This paper aimed to explore the effects of Duzhong Decoction(DZD)-containing serum on the proliferation and osteoblast differentiation of MC3T3-E1 cells through L-type voltage-gated calcium channels(L-VGCCs). L-VGCCs inhibitors, nifedipine and verapamil, were used to block L-VGCCs in osteoblasts. MC3T3-E1 cells were divided into a control group, a low-dose DZD-containing serum(L-DZD) group, a medium-dose DZD-containing serum(M-DZD) group, a high-dose DZD-containing serum(H-DZD) group, a nifedipine group, a H-DZD + nifedipine group, verapamil group, and a H-DZD + verapamil group. The CCK-8 method was used for cell proliferation analysis, alkaline phosphatase(ALP) assay kits for intracellular ALP activity measurement, Western blot for protein expression level in cells, real-time fluorescence quantitative PCR technology for intracellular mRNA expression level determination, fluorescence spectrophotometer for free Ca~(2+) concentration determination in osteoblasts, and alizarin red staining(ARS) for mineralized nodule formation in osteoblasts. The experimental results show that compared to the control group, DZD groups can promote MC3T3-E1 cell proliferation, ALP activity, and mineralized nodule formation, increase intracellular Ca~(2+) concentrations, and upregulate the protein expression of bone morphogenetic protein 2(BMP2), collagen Ⅰ(COL1), α2 subunit protein of L-VGCCs(L-VGCCα2), and the mRNA expression of Runt-related transcription factor 2(RUNX2), and BMP2. After blocking L-VGCCs with nifedipine and verapamil, the intervention effects of DZD-containing serum were inhibited to varying degrees. Both nifedipine and verapamil could inhibit ALP activity, reduce mineralized nodule areas, and downregulate the expression of bone formation-related proteins. Moreover, the effects of DZD-containing serum on increasing MC3T3-E1 cell proliferation, osteoblast differentiation, and Ca~(2+) concentrations, upregulating the mRNA expression of osteoprotegerin(OPG) and protein expression of phosphorylated protein kinase B(p-Akt) and phosphorylated forkhead box protein O1(p-FOXO1), and upregulating phosphatase and tensin homolog(PTEN) expression were reversed by nifedipine. The results indicate that DZD-containing serum can increase the Ca~(2+) concentration in MC3T3-E1 cells to promote bone formation, which may be mediated by L-VGCCs and the PTEN/Akt/FoxO1 signaling pathway, providing a new perspective on the mechanism of DZD in treating osteoporosis.
Animals ; Osteoblasts/metabolism* ; Cell Proliferation/drug effects* ; Cell Differentiation/drug effects* ; Mice ; Drugs, Chinese Herbal/pharmacology* ; Calcium Channels, L-Type/genetics* ; Alkaline Phosphatase/genetics* ; Serum/chemistry* ; Cell Line ; Osteogenesis/drug effects* ; Bone Morphogenetic Protein 2/genetics*

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of primary intracranial DICER1-mutant sarcoma in order to better understand this tumor type.Methods:A retrospective analysis was conducted on 7 cases of primary intracranial DICER1-mutant sarcoma diagnosed in the Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China between 2021 and 2023 using next-generation sequencing. At the same time, 10 gliosarcomas, 4 intracranial FET::CREB fusion-positive mesenchymal tumors, 4 malignant meningiomas, 3 malignant solitary fibrous tumors, 3 malignant peripheral nerve sheath tumors, 3 synovial sarcomas and 3 rhabdomyosarcomas (total 30 cases) were selected as control.Results:Among the 7 patients with primary intracranial DICER1-mutant sarcoma, 6 were male and 1 was female, aged 10-32 years (median, 23 years). The tissue morphology was predominantly spindle or pleomorphic sarcoma-like, with 6 cases exhibiting eosinophilic globules, and 3 cases showing rhabdomyoblastic or rhabdomyosarcoma-like cell differentiation. Immunohistochemistry revealed focal desmin expression in 3 cases (3/7), ATRX loss in 3 cases (3/7), and p53 mutant pattern in 4 cases (4/7). Additionally, 4 cases (4/7) showed focal or diffuse SALL4 expression, whereas the control cases (30 cases) did not exhibit SALL4 protein expression, suggesting that SALL4 may possess certain auxiliary diagnostic value. Next-generation sequencing confirmed that all 7 cases of primary intracranial DICER1-mutant sarcoma harbored mutations in the DICER1 gene, with 5 cases having the mutation site at p.E1813D. Until May 2024, all 7 patients were alive.Conclusions:Primary intracranial DICER1-mutant sarcoma is a rare tumor. Understanding its morphological characteristics, immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.

