To address the current issue of low performance in predicting the binding affinity between antigenic peptides and specific MHC class II molecules, which fails to meet clinical requirements, we proposed T5MHCII, a deep learning-based prediction model for the affinity of MHC II class molecules to peptides. The model employed the knowledge previously acquired from the protein language model ProtT5 to extract the amino acid sequences via a transfer learning approach, thereby generating high-quality characterizations. This knowledge was then integrated with the robust learning abilities of deep learning to develop a novel model with enhanced predictive capabilities. The results of the five-fold cross-validation demonstrated that the model exhibited superior performance compared to NetMHCIIpan-3.2, PUFFIN, DeepMHCII, and RPEMH, with an AUC of 0.893±0.003 and a PCC of 0.780±0.006. The leave-one-out cross-validation (LOOCV) further demonstrated that the model exhibited enhanced generalization capabilities. This study proposes a novel approach to enhance the precision of peptide-MHCII prediction in the context of limited data affinity through the application of deep learning techniques.

ObjectiveThis study aimed to evaluate the clinical efficacy of Ruyi Zhenbaowan（RYZBW）in the treatment of initial and early knee osteoarthritis （KOA） through a prospective multicenter，randomized，double-blind，and placebo-parallel controlled trial. MethodFrom October 13^th， 2021 to December 25^th， 2021， 240 KOA subjects meeting the acceptance criteria were enrolled in 15 sub-centers including Wangjing Hospital， Chinese Academy of Chinese Medical Sciences， and they were randomly divided into observation group and control group， with 120 cases in each group. The intervention measures for the observation group were RYZBW + health education， and the intervention measures for the control group were RYZBW placebo + health education. The intervention period in both groups was four weeks， and they were followed up for four weeks after the intervention. The primary outcome measure was the total score of Western Ontario and McMaster University Osteoarthritis Index score （WOMAC score）， and the secondary outcome measures were the response rate of visual scale （VAS） pain score， WOMAC sub item scores （joint pain， joint stiffness， and joint function）， quality of life （SF-12） score， and traditional Chinese medicine （TCM） syndrome score. Result（1） Efficacy evaluation. The marginal model results showed that the observation group was better than the control group in improving the WOMAC total score and WOMAC pain score in the treatment of KOA with RYZBW， and the difference was statistically significant （P<0.05）. There was no significant difference between the two groups in improving VAS score response rate， WOMAC function score， WOMAC stiffness score， SF12-PCS （quality of life-physical health） score， SF12-MCS （quality of life-mental health） score， and TCM syndrome score. （2） Subgroup analysis. ① In terms of VAS score response rate， the response rate of the observation group was higher than that of the control group for subjects with baseline VAS score of （4， 5］， and the difference was statistically significant （P<0.05）. ② In terms of TCM syndrome score， for subjects aged ［56， 60］ and ［61， 65］， the decrease in total TCM syndrome score in the observation group was better than that in the control group， and the difference was statistically significant （P<0.05）. ConclusionTibetan medicine RYZBW has good clinical efficacy in improving WOMAC total score， VAS score response rate， WOMAC pain score， WOMAC function score， and TCM syndrome score for patients with initial and early KOA， which can fill the lack of Tibetan medicine RYZBW in the treatment of KOA and make a demonstration study for the inheritance and development of ethnic medicine.

BACKGROUND:Distal tibial tuberosity-high tibial osteotomy is a surgical treatment for knee osteoarthritis,but there is still a lack of clinical studies on its effect on ankle joints. OBJECTIVE:To observe the effects of distal tibial tuberosity-high tibial osteotomy on ankle angle on coronal plane of the radiography of the full length of lower limb in weight loading. METHODS:Data of 40 patients(41 knees)with distal tibial tuberosity-high tibial osteotomy from March 2021 to March 2022 were retrospectively analyzed,including 31 females and 9 males,20 left knees and 21 right knees,aged 49-75 years,mean(63.44±6.57)years.The radiographic data of the full length of the lower limb in weight loading were collected before,week 2 and week 48 postoperatively.Hip-knee-ankle angle,talar tilt angle,tilt angle of the ankle,tibiocrural angle,and tibial articular surface angle were measured before and after surgery. RESULTS AND CONCLUSION:(1)Hip-knee-ankle angle improved from(-6.24±3.69)° before operation to(2.59±3.49)° week 2 postoperatively and(2.15±3.49)° week 48 postoperatively.The tilt angle of the ankle changed from(-7.90±3.11)° before operation to(-2.51±2.59)° week 2 postoperatively and(-2.46±2.42)° week 48 postoperatively,with statistically significant difference(P<0.001).(2)There was no significant difference in talar tilt angle,tibiocrural angle,and tibial articular surface angle before and week 2 postoperatively.(3)No significant difference in the angle changes was detected between week 2 and week 48 postoperatively.(4)It is indicated that distal tibial tuberosity-high tibial osteotomy can not only correct genu varus but also improve ankle angle.This result remains stable after 48 weeks of weight-bearing activities.

