BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.

Objective To determine the body weights and blood physiological and biochemical indicators in the Macaca mulatta brevicaudus(M.m.brevicaudus),to provide a reference for the breeding of experimental animals.Methods A total of 180 wild M.m.brevicaudus(female and male)from the South Bay Macaque Reserve in Lingshui were selected as the research subjects.Body weights were measured using electronic scales and blood samples were collected.Routine blood indicators(red blood cell count,hemoglobin,white blood cell count,and platelet count)were detected using an automated blood cell analyzer,and biochemical indicators(alanine aminotransferase,aspartate aminotransferase,glucose,blood urea nitrogen)were measured using an automated biochemical analyzer.Data were analyzed using SPSS 18.0 software for descriptive statistics,and differences in body weights and blood indicators between sexes and age groups were compared using t-tests.Results Adult male wild M.m.brevicaudus were significantly heavier than females(P＜0.05);however,there were no significant differences in complete blood cell counts between female and male macaques(P＞0.05).In terms of blood biochemical indicators,lactate dehydrogenase and total bilirubin levels differed significantly between female and male M.m.brevicaudus(P＜0.05),but there were no significant differences in any other biochemical indicators.Conclusions This study established baseline data on the body weights and blood physiological and biochemical indicators of wild M.m.brevicaudus,providing a reference for their future breeding as experimental animals.

As an independent first-level discipline,an appropriate classification of nursing science is significant.In China,each nursing degree-granting institution has developed its own secondary-level discipline directions based on its research characteristics and strengths,with varying names and research scopes.Furthermore,there is no unified global classification system.This paper,based on the characteristics of nursing as a discipline and combined with China's discipline classification principles,used literature analysis,comprehensive classification,philosophical reflection,logical reasoning,and expert consultation methods to explore the connotation of nursing,its unique research objects and scope,and to construct a secondary-level discipline classification system for nursing science that is suitable for China's national conditions.The paper also discussed the challenges faced by the nursing discipline and its future development directions,providing theoretical and practical guidance for the development of the nursing discipline.

Objective To determine the body weights and blood physiological and biochemical indicators in the Macaca mulatta brevicaudus(M.m.brevicaudus),to provide a reference for the breeding of experimental animals.Methods A total of 180 wild M.m.brevicaudus(female and male)from the South Bay Macaque Reserve in Lingshui were selected as the research subjects.Body weights were measured using electronic scales and blood samples were collected.Routine blood indicators(red blood cell count,hemoglobin,white blood cell count,and platelet count)were detected using an automated blood cell analyzer,and biochemical indicators(alanine aminotransferase,aspartate aminotransferase,glucose,blood urea nitrogen)were measured using an automated biochemical analyzer.Data were analyzed using SPSS 18.0 software for descriptive statistics,and differences in body weights and blood indicators between sexes and age groups were compared using t-tests.Results Adult male wild M.m.brevicaudus were significantly heavier than females(P＜0.05);however,there were no significant differences in complete blood cell counts between female and male macaques(P＞0.05).In terms of blood biochemical indicators,lactate dehydrogenase and total bilirubin levels differed significantly between female and male M.m.brevicaudus(P＜0.05),but there were no significant differences in any other biochemical indicators.Conclusions This study established baseline data on the body weights and blood physiological and biochemical indicators of wild M.m.brevicaudus,providing a reference for their future breeding as experimental animals.

AIM:To establish a physiological-based pharmacokinetic(PBPK)model of ertapen-em in elderly patients with chronic kidney disease,and to analyze the pharmacokinetic/pharmacody-namic index f％ T＞MIC at different doses.METH-ODS:The physicochemical properties and pharma-cokinetic characteristics of ertapenem were collect-ed by reviewing the literature and databases,and a healthy adult model was established in PKSim? software,and then extrapolated to the PBPK model of the elderly.The clinical pharmacokinetic re-search data were used to optimize and validate the model,and the mean folding error(MFE)was used as the index to evaluate the prediction perfor-mance of the model.The final model was used to simulate the in vivo exposure of elderly patients with chronic kidney disease after administration,and the pharmacokinetic/pharmacodynamic index of commonly used clinical dosing regimens was an-alyzed,and the recommended dosing regimens were given.RESULTS:The MFE of the area under the curve(AUC0-t),peak concentration(Cmax)and peak time(Tmmax)predicted by the established PBPK model of ertapenem in adults were 0.92,0.79 and 1.02,respectively,and the predicted value of the optimized PBPK model of ertapenem in the elderly was also consistent with the observed value of 0.5＜MFE＜2 standards,all of which have good predictive performance.With f％ T＞MIC greater than 40％as the drug efficacy target,the minimum inhibitory concentration(MIC)is 0.5-1 μg/mL for sensitive bacteria,and elderly patients with chronic kidney disease can consider reducing the drug dose as ap-propriate.CONCLUSION:The PBPK model of ertap-enem in elderly patients with renal insufficiency has been successfully established,and the model has good prediction performance and provides a reference for clinical personalized medication in el-derly patients with renal insufficiency.