BackgroundCompared with absenteeism， health-related productivity loss has a long-lasting negative effect， and poses a greater harm and loss. The health-related productivity loss is mediated by self-efficacy， and perceived social support has been shown to have an impact on health-related productivity loss， whereas the interaction mechanism among the three remains unclear. ObjectiveTo investigate the status of perceived social support， occupational coping self-efficacy and health-related productivity loss among ICU nurses， and to test the mediation role of perceived social support in the relationship between occupational coping self-efficacy and health-related productivity loss. MethodsFrom September to November， 2021， purposive sampling technique was adopted to select 468 ICU nurses in 8 tertiary hospitals in Sichuan Province. Subjects were assessed using self-made general information questionnaire， Perceived Social Support Scale （PSSS）， Occupational Coping Self Efficacy Scale for Nurses （OCSE-N） and Stanford Presenteeism Scale-6 （SPS-6）. Pearson correlation analysis was used to examine the correlation among variables. Amos 24.0 was utilized to test the mediation role of perceived social support in the relationship between occupational coping self-efficacy and health-related productivity loss. ResultsA total of 415 ICU nurses completed the valid questionnaire survey. ICU nurses scored （63.13±11.62） on PSSS， （22.24±6.15） on OCSE-N， and （16.83±4.24） on SPS-6. Health-related productivity loss was detected in 279 ICU nurses （67.23%）. Correlation analysis denoted that PSSS total score was positively correlated with OCSE-N total score （r=0.348， P<0.05）， and negatively correlated with SPS-6 total score （r=-0.274， P<0.05）. OCSE-N total score was negatively correlated with SPS-6 total score （r=-0.421， P<0.05）. The direct effect value of occupational coping self-efficacy on health-related productivity loss was -0.401， and perceived social support showed a mediation role in the relationship between occupational coping self-efficacy and health-related productivity loss （the indirect effect value was -0.052， accounting for 11.48% of the total effect）. ConclusionThe occupational coping self-efficacy of ICU nurses may affect the health-related productivity loss through the action path of perceived social support.［Funded by Scientific Research Project of Sichuan Provincial Health Commission （number， 19PJ042）］

Aim To investigate the synergistic sensiti-zation effect of saikosaponin D(SSD)combined with temozolomide(TMZ)on glioblastoma cells(GBM)and its molecular mechanism.Methods The sensitiv-ity of RG-2,U251 and LN-428 GBM cell lines to SSD and TMZ was analyzed by CCK-8 method combined with HE staining,and the optimal compatible concen-tration was screened.The effect of HE staining com-bined with Hoechst fluorescence staining on the prolif-eration of GBM cell line was detected by clonal forma-tion experiment.The autophagosome formation of GBM cells was observed by monodansylcadaverine(MDC)staining.The expression and distribution of endoplas-mic reticulum stress-related factors and apoptosis and autophagy proteins were detected by Western blot and ICC.Results The sensitivity order of GBM cells to TMZ was RG-2＞U251＞LN-428.The results of com-bined administration showed the synergistic inhibitory effect of SSD combined with TMZ on proliferation of GBM cell lines,which was confirmed by cell cloning formation experiment.Compared with the TMZ group,Hoechst fluorescence staining showed a significant in-crease in the number of nuclear bright staining in the combined administration group.MDC fluorescence staining showed that there were more dense green parti-cles in the cytoplasm of SSD/TMZ plus group than that of TMZ group.Western blot results showed that com-pared with TMZ group,the expression of ER stress markers GRP78,CHOP,p-PERK and ATF6 signifi-cantly increased in SSD/TMZ group(P＜0.05).The expressions of apoptosis proteins caspase-12,caspase-9,caspase-3,cleaved caspase-3,Bax and autophagy proteins LC3 and Beclin-1 significantly increased(P＜0.05),which were verified by ICC test.Conclusions SSD can cooperate with TMZ to inhibit the prolifera-tion of GBM cells and induce apoptosis and autophagy,and enhance the sensitivity of GBM cells to TMZ by ac-tivating endoplasmic reticulum stress pathway.

