Traditional development of small protein scaffolds has relied on display technologies and mutation-based engineering, which limit sequence and functional diversity, thereby constraining their therapeutic and application potential. Protein design tools have significantly advanced the creation of novel protein sequences, structures, and functions. However, further improvements in design strategies are still needed to more efficiently optimize the functional performance of protein-based drugs and enhance their druggability. Here, we extended an evolution-based design protocol to create a novel minibinder, BindHer, against the human epidermal growth factor receptor 2 (HER2). It not only exhibits super stability and binding selectivity but also demonstrates remarkable properties in tissue specificity. Radiolabeling experiments with ^99mTc, ⁶⁸Ga, and ¹⁸F revealed that BindHer efficiently targets tumors in HER2-positive breast cancer mouse models, with minimal nonspecific liver absorption, outperforming scaffolds designed through traditional engineering. These findings highlight a new rational approach to automated protein design, offering significant potential for large-scale applications in therapeutic mini-protein development.

Objective:To investigate the BRAF(V600E)gene mutation of pediatric papillary thyroid carcinoma (PTC) and refine their clinicopathological correlates. Methods:Tumor tissue samples of pediatric PTCs (≤18 years old) were collected from tumor tissue bank of Tianjin Medical University Cancer Institute and Hospital from January 2012 to December 2016.The medical records of 22 patients with pediatric PTC were reviewed retrospectively.The frequencies of BRAF(V600E) mutation were evaluated and the correlation between BRAF(V600E) mutation and clinical characteristics were analyzed. Results:BRAF(V600E) mutations were present in 45.5% of cases (10 cases). BRAF(V600E) mutation in pediatric PTC was obviously lower than that in adults PTC(77.7%) ( χ2=11.250, P=0.001). BRAF(V600E) mutation in>12-year-old group (66.7%) was remarkably higher than that in ≤12-year-old group (20.0%) ( P<0.05). BRAF(V600E) mutation in female (69.2%) was greatly higher than that in male (11.1%) ( P<0.05). There was no significant correlation with BRAF(V600E) mutation and multiple tumor, tumor size, highly invasive subtype, extrathyroidal extension, lymph node metastasis and radiological history of infants (all P>0.05). The median follow-up time was 45 months.No patients died and BRAF(V600E) mutation was not associated with the increase of recurrence rate ( P>0.05). Conclusions:BRAF(V600E)gene mutation in pediatric PTC is lower than that in adults. BRAF(V600E) mutation does not portend a more aggressive clinical biological behavior in pediatric PTC.

Objective:To evaluate the role of Tg in diagnosis of lateral cervical lymph node recurrence in papillary thyoid cancer(PTC)after radioactive iodine(RAI) therapy.Methods:From Jan 2012 to Aug 2018, 22 PTC patients who received RAI therapy after operation were reoperated for lateral cervical lymph node recurrence. The clinical data was retrospectively analyzed.Results:The median recurrence time was 30.5 (5-86) months. All 22 patients received RAI therapy after the first operation, and the median dose of RAI was 250mCi(100-700 mCi) and the episode of RAI therapy ranged from 1 to 4. All 22 PTC patients underwent neck reoperation, among which 20 cases were identified to have lymph node metastasis. The median number of lymph nodes dissected was 31 (8-83) and median number of metastatic lymph nodes was 4 (1-19) . The diagnostic accuracy of ultrasonography in detecting lymph node metastasis was 90.9%. Before reoperation, the median Tg was 1.305 (0.10-99.51) μg/L, with the cutoff value of Tg being 0.2 μg/L, and its sensitivity and specificity were 80.0% and 100%, respectively. The median stimulated Tg was 5.89 (0.14-255.80) μg/L in the 10 patients, with the cutoff value of stimulated Tg of 2 μg/L, and its sensitivity and specificity were 88.9% and 100%, respectively.Conclusions:The serum Tg level is helpful for monitoring the recurence of PTC, but recurrence cannot be completely ruled out for those with low Tg.

