Peptides are a particular molecule class with inherent attributes of some small-molecule drugs and macromolecular biologics, thereby inspiring continuous searches for peptides with therapeutic and/or agrochemical potentials. However, the success rate is decreasing, presumably because many interesting but less-abundant peptides are so scarce or labile that they are likely 'overlooked' during the characterization effort. Here, we present the biochemical characterization and druggability improvement of an unprecedented minor fungal RiPP (ribosomally synthesized and post-translationally modified peptide), named acalitide, by taking the relevant advantages of metabolomics approach and disulfide-bridged substructure which is more frequently imprinted in the marketed peptide drug molecules. Acalitide is biosynthetically unique in the macrotricyclization via two disulfide bridges and a protease (AcaB)-catalyzed lactamization of AcaA, an unprecedented precursor peptide. Such a biosynthetic logic was successfully re-edited for its sample supply renewal to facilitate the identification of the in vitro and in vivo antiparkinsonian efficacy of acalitide which was further confirmed safe and rendered brain-targetable by the liposome encapsulation strategy. Taken together, the work updates the mining strategy and biosynthetic complexity of RiPPs to unravel an antiparkinsonian drug candidate valuable for combating Parkinson's disease that is globally prevailing in an alarming manner.

Objective:To compare the diagnostic efficiency of colloidal gold dipstick method (PTH dipstick method) with that of doctors’ experience method based on nano-carbon method for rapid identification of parathyroid gland in thyroidectomy of thyroid cancer.Methods:From March to July 2020, 90 patients underwent thyroid surgery in the Friendship Hospital, Capital Medical University participated in the experimental study, and 155 samples underwent empirical judgment, parathyroid dipstick and pathological examination. All operations were performed by senior specialists. SPSS statistics 17.0 software was used for statistical analysis.Results:Seventy-four cases of parathyroid gland confirmed by both pathology and empirical judgment, and 81 cases of non-parathyroid gland confirmed by pathology; 130 cases of parathyroid glands confirmed by both PTH dipstick method and pathology, and 22 cases of non-parathyroid glands confirmed by pathology. The accuracy rate of PTH dipstick method was 85.53% which was much higher than that of empirical judgment method (47.74%). The data were statistically significant ( χ2=49.14, P<0.05). The sensitivity of PTH method was 95.89%, the specificity of PTH method was 75.94%, and the Youden index was 0.7183. The sensitivity of empirical judgment method was 81.3%, the specificity of empirical judgment method was 47.74%, and the Youden index was 0.2904. Conclusions:The diagnostic efficiency of the PTH method is higher than that of empirical judgment method to identify parathyroid gland in thyroid surgery. The two methods can be used together to increase the protection of parathyroid gland during operation.

Objective:To investigate the diagnostic value of circular RNA circ_100367 in thyroid cancer (THCA) and its relationship with immune-related factors.Methods:According to the data chip provided by the National Center for Biotechnology Information (NCBI) website, the differentially expressed circRNAs in THCA were analyzed, then circ_100367 was included in this study. The serum of 175 THCA patients and healthy people were collected, and the expression levels of circ_100367 and its linear transcript DCAF8 mRNA in serum samples were detected by qRT-PCR, and the correlation between circ_100367 and DCAF8 was calculated. The correlation between the expression of circ_100367 and the clinicopathological characteristicsof the patients, immune infiltration level and immunosuppressive factor PD-1 was analyzed.Results:Compared with serum of healthy people (1.00±0.37) , expression level of circ_100367 in serum of THCA patients was significantly increased (1.37±0.41) ( t=8.80, P<0.001) , and there was no significant difference in DCAF8 mRNA expression ( t=1.67, P=0.095) , but circ_100367 was positively correlated with DCAF8 mRNA expression ( r=0.17, P=0.028) . Analysis of expression and clinicopathological characteristics of circ_100367 showed that compared with patients in M0 group (1.26±0.40) , circ_100367 was overexpressed in M1 and Mx patients (1.43±0.40) ( t=2.63, P=0.009) ; compared with N0 patients (1.24±0.36) , circ_100367 was overexpressed in serum of N1 and Nx patients (1.45±0.42) ( t=3.48, P=0.001) ; compared with serum of patients with negative lymph node detection (1.28±0.36) , circ_100367 was overexpressed in serum of positive patients (1.42±0.43) ( t=2.14, P=0.034) ; compared with T1+T2 stage patients (1.30±0.37) , circ_100367 expression was overexpressed in serum ofT3+T4 patients (1.40±0.43) ( t=2.22, P=0.028) . Analysis of the expression and immune infiltration levels of circ_100367 found that highly expressed circ_100367 was associated with CD8+ T cells ( r=0.25, P=0.024) , macrophages ( r=0.22, P=0.038) , CD4+ T cells ( r=0.25, P=0.020) and B cell ( r=0.23, P=0.033) levels. The expression of circ_100367 was also positively correlated with the immunosuppressive factor PD-1 ( r=0.19, P=0.011) . Conclusion:circ_100367 can be used as a marker for the diagnosis of THCA and its expression is strongly correlated with immune-related factors.

