[MAX germline mutation-associated pheochromocytoma-paraganglioma syndrome: multiple endocrine neoplasia type 5].

The individualized precision management of hereditary pheochromocytoma (PHEO) and paraganglioma (PGL) syndromes (PPGLs) based on molecular diagnosis and molecular subtype is becoming more popular. The newly discovered MAX germline mutation-associated PPGLs are autosomally dominant and rare. To raise awareness and explore the effective management of individual diagnosis and treatment, the relevant literature published between January 2011 and February was systematically reviewed. There were a total of 101 patients in the 77 families, involving all 5 exons, containing 44 types of MAX germline mutations and mostly concentrated in exons 3 and 4 (64.4%), the main mutations were nonsense mutations and missense mutations (73.2%), and some were large fragment deletions or insertions, intron variant, gene fusion mutations were relatively infrequent. Furthermore, about 10% of the patients had a paternal parent-of-origin effect. Among the 101 patients, 96 (95.0%) developed PHEO including 15 metastatic PHEO, 61 bilateral PHEO and 35 unilateral PHEO. The age of diagnosis was (31.7±10.9) years (range: 13 to 80 years). The male to female ratio was 1.2∶1. Eleven were accompanied with chest and abdominal PGL. Eight (7.9%) were accompanied by functional pituitary adenoma. And 12 (11.9%) developed other neuroendocrine tumors (NET), of which 8 were accompanied by PHEO, including 4 hyperparathyroidism, 1 gangliocytoma and neuroblastoma, 1 pancreatic NET, 1 medullary thyroid carcinoma and 1 C cell hyperplasia. Six presented concomitant non-NET, including 1 tongue squamous cell carcinoma, 1 papillary thyroid carcinoma, 1 prostate cancer, 1 renal oncocytoma, 1 breast cancer with renal oncocytoma, and 1 thoracic chondrosarcoma with multifocal adenocarcinoma of lung. The remaining 5 cases (5.0%), including 4 other NET (2 ganglioblastoma, 1 abdominal neuroblastoma and 1 pancreatic NET) and 1 asymptomatic child, did not present PHEO. The MAX germline mutation may cause a novel multiple endocrine neoplasia, which can be described as type 5. A comprehensive baseline assessment of neural crest cell-derived diseases such as PPGL, pituitary adenoma, hyperparathyroidism, and/or gangliocytoma (neuroblastoma) was recommended for all people with MAX germline mutations, and the risk of bilateral and/or metastatic PHEO should also be considered. In contrast, patients with PPGLs combined with other NET, such as functional pituitary adenoma, should undergo genetic testing and pedigree screening that includes at least the MAX gene.

Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma.

BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.

[Interpretation on Expert systematic review on the choice of conduits for coronary artery bypass grafting endorsed by the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons in 2023].

Expert systematic review on the choice of conduits for coronary artery bypass grafting: endorsed by the European Association for Cardio-Thoracic Surgery and the Society of Thoracic Surgeons published in 2023 made recommendations for the selection of bypass vessels. The left internal thoracic artery-anterior descending branch anastomosis represents the accepted gold standard. Radial artery could achieve a better long-term patency rate and a reduction in adverse cardiac events compared to the great saphenous vein. Radial artery graft using an open harvesting method should be chosen to graft the target vessel with low competitive coronary flow, with the use of vasodilators for the first year. There was no clear evidence of better patency for the right internal thoracic artery compared to the great saphenous vein. The bilateral internal thoracic artery had better long-term survival compared to great saphenous vein but may be associated with a higher risk of deep sternal wound infection and should be avoided in high-risk patients. The impact of skeletonization of the internal thoracic artery on graft patency and cardiovascular outcomes was unclear. Endoscopic vein harvest reduced the risk of leg wound complications and was associated with reduced long-term patency. The patency of the no-touch great saphenous vein was significantly better than that of conventional great saphenous vein. A significantly higher risk of complications at the harvesting site and no clear evidence of better long-term clinical outcomes were found in the no-touch great saphenous vein compared to the conventional. There was limited data on the use of right gastroepiploic artery and skeletonized harvesting, which should be used to bypass target vessels in patients with low competitive flow.

