[Stepwise treatment of complex intestinal fistulas and strategies of nutritional support treatment].

Intestinal fistula is one of the common diseases and complications in abdominal surgery. It does not only cause severe abdominal infections but also leads to obstruction, bleeding, malnutrition, and may develop into complex intestinal fistulas, resulting in increased challenges in treatment, elevated treatment costs, and increased risk of patient mortality. At present, the treatment of intestinal fistula mainly adopts a three-stage approach: (1) early diagnosis, (2) mid-term nutritional support treatment, and (3) definitive surgical treatment. Nutritional support treatment can significantly reduce patient mortality and improve recovery. Due to the difficulty, complexity, and diversity of intestinal fistula treatment, and the fact that complex intestinal fistulas are currently a challenge in the treatment of intestinal fistulas, this article will introduce the progress and difficulties at different stages, and explore the future treatment direction of intestinal fistulas from the perspective of interdisciplinary cooperation.

Biopsy-tract haemocoagulase injection reduces major complications after CT-guided percutaneous transthoracic lung biopsy.

AIM: To determine whether the injection of haemocoagulase into the biopsy tract can reduce pneumothorax and pulmonary haemorrhage after computed tomography (CT)-guided percutaneous transthoracic lung biopsy (PTLB). MATERIALS AND METHODS: A retrospective study was performed involving patients with undiagnosed pulmonary lesions scheduled for PTLB between January 2020 and March 2021. Patients were assigned to the haemocoagulase group or the non-haemocoagulase group. After CT-guided biopsies were performed with a 17 G coaxial system, patients in the haemocoagulase group received a haemocoagulase injection (0.2-0.5 units) in the biopsy tract as the sheath was withdrawn. Postoperative image studies were performed to evaluate complications, including pneumothorax and pulmonary haemorrhage. Factors, including the patient's position, lesion location, and pathological results, were evaluated to determine their associations with the complications. RESULTS: A total of 100 patients were included, with 44 men and a mean age of 53 years old. The overall incidences of pneumothorax and pulmonary haemorrhage were 15% and 13%, respectively. The incidences of pneumothorax and pulmonary haemorrhage were statistically significantly lower in the haemocoagulase group (8% and 6%, respectively) than in the non-haemocoagulase group (22% and 20%, respectively; p=0.04 and 0.03, respectively). There was no statistically significant difference in haemoptysis between the haemocoagulase (6%) and non-haemocoagulase (2%) groups (p=0.23). There were also no statistically significant associations of pneumothorax or pulmonary haemorrhage with the patients' positions, lesion location, or pathological results. CONCLUSION: Biopsy tract haemocoagulase injection reduced the incidences of postoperative pneumothorax and pulmonary haemorrhage after PTLB.

Combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor clinical outcomes in patients with COVID-19: a multicentre retrospective cohort study.

OBJECTIVES: Cigarette smoking is an established risk factor for illness severity and adverse outcomes in patients with COVID-19. Alcohol drinking may also be a potential risk factor for disease severity. However, the combined and interactive effects of drinking and smoking on COVID-19 have not yet been reported. This study aimed to examine the combined and interactive effects of alcohol drinking and cigarette smoking on the risk of severe illness and poor outcomes in patients with COVID-19. STUDY DESIGN: This was a multicentre retrospective cohort study. METHODS: This study retrospectively reviewed the data of 1399 consecutive hospitalised COVID-19 patients from 43 designated hospitals. Patients were grouped according to different combinations of drinking and smoking status. Multivariate mixed-effects logistic regression models were used to estimate the combined and interactive effects of drinking and smoking on the risk of severe COVID-19 and poor clinical outcomes. RESULTS: In the study population, 7.3% were drinkers/smokers, 4.3% were drinkers/non-smokers and 4.9% were non-drinkers/smokers. After controlling for potential confounders, smokers or drinkers alone did not show a significant increase in the risk of severe COVID-19 or poor clinical outcomes compared with non-drinkers/non-smokers. Moreover, this study did not observe any interactive effects of drinking and smoking on COVID-19. Drinkers/smokers had a 62% increased risk (odds ratio = 1.62, 95% confidence interval: 1.01-2.60) of severe COVID-19 but did not have a significant increase in the risk for poor clinical outcomes compared with non-drinkers/non-smokers. CONCLUSIONS: Combined exposure to drinking and smoking increases the risk of severe COVID-19, but no direct effects of drinking or smoking, or interaction effects of drinking and smoking, were detected.

