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

BACKGROUND: Leukocyte telomere length (LTL) shortening, a biomarker of telomere attrition, has been linked to multiple diseases. However, the relationship between LTL and digestive diseases remains uncertain. This study aimed to investigate the association between LTL and the risk of digestive diseases. METHODS: A cohort analysis of over 500,000 participants from the UK Biobank (UKB) between 2006 and 2021 was conducted to estimate the associations of LTL with more than 90 common digestive diseases. LTL was quantified using multiplex quantitative polymerase chain reaction, and cases of each disease were determined according to inpatient and primary care data. Multivariable Cox proportional hazards regression analysis was used to evaluate the associations of LTL with the risk of digestive diseases. Furthermore, such associations were also evaluated after stratification by sex and ethnicity. RESULTS: After a mean follow-up time of 11.8 years, over 20 International Classification of Diseases, 10th Revision ( ICD-10 ) codes were showed to be associated with telomere attrition. LTL shortening is associated with an increased risk of several digestive diseases, including gastroesophageal reflux disease (K21: hazard ratio [HR] = 1.30, 95% confidence interval [95% CI]: 1.19-1.42), esophageal ulcer (K221: HR = 1.81, 95% CI: 1.22-2.71), Barrett's esophagus (K227: HR = 1.58, 95% CI: 1.14-2.17), gastritis (K29: HR = 1.39, 95% CI: 1.26-1.52), duodenal ulcer (K26: HR = 1.55, 95% CI: 1.14-2.12), functional dyspepsia (K30X: HR = 1.36, 95% CI: 1.06-1.69), non-alcoholic fatty liver disease (NAFLD) (K760: HR = 1.39, 95% CI: 1.09-1.78), liver cirrhosis (K74: HR = 4.73, 95% CI: 3.27-6.85), cholangitis (K830: HR = 2.55, 95% CI: 1.30-5.00), and hernia (K43: HR = 1.50, 95% CI: 1.17-1.94; K44: HR = 1.29, 95% CI: 1.17-1.42). The risk of rectal polyps (K621: HR = 0.77, 95% CI: 0.63-0.92) decreased per unit shortening of LTL. CONCLUSIONS This study suggests that LTL shortening is associated with an increased risk of most digestive diseases except for rectal polyps. These findings may provide some clues for understanding the pathogenesis of digestive diseases.
Humans ; Male ; Female ; Middle Aged ; Cohort Studies ; Leukocytes/metabolism* ; Telomere/genetics* ; Proportional Hazards Models ; Adult ; Digestive System Diseases/genetics* ; Aged ; Risk Factors ; Telomere Shortening

The transition of cancer cells from epithelial state to mesenchymal state awarded hepatocellular carcinoma (HCC) stem cell properties and induced tumorigenicity, drug resistance, and high recurrence rate. Reversing the mesenchymal state to epithelial state by inducing mesenchymal-epithelial remodeling could inhibit the progression of HCC. Using high-throughput screening, chrysin was selected from natural products to reverse epithelial-mesenchymal transition (EMT) by selectively increasing CDH1 expression. The target identification suggested chrysin exerted its anti-HCC effect through covalently and specifically binding threonine 205 (Thr205) of alpha-enolase (ENO1). For the first time, we revealed that ENO1 bound β-catenin mRNA, and recruited YTHDF2 to identify the m6A modified β-catenin in the 3'-UTR region to degrade β-catenin mRNA. Eventually, the CDH1 gene expression was improved through the regulation of β-catenin mRNA. ENO1/β-catenin mRNA interaction might be a promising target for cellular plasticity reprogramming. Moreover, chrysin could mediate mesenchymal‒epithelial remodeling through increasing degradation of β-catenin mRNA by promoting the binding of ENO1 and β-catenin mRNA. To the best of our knowledge, chrysin is the first reported small molecule inducing β-catenin mRNA degradation through binding to ENO1. The water-soluble derivative of chrysin may be a natural product-derived lead compound for circumventing metastasis, recurrence, and drug resistance of HCC by mediating mesenchymal‒epithelial remodeling.