[Management of radiation-induced intestinal injury:from multi-disciplinary team team to holistic integrative management].

Radiation-induced intestinal injury is a radiation injury of the colon and rectum after radiotherapy for pelvic malignant tumors. This condition affects multiple organs in the pelvis, making treatment challenging. In clinical practice, the most effective protocol is often determined through discussion by a multi-disciplinary team (MDT). However, due to the severity and complexity of radiation enteritis, many patients still experience poor diagnosis and treatment outcomes. Holistic integrative management (HIM) is a rapidly developing concept that has greatly enhanced clinical medicine in recent years. It improves the level of diagnosis, treatment, prevention, and rehabilitation from multiple dimensions of prevention, screening, diagnosis, treatment, and rehabilitation. In the context of radiation-induced intestinal injury, HIM also calls for the implementation of an individualized management system that focuses on the patient as a whole within the healthcare team. From the perspective of HIM, this article introduces some of the latest progress of radiation-induced intestinal injury in recent years.

[Patient experience in the implementation of enhanced recovery after surgery strategy after radical gastric cancer surgery].

Objective: To investigate the experience of patients in the implementation of enhanced recovery after surgery (ERAS) strategy after radical gastrectomy and the factors affecting the treatment experience. Methods: A prospective cohort study was carried out. Patients who were diagnosed with gastric cancer by pathology and underwent radical gastrectomy at the Xijing Digestive Disease Hospital from December 2019 to December 2020 were consecutively enrolled. Those who received emergency surgery, residual gastric cancer surgery, preoperative neoadjuvant chemotherapy, non-curative tumor resection, intraperitoneal metastasis, or other malignant tumors were excluded. Patients' expectation and experience during implementation were investigated by questionnaires. The questionnaire included three main parts: patients' expectation for ERAS, patients' experience during the ERAS implementation, and patients' outcomes within 30 days after discharge. The items on the expectation and experience were ranked from 0 to 10 by patients, which indicated to be unsatisfied/unimportant and satisfied/important respectively. According to their attitudes towards the ERAS strategy, patients were divided into the support group and the reject group. Patients' expectation and experience of hospital stay, and the clinical outcomes within 30 days after discharge were compared between the two groups. Categorical data were reported as number with percentage and the quantitative data were reported as mean with standard deviation, or where appropriate, as the median with interquartile range (Q1, Q3). Categorical data were compared using the Chi-squared test or Fisher's exact test, where appropriate. For continuous data, Student's t test or Mann-Whitney U test were used. Complication was classified according to Clavien-Dindo classification. Results: Of the included 112 patients (88 males and 24 females), aged (57.8±10.0) years, 35 patients (31.3%) were in the support group and 77 (68.7%) in the reject group. Anxiety was detected in 56.2% (63/112) of the patients with score >8. The admission education during the ERAS implementation improved the patients' cognitions of the ERAS strategy [M(Q1, Q3) score: 8 (4, 10) vs. 2 (0, 5), Z=-7.130, P<0.001]. The expected hospital stay of patients was longer than the actual stay [7 (7, 10) days vs. 6 (6, 7) days, Z=-4.800, P<0.001]. During the ERAS implementation, patients had low score in early mobilization [3 (1, 6)] and early oral intake [5 (2.25, 8)]. Fifty-eight (51.8%) patients planned the ERAS implementation at home after discharge, while 32.1% (36/112) preferred to stay in hospital until they felt totally recovered. Compared with the reject group, the support group had shorter expected hospital stay [7 (6, 10) days vs. 10 (7, 15) days, Z=-2.607, P=0.009], and higher expected recovery-efficiency score [9 (8, 10) vs. 7(5, 9), Z=-3.078, P=0.002], lower expected less-pain score [8 (6, 10) vs. 6 (5, 9) days, Z=-1.996, P=0.046], expected faster recovery of physical strength score [8 (6, 10) vs. 6 (4, 9), Z=-2.200, P=0.028] and expected less drainage tube score [8 (8, 10) vs. 8 (5, 10), Z=-2.075, P=0.038]. Worrying about complications (49.1%) and self-recognition of not recovery (46.4%) were the major concerns when assessing the experience toward ERAS. During the follow-up, 105 patients received follow-up calls. There were 57.1% (60/105) of patients who experienced a variety of discomforts after discharge, including pain (28.6%), bloating (20.0%), nausea (12.4%), fatigue (7.6%), and fever (2.9%). Within 30 days after discharge, 6.7% (7/105) of patients developed Clavien-Dindo level I and II operation-associated complications, including poor wound healing, intestinal obstruction, intraperitoneal bleeding, and wound infection, all of which were cured by conservative treatment. There were no complications of level III or above in the whole group after surgery. Compared with the support group, more patients in the reject group reported that they had not yet achieved self-expected recovery when discharged [57.1% (44/77) vs. 22.9% (8/35), χ2=11.372, P<0.001], and expected to return to their daily lives [39.0% (30/77) vs. 8.6% (3/35), χ2=10.693, P<0.001], with statistically significant differences (all P<0.05). Only 52.4% (55/105) of patients returned home to continue rehabilitation, and the remaining patients chose to go to other hospitals to continue their hospitalization after discharge, with a median length of stay of 7 (7, 9) days. Compared with the reject group, the support group had a higher proportion of home rehabilitation [59.7% (12/33) vs. 36.4% (43/72), χ2=4.950, P=0.026], and shorter time of self-perceived postoperative full recovery [14 (10, 20) days vs. 15 (14, 20) days, Z=2.100, P=0.036], with statistically significant differences (all P<0.05). Conclusions: Although ERAS has promoted postoperative rehabilitation while ensuring surgical safety, it has not been unanimously recognized by patients. Adequate rehabilitation education, good analgesia, good physical recovery, and early removal of drainage tubes may improve the patient's experience of ERAS.

