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.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Objective:To access the clinical efficacy and safety of hydroxychloroquine (HCQ) in treatment of IgA nephropathy (IgAN).Methods:The data of IgAN patients who were diagnosed by renal biopsy in the First Affiliated Hospital, College of Medicine, Zhejiang University from May 2016 to August 2020 and had been treated with HCQ for more than 6 months without other immunosuppressants were retrospectively analyzed. The efficacy and side effects were compared between groups according to the baseline urine protein/creatinine ratio (UPCR) or whether combined with renin-angiotensin-aldosterone system inhibitor (RAASi).Results:A total of 121 patients were enrolled, including 45 males (37.19%). At baseline, the median UPCR was 0.69(0.45, 1.00) g/g; the median estimated glomerular filtration rate (eGFR) was 93.46(73.14, 115.67) ml·min -1·(1.73 m 2) -1; the median serum creatinine was 80.00(61.00, 98.00) μmol/L, and the serum albumin was (44.39±3.36) g/L. After HCQ treatment, UPCR and red blood cells were significantly decreased compared with baseline (all P<0.05). Triglyceride, total cholesterol and low-density lipoprotein cholesterol were also significantly decreased during the follow-up period. Serum creatinine, eGFR, serum albumin and serum uric acid remained stable. After 6 months of follow-up, the total remission rate was 56.88%, including 15.60% of partial remission and 41.28% of complete remission; at the end of follow-up, the median follow-up time was 280.00(214.00, 411.00) days and the total remission rate was 56.20%, including 9.92% of partial remission and 46.28% of complete remission. Group analysis showed that the remission rate was 60.53% ( n=76) and 48.48% ( n=33) at 6 months (Mann-Whitney U test, Z=-2.331, P=0.020) and 57.65% ( n=85) and 52.78% ( n=36) at the end of follow-up (Mann-Whitney U test, Z=-1.673, P=0.094) between patients with baseline UPCR<1 g/g and patients with baseline UPCR≥1 g/g; and the remission rate was 66.67% ( n=30) and 53.16% ( n=79) at 6 months (Mann-Whitney U test, Z=1.062, P=0.288) and 61.29% ( n=31) and 54.44% ( n=90) at the end of follow-up (Mann-Whitney U test, Z=0.930, P=0.352) between patients with single HCQ and patients with HCQ+RAASi. For side effects, the eGFR of 2 patients decreased by more than 30% compared with baseline, 1 patient relapsed and 1 patient developed blurred vision. Conclusions:HCQ is safe and effective for the treatment of IgAN.

Objective:To study the efficacy of three-dimensional (3D) CT reconstruction combined with 3D color printing compared with traditional imaging technology in treatment of complex hepatobiliary calculi treated with laparoscopy and choledochoscopy.Methods:A retrospective study was conducted on 128 patients with complex hepatobiliary calculi who underwent hepatobiliary surgery at the Qingdao Chengyang People’s Hospital, Qingdao Municipal Hospital Affiliated to Qingdao University and Qingdao University Affiliated Hospital from January 2019 to December 2019. A comparison was made between patients who underwent three-dimensional CT reconstruction combined with 3D color printing (the study group, n=62) and the traditional imaging technology group (the control group, n=66) on operation time, intraoperative blood loss, liver blood flow occlusion time, stone clearance rate, postoperative complication rate, and recurrence of calculi after operation. Results:The study group was significantly better than the control group in operation time, intraoperative blood loss, porta hepatis occlusion time, hospital stay and treatment cost (all P<0.05). The stone clearance rate of the study group was 96.8% (60/62), which was significantly higher than that of the control group (86.4%, 57/66) ( P<0.05). The incidence of postoperative complications in the study group was 3.2% (2/62), which was significantly lower than that in the control group (18.2%, 12/66) ( P<0.05). There was no significant difference in the stone recurrence rate between the two groups (all P>0.05). Conclusion:Three-dimensional CT reconstruction combined with 3D color printing contributed significantly to the surgical treatment of complex intrahepatic bile duct stones as these imaging technologies significantly improved surgical accuracy, improved stone clearance and reduced postoperative complication rates, and reduced surgical treatment costs.