Objective:To investigate the long-term effects of porcine small intestinal submucosa (SIS) biologic mesh in open Lichtenstein tension-free hernia repair.Methods:The prospective randomized controlled study was conducted. The clinical data of 76 patients with unilateral inguinal hernia who underwent open Lichtenstein tension-free hernia repair in 2 medical centers (52 cases in Tianjin People′s Hospital and 24 cases in China-Japan Friendship Hospital) from August 2013 to March 2014 were selected. Based on random number method, patients were allocated into two groups. Patients undergoing Lichtenstein tension-free hernia repair using Biodesign Surgisis mesh were allocated into control group, and patients undergoing Lichtenstein tension-free hernia repair using SIS biologic mesh were allocated into experiment group. Observa-tion indicators: (1) grouping situations of the enrolled patients; (2) postoperative long-term effects. Follow-up was conducted using telephone interview, text message or mail to detect hernia recurrence or death due to other reasons as the end-point event of patients up to December 2019. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented by M (range), and comparison between groups was conducted using the Mann-Whitney U test. Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test or Fisher exact probability. Results:(1) Grouping situations of the enrolled patients: a total of 76 patients were selected for eligibility. There were 38 cases in the control group and the experiment group, respectively. The number of males and females, age, body mass index, cases with intraspinal anesthesia or local anesthesia (anesthesia method), cases with inguinal hernia on the left side or on the right side, cases classified as type Ⅰ, Ⅱ, Ⅲ, Ⅳ or Ⅴ of Gilbert classification, operation time of the control group were 35, 3, (56±15)years, (23.0±2.0)kg/m 2, 22, 16, 16, 22, 9, 16, 0, 11, 2 and (49±15)minutes, respectively. The above indicators of the experiment group were 34, 4, (54±13)years, (22.9±2.2)kg/m 2, 17, 21, 14, 24, 9, 21, 1, 7, 0, and (53±21)minutes, respectively. There was no significant difference in the above indicators between the two groups ( χ2=0.157, t=0.532, 0.367, χ2=1.317, 0.220, Z=-0.315, t=-0.765, P>0.05). (2) Post-operative long-term effects: 35 patients of the control group were followed up for (68.8±2.7)months, 4 cases of which died due to other reasons, 1 case had hernia recurrence, 1 case had chronic pain and no foreign body sensation and postoperative infection occurred. Thirty-one patients of the experiment group were followed up for (68.8±2.7)months, with no death or above complications. There was no significant difference in hernia recurrence or chronic pain between the two groups ( P>0.05). Conclusion:The long-term effects of biological mesh in open Lichtenstein tension-free hernia repair is satisfactory and there is no difference in the long-term effects between the domestic SIS biological mesh and Biodesign Surgisis mesh.

Objective To investigate the diagnosis and treatment of ectopic para-aortic pheochromocytoma. Methods Clinical data of 2 cases with ectopic para-aortic pheochromocytoma in the Third Affiliated Hospital of Sun Yat-sen University from August 2012 to December 2013 were analyzed retrospectively. The informed consents of both patients were obtained and local ethical committee approval had been received. Both patients were female with the age of 54, 57 years old. The occurrence of disease, diagnosis, treatments and efficacy were observed. Results Case 1 was admitted in hospital for complaint of 1-month distending pain in upper abdominal and ifnding of retroperitoneal space-occupying lesion for 8 d. Solid space-occupying lesion at the right side of mid-upper abdomen was found by abdominal ultrasound and computer tomography (CT) examination. The preoperative diagnosis was abdominal mesenchymoma. Case 2 was admitted in hospital for complaint of palpitation, chest pain and ifnding of hepatic space-occupying lesion for 10 d and had a history of 5-year hypertension. Cystic solid space-occupying lesion in the hepatic caudate lobe was found by abdominal ultrasound, CT and magnetic resonance imaging (MRI) examinations and cystadenoma was suspected. The 2 patients underwent resection of ectopic para-aortic pheochromocytoma under general anesthesia by tracheal intubation. The intraoperative exploration found that touching the tumor had great impacts on blood pressure and heart rate and ectopic para-aortic pheochromocytoma was diagnosed. The patients were transferred to surgical intensive care unit (ICU) for monitoring and treatment. Pheochromocytoma was confirmed by the pathological examination. The patients were recovered and discharged from hospital and remained well till the paper submission date. Conclusions Ectopic para-aortic pheochromocytoma is a rare disease without characteristic clinical features. It is dififcult for preoperative diagnosis. The conifrmation is mainly depends on the pathological ifndings. Surgical resection is the priority of treatment. Fully assessment of operative risk before operation, avoiding touching tumor tissues during operation, complete excision of tumor capsule, close monitoring on the blood pressure after operation can achieve a good clinical treatment outcome.