Rab6A, and Rab7, designated LvRab5B, LvRab6A, and LvRab7, were cloned from Litopenaeus vannamei. The full-length cDNA sequences of LvRab5B, LvRab6A, and LvRab7 were 1383, 873, and 767 nucleotides in length and they encoded proteins of 211, 212, and 205 amino acids, respectively. Using qRT-PCR, the mRNA expression levels of the three proteins were determined in the hepatopancreas of L. vannamei at different stages after infectious hypodermal and hematopoietic necrosis virus and white spot syndrome virus challenge. The results indicated that the mRNA expression levels of LvRab5B, LvRab6A, and LvRab7 were all significantly up-regulated after virus injection, suggesting that these genes may play essential roles in the immune response to viral infection in shrimp.