Objective To investigate upper esophageal sphincter (UES)abnormalities in patients with achalasia (AC),and to analyze the correlation between UES abnormalities and clinical symptoms, treatment efficacy.Methods From February 2012 to December 2014,158 patients with AC and received high resolution manometry (HRM)examination were retrospectivly analyzed.According to whether with UES abnormalities,patients were divided into UES normal group and UES abnormal group.Patients of UES abnormal group were sub-divided into UES hypotensive group (UES resting pressure<34 mmHg, 1 mmHg=0.133 kPa),hypertensive group (UES resting pressure>104 mmHg)and impaired relaxation group (residual pressure>12 mmHg).Analysis of Variance,Kruskal-Wallis H test and Chi square test were performed to compare the clinical data and dynamic characteristics of the patients in each group. Results A total of 74 (46.8%)AC patients had UES abnormalities,the majority of whom were impaired relaxation (35 cases,47.3%).The age of patients in hypotensive group ((60.6 ± 10.1 )years)was significantly older than that of hypertensive group ((43.9 ±11 .1 )years)and impaired relaxation group ((46.8±16.3)years),and the disease course (10 years,4 to 30 years)was obviously longer than that of hypertensive group (6 years,1 to 10 years)and impaired relaxation group (8 years,3 to 15 years),and the differences were statistically significant (F = 7.983,H = 13.816,both P < 0.01).There was no correlation between UES abnormalities and clinical symptoms (P >0.05 ).The results of AC subtyping indicated that type Ⅱ AC accounted 55 .7% (88/158).Type Ⅱ AC cases number of UES normal group and abnormal group was 46 and 42 cases,both was majority (54.8% and 56.8%).Among these patients,123 patients finally received peroral endoscopic myotomy (POEM),47.2%(58/123 )of whom had abnormal UES.More than 85 % patients were satisfied at one month after the operation.And Eckardt scores significantly decreased.There was no significant difference in treatment efficacy between the two groups.Conclusions Most AC patients are with UES abnormality,and impaired relaxation is more common.There is no correlation between UES abnormalities and major symptoms.There is no predictive role of UES abnormalities in treatment efficacy of POEM in AC patients.

Objectives To detect the expression of serum high mobility group box-1 (HMGB1) and explore its changes in rats with acute necrotizing pancreatitis (ANP).Methods Intraperitoneal injection of 20％ L-arginine in the dosage of 250 mg/100 g twice every 1 hour was used to establish ANP rat model.Intraperitoneal injection of normal saline solution in equal volume was performed in control rats.Rats were sacrificed at 6 h,18 h,24 h,36 h,48 h,72 h and 96 h after injection.Blood samples were collected to detect serum amylase and HMGB1 level.Pancreatic tissue was collected for pathological examination.Realtime PCR was applied to detect the mRNA expression of HMGB1 in pancreatic tissue.Werstem blot was used to determine HMGB1 protein expression in pancreatic tissue.Results Serum amylase level began to increase at 6 h after modeling,reached the peak at 18 h [(5 070 ± 603) U/L] and returned to normal level after 48 h.Serum amylase activity at 6 h and 18 h in ANP group was much higher than that in control group (1 844 ± 181)U/L(P＜0.05).The expression of HMGB1 began to increase at 6 h,reached to the peak at 36 h [(288.5 ±42.1)μg/L],and then decreased gradually.HMGB1 expressions at each time point in ANP group were significantly higher than those in control group (31.6 ± 10.1) μg/L],and the differences were statistically significant (all P ＜ 0.05).Pathological scores in pancreatic tissues in ANP group were higher than those in control group 0.38 ± 0.52,and the differences were statistically significant (P ＜ 0.05).HMGB1 mRNA expressions at t 6 h,18 h,24 h,36 h,48 h,72 h and 96 h in ANP group were 1.23 ±0.25,2.60 ± 0.46,3.23 ± 0.34,4.77 ± 0.66,2.88 ± 0.56,2.05 ± 0.20,1.33 ± 0.28,which were significantly higher than those in control group 0.44 ± 0.09,and the relative expression of HMGB1 in ANP group at 36 h was significantly higher than those at other time points (all P ＜ 0.05).HMGB1 protein expression in pancreatic tissue in ANP group at 6 h,18 h,36 h,72 h were 1.14 ±0.02,1.15 ±0.01,1.22 ±0.01,1.22 ±0.04,which obviously higher than those in control group(1.0),and HMGB1 expression in ANP group at 36 h was higher than those at other time points (all P ＜ 0.05).Conclusions HMGB1 may participate in systematic inflammation as one of the late inflammatory mediators during ANP.