As an independent first-level discipline,an appropriate classification of nursing science is significant.In China,each nursing degree-granting institution has developed its own secondary-level discipline directions based on its research characteristics and strengths,with varying names and research scopes.Furthermore,there is no unified global classification system.This paper,based on the characteristics of nursing as a discipline and combined with China's discipline classification principles,used literature analysis,comprehensive classification,philosophical reflection,logical reasoning,and expert consultation methods to explore the connotation of nursing,its unique research objects and scope,and to construct a secondary-level discipline classification system for nursing science that is suitable for China's national conditions.The paper also discussed the challenges faced by the nursing discipline and its future development directions,providing theoretical and practical guidance for the development of the nursing discipline.

Objective:To investigate the early clinical effects of orthopedic surgery robot-assisted double Endobutton titanium plate internal fixation in the treatment of fresh acromioclavicular joint dislocation.Methods:Thirty-nine patients with fresh acromioclavicular joint dislocation were included from January 2020 to January 2022. A total of 19 patients were treated with double Endobutton suspension internal fixation assisted by the domestic third-generation orthopaedic surgical robot (TiRobot ? 2.0) Dimensity system. There were Rockwood type III in 11 cases, type IV in 8 cases. Twenty cases were treated with conventional incision double Endobutton internal fixation, with Rockwood type III in 13 cases, type V in 7 cases. The operation duration, blood loss volume, incision length and hospitalization time were compared between the two groups. The following CT parameters of acromioclavicular joint at 2 days and 1 year after operation, distance between distal inferior cortex of clavicle and subacromial cortex, distance between upper and lower endobuttons, horizontal distance between anterior edge of distal clavicle and anterior edge of acromion and diameter of coracoid process and diameter of clavicular tunnel were measured. The visual analogue score (VAS), Constant-Murley shoulder function score and shoulder abduction activity were also evaluated before and at 12 months after operation. Results:The follow-up duration was 10.8±2.4 months in the robot group and 11.5±3.1 months in the routine group. The VAS score of the robot group decreased from 5.3±2.1 to 0.3±0.2 at 12 months after operation ( t=10.46, P=0.014). The Constant-Murley score increased from 55.6±6.4 to 92.0±4.2. The range of shoulder abduction increased from 42.2°±5.4° to 172.6°±6.1° ( t=17.24, P<0.001). The operation duation of the robot group was 74.4±6.6 min, which was longer than that of the conventional group 61.7±7.2 min ( t=5.43, P=0.037). There was no significant difference in VAS score, Constant-Murley score, shoulder abduction activity or CT measurement between the two groups ( P>0.05). During the follow-up, two cases in the robot group had cortical osteolysis on the supraclavicular surface, one case in the conventional group had loss of reduction, one case in the supraclavicular cortical osteolysis, and 4 cases in the cortical defect on the side of the coracoid process tunnel. Conclusion:Orthopedic robot-assisted and conventional incision with double Endobutton titanium plate internal fixation in treating fresh acromioclavicular joint dislocation can achieve satisfied early clinical effects. Accurate establishment of clavicle and coracoid bone tunnel assisted by robot can overcome the defects of bone tunnel deviation in conventional incision operation and can prevent reduction and bone loss. However, robot-assisted and conventional incision Endobutton internal fixation could enlarge bone tunnel.

