Acral melanoma(AM)is the most common histologic subtype of melanoma in dark-skinned patients and is associated with a worse prognosis and a high mortality rate,largely due to the inconspicuous nature of early-stage lesions,which can lead to late diagnosis.Because of the overlapping clinical and histopathological features of AM with other forms of cutaneous melanomas,early detection of AM requires a multidisciplinary approach that integrates various diagnostic modalities,including clinical examination,dermoscopy,histopathology,molecular testing,radiological imaging,and blood tests.While surgery is the preferred method of treatment for AM,other therapeutic options may be employed based on the stage and underlying etiology of the disease.Immune checkpoint inhibitors,molecular targeted therapy,radiotherapy,chemotherapy,and oncolytic virotherapy represent promising advanced treatment options for AM.In this review,we provide an overview of the latest advancements in diagnostic and therapeutic methods for AM,highlighting the importance of early detection and the prompt,individualized management of this challenging disease.

Objective:To investigate the status of cognition and clinical management of prolonged mechanical ventilation(PMV) among medical staffs in pediatric intensive care unit(PICU) in China, and in order to improve the awareness of PICU medical staffs on PMV and standardize the management of PMV.Methods:The cross-sectional study was conducted with doctors and nurses in PICUs of the collaborative group as the survey objects from July 12 to September 12, 2020.The questionnaire was issued, collected and checked by the Children′s Hospital of Fudan University.Results:(1) PMV related settings: Nine out of eleven hospitals had established PMV multidisciplinary teams, respiratory techniques such as diaphragm ultrasound and airway peak flow monitoring could be respectively executed in 72.7% and 36.4% of PICU.Pulmonary rehabilitation techniques such as airway clearance techniques, induced spirometer exercise, external diaphragm pacemaker stimulation, transfer bed exercise, balloon blowing, hyperbaric oxygen therapy could be respectively executed in 100.0%, 9.1%, 9.1%, 9.1%, 27.3% and 27.3% of PICU, respectively.(2) The cognitive status quo of children′s PMV: The most medical staffs agreed with the view that PMV referred to the children′s continuous mechanical ventilation for more than two weeks.Sixty percent of medical staffs believed that children with PMV had basic central nervous system diseases, and 62.7% of medical staffs believed that the most common causes of difficulty in PMV weaning was abnormal brain function.(3) The cognitive status quo of the children′s PMV management in PICU: Respondents believed that the most commonly used mechanical ventilation mode was synchronized intermittent mandatory ventilation+ pressure support ventilation in children′s PMV during stable disease.Ninety-two percent of medical staffs performed the spontaneous breathing test when weaning.And 58.7% of the respondents agreed to perform tracheotomy for the children during 3 to 4 weeks of mechanical ventilation.More than half of medical staffs would execute diaphragm function assessment, bedside rehabilitation training, nutritional assessment, analgesia and sedation assessment for children with PMV.(4) The cognitive status quo of the children′s PMV management of transition from hospital to family: 54.5% of PICU provided family care training to the family members before the children were discharged from the hospital.One center established the PMV specialized outpatient clinic.45.5% of PICU would follow up these discharged children one month later.Conclusion:At present, PICU medical staffs have different awareness of children′s PMV related problems in China.And children′s PMV lacks a systematic plan regarding diagnosis, treatment and management.

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.
Animals ; Imaging, Three-Dimensional ; Mice ; Neural Networks, Computer ; Spinal Cord/diagnostic imaging* ; Synchrotrons ; X-Ray Microtomography

Effective methods for visualizing neurovascular morphology are essential for understanding the normal spinal cord and the morphological alterations associated with diseases. However, ideal techniques for simultaneously imaging neurovascular structure in a broad region of a specimen are still lacking. In this study, we combined Golgi staining with angiography and synchrotron radiation micro-computed tomography (SRμCT) to visualize the 3D neurovascular network in the mouse spinal cord. Using our method, the 3D neurons, nerve fibers, and vasculature in a broad region could be visualized in the same image at cellular resolution without destructive sectioning. Besides, we found that the 3D morphology of neurons, nerve fiber tracts, and vasculature visualized by SRμCT were highly consistent with that visualized using the histological method. Moreover, the 3D neurovascular structure could be quantitatively evaluated by the combined methodology. The method shown here will be useful in fundamental neuroscience studies.

