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 relationship between caspase recruitment domain protein 9 (CARD9) level and inflammatory response in cerebral tissue of ischemic brain injury mice.Methods:Totally 24 SPF BALB/c male mice were randomly(random number) divided into 4 groups: sham operated group, ischemia 3 h group, ischemia 6 h group, and ischemia 12 h group, 6 mice in each group. The permanant middle cerebral artery occlusion (pMCAO) model in the ischemia groups was established by using line embolism to block blood flow. Mice in each group were sacrificed at the predetermined time point after operation. CARD9 and p-p65NF-κB levels were detected by Western blot, and the inflammatory factors mRNA and protein including TNF-ɑ, IL-lβ and IL-6 were detected by RT-PCR and ELISA, respectively. The data were analyzed by SPSS 21.0 software, the comparison of measurement data between each two groups was analyzed by independent sample t test, and the correlations between CARD9 and inflammatory factors were analyzed by Pearson analysis. Results:Compared with the sham operated group, the CARD9 levels in the ischemia 3 h, 6 h and 12 h groups were increased significantly [(0.325±0.011) vs. (0.462±0.019), P=0.036; (0.735±0.036), P=0.003; (0.903±0.024), P=0.001], the p-p65NF-κB levels in the ischemia 3 h, 6 h and 12 h groups were increased significantly [(0.227±0.016) vs. (0.316±0.017), P=0.041; (0.445±0.021), P=0.016; (0.671±0.039), P=0.008], the TNF-ɑ levels in the ischemia 3 h, 6 h and 12 h groups were significantly increased [(0.53±0.06) vs. (1.06±0.10), P=0.009; (1.47±0.15), P=0.004; (2.78±0.18), P=0.001], the IL-lβ levels in the ischemia 3 h, 6 h and 12 h groups were significantly increased [(0.55±0.07) vs. (1.01±0.11), P=0.009; (2.13±0.16), P=0.003; (3.09±0.18), P=0.001], and the IL-6 levels in the ischemia 3 h, 6 h and 12 h groups were significantly increased [(1.99±0.18) vs. (4.10±0.41), P=0.006; (8.54±0.84), P=0.002; (11.56±0.96), P=0.001]. Pearson analysis showed that CARD9 was positively correlated with the p-p65NF-κB and TNF-ɑ, IL-lβ, IL-6 ( r=0.894, P=0.001; r=0.747, P=0.008; r=0.810, P=0.001; r=0.773, P=0.007). Conclusions:A positive correlation exists between CARD9 and inflammatory responses in the early stage of ischemic brain injury in mice

Objective:To evaluate the diagnostic efficacies of computed tomography (CT), clinical manifestations and 2019 novel coronavirus (2019-nCoV) nucleic acid test results for the screening and diagnosis of novel coronavirus pneumonia.Methods:The clinical data of suspected cases with corona virus disease 2019 (COVID-19) visited fever clinic or stayed in emergency room of the First Affiliated Hospital of Nanchang University from January 23 to February 9, 2020 were collected. Totally 274 cases who met the inclusion criteria were enrolled. Four screening schemes including chest CT screening, scoring, chest CT and scoring series screening, chest CT and scoring parallel screening were designed. The statistical analysis was performed by using chi-square test. The sensitivities, specificities and the areas under the receiver operator characteristic curve of the four screening schemes were calculated, and the diagnostic efficacies were evaluated.Results:Among the 274 cases, 93.80%(257/274) presented with typical clinical symptoms, 47.81%(131/274) had epidemiological history, and the blood routine examination results of 45.26%(124/274) cases met the positive criteria of the scoring , and chest CT results of 43.07%(118/274) cases met the positive criteria of chest CT screening. The 2019-nCoV nucleic acid test positive rate of cases with epidemiological history was 30.53%(40/131), which was higher than that of cases without epidemiological history (9.09%(13/143)), and that of cases with typical imaging performance on chest CT was 40.68%(48/118), which was higher than cases without typical imaging performance (3.21%(5/156)). The differences between the above groups were both statistically significant ( χ2=20.150、60.468, respectively, both P<0.01). The positive rates of viral nucleic acid detection in cases with positive findings of chest CT screening, scoring, series screening, and parallel screening were 40.68%(48/118), 23.74%(47/198), 44.68%(42/94) and 23.87%(53/222), respectively, while those in cases with negative findings of the four screening schemes were 3.20%(5/156), 7.89%(6/76), 6.11%(11/180) and 0(0/52), respectively. The positive rates of the four screening schemes were all significantly different from that of viral nucleic acid detection ( κ=0.402, 0.100, 0.431, 0.106, all P<0.01). The chest CT screening method had a sensitivity of 90.57%and a specificity of 68.33%, and an area under the operating characteristic curve of the subject was 0.794, which had higher diagnostic value than those of the other three screening schemes. Conclusions:For the screening and diagnosis of COVID-19 cases, epidemiological history, positive 2019-nCoV nucleic acid test with ≥2 typical clinical manifestations have highly diagnostic value. On the basis of the preliminary screening of chest CT examination, flexible analysis of the diagnostic results could improve the diagnostic value of each detection method.