Clinical insights into cisplatin-induced arrhythmia in a patient with locally advanced non-small cell lung cancer: a case report.

OBJECTIVE: Cardiotoxicity is a common adverse effect of many antineoplastic agents, including anthracyclines and paclitaxel. However, it has not been defined as a causal side effect of cisplatin. Here we report on a patient with locally advanced non-small cell lung cancer who developed a cardiotoxic event induced by cisplatin that manifested primarily as arrhythmia. MATERIALS AND METHODS: Intensive cardiac monitoring through electrocardiogram was performed to estimate the severity degree and clinical condition of arrhythmia. RESULTS: The frequency and severity of the arrhythmia had a strong temporal relationship with the administration of cisplatin, that made it likely that cisplatin was responsible for the cardiotoxicity observed. CONCLUSIONS: In the present case report, we discuss the potential factors that may provide pivotal contributions to the patient's susceptibility to cardiotoxicity and review the published studies regarding the cardiotoxic influence of cisplatin. We also outline the critical points that oncologists should be aware of when dealing with such high-risk patients.

Bone marrow mesenchymal stem cells promote the progression of prostate cancer through the SDF-1/CXCR4 axis in vivo and vitro.

PURPOSE: The aim of this study was to investigate the involvement of the SDF-1/CXCR4 axis in the process of BMMSC homing in prostate cancer (PCa) in vivo and in vitro. METHODS: After verification of BMMSCs, we fixed the concentration gradient of SDF-1 for BMMSC cultivation to analyze CXCR4 expression by qRT-PCR and flow cytometric analysis. Furthermore, we developed a non-contact co-culture system and explored the participation of the SDF-1/CXCR4 axis in PCa using qRT-PCR, flow cytometry, and ELISA. In addition, A green fluorescent protein (GFP)-transplanted methylnitrosourea (MNU)-induced PCa mouse model was established to investigate the CXCR4 expression in vivo. RESULTS: The CXCR4 expression was up-regulated with the increase in SDF-1 concentrations, and elevated SDF-1 had a significant promoting effect on cell proliferation and migration in BMMSCs. Moreover, the CXCR4 expression of BMMSCs was significantly increased in the non-contact co-culture model with vascular endothelial cells (VECs), and analysis of this model also showed that the proliferation and migration of BMMSCs were promoted in the presence of VECs. The ELISA assay showed that the SDF-1 levels in the co-culture model at 48 h were significantly increased. Twenty of the GFP-transplanted mice were divided into a PCa group and a control group, and four GFP-transplanted mice were observed to have prostate tumorigenesis. It also showed that CXCR4 was obviously increased in the prostate tissue of PCa mice. CONCLUSION: Our findings suggest that BMMSCs could home and promote the proliferation and migration of PCa through the SDF-1/CXCR4 axis in vivo and in vitro.

[Clinical features of 123 patients with hyperinsulinemic hypoglycemia auxiliarily diagnosed by 18F-DOPA-PET CT scanning].

Objective: To summarize the clinical features and therapeutic outcomes of patients with hyperinsulinemic hypoglycemia (HH) auxiliarily diagnosed by 18F-DOPA positron emission tomography (PET) CT scanning. Methods: The clinical data of 123 patients who were diagnosed with hyperinsulinemic hypoglycemia by comprehensive clinical diagnostic procedures in the Department of Pediatric Endocrinology and Inherited Metabolic Diseases, Children's Hospital of Fudan University between January 2016 and December 2020 were retrospectively analyzed. Clinical data such as gender, age of onset, province, concurrent serum insulin level measured during hypoglycemia, lesion type of pancreas by 18F-DOPA-PET CT scanning, genetic test results, and treatment were collected successively. The clinical features and therapeutic outcomes were compared between patients with focal and diffuse pancreatic lesions. T test, Rank sum test, and χ² test were used for comparison between groups. Results: A total of 123 patients with hyperinsulinemic hypoglycemia (72 males and 51 females), whose average age of onset was 3 days (ranging from 1 day to 4 860 days), were recruited from 24 provinces. The concurrent serum insulin level was 7.1 (0.4-303.0) mU/L during hypoglycemia. 18F-DOPA-PET CT scanning identified focal lesions in 25.2% (31/123) and diffuse lesions in 74.8% (92/123) of the patients; 64.2% (79/123) of the HH cases were found to have pathogenic gene variants, in which 88.6% (70/79) were found to have KATP channel related genes (61 in ABCC8 and 9 in KCNJ11 mutations). Thirty-seven patients (17 focal and 20 diffuse) received surgical treatment with a success rate of 67.6% (25/37). The effective rate of diazoxide for children with diffuse type was significantly higher than that of children with focal group (28.3% (26/92) vs. 9.7% (3/31), χ²=10.31, P=0.001). Conclusions: 18F-DOPA-PET CT scan can improve the success rate of surgery. Comprehensive diagnosis of the etiology of hyperinsulinemic hypoglycemia by genetic analysis and 18F-DOPA-PET CT scanning can result in better treatment and prognosis.

