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.

Sensorineural hearing loss (SNHL), the most commonly-occurring form of hearing loss, is caused mainly by injury to or the loss of hair cells and spiral ganglion neurons in the cochlea. Numerous environmental and physiological factors have been shown to cause acquired SNHL, such as ototoxic drugs, noise exposure, aging, infections, and diseases. Several programmed cell death (PCD) pathways have been reported to be involved in SNHL, especially some novel PCD pathways that have only recently been reported, such as ferroptosis, necroptosis, and pyroptosis. Here we summarize these PCD pathways and their roles and mechanisms in SNHL, aiming to provide new insights and potential therapeutic strategies for SNHL by targeting these PCD pathways.
Humans ; Hearing Loss, Sensorineural/metabolism* ; Necroptosis/drug effects* ; Pyroptosis/drug effects* ; Ferroptosis/drug effects* ; Animals

Objective To compare the effects of visual rigid laryngoscope and visual laryngoscope in nasotracheal intubation(NTI)for patients with cervical spine immobilization simulated difficult airway.Methods Ninety patients scheduled for selective surgery under general anesthesia requiring NTI,52 males and 38 females,aged 18-64 years,BMI 18.5-25.0 kg/m2,ASA physical status Ⅰ or Ⅱ,were scheduled for selective surgery under general anesthesia requiring NTI.Before anesthesia induction,the spinal surgeon selected an appropriate cervical collar and adjusted it to fix patient's neck to establishing difficult airway sim-ulation model.All patients were randomly assigned into two groups:visual rigid laryngoscope(group R)and common visual laryngoscope(group C),45 patients in each group.NTI was performed using either visual rigid laryngoscope or visual laryngoscope in groups R and C,respectively.The nasal passage time,glottic exposure time,intubation time,number of successful first intubation attempts,and intubation attempts were recorded.Glottic exposure was assessed using the Cormack-Lehane(C-L)grading system,and the intuba-tion condition was quantitatively evaluated using the modified nasal intubation difficulty scale(NIDS).The blood pressure and heart rate were measured at baseline(T1),immediately after intubation(T2),and at 1 minute(T3)and 3 minutes(T4)after intubation.The occurrence of intubation-related complications(nasal bleeding,sore throat,hoarseness)was recorded.Results Compared with group C,the nasal passage time and proportion of successful intubations without difficulty were significantly increased in group R,and the glottic exposure time and intubation time were significantly decreased in group R(P<0.05).Compared with group C,the HR and MAP at T2 and T3 were significantly decreased in group R(P<0.05).Com-pared with group C,group R had significantly lower incidence rates of nasal bleeding,sore throat,and hoarseness(P<0.05).There were no statistically significant differences in the first intubation success rate,number of intubation attempts,or C-L grade between the two groups.Conclusion Patients with cer-vical spine immobilization simulated difficult airway,both visual rigid laryngoscope and visual laryngoscope can be performed safely and effectively in NTI.Compared with visual laryngoscope,visual rigid laryngoscope can provide faster glottic exposure,shorter intubation time,lower intubation difficulty,less hemodynamic impact,and lower incidence of complications.

The Spt-Ada-Gcn5-acetyltransferase (SAGA) is an ancillary transcription initiation complex which is highly conserved. The ADA1 (alteration/deficiency in activation 1, also called histone H2A functional interactor 1, HFI1) is a subunit in the core module of the SAGA protein complex. ADA1 plays an important role in plant growth and development as well as stress resistance. In this paper, we performed genome-wide identification of banana ADA1 gene family members based on banana genomic data, and analyzed the basic physicochemical properties, evolutionary relationships, selection pressure, promoter cis-acting elements, and its expression profiles under biotic and abiotic stresses. The results showed that there were 10, 6, and 7 family members in Musa acuminata, Musa balbisiana and Musa itinerans. The members were all unstable and hydrophilic proteins, and only contained the conservative SAGA-Tad1 domain. Both MaADA1 and MbADA1 have interactive relationship with Sgf11 (SAGA-associated factor 11) of core module in SAGA. Phylogenetic analysis revealed that banana ADA1 gene family members could be divided into 3 classes. The evolution of ADA1 gene family members was mostly influenced by purifying selection. There were large differences among the gene structure of banana ADA1 gene family members. ADA1 gene family members contained plenty of hormonal elements. MaADA1-1 may play a prominent role in the resistance of banana to cold stress, while MaADA1 may respond to the Panama disease of banana. In conclusion, this study suggested ADA1 gene family members are highly conserved in banana, and may respond to biotic and abiotic stress.
Musa/genetics* ; Phylogeny ; Fungal Proteins ; Cell Nucleus ; Histones ; Stress, Physiological/genetics*

