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.

Background:Following the short-term outbreak of coronavirus disease 2019(COVID-19)in December 2022 in China,clinical data on kidney transplant recipients(KTRs)with COVID-19 are lacking.Methods:We conducted a single-center retrospective study to describe the clinical features,complications,and mortality rates of hospitalized KTRs infected with COVID-19 between Dec.16,2022 and Jan.31,2023.The patients were followed up until Mar.31,2023.Results:A total of 324 KTRs with COVID-19 were included.The median age was 49 years.The median time between the onset of symptoms and admission was 13 d.Molnupiravir,azvudine,and nirmatrelvir/ritonavir were administered to 67(20.7%),11(3.4%),and 148(45.7%)patients,respectively.Twenty-nine(9.0%)patients were treated with more than one antiviral agent.Forty-eight(14.8%)patients were treated with tocilizumab and 53(16.4%)patients received baricitinib therapy.The acute kidney injury(AKI)occurred in 81(25.0%)patients and 39(12.0%)patients were admitted to intensive care units.Fungal infections were observed in 55(17.0%)patients.Fifty(15.4%)patients lost their graft.The 28-d mortality rate of patients was 9.0%and 42(13.0%)patients died by the end of follow-up.Multivariate Cox regression analysis identified that cerebrovascular disease,AKI incidence,interleukin(IL)-6 level of>6.8 pg/mL,daily dose of corticosteroids of>50 mg,and fungal infection were all associated with an increased risk of death for hospitalized patients.Conclusions:Our findings demonstrate that hospitalized KTRs with COVID-19 are at high risk of mortality.The administration of immunomodulators or the late application of antiviral drugs does not improve patient survival,while higher doses of corticosteroids may increase the death risk.

Objective To quantify operation characteristics of the ankle rotating-traction-poking manipulation (RTPM) for treating acute lateral ankle sprain by using motion capture technology, so as to provide objective references for standardized operation of RTPM and its education inheritance. Methods A professional physiotherapist performed the RTPM on 60 volunteers with acute lateral ankle sprain. Motion capture system was used to acquire effective kinematic data during the RTPM, so as to make analysis and summarize rules. Results The average time of ankle rotating for six circles was 11.36 s and the average time of ankle traction and poking was 3.42 s. The average displacement of ankle traction was 36.94 mm and the average displacement of ankle poking was 22.44 mm. The average angle of ankle traction was 23.27°, and the average angle of ankle poking was 22.76°. During the RTPM for treating acute lateral ankle sprain, the average linear velocity of ankle rotating was 58.28 mm/s, and the average linear velocity of ankle traction and poking was 23.81 mm/s. The linear acceleration of ankle rotating was 0.43 mm/s2, and the linear acceleration of ankle traction and poking was 0.54 mm/s2. Conclusions The RTPM can be applied in clinical practice. During the RTMP, the principle of gentleness, rhythmicity and continuity should be followed. Under the premise of following physiological characteristics of ankle joint, treatment of the sprained ankle should be carried out with slow and uniform speed continuously.

Rutin,a flavonoid found in fruits and vegetables,is a potential anticancer compound with strong anti-cancer activity.Therefore,electrochemical sensor was developed for the detection of rutin.In this study,CoWO4 nanosheets were synthesized via a hydrothermal method,and porous carbon(PC)was prepared via high-temperature pyrolysis.Successful preparation of the materials was confirmed,and character-ization was performed by transmission electron microscopy,scanning electron microscopy,and X-ray photoelectron spectroscopy.A mixture of PC and CoWO4 nanosheets was used as an electrode modifier to fabricate the electrochemical sensor for the electrochemical determination of rutin.The 3D CoWO4 nanosheets exhibited high electrocatalytic activity and good stability.PC has a high surface-to-volume ratio and superior conductivity.Moreover,the hydrophobicity of PC allows large amounts of rutin to be adsorbed,thereby increasing the concentration of rutin at the electrode surface.Owing to the syn-ergistic effect of the 3D CoWO4 nanosheets and PC,the developed electrochemical sensor was employed to quantitively determine rutin with high stability and sensitivity.The sensor showed a good linear range(5-5000 ng/mL)with a detection limit of O.45 ng/mL.The developed sensor was successfully applied to the determination of rutin in crushed tablets and human serum samples.