Objective:To explore the risk factors for mortality in pediatric acute respiratory distress syndrome (PARDS) requiring extracorporeal membrane oxygenation (ECMO) support.Methods:Clinical data of 109 patients with severe PARDS supported by ECMO, who were hospitalized in 6 ECMO centers in China from September 2012 to February 2020, were retrospectively analyzed. They were divided into survival group and death group according to the prognosis. Chi-square test and rank sum test were used to compare the variables between the two groups, including the demographic data, laboratory examination results, clinical data before and after ECMO, and other supportive treatment. Univariate and multivariate Logistic regression models were used to analyze the prognostic risk factors.Results:In these 109 cases, 54 died and 55 survived. Compared with the survival group, the death group had higher incidences of acute kidney injury (AKI) (48.1% (26/54) vs. 21.8% (12/55) , χ2=8.318, P=0.004) and coagulation dysfunction (22.2% (12/54) vs. 7.3% (4/55) , χ2=4.862, P=0.027), and higher rate of renal replacement therapy (48.1% (26/54) vs. 21.8% (12/55) , χ2=9.694, P=0.008) during ECMO support. Logistic regression analysis showed that continuous renal replacement therapy (CRRT) and AKI were independent risk factors for death in patients with severe PARDS requiring ECMO support ( HR=3.88,95% CI 1.04-14.52, HR=4.84,95% CI 1.21-19.46, both P<0.05). Conclusion:AKI and CRRT are independent risk factors for predicting mortality in patients with severe PARDS requiring ECMO support.

Objective:To assess antimicrobial activity of Fe 3O 4 nanozymes against Candida albicans. Methods:Fe 3O 4 nanozymes were prepared by using a modified hydrothermal synthesis method. Candida albicans suspensions were divided into 4 groups: nanozyme group treated with 0.5 g/L Fe 3O 4 nanozymes, H 2O 2 group treated with 0.1% H 2O 2, combination group treated with 0.5 g/L Fe 3O 4 nanozymes and 0.1% H 2O 2, and control group receiving no treatment. Candida albicans in the above 4 groups was all cultured with Sabouraud liquid medium, the absorbance value at 600 nm was detected every 2 hours, and the growth of Candida albicans was observed. After 2-hour treatment, the morphology of Candida albicans in the 4 groups was observed by scanning electron microscopy; after plate coating, Candida albicans was cultured at 36 ℃ for 48 hours, colonies were observed and counted, and the inhibition rate of colony formation was calculated. One-way analysis of variance was used for comparing means among several groups, and least significant difference (LSD) - t test for multiple comparisons. Results:A relatively stable survival curve of Candida albicans was observed in the control group, while the growth of Candida albicans was inhibited in the nanozyme group, H 2O 2 group and combination group. The colony count significantly differed among the control group, H 2O 2 group, nanozyme group and combination group (124 830 ± 45 170, 86 330 ± 13 960, 91 670 ± 31 370 and 30 330 ± 3010 respectively; F = 9.41, P < 0.05) , and was significantly lower in the combination group than in the control group ( t = 4.63, P < 0.05) . There was a significant difference in the colony-formation inhibition rate among the H 2O 2 group, nanozyme group and combination group (30.84% ± 5.00%, 26.57% ± 11.24%, 75.70% ± 2.42% respectively; F = 9.413, P < 0.01) , and the combination group showed a significantly higher inhibition rate compared with the H 2O 2 group and nanozyme group ( t = 8.08, 4.27 respectively, both P < 0.01) . Scanning electron microscopy showed changes in the morphology of Candida albicans treated with H 2O 2 and nanozymes alone or in combination, including shrinkage, rupture and even collapse. Conclusion:Fe 3O 4 nanozymes combined with H 2O 2 have obvious antimicrobial effect against Candida albicans.

Objective To investigate the effect of hyperoside on proliferation and killing activity of NK cells against pancreatic cancer PANC1 cells in vitro,and explore its potential mechanism.Methods Peripheral blood mononuclear cells of healthy donors were isolated,NK cells were induced with medium contained with IL-2 and different concentrations of hyperoside (0.3,1.6,8,40 and 200 μg/ml) for 12 days.Cell viability was observed by trypan blue staining.Phenotype and perforin,granzyme B expression of NK cells were detected by flow cytometry.Killing activity of NK cells against PANC1 cells were analyzed with lactate dehydrogenase (LDH) releasing method.Results The proportion of NK cells in control group and experimental group treated with different concentration of hyperoside both reached about 80％,respectively.The proliferation of CDs-CD56 + NK cells treated by hyperoside at 0.3,1.6 and 8 μg/ml was (93.76 ±8.77),(106.67 ± 12.35) and (118.50 ± 11.51) times,respectively,which were significantly higher than (73.70 ± 9.43) times of the control group.The expressions of perforin in NK cells treated with hyperoside at 1.6,8 and 40 μg/ml were significantly higher than those of the control group [(82.34 ± 2.90) ％,(89.15 ±3.54) ％,(81.78 ± 2.81)％ vs (72.93 ± 2.06)％].The expressions of granzyme B in NK cells treated with hyperoside at 1.6 and 8 μg/ml were significantly higher than those of the control group [(87.30 ± 1.70) ％,(92.16 ±3.05)％ vs (82.35 ±2.73)％].The killing activity of NK cells against PANC1 cells treated by hyperoside at 1.6 and 8 μg/ml was significantly higher than those of the control group [(63.18 ± 3.77)％,(65.34 ± 4.97) ％ vs (52.16 ± 5.48) ％].The differences were statistically significant (all P ＜ 0.05).Conclusions Hyperoside could promote the proliferation of NK cells at certain concentrations and maybe enhance the killing effect against pancreatic cancer PANC1 cells through up-regulating the expression of perforin and granzyme B in NK cells.