Objective To investigate the immediate therapeutic efficacy of Kuanxiong Aerosol on improving the angina pectoris in the patients complicated with intermediate coronary stenosis(ICS),and to observe its effect on resting full-cycle ratio(RFR),corrected TIMI(thrombolysis in myocardial infarction)frame count(CTFC)in angiography,and coronary serum inflammatory factors.Methods Sixty angina pectoris patients with ICS admitted to the Cardiovascular Department of Dade Road Hospital,Guangdong Provincial Hospital of Traditional Chinese Medicine from March 2023 to March 2024 were randomly divided into the trial group and the control group,with 30 patients in each group.The trial group was given four consecutive sprays of Kuanxiong Aerosol by sublingual spray,and the control group had no intervention but just was given the monitoring for 10 minutes.Before and after the intervention,the changes of coronary RFR,CTFC,Visual Analogue Scale(VAS)score of chest pain,and the serum levels of C-reactive protein(CRP),interleukin 6(IL-6)and lipoprotein-associated phospholipase A2(Lp-PLA2)in the two groups were observed.Moreover,the incidence of adverse reactions during the intervention in the two groups of patients was compared.Results(1)After the intervention,the coronary RFR value of the trial group was increased significantly compared with that before intervention(P<0.01),while the coronary RFR value of the control group was not increased significantly compared with that before intervention(P>0.05);the comparison between the two groups showed that the effect on increasing the coronary RFR value in the trial group was superior to that in the control group(P<0.05).(2)After intervention,the CTFC value of the trial group was significantly decreased compared with that before intervention(P<0.01),while the CTFC value of the control group was not significantly decreased compared with that before intervention(P>0.05);the intergroup comparison showed that the trial group tended to have a better effect on the decrease of CTFC value than the control group,but the difference being not statistically significant(P>0.05).(3)After the intervention,the chest pain VAS score of the trial group was significantly reduced compared with that before intervention(P<0.01),while the pre-and post-treatment changes of the score in the control group was not significant(P>0.05);the intergroup comparison showed that the decrease of the chest pain VAS score in the trial group was superior to that in the control group(P<0.01).In particular for immediate therapeutic efficacy,Kuanxiong Aerosol achieved the effective rate of 96.67%(29/30)for relieving chest pain 10 minutes after sublingual spraying,which was significantly superior to that of the control group[10.00%(3/30)],and the comparison between the two groups showed that the difference was statistically significant(P<0.001).(4)After the intervention,the Lp-LPA2 value of the trial group was decreased compared with that before intervention(P<0.05),while the CRP and IL-6 values of the trial group as well as the CRP,IL-6,and Lp-LPA2 values of the control group were all not significantly decreased compared with those before intervention(P>0.05).The intergroup comparison showed that the trial group's effect on the decrease of Lp-LPA2 value was significantly superior to that of the control group(P<0.05).(5)Before and after the intervention,no obvious changes of the general vital signs in the two groups were shown,no drug-related adverse occurred,either.Conclusion Kuanxiong Aerosol can immediately improve the coronary physiological function indicators of angina pectoris patients with ICS,increase the coronary flow rate,and inhibit inflammatory response of the coronary artery to some degree,thus to alleviate the symptoms of angina pectoris in patients with ICS.

Objective To analyze the clinical characteristics and prognosis of patients with spon-taneous coronary artery dissection(SCAD).Methods A retrospective analysis was conducted in 40 patients with acute myocardial infarction(AMI).All patients were diagnosed with SCAD during hos-pitalization through coronary angiography(CAG)or intravascular ultrasound(IVUS).The clinical characteristics,CAG or IVUS findings,and treatment regimens of the patients were analyzed,and their prognosis was assessed through follow-up.Results Among 40 SCAD patients,there were 11 males and 29 females,with a mean age of(53.04±9.15)years.Twelve patients had identified causative factors,and seven patients presented with chest pain as the initial symptom.CAG or IVUS results showed that a total of 69 SCAD lesions were detected in 40 patients,with 15 patients having a single lesion.The primary treatment approach for the patients was medical therapy.The median fol-low-up duration was 34 months(ranging 2 to 48 months),during which 5 major adverse cardiovascu-lar and cerebrovascular events(MACCE)occurred.The patients were divided into MACCE group(5 patients)and non-MACCE group(35 patients)based on occurrence of MACCE.The mean age and the incidence of regional wall motion abnormalities on echocardiography were higher in the MACCE group than in the non-MACCE group(P＜0.05).Conclusion SCAD has distinct imaging features on CAG,and IVUS can confirm the diagnosis.Most patients are treated with medical therapy and have a generally favorable prognosis.However,patients with older age or regional wall motion abnormali-ties on echocardiography have poorer prognosis.

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.

Food poisoning caused by Nassariidaes has occurred frequently in coastal areas of China, especially in summer and autumn. Nassariidaes poisoning can be manifested as lip and tongue paralysis, dizziness, headache, nausea and vomiting, arrhythmia and even respiratory failure. We admitted a case of respiratory failure caused by eating Nassariidaes. After timely respiratory support, hemoperfusion and other active treatment, the patient was recovered and was discharged. This paper summarized clinical characteristics and treatment of Nassariidaes poisoning, in order to provide reference for clinical diagnosis and treatment of similar cases.

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 understand the status and coping strategies of death anxiety among military nurses participating in emergency public health incident response, and to provide references for improving their coping abilities.Methods:A purposive sampling and snowball sampling method were used to select 15 nurses from multiple military hospitals who supported the emergency public health incident. One-on-one semi-structured interviews were conducted, and the Colaizzi's seven-step analysis method was used to analyze the interview data.Results:Four themes were identified: the occurrence of death anxiety at different time points; the presence of significant outbreaks of death anxiety; multiple factors that help military nurses alleviate death anxiety; and the intrinsic motivation and gains of military nurses participating in the response.Conclusions:It is crucial to monitor the occurrence and changes in death anxiety among nurses throughout the entire cycle of emergency public health incidents. Managers should focus on value guidance, leverage individual positive strengths to cope with death anxiety, enhance information and social support, reinforce training on infectious disease prevention and death education, and reduce the level of death anxiety among military nurses and improve their coping abilities.

Food poisoning caused by Nassariidaes has occurred frequently in coastal areas of China, especially in summer and autumn. Nassariidaes poisoning can be manifested as lip and tongue paralysis, dizziness, headache, nausea and vomiting, arrhythmia and even respiratory failure. We admitted a case of respiratory failure caused by eating Nassariidaes. After timely respiratory support, hemoperfusion and other active treatment, the patient was recovered and was discharged. This paper summarized clinical characteristics and treatment of Nassariidaes poisoning, in order to provide reference for clinical diagnosis and treatment of similar cases.