Objective:To compare the clinical efficacy of hyperbaric oxygen combined with herbal cake-separated moxibustion on umbilicus and retention enema in treating acute radiation proctitis（ARP），and to statistically analyze their rates of acceptance and satisfaction.Methods:A total of 64 patients with ARP after radiotherapy for cervical cancer treated in Linyi Central Hospital from June 2016 to December 2021 were selected and divided into observation group（ n=32）and control group（ n=32）according to the number table method. The control group was treated with（Smecta and Kangfuxin solution）retention enema combined with hyperbaric oxygen，and the observation group was treated with herbal cake-separated moxibustion on umbilicus combined with hyperbaric oxygen. The degree of rectal injury before and after radiotherapy was evaluated according to the criteria of the Radiation Therapy Oncology Group（RTOG），and the clinical efficacy was analyzed. The symptom score and total score of ARP patients were calculated by international scoring standards for long-term complication of radiotherapy，and the satisfaction rate and acceptance rate of the two groups were analyzed. Results:After four courses of treatment，compared with the same group before treatment，the classifications of clinical symptoms in both the observation group and the control group were significantly improved（ P < 0.01），but there was no significant difference between the observation group and the control group（ P > 0.05）. The acceptance rate and satisfaction rate of patients treated with herbal cake-separated moxibustion on umbilicus in the observation group was significantly higher than that in the control group（ P < 0.01）. Conclusion:Both hyperbaric oxygen combined with herbal cake-separated moxibustion on umbilicus and retention enema in treating ARP can achieve good clinical therapeutic effect. As a non-invasive approach，the herbal cake-separated moxibustion on umbilicus can avoid aggravating rectal mucosa and perianal injury caused by repeated drug enema. Meanwhile，the herbal cake-separated moxibustion on umbilicus is simple and easy to operate，with less pain for patients，high rates of acceptability and satisfaction，which can be popularized and applied.

Objective:To compare the clinical efficacy of hyperbaric oxygen combined with herbal cake-separated moxibustion on umbilicus and retention enema in treating acute radiation proctitis（ARP），and to statistically analyze their rates of acceptance and satisfaction.Methods:A total of 64 patients with ARP after radiotherapy for cervical cancer treated in Linyi Central Hospital from June 2016 to December 2021 were selected and divided into observation group（ n=32）and control group（ n=32）according to the number table method. The control group was treated with（Smecta and Kangfuxin solution）retention enema combined with hyperbaric oxygen，and the observation group was treated with herbal cake-separated moxibustion on umbilicus combined with hyperbaric oxygen. The degree of rectal injury before and after radiotherapy was evaluated according to the criteria of the Radiation Therapy Oncology Group（RTOG），and the clinical efficacy was analyzed. The symptom score and total score of ARP patients were calculated by international scoring standards for long-term complication of radiotherapy，and the satisfaction rate and acceptance rate of the two groups were analyzed. Results:After four courses of treatment，compared with the same group before treatment，the classifications of clinical symptoms in both the observation group and the control group were significantly improved（ P < 0.01），but there was no significant difference between the observation group and the control group（ P > 0.05）. The acceptance rate and satisfaction rate of patients treated with herbal cake-separated moxibustion on umbilicus in the observation group was significantly higher than that in the control group（ P < 0.01）. Conclusion:Both hyperbaric oxygen combined with herbal cake-separated moxibustion on umbilicus and retention enema in treating ARP can achieve good clinical therapeutic effect. As a non-invasive approach，the herbal cake-separated moxibustion on umbilicus can avoid aggravating rectal mucosa and perianal injury caused by repeated drug enema. Meanwhile，the herbal cake-separated moxibustion on umbilicus is simple and easy to operate，with less pain for patients，high rates of acceptability and satisfaction，which can be popularized and applied.

