BACKGROUND:Studies have reported that alendronate intake significantly increases bone mineral density in patients with osteoporosis. OBJECTIVE:To analyze and compare the changes in metabolites before and after alendronate intervention in ovariectomized rats by chromatography-mass spectrometry,and to further explore the specific mechanism and target of alendronate in the treatment of osteoporosis. METHODS:A total of 36 female Sprague-Dawley rats were randomly divided into model group,alendronate sodium group and sham operation group.The osteoporosis model was established by ovariectomy in the first two groups.Four weeks after modeling,the rats in the alendronate group were intragastrically given alendronate sodium,while those in the sham operation group and model group were given equal volume of normal saline.After 12 weeks of continuous gavage,the metabolites of the lumbar spine were analyzed by chromatography-mass spectrometry,and the common differential metabolites were obtained,which were analyzed by bioinformatics such as Kyoto Gene and Genome Encyclopedia pathway. RESULTS AND CONCLUSION:Totally 17 different metabolites were obtained in the three groups.The enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes showed that alendronate sodium could regulate unsaturated fatty acid biosynthesis,linoleic acid metabolism and other pathways to protect ovariectomized rats.These results indicate that alendronate sodium may exert its anti-osteoporosis effect by interfering with unsaturated fatty acid bioanabolism and linoleic acid metabolism,so as to achieve the purpose of preventing osteoporosis

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To observe and evaluate the clinical efficacy and safety of albumin-bound paclitaxel as first-line treatment for patients with advanced pancreatic cancer in China, and to explore the prognosis-related molecules in pancreatic cancer based on next-generation sequencing (NGS) of tumor tissues.Methods:From December 2018 to December 2020, patients with locally advanced or metastatic pancreatic cancer were recruited to accept albumin-bound paclitaxel as first-line treatment in the oncology departments of 24 hospitals in East China. The primary endpoints were overall survival (OS) and treatment related adverse events, and the secondary endpoint was progression-free survival (PFS). Adverse effects were graded using Common Terminology Criteria for Adverse Events 5.0 (CTCAE 5.0). NGS sequencing on the primary or metastatic tissue samples of pancreatic cancer obtained through surgical resection or biopsy was performed.Results:This study recruited 229 patients, including 70 patients with locally advanced pancreatic cancer (LAPC) and 159 patients with metastatic pancreatic cancer (mPC). The disease control rate was 79.9% and the objective response rate is 36.3%.The common adverse effects during treatment were anaemia (159 cases), leucopenia (170 cases), neutropenia (169 cases), increased aminotransferases (110 cases), and thrombocytopenia (95 cases), and the incidence of grade 3-4 neutropenia is 12.2% (28/229). The median follow-up time was 21.2 months (95% CI: 18.5-23.1 months). The median PFS (mPFS) was 5.3 months (95% CI: 4.37-4.07 months) and the median OS (mOS) was 11.2 months (95% CI: 9.5-12.9 months). The mPFS of patients with LAPC was 7.4 months (95% CI: 6.6-11.2 months), and their mOS was 15.5 months (95% CI: 12.6-NA months). The mPFS of patients with mPC was 3.9 months (95% CI: 3.4-5.1 months), and their mOS was 9.3 months (95% CI: 8.0-10.8 months). Multivariate Cox regression analysis showed that clinical stage ( HR=1.47, 95% CI: 1.06-2.04), primary tumor site ( HR=0.64, 95% CI: 0.48-0.86), Eastern Cooperative Oncology Group Performance Status (ECOG PS) score ( HR=2.66, 95% CI: 1.53-4.65), and whether to combine radiotherapy ( HR=0.65, 95% CI: 0.42-1.00) were independent influencing factors for the PFS of these patients. The primary tumor site ( HR=0.68, 95% CI: 0.48-0.95), ECOG score ( HR=5.82, 95% CI: 3.14-10.82), and whether to combine radiotherapy ( HR=0.58, 95% CI: 0.35-0.96) were independent influencing factors of the OS of these patients. The most frequent gene mutations in these advanced stage pancreatic patients were KRAS (89.66%), TP53 (77.01%), CDKN2A (32.18%), and SMAD4 (21.84%) by NGS of tumor tissues from 87 pancreatic cancer patients with sufficient specimens. Further analysis revealed that mutations in CDKN2B, PTEN, FGF6, and RBBP8 genes were significantly associated with an increased risk of death ( P＜0.05). Conclusion:Albumin-bound paclitaxel as first-line treatment demonstrated feasible anti-tumor efficacy and manageable safety for patients with advanced pancreatic cancer in China.