Toripalimab (anti-PD-1) versus high-dose interferon-α2b as adjuvant therapy in resected mucosal melanoma: a phase II randomized trial.

BACKGROUND: No standard of care for mucosal melanoma (MM) in the adjuvant setting has been established. Meanwhile, relapse-free survival (RFS) is only ∼5 months after surgery alone. This phase II trial aimed to compare toripalimab versus high-dose interferon-α2b (HDI) as an adjuvant therapy for resected MM. PATIENTS AND METHODS: From July 2017 to May 2019, 145 patients with resected MM were randomized (1 : 1) to receive HDI (n = 72) or toripalimab (n = 73) for 1 year until disease relapse/distant metastasis, unacceptable toxicity, or withdrawal of consent. The primary endpoint was RFS. The secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), and safety. RESULTS: After a median follow-up of 26.3 months, the number of RFS, OS, and DMFS events was 51 versus 46, 33 versus 29, and 49 versus 44 in the toripalimab arm and the HDI arm, respectively. The median RFS was 13.6 [95% confidence interval (CI) 8.31-19.02] months and 13.9 (95% CI 8.28-19.61) months in the toripalimab arm and the HDI arm, respectively. The DMFS was not significantly different between the two arms [hazard ratio (HR) 1.00; 95% CI 0.65-1.54]. The median OS was 35.1 months (95% CI 27.93 months-not reached) in the toripalimab arm, with no significant difference in all-cause death (HR 1.11, 95% CI 0.66-1.84) for the two arms. The median sums of the patients' actual infusion doses were 3672 mg and 1054.5 MIU in the toripalimab arm and the HDI arm, respectively. The incidence of treatment-emergent adverse events with a grade ≥3 was much higher in the HDI arm than in the toripalimab arm (87.5% versus 27.4%). CONCLUSIONS: Toripalimab showed a similar RFS and a more favorable safety profile than HDI, both better than historical data, suggesting that toripalimab might be the better treatment option. However, additional translational studies and better treatment regimens are still warranted to improve the clinical outcome of MM.

[Questionnaire investigation of radiation rectal injury with anxiety, depression and somatic disorder].

