Protein lysine β-hydroxybutyrylation (Kbhb) is a newly discovered post-translational modification associated with a wide range of biological processes. Identifying Kbhb sites is critical for a better understanding of its mechanism of action. However, biochemical experimental methods for probing Kbhb sites are costly and have a long cycle. Therefore, a feature embedding learning method based on the Transformer encoder was proposed to predict Kbhb sites. In this method, amino acid residues were mapped into numerical vectors according to their amino acid class and position in a learnable feature embedding method. Then the Transformer encoder was used to extract discriminating features, and the bidirectional long short-term memory network (BiLSTM) was used to capture the correlation between different features. In this paper, a benchmark dataset was constructed, and a Kbhb site predictor, AutoTF-Kbhb, was implemented based on the proposed method. Experimental results showed that the proposed feature embedding learning method could extract effective features. AutoTF-Kbhb achieved an area under curve (AUC) of 0.87 and a Matthews correlation coefficient (MCC) of 0.37 on the independent test set, significantly outperforming other methods in comparison. Therefore, AutoTF-Kbhb can be used as an auxiliary means to identify Kbhb sites.
Protein Processing, Post-Translational ; Lysine/chemistry* ; Proteins/chemistry* ; Machine Learning ; Algorithms

Objective To systematically investigate the effects of Dangmu extract syrup on the growth and development of 4-day-old(postnatal day 4,PND4)Sprague-Dawley(SD)rats and its toxic reactions.Methods According to the whole litter design method,128 young mice(PND2)were randomly divided into negative control group and low,medium and high dose groups.From PND4,the animals were orally given pure water,31 g/kg,93 g/kg and 280 g/kg(calculated as raw herb material)of Dangmu extract syrup,respectively,once daily for 18 consecutive days,with a 15 d of recovery phase.During the study period,the general state,growth and development,nerve reflex function,spontaneous behavior,hematology,coagulation,blood biochemistry,immune function,growth hormone and histopathology of the animals in each group were observed or examined.Results After 18 d of continuous administration,compared with the negative control group,GLU(male and female)in the medium and high dose groups increased(P＜0.05 or P＜0.01),LDH(male and female)and AST(male)in the medium and high dose groups,ALT,AST(female)in the high dose group decreased(P＜0.05 or P＜0.01),RET and percentage of RET(male and female)in the low and high dose groups,RET(male)in the medium dose group increased(P＜0.05 or P＜0.01),spleen mass and the organ-to-body mass ratio(male and female)in the low and high dose groups and female in the medium dose group increased(P＜0.05 or P＜0.01).Splenic nodule structures were formed in all dose groups with large size and number,and there was a dose relationship in the degree of changes.After 15 d recovery period,compared with the negative control group,GLU(female)in the low dose group increased(P＜0.05),ALT,AST,ALP,TG(female)in the medium and high dose groups,GGT,TG,TCHO(male)in the medium dose groups,AST,ALP,TG,LDH(male)in the high dose group decreased(P＜0.05 or P＜0.01),RET(female)and percentage of RET(male)in the high dose group increased(P＜0.05).compared with the 18 d of continuous administration,the spleen structures of the animals in each group were more completely developed and the splenic nodule structures were obvious,but no significant difference was noted in the comparison between groups.No significant drug-related changes were observed in other test result.Conclusions Dangmu extract syrup advanced the development of complete spleen structure in 4-day-old SD rats,accompanied by the enhancement of its hematopoietic function,and at the same time,it caused the animals,blood glucose to rise,the enhancement of glucose metabolism function led to the increase of related enzyme consumption,and led to the decrease of some liver function parameters,and showed a dose correlation.There was no gender difference in the changes,which were reversible after stop administration,and the mechanism of the changes needs to be further explored and confirmed.In the clinical trials,attention should be paid to the control of the dose of the test article,and regular monitoring of the spleen and related blood and clinical chemistry parameters.