Objective Space radiation is an important environmental factor affecting the health and efficiency of astronauts.To explore the effects of radiation on electroencephalogram(EEG)signal,and to provide references for further study of the effects of radiation on Central Nervous System(brain)injury.Methods The resting state EEG of radiotherapy volunteers were collected before and after X-ray exposure.The effects of radiation on EEG was studied by means of spectral analysis,nonlinear dynamic characteristic analysis,correlation coefficient analysis and microstate analysis.Results The results show that radiation induced a"slow wave"phenomenon in the EEG spectrum,with a decrease in Gravity Frequency,Sample Entropy,and Lempel-Ziv Complexity,and an increase in Fatigue Index.The average duration and frequency of EEG microstate C both significantly decreased,and the proportion of time for microstate D decreased,while the average correlation coefficient between microstates A and C increased.Conclusion A decrease was induced by radiation in neuronal excitability,which may affect cognitive brain networks and brain attention.This study can provide reference for the study of radiation damage to the Central Nervous System(brain).

To enhance the anti-tumor activity of tumor vaccine targeting PD-L1 based on the nitrated T-epitope(PD-L1-NitraTh),this research compared several adjuvants with different mechanisms to screen out the adjuvant most suitable for PD-L1-NitraTh.The results showed that Poly(I:C),CPG1018,swollen knotted polysaccharide SGP2 and GM-CSF could enhance the immunogenicity of PD-L1-NitraTh when used as adjuvants,with the Poly(I:C)group inducing the highest antibody titer.The results of qPCR for T cell differentiation-related cytokines showed that Poly(I:C)reduced the expression of GATA3 and FoxP3,indicating a strong effect on CD4+T cell differentiation.Besides,compared with other adjuvants,Poly(I:C)could assist PD-L1-NitraTh to increase the infiltration of T cells as well as CD11b+cells within tumor,suggesting that Poly(I:C)may be the suitable adjuvant for tumor vaccines based on the nitrated T epitopes.

PBK is a cancer/testis antigen that exhibits absent expression in various normal human tissues,but undergoes aberrant overexpression upon cellular transformation,thereby promoting the initiation,metastasis and even drug resistance of cancer.Consequently,it represents a novel target for tumor immunotherapy.In this study,PBK-Nitrath,a protein vaccine specifically designed to target PBK by fusing nitrated T epitope with the PBK protein was developed,using the IFN-γ ELISpot method to evaluate the activation level of PBK antigen-specific T cells in the spleen of immunized mice,and conducting in vitro cytotoxicity T cell killing efficacy test to evaluate the killing ability against H22 hepatic carcinoma cells;the anti-tumor activity was evaluated using a H22 hepatic carcinoma subcutaneous transplantation tumor model,and the differentiation of peripheral blood and spleen T lymphocytes and tumor immune infiltration were analyzed by flow cytometry.Results showed that PBK-Nitrath could efficiently induce the activation of antigen-specific T cells against PBK while enhancing cytotoxic T lymphocyte-mediated killing capacity,significantly impede hepatic carcinoma progression in mice and increase the ratio of CD8+CD107a+T cells within peripheral blood and spleen,and facilitate tumor lymphocyte infiltration.Our findings reveal the potential utility of PBK-Nitrath as an effective candidate for tumor vaccine.

Objective:To investigate the clinical and genetic characteristics of children with 45, X/46, XY mosaicism.Methods:The retrospective study included 20 children diagnosed with 45, X/46, XY and 45, X/46, X,+mar mosaicism in the First Affiliated Hospital of Zhengzhou University from 2018 to 2022. The clinical features, gonadal pathology, treatment and follow-up were summarized. Genetic tests were performed by SRY gene test, azoospermia factor region (AZF) deletion test, copy number variation-sequencing (CNV-seq). Age at first diagnosis was compared between boys and girls using independent sample t-test. Results:The 20 patients included 3 boys and 17 girls, and the age at first diagnosis were (7.6±5.5) years, it is (2.1±1.9) years in boys, (8.7±5.4) years in girls, significantly younger for boys ( t=-3.86, P=0.004). The chief complaint was external genitalia malformation for boys, and short stature (13 cases) and dysplastic external genital for girls (4 cases). Five girls presented with features of Turner syndrome. The gonadal phenotypes included mixed gonadal dysplasia (MGD, 6 cases), complete gonadal dysplasia (CGD, 10 cases), unilateral ovotestis (2 cases), possible ovaries (1 case) and undetermined gonad (1 case). One female with dysplastic genital was reassigned to male, and the gender of the remaining cases remained unchanged. Seven females were treated with recombinant human growth hormone. The height increased by (17±7) cm during the (2.9±1.2) years follow-up. No gonadal malignancy was observed. The karyotype was 45, X/46, XY in 16 cases, and 45, X/46, X,+mar in 4 cases. All of the 4 marker chromosomes were derived from Y chromosome confirmed by CNV-seq. SRY gene was detected in all 20 patients genome, and AZF deletion was found in 7 girls. Conclusions:45, X/46, XY mosaicism presented with dysplastic external genital or female with remarkable short stature. Gonadal phenotypes included MGD, CGD and ovotestis. AZF microdeletions were found in the majority of female cases.