Objective: To observe the incidence and treatment of radiation rectal injury complicated with anxiety, depression and somatic symptom disorder. Methods: A cross-sectional survey research method was carried out. Patients with radiation rectal injury managed by members of the editorial board of Chinese Journal of Gastrointestinal Surgery were the subjects of investigation. The inclusion criteria of the survey subjects: (1) patients suffered from pelvic tumors and received pelvic radiotherapy; (2) colonoscopy showed inflammatory reaction or ulcer in the rectum. Exclusion criteria: (1) patient had a history of psycho-somatic disease before radiotherapy; (2) patient was unable to use a smart phone, unable to read and understand the questions in the questionnaire displayed on the phone; (3) patient refused to sign an informed consent form. According to the SOMA self-rating scale, PHQ-15 self-rating scale, GAD-7 and PHQ-9 self-rating scale, the electronic questionnaire of "Psychological Survey of Radiation Proctitis" was designed. The questionnaire was sent to patients with radiation rectal injury managed by the committee through the WeChat group. Observational indicators: (1) radiation rectal injury symptom assessment: using SOMA self-rating scale, radiation rectal injury symptom classification: mild group (≤3 points), moderate group (4-6 points) and severe group (> 6 points); (2) incidence of anxiety, depression and physical disorder: using GAD-7, PHQ-9 and PHQ-15 self-rating scales respectively for assessment; (3) correlation of radiation rectal injury symptom grading with anxiety, depression, and somatic symptom disorder. Results: Seventy-one qualified questionnaires were collected, of which 41 (56.9%) were from Guangzhou. Among the 71 patients, 6 were males and 65 were females; the mean age was (55.7±9.3) years old and 48 patients (67.6%) were less than 60 years old; the median confirmed duration of radiation rectal injury was 2.0 (1.0, 5.0) years. (1) Evaluation of symptoms of radiation rectal injury: 18 cases of mild (25.4%), 27 cases of moderate (38.0%), and 26 cases of severe (36.6%). (2) Incidence of anxiety, depression and somatic disorder: 12 patients (16.9%) without comorbidities; 59 patients (83.1%) with anxiety, depression, or somatic disorder, of whom 2 patients only had anxiety, 1 patient only had depression, 9 only had somatic disorder, 2 had anxiety plus depression, 4 had anxiety plus somatic disorder, 2 had depression plus somatic disorder, and 40 had all three symptoms. (3) correlation of radiation rectal injury grading with anxiety, depression, and somatic symptom disorder: as compared to patients in mild group and moderate group, those in severe group had higher severity of anxiety and somatic symptom disorder (Z=-2.143, P=0.032; Z=-2.045, P=0.041), while there was no statistically significant difference of depression between mild group and moderate group (Z=-1.176, P=0.240). Pearson correlation analysis revealed that radiation rectal injury symptom score was positively correlated with anxiety (r=0.300, P=0.013), depression (r=0.287, P=0.015) and somatic symptom disorder (r=0.344, P=0.003). Conclusions: The incidence of anxiety, depression, and somatic symptom disorder in patients with radiation rectal injury is extremely high. It is necessary to strengthen the diagnosis and treatment of somatic symptom disorder, so as to alleviate the symptoms of patients with pelvic perineum pain and improve the quality of life.

Developmental toxicity of cryptotanshinone on the early-life stage of zebrafish development.

Cryptotanshinone (Cry) has multiple potential functions in treating different diseases. Most studies on Cry focus on its pharmacological effects and mechanisms, but toxicological reports on Cry are rare. Zebrafish is used as a model organism in drug development as it saves costs and time. This work aimed to investigate the toxicity of Cry on zebrafish. Results showed that growth retardation, pericardial edema, and scoliosis occurred when zebrafish embryos were exposed to Cry, indicating its teratogenic effects. Cell apoptosis was observed in the brainstem area of embryos using acridine orange staining, and qPCR showed that caspase-3 was increased in Cry-exposed embryos. The results of locomotor activity and touched-evoke escape reaction experiments showed that Cry significantly reduced the swimming speed and escape reaction time of larvae.

