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.

Pancreatitis is one of the most common inflammatory diseases of the pancreas caused by autodigestion induced by excessive premature protease activation. However, recognition of novel pathophysiological mechanisms remains a still challenge. Both genetic and environmental factors contribute to the pathogenesis of pancreatitis, and the gut microbiota is a potential source of an environmental effect. In recent years, several new frontiers in gut microbiota and genetic risk assessment research have emerged and improved the understanding of the disease. These investigations showed that the disease progression of pancreatitis could be regulated by the gut microbiome, either through a translocation influence or in a host immune response manner. Meanwhile, the onset of the disease is also associated with the heritage of a pathogenic mutation, and the disease progression could be modified by genetic risk factors. In this review, we focused on the recent advances in the role of gut microbiota in the pathogenesis of pancreatitis, and the genetic susceptibility in pancreatitis.

Objective To compare effect between thyroid imaging reporting and data system (TI-RADS) and the Bethesda system for reporting thyroid cytopathology (TBSRTC) in the qualitative diagnosis of thyroid nodule. Methods The clinical data of 665 patients with thyroid nodule (1 598 nodules) from April 2013 to October 2016 were retrospectively analyzed. TBSRTC and TI-RADS were used for qualitative diagnosis of thyroid nodule before operation. Pathological diagnosis was performed after the operation. The diagnostic effect of TI-RADS and TBSRTC were assessed, and the factors leading to the diagnostic errors were analyzed. Results Of 1 598 thyroid nodules, the pathological diagnosis showed that benign nodules were in 202, and malignant thyroid nodules were in 1 396. The diagnostic sensitivity and 85.64%(173/202) vs. 74.75%(151/202) and specificity of malignant nodules by TBSRTC were significantly higher than that by TI-RADS: 91.76% (1 281/1 396) vs. 87.11% (1 216/1 396), and there was statistical difference (P＜0.01). The diagnosis positive rate of malignant nodules with diameter＜1 cm by TBSRTC was significantly higher than that by TI-RADS: 77.63% (59/76) vs. 47.37% (36/76), and there was statistical difference (P＜0.01); there was no statistical difference in diagnosis positive rate of malignant nodules with diameter ≥ 1 cm between 2 methods (P＞0.05). Univariate analysis result showed that the diameter of thyroid nodules in patients with TI-RADS false negative was significantly smaller than that in patients with benign thyroid nodules: (1.01 ± 0.48) cm vs. (1.51 ± 0.45) cm, the incidence of malignant thyroid nodules combined with other thyroid diseases was significantly higher than that in patients with benign thyroid nodules: 41.18% (21/51) vs. 11.32% (158/1 396), and there were statistical differences (P＜0.05); the rate of thyroid dysfunction in patients with TBSRTC false positive was significantly higher than that in patients with malignant thyroid nodules: 18.26% (21/115) vs. 6.93% (14/202), and there was statistical difference (P＜0.05). Conclusions The qualitative diagnosis of thyroid nodule requires the cross-reference of TI-RADS and TBSRTC, and the combination of other clinical indicators of patients can improve the detection rate of malignant thyroid nodules.

Objective To find out the prevalence of iodine deficiency disorders (IDD) and population iodine nutritional status,and to evaluate the intervention effect of iodized salt during the Twelfth Five-Year Plan period,and to provide a scientific basis for adjusting the intervention programs.Methods One town was selected respectively from the east,the west,the south,the north and the central of the entire city,4 villages were selected from each town,15 residents were selected to determine iodide content by quantitative detection;1 primary school was selected respectively from those 5 chosen towns,40 subjects aged from 8 to 10 years old (half male and half female) in each school were selected to collect urine samples for determination of urinary iodine,and to detect the volume of thyroid by palpation;20 pregnant women were chosen respectively from those 5 towns to detect their urinary iodine content and to determine iodine content of their salt samples,10 pregnant women were selected to investigate their healthy knowledge.Results A total of 300 samples of edible salt were tested,the median of salt iodine was 21.2 mg/kg,coverage rate of iodized salt was 97.7％ (293/300),the consumption rate of eligible iodized salt at household level was 90.3％ (271/300);the median of urinary iodine level was 232.4 μg/L in 200 8-10 years old chindren;232.9 μg/L in 100 pregnant women;the prevalence rate of goiter in children aged 8-10 was 3.0％ (6/200);the healthy knowledge rate of pregnant women was 82.0％ (41/50).Conclusions During the Twelfth Five-Year Plan period,Zaoyang has achieved the stage of elimination of IDD,but the situation of iodine nutritionrich children and the iodine nutrition-lack pregnant women are still exist.Therefore,we still need to strengthen the salt market management and insist to spread the knowledge of IDD,to eliminate the non-iodized salt from the market,and to ensure all people in appropriate iodine nutrition.

Nurses working in the department of infectious diseases are under tremendous physical and psychological pressure due to the particularity of the unit. The physical and mental status as well as working attitude of nurses are not optimistic. The nursing teams are widely unstable in hospitals. This paper reviewed studies about nurses working in department of infectious disease, aiming to better understand physical and mental health level of nurses as well as their influencing factors and intervention strategies. It can provide policy recommendations for nursing managers to further stabilize the nursing team. At the same time, this paper finds out the existing deficiencies and enlightenment in previous studies from the perspectives of research direction and research method, and provides references for further researches on flow factors of nurses in department of infectious diseases.

