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 relationship between the expression of claudin 10(CLDN10)and chondroitin sulfate proteoglycan 4(CSPG4)of tissue and clinicopathologic characteristics and prognosis in non-small cell lung cancer(NSCLC).Methods A total of 136 NSCLC patients who underwent surgery in Taizhou People's Hospital,Nanjing Medical University from January 2017 to April 2018 were randomly selected as the study subjects,and these subjects were grouped into survival group(n=63)and death group(n=69)based on follow-up outcomes(survival or death).Specimens of cancer tissue and adjacent tissues excised during surgery were collected from 136 patients.Real-time fluorescence quantitative PCR(RT-qPCR)was applied to detect the expression levels of CLDN10 and CSPG4 in cancer tissue and adjacent tissues.Based on the average expression levels of CLDN10 and CSPG4 in cancer tissues of NSCLC patients,they were grouped into CLDN10 high expression group(n=66),CLDN10 low expression group(n=70)and CSPG4 high expression group(n=71),CSPG4 low expression group(n=65).Multivariate COX regression analysis was used to determine the prognostic factors of NSCLC patients.Kaplan-Meier survival curve was applied to analyze the relationship between the expression levels of CLDN10 and CSPG4 in NSCLC patients and their prognosis.Results The expression level of CLDN10(0.96±0.25)in NSCLC tissues was lower than that in adjacent tissue(1.73±0.42),and the expression level of CSPG4 in NSCLC tissues(1.80±0.46)was higher than that in adjacent tissues(1.04±0.27),with statistical significance(t=18.372,16.617,all P<0.05).Compared with the survival group,the proportion of low undifferentiated,lymph node metastasis and CSPG4 expression of cancer tissues in the death group were higher,and the CLDN10 expression level of cancer tissues in the death group was lower,with statistical significance(t/χ2=8.463,7.423,11.696,6.426,all P<0.05).The five-year survival rate of the high expression group of CLDN10(58.46%)was higher than that of the low expression group(37.31%),and the five-year survival rate of the low expression group of CSPG4(55.56%)was higher than that of the high expression group(40.58%),and the differences were statistically significant(χ2=7.848,4.018,all P<0.05).Multivariate COX analysis results showed that low expression of CLDN10,high expression of CSPG4,low differentiation degree,and lymph node metastasis were all risk factors affecting the prognosis of NSCLC patients(HR=1.362,1.368,1.335,1.314,all P<0.05).Conclusion The expression level of CLDN10 was low and CSPG4 was high in cancer tissues of NSCLC patients,which was closely related to the development and prognosis of NSCLC.

Objective To compare the efficacy of percutaneous transforaminal approach and translaminar approach in the treatment of L5/S1 disc herniation(LDH)under endoscopic discectomy.Methods Adopted a retro-spective case-control study,and selected 62 cases of patients with L5/S1 LDH who were treated with percutaneous endoscopic surgery in the spine surgery department of our hospital from June 2020 to December 2022,and the transforaminal approach was used.(TELD)in 32 cases(TELD group),and interlaminar approach(IELD)in 30 cases(IELD group).The observation indicators included intraoperative fluoroscopy times,operation time,hospitaliza-tion days,hospitalization expenses,leg pain VAS score,ODI score,modified MacNab curative effect evaluation and complications.Results All 62 patients successfully completed the operation and follow-up,and no serious complications occurred.There were statistically significant differences in operation time,fluoroscopy times,and hospitalization expenses between the two groups(P<0.001),but there was no significant difference in hospitaliza-tion days between the two groups(P>0.05).The lower extremity VAS scores at the last follow-up and the last follow-up were significantly improved compared with those before operation(P<0.001),and the ODI scores of the two groups were significantly improved at 2 days,1 month and at the last follow-up(P<0.001).At the same time point,there was no statistical difference(P>0.05);there was no significant difference in the excellent and good rate of surgery between the two groups(P>0.05).11 patients with high iliac crest in the TELD group successfully completed the surgery.Conclusions Both the endoscopic surgery through the intervertebral foramen and the inter-laminar approach can achieve satisfactory results in the treatment of L5/S1 LDH.However,local anesthesia through the intervertebral foramen approach reduces hospitalization costs,and patients with high iliac crest can successfully complete the surgery by selecting a suitable puncture path.The translaminar approach has fewer fluoroscopy times and shorter surgical time,but there is a higher risk of dura mater and nerve damage,which requires careful opera-tion for beginners.