[Short-term efficacy of endoscope assisted arthroplasty for total hip replacement via a minimum invasive direct anterior approach].

Objective: To present the surgical technique of endoscope assisted arthroplasty for total hip replacement via minimum invasive direct anterior approach and analyze its early clinical outcome. Methods: From November 2019 to May 2020, endoscopic total hip arthroplasty via direct anterior approach was performed on 30 patients (32 hips), including 12 males (13 hips) and 18 females (19hips), in the Department of Orthopedics of Fujian Provincial Hospital. The average age of patients was (63±14) years (ranged 32-87 years). The average body mass index (BMI) of the patients was (26.9±4.5) kg/m2. There were 12 cases whose BMI was higher than 28.0 kg/m2 and the maximum BMI was 35.2 kg/m2. The surgery was performed on supine position using a 5-6 cm proximal transverse incision and a distal selective percutaneous puncture incision to perform the acetabulum preparation and the prosthesis implantation with the novel designed split tool under the monitoring of endoscope; the lift-top tractor system was used to raise the femur in the transverse incision for femoral side preparation and prosthesis implantation. Relevant data such as the perioperative status, operation time, postoperative pain score assessed with visual analogue score (VAS), prosthesis position, joint function, lateral femoral cutaneous nerve function and patient satisfaction were recorded to analyze the short-term efficacy. Results: The average length of incision of the 30 cases(32 hips)was (5.9±0.4) cm. All patients in this study had I/A wound healing with no perioperative complications such as infection, poor wound healing and fractures of the proximal femur. The average operation time was (65±14) min, and the average amount of blood loss was (136±56) ml. The average acetabular abduction angle and acetabular antegrade inclinations was 41.4°±3.6° and 16.0°±5.3°, respectively. The resting-state VAS of pain at 6 h and 24 h after operation were all ≤2, and there was no significant difference between the VAS scores after exercise and the VAS scores at the resting state (both P>0.05). There was no statistically significant difference between the VAS scores at the same state at different times (both>0.05). The weight-bearing exercise was applied in all patients within 12 h after surgery. The length of postoperative hospital stays varied from 1 to 3 days((2.0±0.9) days). At the 6th-month follow-up, the Harris score of the hip was 94.7±3.0, which significantly improved when compared with that before the operation (35.5±8.1)(P<0.01). No sensory abnormalities were observed. The satisfaction score of the patients was 9.3±0.5 (full score set to 10). Conclusions: The efficacy and safety of the endoscope assisted total hip arthroplasty for total hip replacement is acceptable. This procedure can help to reduce the compression of the muscles by the retractor in the conventional operation. It can be applied to obese and muscular patients.

[The effect of visualized saphenous nerve block through minimally invasive far medial-subvastus approach on the analgesia after total knee arthroplasty].