Objective To investigate the clinical efficacy of a compound oral sulfate solution for preoperative bowel cleansing in colonic polyp patients.Methods Patients who underwent colonoscopic polypectomy were divided into control group and treatment group according to cohort method methods.Patients in the control group were given compound polyethylene glycol electrolyte powder.They started taking it 4-6 hours before colonoscopy and completed the 4 liters of solution within 2 hours.Patients in the treatment group were given a compound oral sulfate solution.They took 1.5 liters of the solution the evening before surgery and repeated the same dosage on the day of the operation.Intestinal cleanliness was assessed using the Boston bowel preparation scale(BBPS),bowel preparation compliance,drug tolerance,patient satisfaction,and incidence of adverse drug reactions were compared between the two groups.Results Control group and treatment group each consisted of 40 cases.The total BBPS scores for the control group and treatment group were(6.68±1.19)and(7.43±1.23)points,respectively.This difference was statistically significant(P＜0.01).Medication compliance rates in the control group and treatment group were 70.00％(28 cases/40 cases)and 95.00％(38 cases/40 cases),respectively;movement compliance rates were 67.50％(27 cases/40 cases)and 97.50％(39 cases/40 cases)in the two groups,while medication tolerance rates were 67.50％(27 cases/40 cases)and 90.00％(36 cases/40 cases);patient satisfaction with bowel preparation were(1.89±0.75)and(2.42±0.43)points for the control and treatment groups,respectively;statistically significant differences were found between the control and treatment groups in all the above indicators(P＜0.05,P＜0.01,P＜0.001).The main adverse drug reactions in the control and treatment groups were nausea and vomiting,with occurrence rates of 10.00％(4 cases/40 cases)and 5.00％(2 cases/40 cases),respectively.The comparison of adverse drug reactions occurrence rate between the two groups showed no statistically significant difference(P＞0.05).Conclusion Taking compound oral sulfate solution for intestinal preparation,the intestinal cleaning effect is better than that of compound polyethylene glycol electrolyte powder,and the patient's compliance and drug tolerance are higher,and the patient's satisfaction can be effectively improved.

italic>Ardisia crispa (Thunb.) A. DC. is a traditional Miao medicinal herb with significant therapeutic effects in the treatment of sore throat, tonsillitis, edema of nephritis and bruising and rheumatism, etc. Ardisia crispa var. amplifolia and Ardisia crispa var. dielsii are varieties of A. crispa. A. crispa var. amplifolia and A. crispa var. dielsii are controversial in terms of species evolutionary relationships and taxonomic identification. In this study, we sequenced the whole genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii chloroplasts using Illumina platform, assembled, annotated and characterized them, compared the structural features and degree of variation among chloroplast genomes using bioinformatics methods, and also downloaded constructing phylogenetic trees to analyze the phylogenetic relationships of chloroplasts in Primulaceae and Myrsinaceae using whole genome sequence information. The results showed that the complete chloroplast genome sequences of A. crispa var. amplifolia and A. crispa var. dielsii were 156 749 bp and 156 748 bp in length, with 132 genes annotated, including 87 protein-coding genes; the codon preference of A/U was greater than that of G/C; The differences in the coding regions of rps15 and rpoB genes in the comparative genome analysis can be used as loci for molecular identification of the two species; the differences in the coding regions of ycf1, ycf2, rpoC1, ycf3, petD and rpl16 genes in the chloroplast genome compared with those of the same genus can be used as loci for identification of the genus. In the phylogenetic results, A. crispa var. amplifolia and A. crispa var. dielsii were clustered together with 100% support, indicating that they are closely related. In this research, we analyzed the chloroplast genome structure and phylogenetic relationships of A. crispa var. amplifolia and A. crispa var. dielsii, providing an important theoretical basis for their molecular identification, genetic variation, breeding and phylogenetic analysis.