Objective:To explore the application of radiofrequency ablation in breast conserving surgery with breast carcinoma.Methods:With retrospective research methods, a total of 230 patients who were treated with radiofrequency ablation after breast conserving surgery in Beijing Friendship Hospital, Capital Medical University from January 2016 to September 2018 were selected, patients were all females, the median age was 56 yecers, ranged from 27 to 91 years, and the postoperative efficacy, patients′ satisfaction with their appearance and complications were outpatient follow-up.Results:Follow-up for 18 months showed that 2 (0.87%) patients had postoperative recurrence and metastasis, 217 (94.35%) patients were satisfied with the postoperative breast appearance, and 8 patients (3.48%) had skin burns and in- situ sclerosing. Conclusions:Radiofrequency ablation is used in breast conserving surgery, which is simple to operate and has a low incidence of complications. It can strengthen local tumor control and improve the cosmetic effect of breast after conserving surgery, worthy of clinical promotion.

Objective:To investigate the clinical characteristics and risk factors of bronchiolitis obliterans (BO) after adenovirus pneumonia.Methods:Clinical data of 266 children with adenovirus pneumonia hospitalized in Children′s Hospital of Soochow University from January 2011 to December 2017 were retrospectively analyzed.Accor-ding to whether they developed BO, children with adenovirus pneumonia were divided into the BO group and the non-BO group.Clinical features of the BO group and the non-BO group were compared by t test, rank sum test or chi square test.Risk factors were analyzed by Logistic regression approach. Results:Among 266 children with adenovirus pneumonia included, 37 patients were developed into BO group, and their age was significantly younger than that of the non-BO group [12.0(8.0, 17.5) months vs.32.0(13.0, 48.0) months, P<0.001]. Compared with the non-BO group, there were more proportion of preterm infants[10.8%(4/37 cases) vs.3.1%(7/229 cases), P=0.028], more instances of comorbidities [21.6%(8/37 cases) vs.4.4%(10/229), P<0.001] and more children with allergic diseas[35.1%(13/37 cases) vs.20.1%(46/229 cases), P=0.041] in the BO group, and the difference was statistically significant.The duration of fever in the BO group was significantly longer than that of the non-BO group [10(4.0, 13.5) d vs.6(4.0, 9.0) d, P=0.011] children with symptoms of wheezing, shortness of breath, and hypoxemia in the BO group were significantly more than the non-BO group[81.1%(30/37 cases) vs.27.9%(64/229 cases), P<0.001; 64.9%(24/37 cases) vs.5.7%(13/229 cases), P<0.001; 59.5%(22/37 cases) vs.6.6%(15/229 cases), P<0.001]. The platelet count, IgG level, and CD3 -CD 19+ lymphocyte percentage were significantly higher in the BO group than the non-BO group [(364±104)×10 9/L vs.(297±105)×10 9/L, P=0.001; 6.74(4.92, 10.16) g/L vs.5.93(1.00, 8.04) g/L, P=0.016; (33.5±15.3)% vs.(26.1±10.2)%, P=0.008]. In contrast, the percentage of CD3 + CD4 + lymphocytes in the BO group was lower than the non-BO group[(29.1±8.0)% vs.(32.5±9.4)%, P=0.044], the difference was statistically significant.The BO group had a higher rate of mixed bacterial infection than the non-BO groups[37.8%(14/37 cases) vs.16.6%(38/229 cases), P=0.003]. An age<26 months, comorbidities, premature birth history, wheezing, shortness of breath, and hypoxemia were independent risk factors for BO after adenovirus pneumonia( OR=4.808, 30.667, 7.558, 3.909, 8.842, 8.607, all P<0.05). Conclusions:An age of less than 26 months, a history of premature delivery comorbidities, wheezing, shortness of breath and hypoxemia, are independent risk factors for BO after adenovirus pneumonia.Children with above manifestations should receive high resolution CT as soon as possible to determine whether it is BO.