Objective: To report a method of visualized saphenous nerve block (VSNB) through minimally invasive far medial-subvastus approach distal to the adductor canal in total knee arthroplasty (TKA), and investigate the effect of VSNB in this way on postoperative pain relief. Methods: A total of 100 patients with knee osteoarthritis were prospectively included from June 2018 to October 2019, 29 males and 71 females, aged 50-87(70±8) years. All patients undergoing TKA through minimally invasive far medial-subvastus approach were randomized to visualized saphenous nerve block combined with periarticular infiltration analgesia group (Group VSNB+PIA) or only periarticular infiltration analgesia group (Group PIA),50 cases in each group. The visual analogue scale (VAS) was used to evaluate the pain degree of patients. Furthermore, the scores of VAS in resting and active state at 4, 8, 12, 24, 48, 72 hours after operation and the proportion of patients receiving parecoxib within 72 hours after operation were compared between the two groups. Results: There was statistically significant difference between the two groups in terms of VAS scores in resting state after surgery(F=15.295,P<0.05).The postoperative VAS scores of Group VSNB+PIA at 4, 8, 12, 24 hours at resting state were 1.3±0.8, 1.4±0.7, 1.7±0.8, 3.1±0.8 respectively, which were all significantly lower than those of Group PIA (1.6±0.9, 1.8±0.8, 2.3±0.9, 3.6±0.8) (P<0.05). The overall difference in terms of VAS scores at active state after surgery was statistically significant between the two groups(F=18.532, P<0.05). The postoperative VAS scores of Group VSNB+PIA at 4, 8, 12, 24 hours at active state were 2.0±0.8, 2.2±0.7, 2.7±0.6, 3.7±0.7 respectively, which were all significantly lower than those of Group PIA (2.3±0.8, 2.7±0.7, 3.3±0.8, 4.4±0.7)(P<0.05). Fourteen percent of patients (7/50) in VSNB+PIA group accepted parecoxib within 72 hours after surgery, which was significantly lower than that in PIA group (34%, 17/50) (P<0.05). Conclusions: It is easy to expose the saphenous nerve beyond the adductor canal through minimally invasive far medial-subvastus approach. The Combination therapy of VSNB+PIA is more effective than the simple per-articular infiltration analgesia in providing pain relief after total knee arthroplasty.

Long-term survival case of a non-small cell lung cancer bone metastasis patient treated with bone cement, radiation and gefitinib.

OBJECTIVE: We explore the treatment of bone metastases in advanced non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: We reported a 76-year-old female patient, who was diagnosed with NSCLC with bone metastasis eight years ago (stage IVA). Due to unbearable diarrhea, she refused chemotherapy, and we adopted local treatment, including local radiotherapy 50 Gy and bone cement to lumbar spinal metastases, 62 Gy local radiotherapy of primary lung tumor, TKI inhibitor gefitinib and zoledronic acid. RESULTS: She survived more than eight years and is still in follow-up. CONCLUSIONS: The median survival time for NSCLC patients with bone metastases is often less than 1 year. We reported the patient with more than eight years of survival, showed that some special cases can adopt the methods of local treatment including bone cement, treatment benefit patients, radiation therapy and targeted therapy in clinic to expand the survival.

[Surgical site infection after abdominal surgery in China: a multicenter cross-sectional study].

Objective: Surgical site infection (SSI) can markedly prolong postoperative hospital stay, aggravate the burden on patients and society, even endanger the life of patients. This study aims to investigate the national incidence of SSI following abdominal surgery and to analyze the related risk factors in order to provide reference for the control and prevention of SSI following abdominal surgery. Methods: A multicenter cross-sectional study was conducted. Clinical data of all the adult patients undergoing abdominal surgery in 68 hospitals across the country from June 1 to 30, 2020 were collected, including demographic characteristics, clinical parameters during the perioperative period, and the results of microbial culture of infected incisions. The primary outcome was the incidence of SSI within postoperative 30 days, and the secondary outcomes were ICU stay, postoperative hospital stay, cost of hospitalization and the mortality within postoperative 30-day. Multivariable logistic regression was used to analyze risk factors of SSI after abdominal surgery. Results: A total of 5560 patients undergoing abdominal surgery were included, and 163 cases (2.9%) developed SSI after surgery, including 98 cases (60.1%) with organ/space infections, 19 cases (11.7%) with deep incisional infections, and 46 cases (28.2%) with superficial incisional infections. The results from microbial culture showed that Escherichia coli was the main pathogen of SSI. Multivariate analysis revealed hypertension (OR=1.792, 95% CI: 1.194-2.687, P=0.005), small intestine as surgical site (OR=6.911, 95% CI: 1.846-25.878, P=0.004), surgical duration (OR=1.002, 95% CI: 1.001-1.003, P<0.001), and surgical incision grade (contaminated incision: OR=3.212, 95% CI: 1.495-6.903, P=0.003; Infection incision: OR=11.562, 95%CI: 3.777-35.391, P<0.001) were risk factors for SSI, while laparoscopic or robotic surgery (OR=0.564, 95%CI: 0.376-0.846, P=0.006) and increased preoperative albumin level (OR=0.920, 95%CI: 0.888-0.952, P<0.001) were protective factors for SSI. In addition, as compared to non-SSI patients, the SSI patients had significantly higher rate of ICU stay [26.4% (43/163) vs. 9.5% (514/5397), χ(2)=54.999, P<0.001] and mortality within postoperative 30-day [1.84% (3/163) vs.0.01% (5/5397), χ(2)=33.642, P<0.001], longer ICU stay (median: 0 vs. 0, U=518 414, P<0.001), postoperative hospital stay (median: 17 days vs. 7 days, U=656 386, P<0.001), and total duration of hospitalization (median: 25 days vs. 12 days, U=648 129, P<0.001), and higher hospitalization costs (median: 71 000 yuan vs. 39 000 yuan, U=557 966, P<0.001). Conclusions: The incidence of SSI after abdominal surgery is 2.9%. In order to reduce the incidence of postoperative SSI, hypoproteinemia should be corrected before surgery, laparoscopic or robotic surgery should be selected when feasible, and the operating time should be minimized. More attentions should be paid and nursing should be strengthened for those patients with hypertension, small bowel surgery and seriously contaminated incision during the perioperative period.

