Targeted covalent inhibitors, primarily targeting cysteine residues, have attracted great attention as potential drug candidates due to good potency and prolonged duration of action. However, their discovery is challenging. In this research, a database-assisted liquid chromatography-tandem mass spectrometry (LC-MS/MS) strategy was developed to quickly discover potential cysteine-targeting compounds. First, compounds with potential reactive groups were selected and incubated with N-acetyl-cysteine in microsomes. And the precursor ions of possible cysteine-adducts were predicted based on covalent binding mechanisms to establish in-house database. Second, substrate-independent product ions produced from N-acetyl-cysteine moiety were selected. Third, multiple reaction monitoring scan was conducted to achieve sensitive screening for cysteine-targeting compounds. This strategy showed broad applicability, and covalent compounds with diverse structures were screened out, offering structural resources for covalent inhibitors development. Moreover, the screened compounds, norketamine and hydroxynorketamine, could modify synaptic transmission-related proteins in vivo, indicating their potential as covalent inhibitors. This experimental-based screening strategy provides a quick and reliable guidance for the design and discovery of covalent inhibitors.

Objective To investigate the application value of procalcitonin(PCT),neutrophil-to-lym-phocyte ratio(NLR)and C-reactive protein to albumin ratio(CAR)in the short-term prognosis of the pa-tients with severe community acquired pneumonia(SCAP).Methods A total of 225 patients with communi-ty-acquired pneumonia(CAP)treated in this hospital from July 2021 to December 2022 were selected as the study subjects and divided into the SCAP group and non-SCAP group.Then the patients with SCAP were di-vided into the survival group and death group according to their survival state in 28 d.The general data and re-lated laboratory indexes were collected.NLR and CAR were calculated.The binary logistic regression was a-dopted to analyze the risk factors of death on 28 d for the SCAP patients.The receiver operating characteristic(ROC)curve was drawn and the area under the curve(AUC)was calculated to evaluate the predictive value of relevant indicators.Results The age,levels of PCT,NLR,CAR,WBC and NEU,and the proportion of cor-onary heart disease in the SCAP group were higher than those in the non-SCAP group,while the levels of LYM and ALB were lower than those in the non-SCAP group,and the differences were statistically significant(P＜0.05).The age,levels of PCT,NLR,CAR,WBC and NEU,and the proportion of COPD in the death group were higher than those in the survival group,while the levels of LYM and ALB were lower than those in the survival group,and the differences were statistically significant(P＜0.05).The binary logistic regres-sion analysis showed that the age(OR=1.069,95％CI:1.020-1.120),chronic obstructive pulmonary dis-ease(OR=5.633,95％CI:2.019-15.712),PCT(OR=1.045,95％CI:1.002-1.090)and CAR(OR=2.170,95％CI:1.616-2.915)were the independent influencing factor for the death on 28 d in the patients with SCAP.The ROC curve analysis indicated that AUC,sensitivity and specificity of PCT,NLR and CAR combined detection were superior to those of detection alone,having good predictive value.Conclusion PCT,NLR and CAR have a certain predictive value for death within 28 d in the patients with SCAP.The combined detection has better predictive efficiency.

