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 preliminarily evaluate the effect of tension stimulation on the biological activity of and expression of fibrosis marker genes in keloid fibroblasts (KD-Fbs) .Methods:Three patients who were diagnosed with keloids and received surgical treatment were collected from the Department of Dermatology, Tangdu Hospital, the Fourth Military Medical University from January to March 2017. Human KD-Fbs were isolated from resected keloid tissues, and subjected to primary culture. The third- to sixth-passage KD-Fbs were divided into tension group and control group to be cultured in the tension-based chamber and control chamber respectively, and subjected to tension stimulation and normal culture respectively. Cell counting kit-8 (CCK8) assay was performed to assess the proliferative activity of KD-Fbs after 1-, 2-, 3- and 4-day culture, and the scratch assay to evaluate the migratory ability of KD-Fbs after 1- and 2-day culture. After 48-hour treatment, real-time quantitative PCR and Western blot analysis were performed to determine the mRNA and protein expression of fibrosis markers type Ⅰ collagen, fibronectin and α-smooth muscle actin (α-SMA) in KD-Fbs respectively. Two-independent-sample t test was used for comparisons between 2 groups. Results:CCK8 assay showed that the proliferative activity of KD-Fbs was significantly higher in the tension group than in the control group after 1-, 2-, 3- and 4-day culture ( t=3.05, 7.00, 16.65, 15.19, respectively, all P< 0.05) . After 1- and 2-day culture, the scratch assay showed that the migration rate of KD-Fbs was significantly higher in the tension group (48.65%±3.96%, 100.00%, respectively) than in the control group (9.36%±1.14%, 50.35%±4.23%, t=16.53, 20.35, respectively, both P< 0.01) . Real-time quantitative PCR showed that the mRNA expression of type Ⅰ collagen, fibronectin and α-SMA was significantly higher in the tension group (3.04±0.20, 2.16±0.10, 3.76±0.24, respectively) than in the control group (1.00; t=17.57, 21.01, 20.25, respectively, all P< 0.01) . As Western blot analysis revealed, changes in the protein expression of the 3 fibrosis markers were consistent with their mRNA expression changes (all P< 0.05) . Conclusion:Tension may participate in the fibrosis in keloids by promoting the expression of fibrosis marker genes, and enhancing the proliferative and migratory ability of KD-Fbs.

Objective To analyze the differential expression of D2 and D3 alternative splicing sites of human kinectin in human hepatocellular carcinoma (HCC) tissues, adjacent non-cancerous tissues and normal liver tissues, and to investigate a possible relationship between alternative splicing sites of kinectin and hepatocarcinogenesis. Methods The cDNA was obtained by RT-PCR in 45 coupled HCC cancerous and adjacent tissues, and 10 normal liver tissues. The difference in the expression of D2 and D3 alternative splicing sites in cDNA was examined by semi-quantitative PCR, and statistical analysis was performed. Results The ratio of D2L (long segment contains of the D2 region)/D2S (short segment that does not contain a D2 zone) in hepatocellular cancerous tissues was 2.709 ± 1.025, the ratio of D2L/D2S in adjacent non-cancerous tissues was 1.564 ± 0.357, and the ratio of D2L/D2S in normal liver tissues was 1.507 ± 0.499. The differences were statistically significant (F=29.698, P<0.05);the ratio of D2L/D2S in hepatocellular cancerous tissues was higher than that of adjacent non-cancerous tissues and normal liver tissues (P<0.05). The ratio of D3L (long segment contains of the D3 region)/D3S (short segment that does not contain a D3 zone) in hepatocellular cancerous tissues was 1.232 ± 0.041, the ratio of D3L/D3S in adjacent non-cancerous tissues was 1.156 ± 0.309, and the ratio of D3L/D3S in normal liver tissues was 1.282 ± 0.343. The ratio of D3L/D3S was not significantly different among hepatocellular cancerous tissues, adjacent non-cancerous tissues and normal liver tissues (F = 0.989, P > 0.05). Conclusion Variant containing D2 is over expressed in cancerous tissues and this alteration may be tumor associated.

Alzheimer's disease is a common neurodegenerative disease. One of the main pathology is neurofibrillary tangles in neurons,in which principal component is the phosphorylation of tau protein. Previous studies focused on senile plaques and Aβ levels. Recent studies indicated that the development of tau protein closely associated with Alzheimer's disease, especially the abnormal phosphorylation. This paper reviewed the relationship between tau protein phosphorylation and Alzheimer's disease based on the perspective of protein kinases and phosphatases.