Objective: To explore the application effect of fine needle aspiration cytology and sentinel lymph nodes stain assisted by contrast-enhanced ultrasound in early breast cancer. Methods: A patient with early breast cancer enrolled in Beijing Friendship Hospital, Capital Medical University received fine needle aspiration cytology assisted by contrast-enhanced ultrasonography and the sentinel lymph nodes were stained with blue dye before a standard sentinel lymph nodes biopsy traced with indocyanine green. The axillary status accessed by these two methods were compared. Results: Three sentinel lymph nodes were found and aspirated assisted by contrast-enhanced ultrasonography. Seven sentinel lymph nodes were obtained in sentinel lymph nodes biopsy surgery. All of these sentinel lymph nodes were negative. The stained sentinel lymph nodes could be recognized and dissected in open lymph nodes biopsy surgery. Conclusions Fine needle aspiration cytology assisted by contrast-enhanced ultrasonography could be a substitute for open sentinel lymph nodes biopsy. More related researches should be carry out to further compare these two methods.

Objective: To evaluate the efficacy of radiofrequency ablation in breast-conserving surgery followed neoadjuvant chemotherapy. Methods: Retrospective analysis of 30 cases of breast cancer patients admitted to Beijing Friendship Hospital, Capital Medical University from April 2015 to September 2018. The average age was 54.3 years and the range was 28 to 70 years. For breast invasive ductal cancer, patients underwent breast-conserving surgery after neoadjuvant chemotherapy, and then received radiofrequency ablation. The clinical and pathological characteristics, postoperative complications, recurrence and metastasis, and cosmetic effects were observed. Results: All 30 patients with breast-conserving surgery successfully completed radiofrequency ablation. The average outpatient follow-up was 22.5 months, ranging from 2 to 43 months, without local recurrence or metastasis; skin burns occurred in 2 cases (6.67%), and solid nodules formed in situ in 6 cases (20.00%); cosmetic satisfaction rate was 86.67% (26/30). Conclusions The radiofrequency ablation techniques applied in breast-conserving surgery have a high rate of technical success with relative low complication rates. And the radiofrequency ablation techniques may improve the cosmetic results after breast-conserving surgery and enhance local control.

Objective To provide new experimental evidences associated with the mechanisms of inhaled anesthetics, the effects of sevoflurane on the electric activities of inhibitory interneurons in basal forebrain area (BF) were observed.Methods C57BL/6 mice, aged 2-3 weeks, were used and BF sections were cut for whole patch-clamp recording.Artificial cerebrospinal fluid containing sevoflurane was given and action potential, inhibitory postsynaptic potential were recorded.Results Sevoflurane could increase the frequency of firing rate of inhibitory interneurons in basal forebrain area (P<0.001), which could increase the frequency of action potential caused by depolarization current (P<0.05), and increase the frequency of spontaneous inhibitory postsynaptic currents of pyramidal neurons (P<0.05), while AP-depended miniature inhibitory postsynaptic currents were not significantly changed.Conclusion The basal forebrain inhibitory interneurons are involved in the anesthetic effect of sevoflurane.