Objective This study aimed to construct an index system for nurse performance appraisal based on the quantity,quality,efficiency and technology in holistic nursing mode.Methods Expert interviews and Delphi expert enquiry were used to complete the construction of index system,and SPSS17.0 was used to do data statistics and reliability analysis.Results The nurse performance appraisal index system was constructed which contained 4 level-Ⅰ indicators such as level coefficient,nursing workload scores,nursing quality scoring rate and reward amount and 12 level-Ⅱ indicators.The calculation method of each part was also established.The expert positive coefficients were 94.3％ and 100.0％ respectively,the authority coefficients were 0.83 and 0.84,the importance and feasibility mean scores of every index were 4.27-5.00 and 4.26-4.94,and coefficients of variation were 0.00-0.26 and 0.05-0.26 in 2 rounds of enquiry.The importance of level-Ⅰ or level-Ⅱ indicators and operability coordination coefficients were 0.13-0.43,the significance test showed P ＜ 0.05.Conclusions The design of each dimension of the index system gives full consideration to nurse post management,hierarchical using,the nurse in charge of the patient,grading nursing care and many other factors.Representative of key indicators is strong,and it can reflect the distribution concept that more payment for more contributions,best's best reward and rewarding the good and punishing the bad.

Objective To evaluate the implementation feasibility of the nurse performance appraisal and allocation plan based on the holistic nursing mode, and the clinical effect in mobilizing nursing staff's work enthusiasm and ensuring the quality of nursing service. Methods The nurse performance appraisal and allocation plan were further improved based on the previous research of this index system construction. The model were implemented in 32 clinical departments of Yidu Center Hospital of Weifang City. Four aspects data were collected for analysis six months later to evaluate the effect. They were nurses on merit pay distribution satisfaction, patients′satisfaction, doctors′satisfaction with nursing job, different clinical departments′nursing quality scores. Results Six months later, four factor scores of nurses to the satisfaction of merit pay distribution were significantly improved. The scores of fairness and impartiality evaluation of the merit pay distribution, incentive effect evaluation, pay and return on equity evaluation and performance pay gap rationality evaluation were higher than before [(3.39 ±0.64) points vs. (1.88 ±0.33) points, (3.28 ±0.74) points vs. (1.84 ±0.49) points , (3.28 ±0.71) points vs. (1.88 ±0.42) points and (3.38 ±0.67) points vs. (2.01±0.53) points, t=19.28, 16.22, 18.08, 16.79, all P<0.05]. Patients′satisfaction, doctors′satisfaction with nursing job and different clinical department' nursing quality scores were significantly increased as well [(99.14±0.82) points vs. (96.78±0.84) points, (96.59±0.91) points vs. (93.59±1.27) points and(97.67±0.41) points vs. (95.70±1.13) points]. Difference had statistical significance (t=11.79, 11.63, 9.60, P<0.05). Conclusions The performance salary allocation plan can effectively improve the hospital nurses on performance salary allocation satisfaction, patients′satisfaction, doctor′s satisfaction with nursing work and the quality of nursing department, and has good incentive in arousing the work enthusiasm of nursing staff and in ensuring the quality of nursing service.

Objective　To analyze the clinical indications,efficacy and safety of Chinese minimally invasive percutaneous nephrolithotomy (MPCNL) in treating upper urinary calculi based on our experience.Methods　From June 1992 to September 2010,a total of 10,452 patients (6060 males and 4392 females)with a mean age of (47.6 ± 13.7) years (7 months-93 years) received MPCNL in our center.The mean stone burden was (777.4 ± 740.3) mm2 (20 - 4 080 mm2 ).The data of stone burden,operative techniques,operating time,stone-free rate,major complication,hospital stay and stone composition were investigated.　Results　Of the 10 452 cases,11 801 procedures were performed on 10 876 (5493 left and 5383right) renal units,including 10 102 first stage procedures,1604 secondary procedures,86 third procedures and 9 fourth procedures.There were 11 830 tracts established,including 373 (3.15％ ) tracts of 14 F,7867 (66.50％) tracts of 16 F and 3590 (30.35％) tracts of 18 F.There were 1207 (10.20％),9174(77.55％) and 1449 (12.25％) punctures located in upper,middle and lower pole,respectively.956(8.79％) renal units were managed with multiple tracts,which including 2 tracts in 846 (7.78％) units,3tracts in 85 (0.78％) units,4 tracts in 18 (0.17％) units and 5 tracts in 7 (0.06％) units.Pneumatic lithotripsy was used in 8563 (72.56％) procedures,Holmium:YAG laser lithotripsy was used in 2981(25.26％)　procedures and Pneumatic lithotripsy + Holmium: YAG laser lithotripsy was used in 257(2.18％) procedures.762 (7.29％) cases needed ESWL to clean the stone after MPCNL.The average operating time was ( 101.3 ± 44.2) min ( 10 -240 min).The stone-free rate of MPCNL was 89.9％,which increased to 93％ by adjunctive ESWL.And the mean hospital stay was ( 13.2 ± 6.4) days (2 - 72 days).The major complications happened on 321 (3.07％) cases,including 294 (2.81％ ) cases of blood transfusion,12 (0.11％ ) cases of sepsis,2 (0.02％) cases of renal abscess,9 (0.09％) cases of pleura injury,2 (0.02％) cases of colon injury and 2 (0.02％) cases of death.53 (0.51％) cases needed selective renal arterial embolization to achieve hemostasis.The main stone compositions were analyzed in 4345 cases.Calcium oxalate,calcium phosphate,magnesium ammonium phosphate,uric acid,ammonium urate,carbapatite and cystin were 91.74％,90.33％,14.91％,17.77％,4.83％,8.47％ and 0.51％,respectively. Conclusions　MPCNL is an effective and safe treatment option for all kinds of upper urinary calculi in patients at all ages with a high stone free rate and low major complication rate.