Effects of brain games on global cognition among older Filipinos

Objective@#This study ascertained the effects of brain games on global cognition among older Filipinos.@*Methods@#A quasi-experimental design was used. The participants were 60 elderly Filipinos, aged 60 to 93 years, residing in Baguio City, and were not engaging in any physical or nutritional interventions to improve cognitive function. None have subclinical cognitive impairments as screened using the Mini-Cognitive Examination. The Addenbrooke's Cognitive Examination-III (ACE-III) tool which correlated significantly with standard neuropsychological tests, and provided a high internal reliability score of 0.88, was used. Data were analyzed using descriptive and inferential statistics.@*Results@#Pretest mean scores of both active control and experimental groups increased in the posttest. Additionally, both coloring and brain games had extremely significant effects on global cognition (p=0.0001). Lastly, the unrelated t-test revealed extremely significant difference between the effects of brain games and coloring on global cognition (p=0.0001).@*conclusions@#Based on the results, brain games showed evidence of effectiveness in improving global cognition, and that compared to coloring, it is more effective in improving global cognition among older Filipinos. Variables like motivation and expectancy effects influence the improvement in global cognition among older Filipinos. Lastly, cognitive training using brain games show promise as a non-pharmacologic intervention to address cognitive decline.

[Effects of intraoperative graft flow measurements on the early mid-term outcomes after off-pump coronary artery bypass grafting].

OBJECTIVE: To investigate and analyze the relationship between intraoperative graft flow measurements and the early mid-term outcomes after off-pump coronary artery bypass grafting (OPCAB). METHODS: Patients who underwent isolated OPCAB in the Department of Cardiac Surgery of Peking University People's Hospital from January 2013 to June 2016 were included. Perioperative characteristics, graft flow measurements and postoperative follow-up outcomes were retrospectively collected. Comparison was made between flow measurements of grafts and the early mid-term outcomes. Flow measurements of grafts included the mean flow (MF) and the pulsatility index (PI). The early outcomes included peri-operative myocardial infarction (PMI), use of an intra-aortic balloon pump (IABP), reoperation for all causes, new-onset atrial fibrillation and in-hospital or 30-day mortality. RESULTS: A total of 463 patients were included in the study. Mean age was (62.80±8.36) years, and 24.8% were females. The total number of grafts was 1 435, which averaged 3.10 grafts per patient. The MF and PI were separately (32.34±14.45) mL/min and 2.87±0.92. Of all the patients, 23(5%) had PMI, and 11 used IABP. Observed in-hospital or 30-day mortality was 0.86% (4 patients). Compared with non-PMI group, the MF was lower and the PI was higher in the PMI group (P<0.05). However, the differences of other early outcomes had no statistical significance between the PMI group and the non-PMI group. The lower MF (Wald=5.684, P=0.017, 95%CI: 0.894-0.989) and the higher PI (Wald=9.040, P=0.003, 95%CI: 1.252-2.903) were risk factors of PMI in multivariable Logistic regression modeling. The longest follow-up time was 37 months, and 7 patients died. The differences of graft flow measurements between the surviving group and the nonsurvivors had no statistical significance, but overall mid-term survival was lower in patients with poor left internal mammary artery (LIMA) to left anterior descending artery (LAD) graft flow (MF<10 mL/min; OR=9.6, P<0.05). CONCLUSION: Intraoperative graft flow parameters during OPCAB can predict the early mid-term outcomes. The lower MF and the higher PI should increase the rate of PMI. A lower flow of LIMA to LAD graft (<10 mL/min) should increase the rate of midterm mortality, but further research will be needed to confirm and explore the findings.

[Impact of first-line chemotherapy on renal function in patients with advanced upper tract urothelial carcinoma].