Objective:To compare the mid- to long-term clinical outcomes of arthrolysis versus revision arthroplasty for arthrofibrosis-related stiffness following total knee arthroplasty (TKA).Methods:A retrospective analysis was conducted of the 20 patients (26 knees) with post-TKA arthrofibrosis who had been treated at Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital between January 2004 and January 2020. The patients were divided into 2 groups based on their treatment: an arthrolysis group of 8 cases (10 knees) [1 male (2 knees)and 7 females (8 knees); median age: 44.0 (21.0, 62.0) years] and a revision arthroplasty group of 13 cases (16 knees) [4 males (6 knees)and 9 females (10 knees); median age: 41.5 (30.0, 56.0) years]. The knee range of motion (ROM) and the American Hospital for Special Surgery (HSS) knee score as well as their improvements were compared between preoperation and the last follow-up, as well as between the 2 groups; the satisfaction of the patients at the last follow-up was compared between the 2 groups.Results:No significant differences in the baseline characteristics were observed between the 2 groups, indicating comparability ( P>0.05). The preoperative knee ROM [55.0° (48.8°, 61.3°)] and HSS knee score [54.0 (47.0, 61.8) points] in the arthrolysis group were significantly higher than those in the revision group [27.5° (6.3°, 50.0°), 33.0 (27.3, 47.8) points] ( P<0.05). In the arthrolysis and revision arthroplasty groups, the knee ROMs [90.0° (65.0°, 100.0°), 90.0° (63.5°, 98.8°)] and HSS knee scores [(69.8±19.9) points, (77.6±11.3) points] at the last follow-up were significantly improved compared with those before operation ( P<0.05). In the revision arthroplasty group, the improvement in knee ROM (48.9°±21.7°) was insignificantly larger than that in the arthrolysis group (34.5°±13.2°) ( P>0.05), but the improvement in HSS knee score [39.5 (25.3, 57.0) points] was significantly larger than that in the arthrolysis group [16.0 (10.5, 25.3) points] ( P<0.05). Respectively, 14 and 3 knees in the revision arthroplasty group and the arthrolysis group resulted in patient satisfaction, showing a significant difference between the 2 groups ( P<0.05). Conclusions:Both arthrolysis and revision arthroplasty can significantly improve knee ROM and HSS knee score in post-TKA arthrofibrosis. However, since revision arthroplasty demonstrates superior improvements in HSS knee score and patient satisfaction, it is preferable for patients with lower preoperative knee ROM.

Objective To investigate the effects of the polymer pharmaceutical excipient methoxy poly-ethylene glycol poly-lactic acid(mPEG-PLA)in Sprague-Dawley(SD)rats and Beagle dogs and its toxicological reactions,to provide a reference for its safe clinical use.Methods SD rats and Beagle dogs(male∶female ratios,1∶1)were divided randomly into control group and low,medium,and high dose mPEG-PLA groups(70,210,700 mg/kg).Animals received intravenous mPEG-PLA once a day for 90 days,followed by a 28-day recovery period.Indicators including clinical observations,food intake,body weight,hematology,blood biochemistry,immune function,and pathological examination were recorded.Results Compared with the control group,(1)food intake was decreased(P＜0.01)and body weight was increased(P＜0.05 or P＜0.01)after 90 days of continuous administration,with similar changes in the medium and high dose groups in both rats and dogs.In addition,MONO/MONO％,RBC,MCH,MCHC,HCT,HGB,PLT,TP,ALB,GLB,and Fbg were all decreased(P＜0.05 or P＜0.01)and coagulation indexes(e.g.,APTT)were increased(P＜0.05 or P＜0.01).Organ weights and the organ-to-body/brain weight ratios of the liver and spleen were increased(P＜0.05 or P＜0.01),and histopathology indicated numerous foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla.DBIL and TBIL also increased in rats in the high dose group(P＜0.05 or P＜0.01),while the dogs experienced skin swelling or scabs,abdominal swelling,vomiting,decreased activity,high albuminuria,and ascites,and the renal glomerular cells showed vacuoles.(2)After 28 days of recovery,rats and dogs in the medium and high dose groups showed a few foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla,as well as decreased of food intake in dogs.The MCHC,PLT,and TP decreased in dogs in the high dose group(P＜0.05),and the liver and spleen weights and organ coefficients in rats increased(P＜0.05 or P＜0.01),while the MONO％decreased in male rats in the medium dose group(P＜0.05).Conclusions Administration of mPEG-PLA 210 and 700 mg/kg for 90 days caused blood mononuclear cells to enter and aggregate in the liver,spleen,lymph nodes,and other tissues in SD rats and Beagle dogs,leading to secondary tissue structural damage.Protein and fibrinogen synthesis and bilirubin metabolism in the liver decreased,leading to abnormal coagulation function,and decreased intravascular colloid osmotic pressure resulted in edema and bleeding.The result suggest that the liver,spleen,kidney,and lymph nodes are target organs for mPEG-PLA toxicity,with dose-dependent and reversible effects and species differences,but no significant sex differences.Clinical monitoring of related organ functions is needed to avoid secondary damage.