Objective To evaluate the therapeutic effect of botulinum toxin type A(BTX-A)in patients with rosacea erythema telangiectasia and analyze the characteristics of dermoscopy.Methods Thirty patients with erythema telangiectasia rosacea treated in our hospital from January 2021 to August 2023 were collected as the observation targets.All of them received oral drugs(doxycycline hydrochloride combined with hydroxychloroquine sulfate),and were randomized,double-blind,face-divided.The patients with rosacea were injected with botulinum toxin type A(treatment side)and normal saline(control side)respectively,and the skin physiological indexes(transepidermal water loss,oil content,cuticle water content,erythema index)of the patients before and after treatment were compared.The vascular changes before and after dermoscopic treatment were analyzed,and the incidence of adverse reactions of the patients were calculated.Results After treatment,compared with the control side,the water loss,erythema index and oil content in the epidermis of the treatment side were decreased,and the water content in the stratum corneum was increased after treatment,with statistical significance(P<0.05).There was no difference before and after treatment on the control side(P>0.05).On the treatment side,the therapeutic effect was the best at 4 weeks after treatment,and the effect lasted until the 8th week,with no statistical significance(P>0.05),and the therapeutic effect was weakened at 8 weeks to 12 weeks,with statistical significance(P<0.05).The results of dermoscopy showed that after 4 weeks of treatment,compared with before treatment,the distribution proportion of dark red background,red background and polygonal blood vessels decreased,while the distribution proportion of light red background,linear blood vessels,branched blood vessels and punctured blood vessels increased,with statistical significance(P<0.05).There were no significant differences in yellow and red background and blood vessel distribution(P>0.05).The incidence of adverse reactions was 6.67%in the control group and 10.00%in the treatment group,with no statistical difference between the two groups(P>0.05).Conclusion BTX-A has a significant improvement effect on the symptoms of erythematous telangiectatic rosacea with high safety.

At the time of the reform and adjustment of discipline transformation,the Institute of Respiratory and Critical Care Medicine,the 8th Medical Center of Chinese PLA General Hospital,relies on Beijing Key Laboratory of Organ Transplantation and Immunology Regulatory,to build a multidisciplinary postgraduate joint training mode based on immunology.From the aspects of indi-vidualized postgraduate training background,teaching mode,ability training,etc.,the practice mode of joint training of postgraduates in multiple clinical disciplines is explored.In order to cultivate medical thinking talents with systematic and holistic theory,and pre-pare for future clinical work.

Objective:To investigate the genetic risk factors and prognosis of 190 patients with myelodysplastic syndrome(MDS). Methods:The clinical data of 190 patients with MDS admitted to the Department of Hematology,The First Affiliated Hospital of Chongqing Medical University from January 2015 to October 2020 were analyzed retrospectively,and the genetic background and survival curve of the patients were also analyzed. Results:MDS patients with higher risk according to International Prognostic Score System(IPSS)stratification at the time of initial diagnosis had more frequent and complex types of gene mutation and chromosomal abnormalities,indicating poor prognosis.The choice of treatment is associated with the prognosis of MDS patients with intermediate risk(IPSS stratification),and the relative risk of the overall survival rate of patients treated with hypomethylating agents is higher than that of patients on concomitant medication. Conclusion:MDS patients with higher-risk(IPSS stratification)have more complex genetic risk factors and lower survival rate than those with lower-risk(IPSS stratification).MDS patients with multiple genetic risk factors have a poor prognosis,and the type of gene mutation is a predictor of prognosis.

Corona virus disease 2019 （COVID-19） has led to more than 500 million cases， including 6.19 million deaths. Mutated strains of SARS-CoV-2 （alpha， beta， gamma， delta and omicron） have successively emerged. Currently the omicron variant is gradually replacing the delta variant， driving a surge of cases in most countries including China， posing a great challenge to the prevention and treatment of COVID-19. In the face of the severe pandemic situation， a large number of non-medical volunteers are fighting on the front lines of the war against the pandemic and are vulnerable to exposure due to lack of professional knowledge. This paper introduces the routine skills training of volunteers and emergency response， aiming to provide behavioral guidance for non-medical volunteers in designated isolation facilities.

Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Disease-Free Survival ; Etoposide ; Hematopoietic Stem Cell Transplantation ; Humans ; Lymphoma/therapy* ; Neoplasm Recurrence, Local ; Retrospective Studies ; Transplantation, Autologous

Objective To investigate the value of mean platelet volume(MPV)combined with red blood cell distribution width(RDW)in prognosis of severe acute pancreatitis(SAP). Methods 65 SAP patients from January 1,2013 to December 31,2016 were included in the study and were divided into pospital death group(n=7) and survival group(n = 58). The basic clinical data of two groups were compared,the risk factors for hospital death and the prognostic value of MPV and RDW were analyzed. Results Compared with the survival group,the APACHEⅡ score,RDW,PLT,MPV,PDW were statistically different(P < 0.05). Logistic regression analysis was used to show APACHEⅡ score(OR = 1.793,95% CI: 1.212 ~ 2.654),PLT(OR = 0.982,95% CI: 0.967 ~0.997),MPV(OR=2.964,95% CI: 1.341~6.549),PDW(OR=1.470,95% CI: 1.019~2.122),RDW(OR=3.274,95% CI: 1.271 ~ 8.429)(P < 0.05). ROC curve analysis showed that the area under the curve of APA-CHEII score was 0.861(95% CI: 0.743 ~ 0.979,P = 0.001),MPV was 0.828(95% CI: 0.689 ~ 0.967,P =0.003,RDW was 0.849(95% CI: 0.749 ~ 0.949,P = 0.001),MPV+RDW was 0.914(95% CI: 0.832 ~ 0.997, P = 0.000). Conclusion The APACHEⅡ score,PLT,MPV,PDW,RDW are all the independent risk factors for hospital death with SAP. MPV combined with RDW has an important reference value for the prognosis of SAP patients.