Objective: To observe the impact of first-line chemotherapy on renal function in patients with unresectable/metastatic upper tract urothelial carcinoma(UTUC). Methods: A total of 222 (130 males and 92 females) unresectable/metastatic upper tract urothelial carcinoma patients were included in the study between January 2005 and May 2017, with age of 29 to 87 (62.4±10.1) years old. The serum creatinine level and estimated glomerular filtration rate (eGFR) were compared before and after first-line chemotherapy. And predictive factors for decreased renal function were analyzed in logistic regression model. Results: After the first-line chemotherapy, the average serum creatinine level increased, with a median changing value of 1.5 µmol/L. Howerver, the eGFR improved, with a median changing value of 0.5 ml·min-1· (1.73 m2)-1, but the differences were not statistically significant (all P>0.05). In 149 patients who were treated with cisplatin-based chemotherapy, the average serum creatinine level increased by 1.31 µmol/L and eGFR improved by 0.14 ml·min-1·(1.73 m2)-1, but the differences were not statistically significant (P>0.05). In multivariate logistic regression model, age more than and equal to 60 years old (OR=0.88, P=0.745) and cisplatin-based chemotherapy (OR=0.95, P=0.893) did not increase the risk of renal dysfunction after first-line chemotherapy. If the time interval between surgery and first-line chemotherapy was more than 1 year, the risk of renal dysfunction due to chemotherapy decreased (OR=0.54, P=0.196). Eastern Cooperative Oncology Group Performance Status (ECOG PS) Scale≥1 (OR=1.81, P=0.131), anemia before treatment (OR=1.14, P=0.764), the cycles of first-line chemotherapy (OR=1.41, P=0.398) may lead to increase the risk of renal dysfunction, but the differences were not statistically significant. However in the patients who accepted nephrectomy, the risk of renal dysfunction after chemotherapy increased, but the difference was still not statistically significant (OR=3.06, P=0.089). Conclusions: First-line chemotherapy, especially the cisplatin-based regimen, had no significant impact on renal function in the patients with UTUC. Nephrectomy maybe a predictive risk factor for decreased renal function after chemotherapy. Adequate assessment of renal function before treatment, hydration and close monitoring during chemotherapy can effectively protect renal function of the patients.

Extraordinary water adsorption characteristics of graphene oxide.

The laminated structure of graphene oxide (GO) confers unique interactions with water molecules which may be utilised in a range of applications that require materials with tuneable hygroscopic properties. The precise role of the expandable interlayer spacing and functional groups in GO laminates has not completely been understood to date. Herein, we report the experimental and theoretical investigations on the adsorption and desorption behaviour of water in GO laminates as a function of relative pressure. We observed that GO imparts high water uptake capacity of up to 0.58 gram of water per gram of GO (g g-1), which is significantly higher than silica gel as a conventional desiccant material. More interestingly, the adsorption and desorption kinetics of GO is five times higher than silica gel. The observed extraordinary adsorption/desorption rate can be attributed to the high capillary pressure in GO laminates as well as micro meter sized tunnel-like wrinkles located at the surface.

BRAF inhibitors: efficacious and tolerable in BRAF-mutant acral and mucosal melanoma.

BRAF inhibitors substantially have impressive clinical efficacy in cutaneous melanoma. However, their role in acral and mucosal melanoma remains unclear. Records were reviewed of patients with metastatic or unresectable BRAF-mutant acral and mucosal melanoma hospitalized and administrated BRAF inhibitors during January 2011 and March 2016. Clinical data were collected to determine PFS, ORR, DCR, OS, and safety. Among 28 acral and 12 mucosal melanoma patients treated with BRAF inhibitors, median PFS were 3.6 (95%CI 3.0-6.4) and 4.4 (95%CI 0.8-12.7) months, median OS were 6.2 (95%CI 6.1-12.1) and 8.2 (95%CI 6.6-19.9) months; ORRs were 38.1% and 20.0%, DCRs were 81.0% and 70.0% in acral and mucosal melanoma, respectively. BRAF inhibitors were well tolerated. The most common adverse effects (AEs) were cutaneous and hematological. Grade 3/4 AEs were relatively rare. In conclusion, BRAF inhibitors have acceptable efficacy and good tolerance in BRAF mutant acral and mucosal melanoma.

The natural history and patterns of metastases from mucosal melanoma: an analysis of 706 prospectively-followed patients.