This article elaborated the connotation of public hospital medical insurance payment system and the importance of reform,summarizing and analyzing the practical exploration of promoting medical insurance payment system reform in the localities.Then it moved on to introduce new progress of medical insurance payment system reform abroad and the emerging mode of medical insurance payment, such as pay for performance,payment by results,and bundled payment.In the end,the authors put forward policy suggestions to improve medical insurance payment system at public hospitals in China, namely to build a modern healthcare payment system in line with the needs of medical service system.Such a system should be guided by comprehensive performance,restrained by cost budgeting, based on a diversified payment mode,and supported by information technology.In addition,it should have scientific payment standard and modern governance mechanism,and keep interactive development with commercial health insurance.

Purpose To evaluate imaging characteristics of normal and dynamic contrast enhanced multi-slice-spiral CT (MSCT) and 18F-FDG PET/CT in the patients with the mesenteric Castleman's disease (CD).Materials and Methods A retrospective analysis was made in 11 patients who were pathologically diagnosed CD and investigated their imaging characteristics of the MSCT and 18F-FDG PET/CT.Results 6 cases showed single lesion,all of them were round or oval.5 cases presented satellite lesions.The maximum diameter was (6.11 ± 1.45)cm.3 cases showed stippled or branch calcification,and 3 cases showed slightly patchy low density.11 cases had clear margins except 1 case.All cases showed the same strong lesion enhancement as that in aorta.9 cases showed significantly enhanced tumor blood vessels around the edge or shadow.The degree of 18F-FDG uptake increased in 11 cases,SUVmax was 3.1-5.7,and the average was (4.16 ± 0.86).Conclusion Multimodality imaging performances play an important role in the diagnosis of mesenteric CD.

BACKGROUND:Autologous island flap transplantation is the main therapy for burn scars. Floating and necrosis of transplanted flaps mainly impact the therapeutic effects. Dexamethasone has immunoregulatory function during trauma and stress process. OBJECTIVE:To investigate the effect of dexamethasone on immune balance of Th1/Th2 and prognosis in patients with burn scars undergoing autologous island flap transplantation. METHODS:Sixty-eight patients with burn scars undergoing transplantation of pedicled island flap were selected and randomly divided into control group and experimental group. Patients in the two groups were treated with negative pressure drainage under skin flap, infection prevention, improvement of microcirculation. After that, dexamethasone sodium phosphate (0.2 mg/kg) was immediately given in the experimental group, and the dose gradualy decreased after 3 days until drug withdrawal at 7 days. Levels of Th1, Th2, Th1/Th2 and interferon-γ, interleukin-4 were compared between the two groups before and 1 week after transplantation. In addition, incidence rates of skin flap necrosis, hemodynamic disorder, and effusion were compared between the two groups. RESULTS AND CONCLUSION:The levels of Th1, Th2, Th1/Th2, interferon-γ and interleukin-4 had no obvious differences between the two groups before flap transplantation. At 1 week after transplantation, the levels of Th1 and Th1/Th2 were higher, while the levels of Th2, interferon-γ and interleukin-4 were lower in the experimental group than the control group. Moreover, the incidence of complications was also lower in the experimental group than the control group. In conclude, dexamethasone can decrease the incidence of complications after island flap transplantation, which is maybe the result of adjusting immune balance of Th1/Th2.