Objective: To explore the application and effect of superficial temporal fascia flap combined with avulsion auricular tissue in emergency auricular restoration. Methods: From June 2015 to December 2015, 6 patients with auricular large area complete avulsion were underwent treatment in Department of Plastic Surgery of General Hospital of Shenyang Military. After thorough debridement, the auricular cartilage scaffold of the avlusion ear and skin was completely stripped. The auricular cartilage was repositioned on its anatomical site and subsequently covered by superficial temporal fascia flap. The free skin was stripped as full-thickness graft to cover the surface of reconstructed ear. Results: All 6 patients with auricle large area complete avulsion achieved immediate repair under emergency condition. The operations were successfully completed and the ears were healed primarily. The patients were followed-up for one year. Five patients with partial auricular avulsion achieved obvious reconstructed auricle profile. The color of reconstructed ear was close to the surrounding skin and the cranioauricular angle was nearly normal. Patients and their families were very satisfied. One patient of total auricular reconstruction had auricular contracture. The auricle profile was not obvious with small size, morphological changes and external auditory canal stenosis. Conclusions Avulsion auricle and temporal superficial fascia flap can be used to repair partial auricle defects as a first-stage repair with ideal results. It is the best choice for large auricle defects in emergency cases.

Objective To explore the role of the visceral afferent nerve hyperesthesia and acid-sensing ion channel 1 (ASIC1) in rats with reflux esophagitis (RE).Methods Sixty male Sprague-Dawley rats were selected and animal model was established.Rats were divided into control group (n=20) and RE group (n=40).The esophageal mocosa biopsy were routinely performed in two groups.The esophageal specific DRG neurons were identified by 1,1'dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate tracing method and the whole-cell patch clamp assay was performed.The expression of ASIC1 in esophageal mucosa and thoracic spine cord three to five segments at protein level and mRNA level were detected by Western blotting and quantitative real time-polymerase chain reaction (qPCR).Two independent samples t test was performed for statistical analysis.Results The body weight of RE group was significantly lower than that of control group ((179.41±-16.38) g vs (290.75 ±-22.20) g),and the difference was statistically significant (t=17.090,P＜ 0.01).Esophageal basal cell hyperplasia,papillary elongation,vascular dialation and congestion,inflammatory cells infiltration were found in RE group rats.The results of whole-cell patchclamp showed depolarization of the resting potential of esophageal-specific DRG neurons of RE group was more significant than that of control group (-(46.20 ± 1.92) mV vs-(51.60 ± 1.52) mV),and the difference was statistically significant (t=4.930,P＜0.01).The threshold current of RE group was much lower than that of control group ((18.00±13.04) pAvs (80.00±12.25) pA),and the difference was statistically significant (t=7.750,P＜0.01).When stimulated with two to three times the threshold current,the frequency of action potential of RE group significantly increased (5.80 ±1.48 vs 3.00 ±1.58,10.60±2.30 vs 5.20±1.92),and the differences were statistically significant (t=2.890 and 4.030,both P＜0.01).The results of Western blotting indicated that the expression of ASIC1 in esophageal mucosa of RE group was significatly lower than that of control group (0.614±0.120 vs 0.976±0.283),and the difference was statistically significant (t =2.885,P＜ 0.05),while there was no statistically significant difference in the expression of ASIC1 in DRG between RE group and control group (0.804 ± 0.182 vs 1.032±0.316;t=1.528,P＞0.05).The results of qPCR showed that the expression of ASIC1 mRNA in esophageal mucosa of RE group was lower than that of control group (0.694 ± 0.118 vs 1.036 ±0.137),and the difference was statistically significant (t=4.642,P＜0.01).However there was no statistically significant difference in ASIC1 at mRNA level between RE group and control group (1.002± 0.074 vs 0.985±0.120;t=0.294,P＞0.05).Conclusion The sensitivity of esophageal visceral afferent nerve of rats in RE group increases and ASIC1 may negatively regulate the formation of esophageal visceral hypersensitivity.