[Identification and functional study of the Schistosoma japonicum epidermal growth factor receptor gene].

OBJECTIVE: To characterize the epidermal growth factor receptor (EGFR) gene in Schistosoma japonicum (SjEGFR gene) and investigate the role of the EGFR gene in regulating the growth, reproductive system, maturation and fecundity of S. japonicum. METHODS: Rapid amplification of cDNA ends (RACE) was performed to obtain the full length of the SjEGFR gene, and the SjEGFR gene expression was quantified in different developmental stages of S. japonicum using a quantitative real-time PCR (qPCR) assay. The tissue localization of the SjEGFR gene was detected in 22-day parasite using whole-mount in situ hybridization (WISH). Following RNA interference (RNAi)-induced knockdown of the SjEGFR gene, the worm length, pairing rate and worm burden of S. japonicum were measured, and the worm morphology was observed using optical microscopy and confocal microscopy. RESULTS: The SjEGFR gene was identified with a conserved tyrosine-kinase active site, and the SjEGFR gene expression was detected at various developmental stages in male and female parasites. WISH showed that the transcript of the SjEGFR gene was localized on the tegument and in the digestive organs of S. japonicum. RNAi-induced SjEGFR knockdown resulted in marked suppression of the worm growth, smaller size of male testicles that contained more immature spermatocytes, and apparent impairment of ovary and vitelline gland development. In addition, no eggs were found in the uterus of SjEGFR knocked-down female parasites, indicating the interruption of egg production. CONCLUSIONS: Inhibition of SjEGFR expression may remarkably suppress the growth and maturation of S. japonicum, and interrupt the egg production.

[Common peroneal nerve "pre-release" to avoid nerve palsy in total knee arthroplasty for severe valgus deformities].

Objective: To investigate the clinical efficacy of common peroneal nerve "pre-release" to avoid nerve palsy in total knee arthroplasty for severe valgus deformities. Methods: Twenty patients (22 knees) with severe valgus deformities were prospectively and continuously included in Fujian Province Hospital from January 2010 to January 2016. Medial parapatellar arthrotomy, femoral distal resection using the intramedullary cutting guide with 3° to 5° of valgus and the common peroneal nerve "pre-release" was performed, the patella was routinely resurfaced. A common peroneal nerve checking was performed (LSUHSC system), then, these outcomes were collected independently using visual analogue scale (VAS) of pain, Knee Society Score (KSS), Hospital for Special Surgery Knee Score (HSS), range of motion of knees (ROM), femorotibial angle (FTA), hip-knee-ankle angle (HKA), condylar-hip angle (CHA), plateau- ankle angle (PAA). The paired t test was used to compare the data before and after the operation. Results: Patients were followed up for 18 to 55 (mean, (38±8) months). According to Krackow's classification, all cases were typed Ⅱ. All the patients had a completely normal motor (grade 5) and sensory (LSUHSC score was 5) nerve function of common peroneal nerve postoperatively. No decrease or loss in muscle strength and cutaneous sensation associated with common peroneal nerve was found. The VAS of pain, KSS, HSS, ROM, HKA, CHA, and PAA were all improved after the operation when compared with those before the operation (t=21.602, -70.238, -82.455, -20.560, 16.058, 9.682, 3.439, all P<0.05). The alignment of lower limbs was corrected basically, and the FTA decreased from 31.7°±8.0° before operation to 5.0°±2.0° at the last follow-up, the differences was statistically significant (t=16.725, P<0.05). No common peroneal nerve palsy and transient or late-onset palsy occurred, and no revision was needed for instability during the follow-up in all the patients. Conclusion: Common peroneal nerve "pre-release" for severe valgus knees may be an effective method in protecting the nerve.