Objective To investigates the diagnostic value of infrared thermography-based skin temper-ature monitoring for lower extremity arterial disease(LEAD)in patients with diabetic foot.Methods A total of 160 patients with diabetic foot admitted to the hospital from March 2023 to December 2024 were selected as the research subjects and divided into the LEAD group(n=120)and the non-lesion group(n=40)based on the diagnostic results of color Doppler ultrasound.Spearman analysis was used to evaluate the correlation be-tween the relative temperature of diabetic foot ulcer(DFU)wounds measured by infrared thermography and the diameter and blood flow of lower limb arteries.Stepwise logistic regression analysis was performed to i-dentify the influencing factors of LEAD and subgroup analysis was conducted based on the presence or absence of infection.Receiver operating characteristic(ROC)curve analysis was used to assess the diagnostic efficacy of DFU wound relative temperature for LEAD and lower limb arterial atherosclerotic plaques,lumen stenosis,and lumen occlusion.Results There were statistically significant differences between the two groups in DFU wound temperature,skin temperature at the same site on the healthy side,DFU wound relative temperature,ankle brachial index(ABI),C-reactive protein(CRP),uric acid,and the peak velocity(PSV)and pulsatility index(PI)levels of the femoral artery,popliteal artery,and dorsalis pedis artery,as well as the proportions of lower limb arterial atherosclerotic plaques and lumen stenosis(P＜0.05).Spearman analysis showed that the relative temperature of DFU wounds was negatively correlated with PSV of the femoral artery,popliteal arter-y,and dorsalis pedis artery,and positively correlated with PI(P＜0.05).Univariate logistic regression analy-sis indicated that ABI,DFU wound relative temperature,uric acid,and the PSV and PI of the femoral artery,popliteal artery,and dorsalis pedis artery were influencing factors for LEAD(P＜O.05).Multivariate logistic regression analysis revealed that DFU wound relative temperature and uric acid were influencing factors for LEAD in diabetic foot(P＜0.05).Subgroup analysis showed that DFU wound relative temperature was an in-fluencing factor for LEAD in diabetic foot(P＜0.05),and there was no interaction between diabetic foot in-fection and the relationship between DFU wound relative temperature and LEAD in diabetic foot(P＞0.05).The area under the curve(AUC)for predicting LEAD using DFU wound relative temperature was 0.923,with the cut-off temperature being 5.4 ℃.The AUCs for predicting lower limb arterial atherosclerotic plaques,lumen stenosis,and lumen occlusion were 0.720,0.657,and 0.554,respectively,with the cut-off temperatures being 5.6,6.3,and 4.6 ℃,respectively.Conclusion DFU wound surface relative temperature of infrared thermog-raphy can effectively diagnose LEAD in diabetic foot.

Targeted covalent inhibitors,primarily targeting cysteine residues,have attracted great attention as potential drug candidates due to good potency and prolonged duration of action.However,their dis-covery is challenging.In this research,a database-assisted liquid chromatography-tandem mass spec-trometry(LC-MS/MS)strategy was developed to quickly discover potential cysteine-targeting compounds.First,compounds with potential reactive groups were selected and incubated with N-acetyl-cysteine in microsomes.And the precursor ions of possible cysteine-adducts were predicted based on covalent binding mechanisms to establish in-house database.Second,substrate-independent product ions produced from N-acetyl-cysteine moiety were selected.Third,multiple reaction monitoring scan was conducted to achieve sensitive screening for cysteine-targeting compounds.This strategy showed broad applicability,and covalent compounds with diverse structures were screened out,offering structural resources for covalent inhibitors development.Moreover,the screened compounds,norket-amine and hydroxynorketamine,could modify synaptic transmission-related proteins in vivo,indicating their potential as covalent inhibitors.This experimental-based screening strategy provides a quick and reliable guidance for the design and discovery of covalent inhibitors.

This study investigated the prevalence and potential mechanisms of gentamicin heterore-sistance in Streptococcus isolates from dairy cows.In this study,A total of 39 Streptococcus isola-ted from raw milk were collected,and the minimum inhibitory concentration(MIC)of gentamicin and other drugs on the isolates was determined by micro broth dilution method,and the K-B paper diffusion method,colony analysis profile(PAP),and resistance stability test were used to investigate the heteroresistance characteristics of Streptococcus,and the mechanism of heteroresis-tance was analyzed based on whole genome sequencing and resequencing.Seven suspected heterore-sistance strains were identified by K-B paper diffusion method,accounting for 17.95％(7/39)of the total number of suspected strains.PAP confirmed that the MIC to MNIC ratio of L147,L108 and L174 was greater than 8,and the frequency of resistant subgroups ranged from 1.38×10-5 to 8.18 × 10-5,which was greater than 1 × 10-7,confirming that they were heteroresistance strains.Resistance stability tests revealed that the resistant subpopulations of all three strains were not stably inherited.Whole-genome sequencing revealed mutations in the ribosomal target genes of aminoglycoside antibiotics,rsmA,rsmB and rsmE,compared with the reference genome,which may lead to heteroresistance to gentamicin in Streptococcus.The occurrence of heteroresistance of Streptococcus to gentamicin is high in dairy sources,so more attention should be paid to the occur-rence of heteroresistance when using gentamicin for clinical treatment.