Objective:To evaluate and summarize the best evidence on fatigue management in children with tumors both domestically and internationally, providing reference for medical and nursing staff to improve fatigue symptoms in children.Methods:The evidence on fatigue management in children with tumors, including best practices, recommended practices, guidelines, systematic reviews, evidence summaries, and expert consensus, was systematically retrieved from clinical decision support systems, guideline websites, professional association websites, and databases both domestically and internationally. The search period was from database establishment to April 2023. Two researchers independently conducted literature quality evaluation and evidence extraction.Results:A total of 17 articles were included, including four guidelines and 13 systematic reviews. Thirty-two best pieces of evidence were extracted from six aspects of assessment and screening, identification of risk factors, health education, exercise intervention, medication intervention, and other interventions of fatigue in children with tumors.Conclusions:The best evidence for fatigue management in children with tumors is summarized, which can provide a basis for medical and nursing staff to improve their fatigue symptoms. It is recommended that medical and nursing staff combine clinical context, professional opinions, and patient wishes to screen the best evidence and develop personalized fatigue management programs.

The aim of the study was to develop a simple, rapid and accurate LC-MS/MS method for the determination of digoxin.Digoxin-d3 was taken as the internal standard (IS), and sample preparation was achieved by liquid-liquid extraction.Chromatographic separation was performed on a Kinetex C18 column (2.1 mm × 50 mm, 2.6 μm; Phenomenex) using an isocratic elution with merely 2 min for each sample.The mobile phase consisted of water and acetonitrile solutions, both containing 1 mmol/L ammonium acetate and 1 mmol/L formic acid (55∶45).The detection was conducted on a TripleQuadTM 4500MD mass spectrometer coupled with electrospray ionization interface under positive-ion multiple reaction monitoring mode.The transitions were m/z 798.5 → 651.3 and m/z 801.6 → 654.4 for digoxin and digoxin-d3, respectively.Results showed that the method was linear over the range of 0.100-20.0 ng/mL.The selectivity, accuracy and precision, recovery and stability of the method were all within the acceptable limits with no matrix effect.This method was successfully applied to a girl treated with digoxin with substantial improvement of therapeutic effect and elimination of toxic reaction, so it can provide valuable fuidance and reference for individualized medication in clinical practice.

Objective:To examine the application value of alternative pancreatic fistula risk score system(a-FRS) for patients with clinically relevant postoperative pancreatic fistula(CR-POPF) after laparoscopic pancreaticoduodenectomy(LPD).Methods:Clinical data of 400 patients who underwent LPD at Department of Hepatobiliary and Pancreatic Surgery,Jilin University First Hospital,from April 2015 to August 2019 were retrospectively analyzed.There were 217 males and 183 females, with age of ( M( Q R)) 58 (53) years (range:26 to 93 years) and body mass index of (23.0±2.7) kg/m 2 (range:19.4 to 27.1 kg/m 2).Preoperative CA19-9 was (171.6±212.7) U/ml (range:32.1 to 762.6 U/ml), and preoperative CA125 was (18.6±22.9) U/ml (range:9.0 to 112.3 U/ml).Univariate analysis and multivariate Logistic regression analysis were implemented to find independent risk factors in CR-POPF.According to 3 indicators of a-FRS system(pancreatic texture,main pancreatic duct diameter,and body mass index),receiver operator characteristic curve was used to prospectively analyze the clinical value of CR-POPF. Results:CR-POPF occurred in 60 patients(15.0%) among the 400 LPD patients,including 54 patients(13.5%) with grade B pancreatic fistula and 6 patients(1.5%) with grade C pancreatic fistula.Univariate and multivariate Logistic regression analysis results showed that soft pancreas,diameter of main pancreatic duct ≤3 mm,and body mass index>23 kg/m 2 were the independent risk factors for CR-POPF after LPD.The incidence of CR-POPF was 1.9% in the group with low pancreatic fistula risk(0 to 5%),5.9% with moderate pancreatic fistula risk(>5% to 20%),and 80.7% with high pancreatic fistula risk(>20%).a-FRS prospectively predicted the sensitivity and specificity of CR-POPF after LPD was 76.7% and 96.8%,positive predictive value was 80.7%,negative predictive value was 95.9%,positive likelihood ratio was 23.66,negative likelihood ratio was 0.24,and area under the curve was 0.735(95% CI:0.668-0.799). Conclusion:a-FRS system has great clinical application value in predicting CR-POPF after LPD,which can provide basis for early risk prediction of CR-POPF and timely related clinical intervention.