Objective:To compare the effects of laparoscopic and surgical catheterization on catheter-related complications and microinflammation in uremic peritoneal dialysis (PD) patients.Methods:According to different catheterization methods, 98 uremic patients who were scheduled to undergo peritoneal dialysis in the First People's Hospital of Jiande from January 2014 to March 2019 were divided into group A (38 cases), group B (60 cases). Laparoscopic catheterization was used in group A, and incision catheterization was used in group B. Surgical parameters, catheter complications, microinflammation and survival rate of early catheterization were observed in the two groups.Results:The operation time of group A was (35.00±3.14)min, which was shorter than that of group B [(50.00±5.17)min], and the operation cost of group A was (5 800.0±318.9)CNY, which was higher than that of group B [(3 400.0±297.4)CNY], and the visual analogue score (VAS) of group A was (2.33±0.31)points, which was lower than that of group B [(3.25±0.49)points], there were statistically significant differences between the two groups ( t=11.540, 9.317, 10.328, 36.578, all P<0.05). The incidence of catheter-related complications in group A was 10.53%(4/38), which was significantly lower than 28.33%(17/60) in group B (χ 2=4.383, P<0.05). There were no statistically significant differences in high-sensitivity C-reactive protein (hs-CRP), interleukin-6(IL-6) and tumor necrosis factor-alpha (TNF-alpha) levels between group A and group B before catheterization (all P>0.05). After catheterization, the levels of hs-CRP, IL-6 and TNF-alpha in group B were (12.52±3.75)mg/L, (12.02±3.76)ng/L, (15.92±5.72)ng/L, respectively, which were higher than those in group A [(9.63±2.36)mg/L, (9.11±3.54)ng/L, (13.41±5.61)ng/L] ( t=4.244, 4.081, 4.510, all P<0.05). After 2 months of follow-up, the survival rate of dialysis tube technique was 89.47%(34/38) in group A and 71.67%(43/60) in group B, there was statistically significant difference between the two groups (χ 2=4.382, P<0.05). Conclusion:Application of laparoscopic catheterization in uremic PD patients has satisfactory effect, light pain, fewer complications, mild inflammation and high survival rate of early catheterization technology, which is worthy of clinical promotion.

Objective To understand the situation and genotype distribution of spotted fever group rickettsia (SFGR) in the border area of Tumen River Basin in free ticks in Yanbian Korean Autonomous Prefecture (Yanbian Prefecture), Jilin Province. Methods From April to September, 2017, ticks were collected using flagging method from Hunchun, Tumen, Helong and Longjing cities in the Tumen River basin of Yanbian Prefecture. Outer membrane protein A (ompA) was detected by Polymerase Chain Reaction (PCR), then, the species were identified by gene sequencing and analyzed systematically. The positive rate of pools and MIR(minimum infection rate per 100 ticks,MIR) of SFGR were calculated, and the difference of positive rate of pools among ticks with different characteristics was compared by Chi?square test. Results A total of 3 079 ticks were collected and divided into 536 pools. The positive rate of pools of SFGR nucleic acid was 39.7% (213 pools). The MIR of SFGR was 6.9%.The positive rate of pools of SFGR in Dermacentor silvarum, Haemaphysalis concinna, Haemaphysalis japonica, Haemaphysalis longicornis and Ixodes persulcatus were 80.4% (41/51), 14.0% (25/179), 20.2% (18/89), 78.9% (101/128) and 25.9% (21/81), and the difference was statistically significant (P<0.001). There was statistical difference in the positive rate of pools of SFGR in developmental stages of ticks (P<0.001); the positive rate of pools of female adults, male adults, nymph and larvae were 36.4% (95/261), 34.2% (67/196), 56.3% (40/71) and 7/8, and the MIR was 7.9%, 7.7%, 4.9% and 3.5%. The five genotype was detected which was Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis, Candidatus Rickettsia tarasevichiae,Rickettsia monacensis and have 98%-100% homology with known gene sequences. Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis and Candidatus Rickettsia tarasevichiae showed close evolutionary relationship with known specie (have 98%-100% homology with known gene sequences); Rickettsia monacensis showed Far from evolutionary relationship with known species (have 98% homology with known gene sequences). Conclusion SFGR infection of ticks is common in the border areas of the Tumen River Basin. There was high diversity in SFGR species and tick species in the areas surveyed.