Amplifying "eat me signal" during tumor immunogenic cell death (ICD) cascade is crucial for tumor immunotherapy. Inspired by the indispensable role of adenosine triphosphate (ATP, a necessary "eat me signal" for ICD), a versatile ICD amplifier was developed for chemotherapy-sensitized immunotherapy. Doxorubicin (DOX), ATP and ferrous ions (Fe²⁺) were co-assembled into nanosized amplifier (ADO-Fe) through π‒π stacking and coordination effect. Meanwhile, phenylboric acid-polyethylene glycol-phenylboric acid (PBA-PEG-PBA) was modified on the surface of ADO-Fe (denoted as PADO-Fe) by the virtue of d-ribose unit of ATP. PADO-Fe could display active targetability against tumor cells via sialic acid/PBA interaction. In acidic microenvironment, PBA-PEG-PBA would dissociate from amplifier. Moreover, high H₂O₂ concentration would induce hydroxyl radical (·OH) and oxygen (O₂) generation through Fenton reaction by Fe²⁺. DOX and ATP would be released from the amplifier, which could induce ICD effect and "ICD adjuvant" to amplify this process. Together with programmed death ligands 1 (PD-L1) checkpoint blockade immunotherapy, PADO-Fe could not only activate immune response against primary tumor, but also strong abscopal effect against distant tumor. Our simple and multifunctional ICD amplifier opens a new window for enhancing ICD effect and immune checkpoint blockade therapy.

Background: Nickel-induced allergic contact dermatitis (Ni-ACD) is a global health problem. More detailed knowledge on the skin uptake of haptens is required. This study aimed to investigate the penetration process and distribution of nickel in skin tissues with late phase and early phase of Ni-ACD to understand the mechanisms of metal allergy. Methods: Forty Hartley guinea pigs were divided into four groups according to the NiSO₄ sensitizing concentration and the NiSO₄ challenged concentration: the 5% NiSO₄-group, 5% to 10% (sensitization-challenge; late phase group); 10% NiSO₄-group, 10% to 10% (sensitization-challenge; early-phase group); and the positive and negative controls. Pathological biopsies were performed on each group. The depth profile of nickel element concentration in the skin of guinea pigs was detected by synchrotron radiation micro X-ray fluorescence spectroscopy (SR-μ-XRF) and micro X-ray absorption near-edge spectroscopy (μ-XANES). Results: In each section, the nickel element concentration in both the 5% NiSO₄-group and 10% NiSO₄-group was significantly higher than that in the negative control group. In the upper 300-μm section of skin for the early phase group, the nickel element concentration was significantly higher than that in the lower section of skin. In deeper sections (<200 μm) of skin, the concentration of nickel in the early phase group was approximately equal to that in the late phase group. The curve of the late phase group was flat, which means that the nickel element concentration was distributed uniformly by SR-μ-XRF. According to the XANES data for the 10% NiSO₄ metal salt solution, structural changes occurred in the skin model sample, indicating that nickel was not present in the Ni²⁺ aqueous ionic state but in the nickel-binding protein. Conclusions This study showed that the distribution of the nickel element concentration in ACD skin tissue was different between the early phase and late phase groups. The nickel element was not present in the Ni²⁺ aqueous ionic state but bound with certain proteins to form a complex in the stratum corneum in ACD model tissue.