Objective To study the clinical efficacy of free anterolateral femoral skin flap on the repair of skin and subcutaneous soft tissue defects caused by excision of oversized malignant tumour in the skin. Methods A retrospective review was performed of free anterolateral femoral skin flap reconstructions for oversized malignant tumor cut on body surface since April 2007 to November 2010. There were 6 patients with head and limb squamous cell carcinoma because of bum scar and 3 patients with recurrence of dermatofibrosarcoma protuberans in wall of belly. The area of soft tissue defects ranged from 19 cm × 15 cm to 24 cm × 21 cm, and skin flaps was 20 cm × 16 cm to 25 cm × 22 cm in size. Three cases received radio therapy after operation. Results Nine flaps survived perfectly, one flap survived with partial necrosis and healed after changing dressings. No complications were observed in the donor site, including wound dehiscence, hernia and weakness. Follow-up survey of 12-24 months after the operation showed that the appearance and function in the repaired sites were normal, and norecurrence of the tumors. Conclusion Free transplantation of anterolateral femoral skin flap is relatively an ideal operative type for the repair of soft tissue defects caused by excision of oversized malignant tumour in the skin.

Objective To study the correlation between high resolution computed tomography manifestations and expression of transforming growth factor beta,tumor necrosis factor alpha in radiationinduced lung injury of rats,and to investigate the vslues of cytokine detection and HRCT scanning for the prediction and early diagnosis of radiation-induced lung injury.Methods Forty-eight Sprague-Dawley (SD)rats were randomly divided into eight groups,group A was normal control group.and group BH were irradiated with a single dose of 15 Gy to the lungs.HRCT scanning Wag performed before and 1 week,2,4,8,12,16,24 weeks after radiation in group A-H respectively.The expression of TGF-beta and TNF-alpha were detected with ELISA. All the rats were killed to observe pathological changes of their lungs.HRCT signs,levels of cytokine were simultaneously compared and analyzed.The t-test and Spenrman rank correlation were used for the statistics.Results Four HRCT signs were observed during the 24 weeks after radiation,including ground-glass opacity(1 case),patchy consolidation(8 cases),massive consolidation(7 cases)and fibrosis(3 cases).The average levels of TGF-beta in group B-H[(3.33±0.47),(3.20±0.65),(3.12±0.45),(3.54±0.80),(3.30±1.13),(2.49±0.67),(4.19±0.22)μg/L,respectively]were hisher than the control group[(0.45±0.14)μg/L.P＜0.05].At 24 weeks the average level increased to the highest peak[(4.19 4-0.22)μg/L,P＜0.05].At 1 week and 2,4,8,12 weeks after radiation,the average level of TNF-alpha in radiation group[(236.52±29.01),(214.91±34.53),(270.97±42.12),(208.83±86.51),(208.83±82.23)ng/L]was hisher than the control group[(31.78±0.92)ng/L,P＜0.05].The average level increased to the highest peak [(270.97±42.12)ng/L,P＜0.05]at 4 weeks.The average level at 16 and 24 weeks[(60.63±38.49),(32.07±1.05)ng/L]dropped to the level similar to the control group(P＞0.05).There were no rank correlations between HRCT manifestations and expression of TGF-beta and TNF-alpha(rs=0.5570 and 0.1013.P＞0.05).HRCT signs were correlated with pathological changes.Conciusions The monitoring of TGF-beta and TNF.alpha in the serum after irradiation can predict the development of radiation-induced lung injury.There are no rank correlations between HRCT manifestations and expression of TGF-beta and TNF-alpha.

Objective To evaluate the value of multi-slice spiral CT (MSCT) angiography in diagnosis of thoracic vascularemergency.Methods 25 cases suspected of thoracic vascular emergency were examined with MSCT. Two dimensional and three dimensionalimaging methods were used. Results Central pulmonary embolism 10 cases, aortic dissection 12 cases,aneurysm 2 cases and takayasuarteritis with stricture of kidney artery were found by two dimensional imaging(MPVR,CPR),and the extent, size and details of lesions couldbe showed well. The space relationship and calcifation of aorta were displayed in three dimensional imaging(SSD,VR,MIP). Therelationship between intraluminal embolism and the wall of pulmonary artery, as well as intimal flap and reentry of dissection could bevealuated by CTVE.Conclusion Associated with imaging post processing,MSCT angiography is an effective method in diagnosis of thoracic vascular emergency.