Objective:To evaluate the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on tourniquet-induced hypertension (TIH) in the patients undergoing anterior cruciate ligament reconstruction.Methods:Seventy-four patients of either sex, aged 18-60 yr, of American Society of Anesthesiologists Physical Status classification I or II, with body mass index of 18-30 kg/m 2, undergoing elective anterior cruciate ligament reconstruction under general anesthesia combined with preoperative femoral nerve block, were divided into 2 groups ( n=37 each) using a random number table method: sham stimulation group (group SS) and group taVNS. Group SS received stimulation on the ear lobe and the tail of the helix of the left ear. Group taVNS received stimulation on the cymba concha and the earlobe of the left ear. Both groups received stimulation from 1 h before induction of anesthesia until the end of the procedure (frequency of 30 Hz, pulse width of 300 μs, and amplitude of the strongest current that could be tolerated by the patient in the absence of pain). The tourniquet inflation pressure was 280 mmHg, with an inflation time of 60-90 min. Systolic blood pressure, diastolic blood pressure and heart rate were recorded before tourniquet inflation to assess the development of intraoperative TIH. The consumption of intraoperative propofol, remifentanil, nitroglycerin, esmolol, norepinephrine and atropine was recorded, and the occurrence of postoperative nausea and vomiting, skin itching and headache and dizziness was also recorded. Results:Compared with group SS, the incidence of TIH and the number of patients used nitroglycerin were significantly reduced ( P<0.05), and no significant changes were found in the other parameters in group taVNS ( P>0.05). Conclusions:taVNS can decrease the occurrence of TIH in the patients undergoing anterior cruciate ligament reconstruction.

Objective:To analyze the iodine nutrition status of children aged 8 to 10 years in Zhejiang Province from 2016 to 2021.Methods:A multi-stage stratified sampling method was used to select non-residential children aged 8 to 10 years from 90 counties in Zhejiang Province. A total of 114 103 children were included in the study from 2016 to 2021. Direct titration method and arsenic-cerium catalytic spectrophotometry were used to detect salt iodine content and urinary iodine level, respectively, to evaluate the iodine nutritional status of children. Ultrasound was used to detect thyroid volume and analyze the current prevalence of goiter in school-age children.Results:The age of 114 103 children was (9.04 ± 0.81) years old, with 50.0% of (57 083) boys. The median of iodine content M ( Q1, Q3) in children's household salt was 23.00 (19.80, 25.20) mg/kg, including 17 242 non-iodized salt, 6 173 unqualified iodized salt, and 90 688 qualified iodized salt. The coverage rate of iodized salt was 84.89%, and the coverage rate of qualified iodized salt was 79.48%. The proportion of non-iodized salt increased from 11.85% in 2016 to 16.04% in 2021 ( χ 2trend=111.427, P<0.001). The median of urinary iodine concentration M ( Q1, Q3) in children was 182.50 (121.00, 261.00) μg/L, among which the proportions of iodine deficiency, iodine suitability, iodine over suitability, and iodine excess were 17.25% (19 686 cases), 39.21% (44 745 cases), 26.85% (30 638 cases), and 16.68% (19 034 cases), respectively. The median of urinary iodine concentration in children in inland areas [ M ( Q1, Q3): 190.90 (128.80, 269.00) μg/L] was significantly higher than that in children in coastal areas [ M ( Q1, Q3): 173.00 (113.00, 250.30) μg/L] ( P<0.001). From 2016 to 2021, a total of 39 134 ultrasound examinations were conducted, and 1 229 cases of thyroid enlargement were detected. The goiter rate was 3.14% (95% CI: 2.97%-3.32%). The incidence of goiter in children in coastal areas [3.45% (95% CI: 3.19%-3.72%), 641/18 604] was higher than that in children in inland areas [2.86% (95% CI: 2.64%-3.10%), 588/20 530] ( P=0.001). Conclusion:From 2016 to 2021, the iodine nutrition level of children aged 8-10 years in Zhejiang Province is generally suitable, and the rate of goiter in children meets the limit of iodine deficiency disease elimination standards.

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 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.