MicroRNA-370-3p inhibits cell proliferation and induces chronic myelogenous leukaemia cell apoptosis by suppressing PDLIM1/Wnt/ß-catenin signaling.

Growing evidence has suggested that microRNA-370-3p (miR-370-3p) is downregulated and acts as a suppressor in several cancers. However, the role of miR-370-3p in chronic myeloid leukemia (CML) remains unknown. Here, the expression level and molecular mechanism of miR-370-3p in CML were investigated. Firstly, the expression of miR-370-3p has markedly decreased in the peripheral blood mononuclear cells (PBMCs) of patients with CML and in cell lines. Moreover, miR-370-3p in CML cells upregulated and downregulated proliferation and apoptosis, respectively. Notably, miR-370-3p directly targeted the 3'-untranslated region of PDZ and LIM domain protein 1 (PDLIM1). A negative correlation was observed between the levels of miR-370-3p and PDLIM1 in the PBMCs of patients with CML and healthy volunteers. PDLIM1 was shown to have an oncogenic role in CML cells by promoting proliferation and suppressing apoptosis. Finally, the miR-370-3p-PDLIM1-Wnt/ß-catenin signaling axis was indicated to play an important role in CML progression.

Study Frequency Shift Evaluation of Ultrasound in Fresh and Frozen-thawed Tissues of Cryosurgery by AR Model.

BACKGROUND: Noninvasive monitoring of cryosurgery is important for performing precise monitoring of the freezing process in situ and evaluating postoperative effects after therapy. One potential approach is to monitor the normal and freeze-thawed tissues through ultrasonic backscattered signal processing. OBJECTIVE: A noninvasive method for cryosurgery monitoring based on the analysis of microstructural characteristics of in vitro porcine liver tissues at different state including normal and freeze-thawed tissues by estimating the center frequency of scatterers (CFS) using the autoregressive (AR) cepstrum of ultrasonic backscattered signals. MATERIALS AND METHODS: The method is based on the discrete scattering model described in the tissue characterization literature and the observation that most biological tissues are semi-regular scattering lattices. A total of ten in vitro porcine liver samples were used and freeze by water bath in the experiments. RESULTS: Experimental results show that the CFS in porcine liver tissues decreases after pre-frozen and then thawed. CONCLUSION: The CFS obtained using this method may be used as a characteristic parameter for tissue characterization in noninvasive monitoring the transition zone between frozen and unfrozen tissues during the surgical therapy, and evaluating postoperative effects.

Safety and Efficacy of Aspirin Desensitization Combined With Long-Term Aspirin Therapy in Aspirin-Exacerbated Respiratory Disease.

OBJECTIVES: To assess the safety and efficacy of Aspirin desensitization combined with long-term Aspirin therapy in patients with Aspirinexacerbated respiratory disease (AERD). METHODS: We searched the PubMed, Ovid, Cochrane Library, and Google Scholar databases from inception to October 2018 for articles in English. We only included randomized controlled trials and parallel or cross-over studies in which adults with AERD were randomly assigned to undergo Aspirin desensitization and receive long-term Aspirin therapy or placebo. RESULTS: A total of 869 citations were retrieved, and 6 studies met the criteria for analysis. All studies indicated that nasal symptoms, asthma symptoms, or both improved significantly after Aspirin desensitization. In addition, most studies reported a decline in corticosteroid dosage (oral and inhaled). The 4 studies that reported nasal polyps did not demonstrate a change in nasal polyps with Aspirin therapy compared with placebo. The dropout rates in all studies reviewed ranged from 5.8% to 55.7%, and the most common adverse events were gastrointestinal symptoms. CONCLUSIONS: Clearly, Aspirin desensitization and treatment are beneficial for AERD patients, with relief of nasal symptoms, improvement in asthma control, decrease in daily corticosteroid use, and no fatal adverse events. However, the long-term adverse effects of Aspirin desensitization and optimal dosage of Aspirin merit further investigation.