Objective To explore the mechanisms of ligament of Marshall (LOM) initiat and sustain atrial fibrillation (AF).Methods The electrophysiologic properties of canine LOM were investigated using multipolar catheter mapping(normal canines,n =4,group A;AF canines,n =5,group B).The programmed stimulation were performed in the LOM,PV-left atrium(LA)junction and LA,respectively.Activations maps of LOM were analyzed from episodes of spontaneous onset of AF and initiation of induced AF by a single extrastimulus.The effectives refractory period of each part was compared and statistically analyzed among three parts in each group and between the two groups.LOM were cutted with surgical incision technology.The inducing rate of AF and the mapping rate of double potential and fragmented electrocardiogram were compared and statistically analyzed pro and post isolation of LOM.Results The incidence of abnormal potential of LOM in the two groups was significantly different(P ＜0.01),re-entry cycle(group A 25％ vs.B group 80％),tachycardia(group A 25％ vs.B 100％),double potential(group A 25％ vs.group B 80％),fragmentation potential(group A 25％ vs.group 80％).There was a significant difference in the rate of LOM tachycardia induction before and after LOM intervention in group B (P ＜ 0.05,before 100％ vs.after 20％).Conclusion There are two possible mechanisms of LOM involved in the occurrence and maintenance of AF:one is that LOM induces AF through spontaneous excitation,the other is that LOM participates in the reentry of left atrium and pulmonary vein in the form of bypass to induce and maintain AF.

Objective: To evaluate the efficacy of gastric pull-up and complex laryngotracheal flap in reconstruction for circumferencial defects after resection of hypopharyngeal and cervical esophageal cancers. Methods: A total of 163 cases (152 males, 11 females) with circumferencial defect after resection of hypopharyngeal and cervical esophageal cancers received reconstructive surgeries by gastric pull-up (42 cases) and complex laryngo-tracheal flaps (121 cases), of them 115 cases simultaneously underwent unilateral neck dissection and 20 cases had bilateral neck dissection. Postoperative radiotherapy was used in 67 cases, with a dosage of 40-60 Gy. Results: There were 127 (77.9%) cases with positive metastatic lymph nodes. Of 42 patients with gastric pull-up reconstruction, 39 cases (92.8%) recovered the function of oral swallowing after operation, and 8 cases with cervical esophageal cancer recovered the functions of oral swallowing and speech after gastroesophageal anastomosis reconstruction. There were 3 (7.1%) cases died of surgery and 8 cases with surgical complications. Reconstruction of upper digestive tract with combined laryngotracheal flap was successful in all 121 cases, with recovered oral swallowing function after operation. No patient died of surgery but 24 cases had complications, mainly pharynx skin fistula or wound infection, which were cured by conservative treatments. The 1-, 3- and 5-year survival rates for 163 patients were 69.8%, 50.5% and 34.3%, respectively. The independent factors for prognosis included T4 (P<0.001) and N+ (P=0.042). Conclusions The complex of laryngotracheal flap with pectoralis major myocutaneous flap is suitable for most advanced hypopharyngeal cancer after resection of the tumor and reconstruction of circumferencial defect. It is simple technology, low and slight complication rate. The minority is not suitable for the application of pectoralis major myocutaneous flap can be used instead of free anterolateral thigh flap. Gastric pull-up for reconstruction of upper digestive tract is suitable for most patients with cervical esophageal cancer and hypopharyngeal carcinoma invading the cervical esophagus who are not suitable for laryngotracheal flap reconstruction, with good swallowing function after surgery. However, it is prudent to choose operative indications because of serious surgical trauma and risks for complications.

Objective To explore the value of mast cell tryptase and brain natriuretic peptide(BNP)in the differential diagnostic of sudden death due to hypersensitivity and coronary atherosclerotic heart dis-ease.Methods Totally 30 myocardial samples were collected from the autopsy cases in the Department of Forensic Pathology, Shanxi Medical University during 2010—2015. All samples were divided into three groups:death of craniocerebral injury group, sudden death of hypersensitivity group and sudden death of coronary atherosclerotic heart disease group, 10 cases in each group. Mast cell tryptase and BNP in myocardium were detected by immunofluorescence staining and Western Blotting.Results Immunofluo-rescence staining showed that the positive staining mast cell tryptase appeared in myocardium of sudden death of hypersensitivity group and coronary atherosclerotic heart disease group. Among the three groups, the expression of mast cell tryptase showed significantly differences through pairwise comparison(P<0.05); The expression level of BNP in sudden death of coronary atherosclerotic heart disease group were significantly higher than the sudden death of hypersensitivity group and death of craniocerebral injury group(P<0.05). The difference of the expression level of BNP between the sudden death of hypersensitivity group and the death of craniocerebral injury group had no statistical significance(P>0.05).Conclusion The combined detection of the mast cell tryptase and BNP in myocardium is expected to provide help for the forensic differential diagnosis of sudden death due to hypersensitivity and coronary atherosclerotic heart disease.