Objective To analyze the clinical efficacy of the laparoscopic breast-conserving surgery combined with radiofrequency ablation to treat the early-stage breast cancer.Methods We collected 55 patients diagnosed early-stage breast cancer in retrospect,which started from January 2014 to December 2016.Twenty-seven of them were performed the laparoscopic breast-conserving surgery combined with radiofrequency ablation while others went through laparoscopic breast-conserving surgery without radiofrequency ablation.Meanwhile,we adopted the student t-test and the chi-square test to compare results of two groups.More specific,the main indexes of this study are including the post-operative local recurrence,the incidence of fat liquefaction or the incision-infection,operation time,post-operative hospital stay and the hospitalization expense.Results The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had low local-recurrence than the laparoscopic breastconserving surgery group (0 and 7.69％).Additionally,there were no statistical differences between two groups in the incidence of fat liquefaction.However,The laparoscopic breast-conserving surgery combined with radiofrequency ablation group had more hospitalization expense than the laparoscopic breast-conserving surgery group [(4.1 ± 0.7) ten thousand yuan and (2.3 ± 0.6) ten thousand yuan,P ＜ 0.05].Conclusions Although the laparoscopic breast-conserving surgery combined with radiofrequency ablation group remarkably increased the hospitalization expense because of the utility of the radiofrequency ablation related apparatus,it may provide the probability of shaving more residual tumor cell and may low down the recurrence,especially not rising up the incidence of the post-operative fat liquefaction.Therefore,this surgery method might be one of the potential developments in the minimal-invasive of early stage breast cancer.

Objective To explore the relationship between esophageal carcinoma extensive infiltration and lesion length and 252 Cf intracavitary brachytherapy,and to evaluate its prognostic influence.Methods Thirty-two patients with esophageal carcinoma were treated by external beam and 252Cf intracavitary radiation.The patients were first treated with conventional fractionated radiation to a dose of 38 Gy over 4 weeks,with 5 daily fractions of 2 Gy per week,and then treated with external and intracavitary radiation concomitantly (4.0 Gy per fraction,once a week on every Saturday to 12 Gy in 3 fractions).The total dose of external irradiation was 50 Gy.Results The local control rate (LCR) at 1,3 and 5 years was 93.75％,76.70％ and 65.75％ in the patients with ≤5 cm lesion (NMT5 group),and 60.94％,27.08％ and 27.08％ in the patients with ＞5 cm lesion (MT5 group),respectively (x2 =7.01,P ＜ 0.05).The 1-,3-and 5-year survival rate (SR) was 93.75％,56.25％ and 43.75％ in the NMT5 group,and 75.00％,18.75％,12.50％ in the MT5 group,respectively (x2 =5.96,P ＜ 0.05).The LCR at 1,3 and 5 years was 92.31％,73.85％ and 61.54％ in the patients with ≤1.5 cm infiltration depth (NMT1.5 group),and 67.67％,35.45％ and 35.45％ in the patients with ＞ 1.5 cm infiltration depth (MT1.5 group),respectively (x2 =3.87,P ＜ 0.05).The 1-,3-and 5-year SR was 92.31％,61.54％ and 46.15％ in the NMT1.5 group,and 73.68％,21.05％ and 15.79％ in the MT1.5 group,respectively (x2 =6.24,P ＜ 0.05).LCR and SR in the patients with ≤5 cm lesion and ≤2 cm infiltration depth were significantly better than those with ＞ 5 cm lesion and ＞ 2 cm infiltration depth (x2 =10.09,7.97,P ＜ 0.05).Conclusions The patients with ≤5 cm lesion length or those with ≤ 1.5 cm infiltration depth,might become the most adaptable indication for 252 Cf intracavitary radiation.In addition,those patients with ≤2 cm infiltration depth and ≤5 cm lesion length were also suitable for 252Cf intracavitary radiation.