Objective To explore the efficacy and safety of dexmedetomidine combined with propofol on double-balloon enteroscopy.Methods Forty cases of patients ASA Ⅰ-Ⅱ grade who underwent double-balloon enteroscopy were divided into dexmedetomidine combined with propofol group (combine group) and propofol group by random digits table with 20 cases each group.Combine group was given load 0.7 μg/kg (intravenous infusion for 10 min) before induction and 0.2 μg/ (kg·h) continuous infusion during the surgery.All the patients were used propofol by target concentration with 2.5-4.0 mg/L for target-controlled infusion heart rate (H R),mean arterial pressure (MAP),respiratory rate (RR),peripheral oxygen saturation (SpO2) were recorded before examination(T0),eye lash reflex time(T1),during the perform (T2),the end of check (T3),sedation score,induction time,recovery time,total propofol amount,rates of adverse reaction and satisfaition were recorded.Results The induction time,recovery time was no statistically significant difference between two groups (P ＞ 0.05).The RR,SpO2 was no statistically significant difference between two groups at different time points (P ＞0.05).The HR at T1,T2 in combine group was significantly lower than that at T0 and in propofol group same period[(65.8 ± 7.3),(68.6 ± 8.2) times/min vs.(84.6 ± 7.1) and (77.6 ± 7.2),(89.6 ± 8.4) times/min,P ＜ 0.05].The MAP at T1 in combine group was significantly higher than that at T0 and in propofol group same period [(88.9 ± 9.4) mm Hg (1 mm Hg =0.133 kPa) vs.(81.3 ± 4.5) and (73.5 ± 6.8) mm Hg,P ＜ 0.05],at T2 was significantly lower than that in propofol group [(80.6±6.6) mm Hgvs.(88.5 ±7.6) mm Hg,P＜0.05].Sedation score 1 score 18 cases,2 scores 2 cases in combine group; 1 score 3 cases,2 scores 17 cases in propofol group,the difference was statistically significant (P ＜ 0.05).Combine group apnea two cases,moving,choking three cases,propofol group were eight cases and seven cases,the difference was statistically significant (P ＜ 0.05).The total propofol amount in combine group was significantly lower than that in propofol group [(421 ± 76) mg vs.(638 ± 89) mg,P ＜ 0.05].Conclusion Dexmedetomidine composite target controlled infusion of propofol used for double-balloon enteroscopy can produce good narcotic analgesic which is safe and effective anesthesia.

Objective To analyze the efficacy of early management of eomplications in patients with multi-ple traumas by applying the damage control theory. Method All total of 116 patients admitted to Wuhan Tongji Hospital between Jan 2006 and Jan 2008 were included in this retrospective study and were classified according to treatment method. Overall, 55 cases underwent damage control operations and 61 cases underwent conventional management. The groups of patients were compared in terms of parameters such as length of operation time, time to resuscitate from shock, lethal triad of death (LTD), complications and treatment outcomes after operation. Results The length of operation time was (67.43±19.52) min, resuscitation time from shock was (6.77±3.16) h and LTD was (11.54±4.10) h in the damage control group, and (163.95±55.41) min, (22.51±11.65) h and (34.55±5.63) h, respectively, in the conventional group, with significant differences between the two groups (P< 0.01). The per capita complication and mortality rates were 227.27 % and 3.64 %, respectively, in the dam-age control group and 363.93 % and 9.84%, respectively, in the conventional group (P <0.05). Couclusions Here, we demonstrated that early management of patients with multiple traumas undergoing operations by apply-ing the damage control theory significantly decreased the operation time, and decreased time to resuscitation from shock and LTD. Furthermore, this approach significantly reduced the incidence of comphcations and the mortality rate of patients with severe multiple traumas.

In recent 10 years, using radiofrequency catheter ablation, our medical center has treated 4865 cases of paroxysmal supraventricular tachycardia (PSVT). To improve clinical practice, a retrospective analysis of this group was made. In this group, 2092 cases were atrioventricular reentry tachycardia (AVRT), including 1415 left accesory pathway and 677 right accesory pathway, and 2773 cases were atrioventricular nodal reentry tachycardia (AVNRT). The total success rate of radiofrequency treatment is 99.71%; the recurrence rate after half a year 1.73%; the total complication rate 1.25%. In conclusion, radiofrequency ablation is a safe and effective treatment for tachycardia with high rate of success and low rate of complication.
Adult ; Catheter Ablation ; Female ; Humans ; Male ; Retrospective Studies ; Tachycardia, Paroxysmal ; surgery ; Tachycardia, Supraventricular ; surgery ; Young Adult

Objective To assess the value of 18 F-FDG PET imaging in the localization of epileptic foci.Methods 18 F-FDG PET were performed in 22 patients with medically intractable epilepsy (15 males,7 females,mean years:19.0 years,mean duration:8.2 years). The open skull operations were undergone in 21 patients according to the results of 18 F-FDG PET, combining with scalp EEG and CT or/and MRI. 1 patient was refered for stereotactic operation. During operation,EcoG was detected for identifying the site of epileptogenic focus and lobectomy was performed . All specimens were examninated with the pathological tests. All patients were followed up for the curative effects. Results PET showed abnormalities in 21 patients(95.5%). Among them,single or multiple focal hypometabolisms were found in 20 patients and focal hypermetabolism in 1 patient. The scalp EEGs showed abnormalities in 17 patients(77.3%),but 8 of them did not showed clear latreralizing manifestations.The abnormalities were found on MR or/and CT in only 5 cases (22.7%).The epileptogenic foci detected by PET were consistent well with EcoG in 18cases(85.7%), consistent approximately in 2 cases and not consistent in 1 cases .Among 19 patients with abnormal PET findings , the pathological abnormalities were found in 18 cases (94.7%).No pathological abnormality was found in the patients with nomal PET imaing. After the open skull operations, 9 patients (42.9%) becomed seizure free . 9 patients (42.9%) had more than 50% seizure reduction and 3 patients (14.3%)showed no improvement. The patient treated with stereotactic operation also showed no significant improvement.Conclusion 18 F-FDG PET imaging is a sensitive and accurate modality to localizate the epileptic foci and has important clinical value in surgical therapy.