Objective To systematically investigate the effects of Dangmu extract syrup on the growth and development of 4-day-old(postnatal day 4,PND4)Sprague-Dawley(SD)rats and its toxic reactions.Methods According to the whole litter design method,128 young mice(PND2)were randomly divided into negative control group and low,medium and high dose groups.From PND4,the animals were orally given pure water,31 g/kg,93 g/kg and 280 g/kg(calculated as raw herb material)of Dangmu extract syrup,respectively,once daily for 18 consecutive days,with a 15 d of recovery phase.During the study period,the general state,growth and development,nerve reflex function,spontaneous behavior,hematology,coagulation,blood biochemistry,immune function,growth hormone and histopathology of the animals in each group were observed or examined.Results After 18 d of continuous administration,compared with the negative control group,GLU(male and female)in the medium and high dose groups increased(P＜0.05 or P＜0.01),LDH(male and female)and AST(male)in the medium and high dose groups,ALT,AST(female)in the high dose group decreased(P＜0.05 or P＜0.01),RET and percentage of RET(male and female)in the low and high dose groups,RET(male)in the medium dose group increased(P＜0.05 or P＜0.01),spleen mass and the organ-to-body mass ratio(male and female)in the low and high dose groups and female in the medium dose group increased(P＜0.05 or P＜0.01).Splenic nodule structures were formed in all dose groups with large size and number,and there was a dose relationship in the degree of changes.After 15 d recovery period,compared with the negative control group,GLU(female)in the low dose group increased(P＜0.05),ALT,AST,ALP,TG(female)in the medium and high dose groups,GGT,TG,TCHO(male)in the medium dose groups,AST,ALP,TG,LDH(male)in the high dose group decreased(P＜0.05 or P＜0.01),RET(female)and percentage of RET(male)in the high dose group increased(P＜0.05).compared with the 18 d of continuous administration,the spleen structures of the animals in each group were more completely developed and the splenic nodule structures were obvious,but no significant difference was noted in the comparison between groups.No significant drug-related changes were observed in other test result.Conclusions Dangmu extract syrup advanced the development of complete spleen structure in 4-day-old SD rats,accompanied by the enhancement of its hematopoietic function,and at the same time,it caused the animals,blood glucose to rise,the enhancement of glucose metabolism function led to the increase of related enzyme consumption,and led to the decrease of some liver function parameters,and showed a dose correlation.There was no gender difference in the changes,which were reversible after stop administration,and the mechanism of the changes needs to be further explored and confirmed.In the clinical trials,attention should be paid to the control of the dose of the test article,and regular monitoring of the spleen and related blood and clinical chemistry parameters.