[Effect of aspirin on breast cancer stem cells and stemness of breast cancer].

Objective: To explore the effect of aspirin on the stemness of breast cancer cells and apoptosis induction of breast cancer stem cells. Methods: The 4T1 cells cultured with stem cell culture medium were screened, and immunofluorescence technique, flow cytometry and tumor-forming experiment in vivo were applied to test stem cell characteristics of the tumor spheres. After dealt with aspirin, the apoptosis rate of 4T1 stem cells was analyzed by flow cytometry. The 4T1 cells were cultured in vitro and treated with aspirin, then flow cytometry analysis was used to detect the expression of aldehydedehy drogenase1 (ALDH1), and the expression of stemness genes was tested by Western blot . Then, after culturing the cells with medium containing basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), B27 and N2, the ability of sphere-forming was observed and recorded by microscopy. In vivo BALB/c mice inoculated with 4T1 stem cells were randomly divided into the control group, 10 mg/kg, 30 mg/kg and 100 mg/kg aspirin groups. After 10 days, the mice were dealt with aspirin or NS for 15 days, then the tumor growth was observed and recorded. Results: The ratio of ALDH1 positive cells was up to 78.55%, and 4T1 tumor sphere had a postive expression of ALDH1 and sex determining region Y-box 2 (SOX2). In vivo tumorigenesis abilities of tumor sphere with 1×10(2) 4T1 stem cells could be 75%, while the ratio of normal cells was zero. The ratio of Aspirin-induced apoptosis of 4T1 stem cells at early stage and and late stage increased from 0.36% to 21.61%, and from 4.21% to 21.38%, respectively. Flow cytometry and Western blot assay results indicated that aspirin could reduce the expression of ALDH1, SOX2, octamer-binding transcription factor 4 (OCT4) and NANOG in 4T1 cells. Sphere-forming experiments results showed that aspirin could inhibit sphere forming ability of breast cancer cells. In vivo, aspirin inhibited the growth of tumors with a dose-dependent manner. Conclusion: Aspirin could induce apoptosis of cancer stem cells and reduce stemness of breast cancer, and thus play a growth-inhibiting action on breast cancer.

TMEM45B is a novel predictive biomarker for prostate cancer progression and metastasis.

It is urgently needed to explore the clinical relevance of TMEM45B expression and Prostate cancer(PCa), and determine the predictive significance of TMEM45B as a biomarker for PCa patients.Patient-derived xenograft (PDX) model of PCa with different metastatic potential (LTL-418, LTL-313B, LTL-313H and LTL-331) were developed. The gene expression microarray of LTL-313H and LTL-313B, which derived from a single PCa patient, was performed to identify the candidate biomarker gene, TMRM45B. MSKCC and TCGA PCa patient cohorts were introduced to analyzed the clinical significance of TMEM45B expression. Quantitative Real-Time PCR (qRT-PCR) revealed that there was a significant increase of TMEM45B expression in high metastatic potential tumor lines LTL-313H and LTL-331 compared with the other two low metastatic potential tumor lines(LTL-418, LTL-313B). In MSKCC PCa cohort, the mRNA level of TMEM45B in patients with metastasis was significantly higher than that in primary PCa (P=0.001) and begin prostate hyperplasia (BPH) patients (P<0.001). In addition, the increased TMEM45B expression was positively related with a higher possibility of biochemical recurrence (P=0.016), distant metastasis occurrence(P<0.001) and overall patient survival (P=0.07). Moreover, TMEM45B expression was considered as an independent risk factor for metastasis of PCa based on multivariate logistic regression. Kaplan-Meier analysis showed that patients with elevated TMEM45B had a shorter biochemical recurrence free survival (RFS). For primary PCa patients, subgroup analysis showed that there was a significant association between TMEM45B expression and clinical features in primary PCa cohort. Meanwhile, cases with elevated TMEM45B were more likely to develop metastasis compared to the normal group among N0 primary PCa patients (P=0.010). Primary PCa patient cohort TCGA was used to validate the results, and an obvious relationship was found between TMEM45B and clinical characteristic of PCa (T/N stage, Gleason score, Recurrence / Progress). Furthermore, a significant poor disease free survival (DFS) was investigated in high-level of TMEM45B patients compared with the other remaining cases (P=0.007). Taken together, the increased expression of TMEM45B appears to be significantly associated with prostate carcinoma progression and metastasis which provide a new prognostic biomarker for predicting metastatic potential of PCa patients, especially for primary PCa.