Background: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. Patients and methods: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites. Results: The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%, P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%, P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively. Conclusions: The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.

[Efficacy and the multivariate analysis of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma].

Objective: To investigate the efficacy and the influence factors of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma (mRCC). Methods: Clinical data of mRCC patients with sunitinib administered as the first line treatment from August 2008 to December 2015 were retrospectively reviewed. The efficacy and the influence factors of sunitinib treatment was analyzed using the Kaplan-Meier method and Cox proportional hazards models. Results: In all 166 patients who received sunitinib as first-line treatment, objective response rate was 31.9%, disease control rate was 84.3%. The median progression free survival (PFS) and overall survival (OS) were 11.0 months (95% CI: 9.0-14.0) and 28.0 months (95% CI: 19.0-33.0), respectively. Multivariate analysis showed that pathological types (clear cell carcinoma vs non clear cell carcinoma, HR: 1.889 vs 2.353), time from diagnosis to treatment(<1 year vs ≥1 year, HR: 0.293 vs 0.322) and the number of metastatic sites (1 vs ≥1, HR: 2.360 vs 4.351) were the independent prognostic factors for PFS and OS (P<0.05). Conclusions: The efficacy of sunitinib as first-line treatment in patients with metastatic renal cell carcinoma is similar to reports at home and abroad. The patients with renal clear cell carcinoma, time from diagnosis to treatment> 1 year, and only one metastatic site would get better PFS and OS.

[Efficacy observation of (125)I seed implantation therapy for locoregional recurrent and metastatic breast cancer].

OBJECTIVE: To assess the efficacy and side effects of (125)I seed implantation for locoregional recurrent and metastatic breast cancer, and to discuss its role in the comprehensive therapy of breast cancer. METHODS: Forty-three patients with locoregional recurrent or metastatic breast cancer were included in this study. They received (125)I seed implantation and were followed up to evaluate the efficacy and adverse reactions of the treatment. RESULTS: Among 54 lesions in the 43 cases, there were complete response (CR) in 39, partial response (PR) in 13, stable disease (SD) in 2 patients, with a response rate of 96.3%. All 17 cases with local pain achieved pain relief. With a median follow up of 36 months (range 14 to 60 months), the 1-, 3-, and 5-year local control rate was 85.2%, 53.7% and 1.9%, and the 1-, 3-, and 5-year survival rate was 95.3%, 67.4% and 37.2%, respectively. No serious radiotherapy side effect was observed. CONCLUSION: In patients with unresectable locoregional recurrent or metastatic breast cancer, (125)I seed implantation shows proved efficacy and few complications, and can be an important treatment option.

[The surrounding radiation dose of iodine-125 seeds on normal larynx tissue in rabbits].

Objective:To monitor the change of the radiation dose of the rabbits which were implanted rasioactive 125I seed into the normal laryngeal tiseue at different time,and to evaluate the safety of radiation protection. Method:Sixty New Zwaland rabbits, weighing 2.15-2.30 kg，were randomly divided into 5 groups:7 d,1month,2 month,4 month group and the control group, 12 rabbits in each group Iodine-125 of 0.8 mCi were implanted into the right side of the first trachea ring. At the different time and different distance, the surrounding radiation dose was measured after 4 months of implanting. The results were analyzed in statistics. Result:With the increase of the distance and the prolong of the time, the radiation dose was decreasing，and with the increase of distance,the radiation dose decreased slowly. At the site of 1 meter from the seeds, the detected dose is close to the natural background radiation dose. Conclusion:The clinical application of radioactive 125I seed interstitial implant is easy to protected,the surrounding close contacts is satety.

Long-term dietary sodium restriction increases adiponectin expression and ameliorates the proinflammatory adipokine profile in obesity.