Objective:To study the effects of metformin on marginal bone resorption of implants in patients with type 2 diabetes melli-tus(T2DM)and exercise habit.Methods:63 cases with 73 implants were included.Among them,there were 41 cases(47 implants)without T2DM in group N,10 cases(13 implants)with T2DM and without exercise habit in group M,12 cases(12 implants)with T2DM and exercise habit in the MR group.The patients were followed up at 6 months,1 and 2 years after implantation.The marginal bone loss(MBL).Implantation success rate and peri-implantitis incidence rate were compared among the groups.Results:The bone resorption of the proximal and median margins of the long-term bone level of the implants in the N and MR groups were significantly lower than that in the M group(P=0.001 and P=0.000 5,respectively).The implant success rates of group N,MR and M were 95.74％,100％and 76.92％,respectively.The incidence of peri-implantitis of the three groups was 2.13％,0 and 15.38％,respec-tively.Conclusion:Metformin is more effective in the improvement of the long-term marginal bone resorption of implants,increase the success rate of implants,and reduce the incidence of peri-implantitis in patients with T2DM and exercise habit in the mandibular first molar area.

Incretin promotes insulin secretion through a glucose-dependent mechanism, involving glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). Therefore, their correspondingly specific receptors GLP-1R and GIPR are suitable targets for the treatment of type 2 diabetes. Based on the oral hypoglycemic peptide OHP2 designed by our team, we further designed a new oral hypoglycemic peptide, ODA to reduce glucose. Compared with OHP2, ODA exhibited better lipophilicity as well as the enhanced endocytosis and transcytosis in Caco-2 cells. In addition, ODA remained the ability to activate GLP-1R and enhanced the binding ability to GIPR. The hypoglycemic efficacy of the low-dose ODA (0.53 mg/kg) is comparable to that of OHP2 (1.06 mg/kg). These results indicated that ODA could be a new oral drug with potential for the treatment of type 2 diabetes.

ObjectiveTo explore the clinical efficacy of Gouteng prescription in treating the patients with primary hypertension with anxiety disorder due to yang hyperactivity and heat toxin and the impact of the formula on the balance of inflammatory cytokines. MethodA total of 98 patients diagnosed with primary hypertension and anxiety disorder were randomized into control and observation groups. On the basis of conventional western medicine treatment for hypertension， the control group （47 patients） was treated with Shugan Jieyu capsules for 8 weeks， while the treatment group （51 patients） with Gouteng prescription for 8 weeks. The two groups were compared in terms of the blood pressure level， 24-hour blood pressure variability， Hamilton anxiety scale （HAMA） score， Pittsburgh sleep quality index （PSQI） score， quality of life （SF-36 scale） score， traditional Chinese medicine （TCM） syndrome score and efficacy， incidence of adverse reactions， and the levels of interleukin （IL）-1β， IL-6， IL-10， and IL-4 in the serum of peripheral blood. ResultThe final trial was completed with 95 patients， including 46 in the control group and 49 in the observation group. The treatment in both groups lowered the blood pressure and blood pressure variability （P<0.05， P<0.01）. The observation group outperformed the control group in recovering the systolic blood pressure （SBP）， 24-hour mean systolic blood pressure （24 h SBP）， 24-hour systolic blood pressure variability （24 h SBPV）， and 24-hour diastolic blood pressure variability （24 h DBPV） （P<0.05）. After treatment， the HAMA and PSQI scores in both groups decreased （P<0.05， P<0.01）， and the observation group had lower HAMA and PSQI scores than the control group （P<0.05）. Compared with those before treatment， the SF-36 scores in both groups increased （P<0.05， P<0.01）. After treatment， the observation group had higher scores of physiological function （PF）， bodily pain （BP）， social function （SF）， role-emotional （RE）， and mental health （MH） indicators than the control group （P<0.05）. After treatment， the TCM syndrome scores in both groups decreased （P<0.05， P<0.01）， and the observation group had lower score than the control group （P<0.05）. The total response rate regarding TCM syndrome in the observation group was 85.71% （42/49）， which was higher than that （63.04%， 29/46） in the control group （χ²=6.621， P<0.05）. The treatment in both groups lowered the levels of pro-inflammatory cytokines （IL-1β， IL-6） and elevated the levels of anti-inflammatory cytokines （IL-10， IL-4） （P<0.05， P<0.01）， and the changes were more obvious in the observation group than in the control group （P<0.05）. There were no adverse events during the research process. ConclusionGouteng prescription can recover the blood pressure level， reduce blood pressure variability， suppress anxiety state， improve sleep and quality of life， decrease TCM syndrome score， increase total response rate， lower serum IL-1β and IL-6 levels， and elevate serum IL-10 and IL-4 levels in the patients with primary hypertension complicated with anxiety disorder due to yang hyperactivity and heat toxin. It may exert the effects by regulating the balance of pro-inflammatory and anti-inflammatory cytokines.