Objective: To understand the situation and genotype distribution of spotted fever group rickettsia (SFGR) in the border area of Tumen River Basin in free ticks in Yanbian Korean Autonomous Prefecture (Yanbian Prefecture), Jilin Province. Methods: From April to September, 2017, ticks were collected using flagging method from Hunchun, Tumen, Helong and Longjing cities in the Tumen River basin of Yanbian Prefecture. Outer membrane protein A (ompA) was detected by Polymerase Chain Reaction (PCR), then, the species were identified by gene sequencing and analyzed systematically. The positive rate of pools and MIR(minimum infection rate per 100 ticks,MIR) of SFGR were calculated, and the difference of positive rate of pools among ticks with different characteristics was compared by Chi-square test. Results: A total of 3 079 ticks were collected and divided into 536 pools. The positive rate of pools of SFGR nucleic acid was 39.7% (213 pools). The MIR of SFGR was 6.9%.The positive rate of pools of SFGR in Dermacentor silvarum, Haemaphysalis concinna, Haemaphysalis japonica, Haemaphysalis longicornis and Ixodes persulcatus were 80.4% (41/51), 14.0% (25/179), 20.2% (18/89), 78.9% (101/128) and 25.9% (21/81), and the difference was statistically significant (P<0.001). There was statistical difference in the positive rate of pools of SFGR in developmental stages of ticks (P<0.001); the positive rate of pools of female adults, male adults, nymph and larvae were 36.4% (95/261), 34.2% (67/196), 56.3% (40/71) and 7/8, and the MIR was 7.9%, 7.7%, 4.9% and 3.5%. The five genotype was detected which was Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis, Candidatus Rickettsia tarasevichiae,Rickettsia monacensis and have 98%-100% homology with known gene sequences. Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis and Candidatus Rickettsia tarasevichiae showed close evolutionary relationship with known specie (have 98%-100% homology with known gene sequences); Rickettsia monacensis showed Far from evolutionary relationship with known species (have 98% homology with known gene sequences). Conclusion SFGR infection of ticks is common in the border areas of the Tumen River Basin. There was high diversity in SFGR species and tick species in the areas surveyed.

Objective To understand the situation and genotype distribution of spotted fever group rickettsia (SFGR) in the border area of Tumen River Basin in free ticks in Yanbian Korean Autonomous Prefecture (Yanbian Prefecture), Jilin Province. Methods From April to September, 2017, ticks were collected using flagging method from Hunchun, Tumen, Helong and Longjing cities in the Tumen River basin of Yanbian Prefecture. Outer membrane protein A (ompA) was detected by Polymerase Chain Reaction (PCR), then, the species were identified by gene sequencing and analyzed systematically. The positive rate of pools and MIR(minimum infection rate per 100 ticks,MIR) of SFGR were calculated, and the difference of positive rate of pools among ticks with different characteristics was compared by Chi?square test. Results A total of 3 079 ticks were collected and divided into 536 pools. The positive rate of pools of SFGR nucleic acid was 39.7% (213 pools). The MIR of SFGR was 6.9%.The positive rate of pools of SFGR in Dermacentor silvarum, Haemaphysalis concinna, Haemaphysalis japonica, Haemaphysalis longicornis and Ixodes persulcatus were 80.4% (41/51), 14.0% (25/179), 20.2% (18/89), 78.9% (101/128) and 25.9% (21/81), and the difference was statistically significant (P<0.001). There was statistical difference in the positive rate of pools of SFGR in developmental stages of ticks (P<0.001); the positive rate of pools of female adults, male adults, nymph and larvae were 36.4% (95/261), 34.2% (67/196), 56.3% (40/71) and 7/8, and the MIR was 7.9%, 7.7%, 4.9% and 3.5%. The five genotype was detected which was Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis, Candidatus Rickettsia tarasevichiae,Rickettsia monacensis and have 98%-100% homology with known gene sequences. Candidatus Rickettsia longicornii, Rickettsia raoultii, Rickettsia heilongjiangensis and Candidatus Rickettsia tarasevichiae showed close evolutionary relationship with known specie (have 98%-100% homology with known gene sequences); Rickettsia monacensis showed Far from evolutionary relationship with known species (have 98% homology with known gene sequences). Conclusion SFGR infection of ticks is common in the border areas of the Tumen River Basin. There was high diversity in SFGR species and tick species in the areas surveyed.