Objective:To evaluate the application of blood glucose management evidence in hemodialysis patients with diabetic nephropathy within clinical practice, establish review indicators, and analyze both obstacles and enablers.Methods:Based on the feasibility, appropriateness, meaningfulness, and effectiveness (FAME) principle, the best evidence for blood glucose management in hemodialysis patients with diabetic nephropathy was evaluated. Ultimately, 21 pieces of evidence were included, and review indicators were established. A baseline review was conducted at the Hemodialysis Center of the Department of Nephrology, Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, from August to September 2024. Based on the review findings, obstacles and enablers in the evidence-based practice process were analyzed, and change strategies were developed.Results:A total of 39 review indicators were established. Among these, one indicator achieved a 100.00% implementation rate, four indicators achieved an implementation rate between 80.00% and <100.00%, six indicators achieved an implementation rate between 60.00% and<80.00%, 19 indicators achieved an implementation rate between>0 and<60.00%, and nine indicators achieved a 0 implementation rate. After analyzing each review indicator, the primary obstacles included evidence not being transformed into clear and accessible formats, low awareness among healthcare providers and patients, lack of incentive mechanisms, significant gaps from existing nursing processes, insufficient manpower, need for external support, and requirement for additional training. Additionally, factors that promoted evidence translation included reliable sources of evidence, recognition and support for change from administrators and teams, a culture and experience of change within the team, the potential for change to yield significant benefits, and the availability of resources within the hospital to support the change.Conclusions:There is a significant gap between blood glucose management evidence and clinical practice among hemodialysis patients with diabetic nephropathy. Appropriate change strategies should be developed through clinical review and analysis of obstacles and enablers to promote the translation and application of evidence in clinical practice.

Objective:To evaluate the application of blood glucose management evidence in hemodialysis patients with diabetic nephropathy within clinical practice, establish review indicators, and analyze both obstacles and enablers.Methods:Based on the feasibility, appropriateness, meaningfulness, and effectiveness (FAME) principle, the best evidence for blood glucose management in hemodialysis patients with diabetic nephropathy was evaluated. Ultimately, 21 pieces of evidence were included, and review indicators were established. A baseline review was conducted at the Hemodialysis Center of the Department of Nephrology, Zhongshan Hospital of Traditional Chinese Medicine, Guangzhou University of Chinese Medicine, from August to September 2024. Based on the review findings, obstacles and enablers in the evidence-based practice process were analyzed, and change strategies were developed.Results:A total of 39 review indicators were established. Among these, one indicator achieved a 100.00% implementation rate, four indicators achieved an implementation rate between 80.00% and <100.00%, six indicators achieved an implementation rate between 60.00% and<80.00%, 19 indicators achieved an implementation rate between>0 and<60.00%, and nine indicators achieved a 0 implementation rate. After analyzing each review indicator, the primary obstacles included evidence not being transformed into clear and accessible formats, low awareness among healthcare providers and patients, lack of incentive mechanisms, significant gaps from existing nursing processes, insufficient manpower, need for external support, and requirement for additional training. Additionally, factors that promoted evidence translation included reliable sources of evidence, recognition and support for change from administrators and teams, a culture and experience of change within the team, the potential for change to yield significant benefits, and the availability of resources within the hospital to support the change.Conclusions:There is a significant gap between blood glucose management evidence and clinical practice among hemodialysis patients with diabetic nephropathy. Appropriate change strategies should be developed through clinical review and analysis of obstacles and enablers to promote the translation and application of evidence in clinical practice.