Objective To investigate the effects of the polymer pharmaceutical excipient methoxy poly-ethylene glycol poly-lactic acid(mPEG-PLA)in Sprague-Dawley(SD)rats and Beagle dogs and its toxicological reactions,to provide a reference for its safe clinical use.Methods SD rats and Beagle dogs(male∶female ratios,1∶1)were divided randomly into control group and low,medium,and high dose mPEG-PLA groups(70,210,700 mg/kg).Animals received intravenous mPEG-PLA once a day for 90 days,followed by a 28-day recovery period.Indicators including clinical observations,food intake,body weight,hematology,blood biochemistry,immune function,and pathological examination were recorded.Results Compared with the control group,(1)food intake was decreased(P＜0.01)and body weight was increased(P＜0.05 or P＜0.01)after 90 days of continuous administration,with similar changes in the medium and high dose groups in both rats and dogs.In addition,MONO/MONO％,RBC,MCH,MCHC,HCT,HGB,PLT,TP,ALB,GLB,and Fbg were all decreased(P＜0.05 or P＜0.01)and coagulation indexes(e.g.,APTT)were increased(P＜0.05 or P＜0.01).Organ weights and the organ-to-body/brain weight ratios of the liver and spleen were increased(P＜0.05 or P＜0.01),and histopathology indicated numerous foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla.DBIL and TBIL also increased in rats in the high dose group(P＜0.05 or P＜0.01),while the dogs experienced skin swelling or scabs,abdominal swelling,vomiting,decreased activity,high albuminuria,and ascites,and the renal glomerular cells showed vacuoles.(2)After 28 days of recovery,rats and dogs in the medium and high dose groups showed a few foam-like macrophages in the hepatic sinuses,red spleen pulp,and lymph node medulla,as well as decreased of food intake in dogs.The MCHC,PLT,and TP decreased in dogs in the high dose group(P＜0.05),and the liver and spleen weights and organ coefficients in rats increased(P＜0.05 or P＜0.01),while the MONO％decreased in male rats in the medium dose group(P＜0.05).Conclusions Administration of mPEG-PLA 210 and 700 mg/kg for 90 days caused blood mononuclear cells to enter and aggregate in the liver,spleen,lymph nodes,and other tissues in SD rats and Beagle dogs,leading to secondary tissue structural damage.Protein and fibrinogen synthesis and bilirubin metabolism in the liver decreased,leading to abnormal coagulation function,and decreased intravascular colloid osmotic pressure resulted in edema and bleeding.The result suggest that the liver,spleen,kidney,and lymph nodes are target organs for mPEG-PLA toxicity,with dose-dependent and reversible effects and species differences,but no significant sex differences.Clinical monitoring of related organ functions is needed to avoid secondary damage.

Objective:To compare the mid- to long-term clinical outcomes of arthrolysis versus revision arthroplasty for arthrofibrosis-related stiffness following total knee arthroplasty (TKA).Methods:A retrospective analysis was conducted of the 20 patients (26 knees) with post-TKA arthrofibrosis who had been treated at Department of Orthopedics, The Fourth Medical Center of Chinese PLA General Hospital between January 2004 and January 2020. The patients were divided into 2 groups based on their treatment: an arthrolysis group of 8 cases (10 knees) [1 male (2 knees)and 7 females (8 knees); median age: 44.0 (21.0, 62.0) years] and a revision arthroplasty group of 13 cases (16 knees) [4 males (6 knees)and 9 females (10 knees); median age: 41.5 (30.0, 56.0) years]. The knee range of motion (ROM) and the American Hospital for Special Surgery (HSS) knee score as well as their improvements were compared between preoperation and the last follow-up, as well as between the 2 groups; the satisfaction of the patients at the last follow-up was compared between the 2 groups.Results:No significant differences in the baseline characteristics were observed between the 2 groups, indicating comparability ( P>0.05). The preoperative knee ROM [55.0° (48.8°, 61.3°)] and HSS knee score [54.0 (47.0, 61.8) points] in the arthrolysis group were significantly higher than those in the revision group [27.5° (6.3°, 50.0°), 33.0 (27.3, 47.8) points] ( P<0.05). In the arthrolysis and revision arthroplasty groups, the knee ROMs [90.0° (65.0°, 100.0°), 90.0° (63.5°, 98.8°)] and HSS knee scores [(69.8±19.9) points, (77.6±11.3) points] at the last follow-up were significantly improved compared with those before operation ( P<0.05). In the revision arthroplasty group, the improvement in knee ROM (48.9°±21.7°) was insignificantly larger than that in the arthrolysis group (34.5°±13.2°) ( P>0.05), but the improvement in HSS knee score [39.5 (25.3, 57.0) points] was significantly larger than that in the arthrolysis group [16.0 (10.5, 25.3) points] ( P<0.05). Respectively, 14 and 3 knees in the revision arthroplasty group and the arthrolysis group resulted in patient satisfaction, showing a significant difference between the 2 groups ( P<0.05). Conclusions:Both arthrolysis and revision arthroplasty can significantly improve knee ROM and HSS knee score in post-TKA arthrofibrosis. However, since revision arthroplasty demonstrates superior improvements in HSS knee score and patient satisfaction, it is preferable for patients with lower preoperative knee ROM.