A novel FGFR1-binding peptide attenuates the degeneration of articular cartilage in adult mice.

OBJECTIVE: We previously reported that genetic ablation of (Fibroblast Growth Factors Receptors) FGFR1 in knee cartilage attenuates the degeneration of articular cartilage in adult mice, which suggests that FGFR1 is a potential targeting molecule for osteoarthritis (OA). Here, we identified R1-P1, an inhibitory peptide for FGFR1 and investigated its effect on the pathogenesis of OA in mice induced by destabilization of medial meniscus (DMM). DESIGN: Binding ability between R1-P1 and FGFR1 protein was evaluated by enzyme-linked immuno sorbent assay (ELISA) and molecular docking. Alterations in cartilage were evaluated histologically. The expression levels of molecules associated with articular cartilage homeostasis and FGFR1 signaling were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting and immunohistochemistry (IHC). The chondrocyte apoptosis was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay. RESULTS: R1-P1 had highly binding affinities to human FGFR1 protein, and efficiently inhibited extracellular signal-regulated kinase (ERK)1/2 pathway in mouse primary chondrocytes. In addition, R1-P1 attenuated the IL-1ß induced significant loss of proteoglycan in full-thickness cartilage tissue from human femur head. Moreover, this peptide can significantly restore the IL-1ß mediated loss of proteoglycan and type II collagen (Col II) and attenuate the expression of matrix metalloproteinase-13 (MMP13) in mouse primary chondrocytes. Finally, intra-articular injection of R1-P1 remarkably attenuated the loss of proteoglycan and the destruction of articular cartilage and decreased the expressions of extracellular matrix (ECM) degrading enzymes and apoptosis in articular chondrocytes of mice underwent DMM surgery. CONCLUSIONS: R1-P1, a novel inhibitory peptide for FGFR1, attenuates the degeneration of articular cartilage in adult mice, which is a potential leading molecule for the treatment of OA.

HMGA2 Modulates the TGFß/Smad, TGFß/ERK and Notch Signaling Pathways in Human Lens Epithelial-Mesenchymal Transition.

BACKGROUND AND OBJECTIVE: Multiple signaling pathways coordinately promote epithelial-mesenchymal transition (EMT) in lens epithelial cells (LECs), where transforming growth factor beta (TGFß)-mediated signaling plays a central role. But the mechanism of crosstalk among these pathways remains obscure. The objective of this study is to investigate the regulatory effect of the high mobility group protein A2 (HMGA2) on the signaling pathways in lens fibrosis. METHODS: The human anterior capsulorhexis specimens were collected. The human SRA01/04 LEC line was cultured and treated with recombinant human TGFß2 (5ng/ml). For inhibition of signaling pathways, a selective inhibitor SB431542, U0126 or DAPT was added to LECs respectively. The specific small interfering RNA (siRNA) were transfected to LECs for gene silence. The mRNAs expressions were measured by realtime PCR and the proteins expressions were determined by western blot and immunofluorescent staining. RESULTS: HMGA2 and EMT markers α-smooth muscle actin (SMA), fibronectin (FN) and collagen type I (Col I) were overexpressed in human ASC specimens and TGFß2 stimulated EMT in LECs. While blockage of EMT by a selective inhibitor of TGFß/Smad, TGFß/extracellular signal-regulated kinase (ERK) or Notch signaling pathway could significantly inhibited HMGA2 protein expression. And silence of HMGA2 by siRNA could significantly inhibit TGFß2 induced expression of EMT markers including FN, Col I, collagen type IV (Col IV), key transcription factors Snail and Slug, and remarkably upregulate the epithelial markers E-cadherin and tight junction protein (ZO-1). In addition, silence of HMGA2 gene could abrogate TGFß2 induced phosphorylation of Smad2, Smad3 as well as ERK1/2. Blockage of HMGA2 could also inhibit the upregulation of Jagged1, Notch2, and Notch3 induced by TGFß2. CONCLUSION: This study indicated that HMGA2 functions as a shared effector in TGFß2- induced lens fibrosis, modulating the signaling network necessary for EMT in a positive feedback loop.