Objective To explore the preventive effect of twin-tube laryngeal mask airway on gastric lavage and aspiration pneumonia. Methods Between January 2015 and June 2017, 305 cases of poisoning coma patients were admitted to Emergency Department, The First Affiliated Hospital of Nanchang University. According to the inclusion criteria and exclusion criteria, 255 cases of poisoning coma patients were enrolled and randomly(random number) divided into 3 groups (n=85 in each group):group A (normal gastric lavage machine method), group B (gastric lavage endotracheal intubation), and group C (gastric lavage twin-tube laryngeal mask airway placement). Whether there was aspiration pneumonia within 12 hours after the onset was observed, and the length of hospital stay, hospitalization cost and mortality were recorded. The mean value of the two samples was compared with t test, and the four-grid data were checked by chi-square test. P<0.05 was statistically significant. Results Compared with group A, the incidence of aspiration pneumonia was significantly lower in group B and group C (group A 56.47％, group B 32.94％, group C 23.53％, P<0.01). Compared with group A, the length of hospital stay in group C was shorter [(3.39±2.12) d vs. (6.06±4.91) d,P<0.05], and the hospitalization cost was less [(25687.52±20803.44) yuan vs. (52213.91±37267.56)yuan,P<0.05]. There was no significant difference of mortality between the three groups (P>0.05).Compared with group B, the length of hospital stay in group C was shorter [(3.39±2.12) d vs.(5.51±4.37) d, P<0.05], and the hospitalization cost was less [(25687.52±20803.44)yuan vs.(50887.82±32399.76) yuan, P<0.05]. There was no significant difference of mortality between the three groups (P>0.05). Conclusions Twin-tube laryngeal mask airway for poisoning coma patients with gastric lavage, can not only ensures effective ventilation, but also reduces the probability of concurrent aspiration pneumonia, shortens hospital stay, and reduces hospitalization cost, but has no obvious effect on mortality.

Objective To present our initial experience of using transumbilical multi-stab laparoscopic pyeloplasty(TMLP) as a treatment for the infants younger than 3 months with severe hydronephrosis caused by ureteropelvic junction obstruction (UPJO).Methods Seventy-two infants younger than 3 months with severe hydronephrosis caused by UPJO underwent TMLP from June 2010 to March 2013 in our center.The average age received operation was 34 days (7-87 days).The operative indications included:① prenatal diagnosis of Society of Fetal Urology Grade 4 hydronephrosis; ②ipsilateral differential renal function being less than 40％.Patients were followed up with physical examinations,ultrasound and radionuclide scans.Results The operations were successfully performed in all the 72 patients.Neither conversion nor additional trocars placement was required and there was no intraoperative complication.The average operative time was 75 min (range,53-118 min).The patients were followed up for 6-36 months (mean,12 months).The renal pelvic anteroposterior diameters were reduced and the renal functions were improved (P＜ 0.05).The anastomoses were proved to be patent and the renal parenchymal thickeness increased.In addition,the scars were barely noticeable.Conclusions TMLP for the infants younger than 3 months with severe hydronephrosis caused by UPJO is feasible,safe and less invasive.The cosmetic results are excellent.But the surgery must be operated by rich experienced surgeon.

Objective To observe the expression of heat shock protein 70 (HSP70) in lung of rats after paraquat (PQ) poisoning and to investigate the therapeutic effects of ulinastatin. Method Seventy-two adult healthy SD rats were randomly(random number) divided into control group (group A, n = 24), poisoning group (group B, n =24) and ulinastatin group (group C, n =24). The rat models of acute PQ poisoning were established by intra-gastric administration of 80 mg/kg PQ to rats of group B and group C, and the rats of group C were intra-peritoneally injected with 100 000 IU/kg ulinastatin 30 minutes after poisoning. The expression of HSP70 in lung tissue was observed, and W/D and histopathological changes in lung tissue were compared 12 h,24 h,48 h and 72 hours after poisoning. The expression of HSP70 in lung tissue was assayed by using RT-PCR. All quantitative data were processed with one-way analysis of variance to compare multiple sample means. Results Compared with group A, the expression of HSP70 in the lung of rats in group B and group C increased significantly at all intervals ( P ＜ 0.05). The pathological changes in lung tissue of rats with PQ poisoning showed mainly congestion,leukocytes infiltration and local hemorrhage, and the pathological changes in lung tissue of group C were significantly lessened. Conclusions Ulinastatin may ameliorate the acute lung injury to a certain extent after PQ poisoning in rats by enhancing the expression of HSP70.