Objective:To explore the surgical efficacy of conductive deafness caused by otosclerosis and ossicular malformation with 980 nm fiber laser stapedial floor fenestration.Methods:Data of 58 patients (ears) who were diagnosed with conductive deafness caused by otosclerosis (49 ears) and ossicular malformation (9 ears) treated by 980 nm Diode laser small-fenestra stapedotomy were retrospectively analyzed. Air conduction (AC) thresholds, bone conduction (BC) thresholds, and air-bone gap (ABG) at 0.5, 1, 2, 4 kHz pure tone frequencies were compared before and 3 months after surgery, and the advantages and precautions of 980 nm fiber laser were summarized. Paired t-test (SPSS 26.0 software) was use to analyze the listening data. Results:Fiber optic laser stapes fenestration and artificial stapes implantation were successfully completed in all 57 cases (ears), the hearing of another one patient (ear) with floating malformation of detachment of stapedial floor was lower than that before surgery. Preoperative at 0.5, 1, 2, 4 kHz frequencies of AC thresholds, BC thresholds, and ABG were (65.4±9.7) dB, (27.2±8.9) dB, and (38.2±9.8) dB respectively. Postoperative 3 months at the same frequency of AC thresholds, BC thresholds, and ABG were (42.1±11.3) dB, (26.9±6.6) dB, and (15.2±9.1) dB. Preoperative and postoperative of AC threshold and ABG were statistically significant at 0.5, 1, 2, 4 kHz ( t value was 13.270 and13.948, both P<0.01), and yet the BC threshold was not statistically significant before and after surgery at the same frequency ( t=0.418, P>0.05). Conclusions:980 nm fiber laser stapes floor fenestration is an effective treatment for conductive deafness caused by otosclerosis and ossicular malformation.

ObjectiveTo provide a reference for the diagnosis of amyloidosis in experimental animals through the pathological diagnosis of systemic amyloidosis in a case of a New Zealand white rabbit. MethodsIn a 6-month repeated ocular toxicity study, an abnormal finding was noted during the routine gross anatomical examination of one New Zealand white rabbit. Its organs were prepared as paraffin sections and stained with hematoxylin-eosin (HE) staining and Congo red staining. The histopathological features were observed under optical and polarized light microscopy. ResultsGross anatomical examination of the animal revealed an enlarged spleen and changes in the color and texture of the lung. HE staining showed that the splenic tissue structure was destroyed, the white pulp of the spleen was surrounded by dense amyloid deposition in the form of nodular rings, along with pressure atrophy of the white pulp. Amyloid deposits were also observed in the submandibular lymph nodes, mesenteric lymph nodes, ileum, sacculus rotundus, vermiform appendix, jejunum, cecum, and rectum. Congo red staining showed that the amyloid deposition in the affected organs appeared salmon-pink, and exhibited characteristic apple green birefringence under polarized light microscopy.Conclusion The histo-pathological features of the New Zealand white rabbit are consistent with the diagnostic characteristics of systemic amyloidosis.