Objective:To examine the application value of alternative pancreatic fistula risk score system(a-FRS) for patients with clinically relevant postoperative pancreatic fistula(CR-POPF) after laparoscopic pancreaticoduodenectomy(LPD).Methods:Clinical data of 400 patients who underwent LPD at Department of Hepatobiliary and Pancreatic Surgery,Jilin University First Hospital,from April 2015 to August 2019 were retrospectively analyzed.There were 217 males and 183 females, with age of ( M( Q R)) 58 (53) years (range:26 to 93 years) and body mass index of (23.0±2.7) kg/m 2 (range:19.4 to 27.1 kg/m 2).Preoperative CA19-9 was (171.6±212.7) U/ml (range:32.1 to 762.6 U/ml), and preoperative CA125 was (18.6±22.9) U/ml (range:9.0 to 112.3 U/ml).Univariate analysis and multivariate Logistic regression analysis were implemented to find independent risk factors in CR-POPF.According to 3 indicators of a-FRS system(pancreatic texture,main pancreatic duct diameter,and body mass index),receiver operator characteristic curve was used to prospectively analyze the clinical value of CR-POPF. Results:CR-POPF occurred in 60 patients(15.0%) among the 400 LPD patients,including 54 patients(13.5%) with grade B pancreatic fistula and 6 patients(1.5%) with grade C pancreatic fistula.Univariate and multivariate Logistic regression analysis results showed that soft pancreas,diameter of main pancreatic duct ≤3 mm,and body mass index>23 kg/m 2 were the independent risk factors for CR-POPF after LPD.The incidence of CR-POPF was 1.9% in the group with low pancreatic fistula risk(0 to 5%),5.9% with moderate pancreatic fistula risk(>5% to 20%),and 80.7% with high pancreatic fistula risk(>20%).a-FRS prospectively predicted the sensitivity and specificity of CR-POPF after LPD was 76.7% and 96.8%,positive predictive value was 80.7%,negative predictive value was 95.9%,positive likelihood ratio was 23.66,negative likelihood ratio was 0.24,and area under the curve was 0.735(95% CI:0.668-0.799). Conclusion:a-FRS system has great clinical application value in predicting CR-POPF after LPD,which can provide basis for early risk prediction of CR-POPF and timely related clinical intervention.

Objective To evaluate the effectiveness of swallowing training supplemented with neuromuscular electrical stimulation to provide a reference for clinical treatment and further study.Methods Reports of randomized and controlled trials of surface neuromuscular electrical stimulation in treating post-stroke dysphagia were sought in the Cochrane library,the PubMed and Embase databases,the Cumulative Index to Nursing and Allied Health Literature (CINAHL),and also in the ProQuest,PsycARTICLES,CBMdisc,China National Knowledge Infrastructure (CNKI),CQVIP database and Wanfang databases.All of the literature found was evaluated by 2 researchers according to predefined inclusion and exclusion criteria and the data were extracted and combined.Then meta-analysis was performed using version 5.3 of the RevMan software package.Results Eleven randomized and controlled trials involving 576 patients were included in the meta-analysis.Together,the data showed that swallowing training supplemented by neuromuscular electrical stimulation is significantly more effective than swallowing training alone in improving swallowing function.It reduces the risk of aspiration and improves quality of life.It does not,however,generally shorten the pharyngeal transmit time.Conclusions Swallowing training supplemented with neuromuscular electrical stimulation is a promising approach for treatment of post-stroke dysphagia and warrants further study.

Objective To select NRS to record and analyze influencing factors and management effects of pain for patients with upper limp fracture.Methods Totals of 164 patients with upper limp fracture had been chosen from February 2012 to February 2013, and all of them received PCIA combining with transfused flurbiprofen to relieve pain.We analyzed influencing factors of pain by Logistic regression analysis and recorded the maximum of pain score assessed by NRS at 24 h and 48 h after trauma and compared the pain score during break at 24 h, 48 h and 72 h after operation.Results The gender, age, length of fracture, position of fracture and fracture of AO type brought out different level of pain and those of pain had statistical difference ( P <0.05).The gender (female), age (beyond 60 years old), position of fracture (proximal humerus fracture) and fracture of C type were severe risks to cause pain (P <0.05).The pain scores of proximal humerus fracture, distal end of humerusfracture, radial fracture and ulnar fracture,which assessed by NRS, had statistical difference at 24 h and 48 h after fracture (F=81.756,84.288, respectively;P<0.05), while different position of fracture had high pain score at 24 h than 48 h (t=4.720,5.703,5.888, respectively;P<0.05).Under analgesia after operation at 24 h,48 h and 72 h, female patients had more effective pain control result than males (t=2.857,P<0.05).After 72hrs operation, there were ninety two cases satisfaction, fifty nine cases certain satisfaction and thirteen cases dissatisfaction for the result of pain control.Conclusions Because different gender, age, position of fracture and fracture type result in different level of pain, medical staff should provide reasonable pain management for fracture patient in order to enhance patient’ s satisfactory.

Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases, which as a group can degrade essentially all extracellular matrix components. The proteolytic property of the MMPs is important during wound healing to remove debris and facilitate cell migration. Targeting towards the decreased MMPs activities is a new treatment strategy for healing chronic wounds. Salvia miltiorrhiza is a popular Chinese herb that could promote chronic ulcers healing for topical use. Salvianolic acid B (Sal B) is the most abundant bioactive component in Salvia miltiorrhiza. The research was designed to explore the inhibitory effects of Sal B on MMP-1, MMP-2 and MMP-9 activities.