Objective:To investigate the feasibility and clinical efficacy of percutaneous screw fixation for acetabular anterior column fracture with laser-assisted axial fluoroscopy.Methods:Data of 20 patients (22 sided) with acetabular anterior column fracture treated by percutaneous screw fixation with laser-assisted axial fluoroscopy from January 2017 to December 2018 were retrospectively analyzed. There were 11 males and 9 females with an average of 42.1±3.2 years (range, 24-68 years). There were 7 cases of unilateral acetabular anterior column fracture, 2 cases of bilateral acetabular anterior column fracture (4 sides), 7 cases of anterior column with ipsilateral sacral fracture, and 4 cases of anterior column with sacroiliac joint injury. There were 3 hips of Area I, 6 Area II, 13 Area III of acetabular anterior column fractures according to Nakatani partition. The time from injury to surgery was 5 days (range, 3-11 days). All patients with acetabular anterior column fractures were fixed by percutaneous screw fixation with laser-assisted axial fluoroscopy, and patients with sacral fracture or sacroiliac joint injury were fixed by percutaneous sacroiliac screws with Starr frame-assisted reduction. The time of operation, the number of intraoperative fluoroscopy and the amount of intraoperative bleeding were recorded. Matta scoring criteria were used to assess fracture reduction quality, and hip function was assessed at the last follow-up according to the modified Merle D' Aubigné and Postel scoring system.Results:The average operative time was 22±10 min (range, 20-40 min) with an average times of intraoperative fluoroscopy of 30±8 times (range, 21-45 times), and the amount of intraoperative blood loss was 20±5 ml (range, 10-40 ml). 20 patients were followed up after operation for a period of 14±3.1 months (range, 12-18 months). The quality of postoperative fracture reduction was assessed according to the Matta acetabular fracture reduction criteria: anatomical reduction in 18 hips, satisfactory reduction in 2 hips, unsatisfactory reduction in 2 hips, with an excellent and good rate of 91% (20/22). The fracture healing time was 13±2.2 weeks (range, 11-16 weeks). At the lastest follow-up, hip function was assessed according to the modified Merle D' Aubigné and Postel scoring system: excellent 18, good 3, fair 1, and the satisfactory rate was 95%(21/22). No major neurological, vascular injury, wound infection and ectopic ossification were found during follow-up.Conclusion:Using laser-assisted axial fluoroscopy percutaneous screw to treat acetabular anterior column fracture, the operation is simple. And there is low risk to damage important blood vessels and nerves. This method can shorten the operation time of acetabular anterior column fracture, reduce the amount of blood loss during the operation, and the outcome is satisfactory.

Objective: To study the efficacy, safety and long-term outcomes of integrated strategy of bortezomib-based induction regimens followed by autologous hematopoietic stem cell (ASCT) and maintenance therapy in Chinese multiple myeloma (MM) patients. Methods: 200 MM patients receiving integrated strategy of bortezomib--based induction regimens followed by ASCT and maintenance therapy were retrospectively and prospectively analyzed from December 1. 2006 to April 30. 2018. Results: The complete remission rates (CR) and better than very good partial remission rates (VGPR) after induction therapy, transplantation and maintenance therapy were respectively 31% and 75.5%, 51.8% and 87.7%,73.6% and 93.4%. There was no difference between 4 cycles and more than 5 cycles induction chemotherapy. The negative rate of MRD detection by flow cytometry was 17.6% and 38.2% respectively after induction and 3 months after transplantation. The negative rate of MRD gradually increased during the maintenance therapy. The success rate of high dose CTX combined with G-CSF mobilization was 95.5% and transplantation related mortality (TRM) was zero. The median time to progress (TTP) was 75.3 months and the median overall survival (OS) was 99.5 months. TTP of patients obtaining CR and negative MRD after induction were longer that those of no CR and positive MRD. TTP and OS of patients receiving triple-drug induction and ASCT in early stage were longer than those of double-drug induction and ASCT in late stage. LDH≥240 U/L, high risk cytogenetics, ISS II+III stage and HBsAg positive were prognostic factors at diagnosis. However, only MRD and high risk cytogenetics were independent prognostic factors after transplantation and maintenance therapy. The clinical characteristics of patients of TTP ≥6 years were listed below: light-chain type M protein, ISS I stage, normal level of hemoglobin and platelet, normal LDH, HBsAg negative, chromosome 17p-negative, good response and sustained good response. Conclusions Integrated strategy of bortezomib-based induction regimens followed by ASCT and maintenance therapy can significantly improve the short-term and long-term efficacy. The prognostic factors of TTP in different disease stages were different. Response to treatment, especially MRD, played a more important role in prognostic factors.