BACKGROUND/AIM: Obesity is associated with changes in adiponectin and pro-inflammatory adipokines. Sodium intake can affect adipokine secretion suggesting a role in cardiovascular dysfunction. We tested if long-term dietary sodium restriction modifies the expression of adiponectin and ameliorates the pro-inflammatory profile of obese, diabetic mice. METHODS/RESULTS: Db/db mice were randomized to high sodium (HS 1.6% Na+, n = 6) or low sodium (LS 0.03% Na+, n = 8) diet for 16 weeks and compared with lean, db/+ mice on HS diet (n = 8). Insulin levels were 50% lower in the db/db mice on LS diet when compared with HS db/db (p < 0.05). LS diet increased cardiac adiponectin mRNA levels in db/db mice by 5-fold when compared with db/db mice on HS diet and by 2-fold when compared with HS lean mice (both p < 0.01). LS diet increased adiponectin in adipose tissue compared with db/db mice on HS diet, achieving levels similar to those of lean mice. MCP-1, IL-6 and TNF-α expression were reduced more than 50% in adipose tissue of db/db mice on LS diet when compared with HS db/db mice (all p < 0.05), to levels observed in the HS lean mice. Further, LS db/db mice had significantly reduced circulating MCP-1 and IL-6 levels when compared with HS db/db mice (both p < 0.01). CONCLUSION: In obese-diabetic mice, long-term LS diet increases adiponectin in heart and adipose tissue and reduces pro-inflammatory factors in adipose tissue and plasma. These additive mechanisms may contribute to the potential cardioprotective benefits of LS diet in obesity-related metabolic disorders.

Injury types of victims in the 12th May 2008 Wenchuan earthquake: analysis of 1,038 patients in Jiangyou City.

BACKGROUND: On 12th May 2008, a devastating earthquake of magnitude 8.0 struck Wenchuan, Sichuan Province of China, resulting in tremendous loss of lives and property. METHODS: We conducted an analysis of the types and distribution of the injuries among the wounded treated by a medical rescue team within 1 month following the Wenchuan earthquake in Jiangyou City. RESULTS: Within 1 month following the earthquake, 3,038 patients sustaining various traumatic injuries were treated in the emergency medical facility established based in a local hospital. Of these patients, 1,065 were hospitalized, including more female than male patients, with an average age of 40.2 years. Most of the patients sustained injuries in Pingwu County, which experienced a seismic intensity of level XI. The majority (91.4%) of the hospitalized patients were admitted in the initial 4 days after the earthquake. The injuries were classified into soft tissue injuries (48.0%), fractures (40.0%), complex injuries (3.1%), and other injuries. The injuries involved most frequently the head and face (28.5%), followed by the upper and lower limbs, chest and back, waist and abdomen, pelvis, and spine. Multiple injuries (15.4%) were also common among these patients. CONCLUSION: The devastating earthquake resulted in a large number of patients with soft tissue injuries frequently in the head and fractures involving mainly the limbs, especially the upper limbs. The injuries sustained in earthquakes are usually serious and complex, often with such complications as shock, infection, and crush syndrome. Multiple injuries are common in the event of an earthquake.

Compare activities on regulating lipid-metabolism and reducing oxidative stress of diabetic rats of Tremella aurantialba broth's extract (TBE) with its mycelia polysaccharides (TMP).

Abnormal lipid-metabolism and elevated oxidative stress are the familiar complications of diabetic mellitus. Regulated lipid-metabolism and decreased oxidative stress have become the key indices to cure diabetic complications. The activities of broth extract (TBE) and mycelia polysaccharides (TMP) of Tremella aurantialba, which is one of the best-known multipurpose medicinal fungi in China, were studied using alloxan-induced diabetic rats. TBE contains saponins, while TMP contains polysaccharides. Both TBE and TMP could reduce the blood glucose levels of diabetic rats; TBE had stronger abilities to reduce the levels of total cholesterol and total triglyceride in serum, those of malondialdehyde, and enhance the activities of superoxide dismutase and glutathione reductase in different tissues of diabetic rats (P < 0.01). TBE had slightly stronger abilities to enhance the total antioxidant capability, catalase, and glutathione peroxidase in different tissues of diabetic rats, but no significant difference was found between TBE and TMP groups. All these results indicated that TBE was more capable of regulating lipid-metabolism and decreasing oxidative stress.