This study investigated the prevalence and potential mechanisms of gentamicin heterore-sistance in Streptococcus isolates from dairy cows.In this study,A total of 39 Streptococcus isola-ted from raw milk were collected,and the minimum inhibitory concentration(MIC)of gentamicin and other drugs on the isolates was determined by micro broth dilution method,and the K-B paper diffusion method,colony analysis profile(PAP),and resistance stability test were used to investigate the heteroresistance characteristics of Streptococcus,and the mechanism of heteroresis-tance was analyzed based on whole genome sequencing and resequencing.Seven suspected heterore-sistance strains were identified by K-B paper diffusion method,accounting for 17.95％(7/39)of the total number of suspected strains.PAP confirmed that the MIC to MNIC ratio of L147,L108 and L174 was greater than 8,and the frequency of resistant subgroups ranged from 1.38×10-5 to 8.18 × 10-5,which was greater than 1 × 10-7,confirming that they were heteroresistance strains.Resistance stability tests revealed that the resistant subpopulations of all three strains were not stably inherited.Whole-genome sequencing revealed mutations in the ribosomal target genes of aminoglycoside antibiotics,rsmA,rsmB and rsmE,compared with the reference genome,which may lead to heteroresistance to gentamicin in Streptococcus.The occurrence of heteroresistance of Streptococcus to gentamicin is high in dairy sources,so more attention should be paid to the occur-rence of heteroresistance when using gentamicin for clinical treatment.

Objective To construct and apply an intelligent follow-up information system for patients with cancer pain,providing references for improving the efficiency of hospital follow-up and promoting pain management of patients at home.Methods The intelligent discharge follow-up system for patients with cancer pain includes 2 platforms,namely a patient self-report platform and an administrator operation platform.The administrator operation platform consists of 5 modules,namely the workbench module,the follow-up plan module,the follow-up results module,the health education module and the data statistics module.In January 2022,the system was officially put into clinical application.The use of the system was analyzed,and patients'completion rate,medication compliance,incidence of moderate and severe pain and satisfaction with pain control were compared before(from January 2020 to December 2021)and after(from January 2022 to November 2023)the application of the system.Results At present,this system has been applied in 95 cancer-related wards of our hospital.From January 2022 to November 2023,the number of people who should be followed up was 4 248,and the number of people who actually completed the follow-up was 4 127;the rate of follow-up completion was 97.2%;the rate of timely completion of the follow-up was 94.9%;the rate of automatic follow-up by the system was 40.1%;the rate of patient abnormality report was 31.9%;the rate of timely treatment of patient abnormality report was 89.1%.After the application of the system,the completion rate of pain follow-up was increased,and the difference was statistically significant(P<0.001).After the application of the system,the medication compliance rate of patients with cancer pain increased from 86.9%to 91.0%;the incidence of moderate and severe pain decreased from 6.8%to 5.2%;the satisfaction with pain control increased from 81.0%to 83.5%(P<0.05).Conclusion The intelligent discharge follow-up system for patients with cancer pain can effectively improve the discharge follow-up efficiency and promote the management of patients with cancer pain at home.

A 28-year-old woman presented with a 4-year history of fatigue and sleepiness and was found to have central hypothyroidism and mood disorder. The patient had normal thyroid volume and did not show any other pituitary axis involvement. Over the course of the disease, her symptom improvement matched with the free thyroxine (FT 4) rebound and the adjustment of antipsychotic medication. The patient′s grandmother had central hypothyroidism, and her mother and uncle had lowered or inappropriately normal thyroid stimulating hormone. Hence, genetic involvement was highly suspected, but whole exon sequencing did not reveal a pathogenic variant. Levothyroxine tablets were prescribed to maintain a normal median level of FT 4, and mood disorder medications were adjusted by specialists. Isolated central hypothyroidism is extremely rare, and we report this case aiming to raise awareness of this condition.