Objective:To investigate the feasibility of simultaneous arteriovenous enhancement of neck CT with two-stage injection of contrast agent and its effect on image quality and radiation dose.Methods:A total of 30 patients undergoing neck CT enhancement scan due to space-occupying lesions in Beijing Tongren Hospital, Capital Medical University from February to April 2022 were prospectively included as the experimental group. The neck CT enhancement scan was performed with two-stage injection of contrast agent and arteriovenous simultaneous enhancement. The dosage of contrast agent was calculated according to the patient′s body weight, and the method of two-stage injection was adopted. The dosage of contrast agent in the first stage was 0.7 ml/kg, with normal saline in the middle stage, and the second stage (began at 35 s) was 0.3 ml/kg. A total of 30 patients with gender and age matching with the experimental group from December 2021 to January 2022 were retrospectively collected as the control group. The control group was treated with the traditional arterial phase and venous phase scanning method with the dosage of 1.0 ml/kg contrast agent. The arterial phase was scanned at the 30 s and the venous phase was scanned at the 60 s. The CT values of bilateral carotid arteries and jugular veins in the experimental group were measured, the CT values of bilateral carotid arteries in the arterial phase were measured in the control group, and the CT values of bilateral carotid arteries and jugular veins in the venous phase were measured. Carotid artery enhancement score was performed for images of experimental group and control group in arterial and venous phase, and jugular vein and lesion enhancement score was performed for images of experimental group and control group in venous phase. The effective dose was calculated for both groups. The difference of carotid artery CT values between images was compared by one-way analysis of variance, and LSD method was used for pairwise comparison. The CT values of jugular vein were compared using independent sample t test. Kruskal-Wallis test was used to compare carotid artery enhancement scores, and Nemenyi method was used for pairwise comparison. Jugular vein and lesion enhancement scores and effective dose were compared by Mann-Whitney U test. Results:The CT value of carotid artery of experimental group [left (276±24) HU, right (273±25) HU] was lower than that of control group in arterial phase [left (329±33) HU, right (327±32) HU], and higher than that in the venous phase [left (147±15) HU, right (148±16) HU]. All the differences were statistically significant ( P<0.001). The CT value of jugular vein of experimental group [left (206±18) HU, right (203±19)] was higher than that of control group in the venous phase [left (154±15) HU, right (151±15)], the difference was statistically significant ( t=11.88, 11.76, both P<0.001). There was no significant difference in carotid artery enhancement score between experimental group and control group in arterial phase ( P=0.624), but the carotid artery enhancement score of the experimental group was higher than that of the control group in the venous phase, and the difference was statistically significant ( P<0.001). The scores of jugular vein and lesion enhancement in experimental group were higher than those of control group in venous phase, and the difference was statistically significant ( Z=5.01, P<0.001). The effective dose of the experimental group [2.41(2.04, 2.72) mSv] was decreased by 52.2% compared with the control group [5.04(4.18, 5.44) mSv], and the difference was statistically significant ( Z=-6.24, P<0.001). Conclusions:The neck CT enhanced scan with two-stage injection of contrast agent and arteriovenous simultaneous enhancement method can obtain comprehensive images of arterial and venous phases, and realize simultaneous enhancement of carotid artery, jugular vein and lesions, and reduce radiation dose.

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Objective: To summarize the clinical characteristics of patients with skip metastasis at esophageal resection margin during radical gastrectomy. Methods: This is a descriptive study of case series. Relevant data from 2006 to 2022 were collected from two major gastric cancer consultation and treatment centers: Nanjing Drum Tower Hospital and Jinling Hospital.Characteristics, surgical approach, number of dissected lymph nodes, immunohistochemical staining, and pathological staging were summarized and analyzed. The distribution of residual tumor cells at the esophageal margins was further analyzed at the cellular and tissue levels. Skip metastasis at the esophageal resection margin was defined as a negative esophageal margin with a positive margin in the cephalad donut. Results: Thirty (0.33%, 30/8972) eligible patients, 24 (80.0%) of whom were male, were identified in the two centers. The mean age was 63.9±11.0 years. Seventeen (56.7%) of these patients had papillary or tubular adenocarcinomas, including 13 (43.3%) poorly- and four (13.3%) moderately-differentiated tumors; four (13.3%) had signet-ring cell carcinomas; four (13.3%) mucinous adenocarcinomas; three (10.0%) mixed adenocarcinomas, including two with poorly-differentiated tubular adenocarcinomas mixed with signet-ring cell carcinoma and mucinous adenocarcinoma; and one had a poorly differentiated tubular adenocarcinoma mixed with signet-ring cell carcinoma. Two patients (6.7%) had other types of cancer, namely adenosquamous carcinoma in one patient and undifferentiated carcinoma in the other one. The predominant tumor sites were the lesser curvature (n=26, 86.7%) and the cardia (n=24, 80.0%). The mean tumor diameter was 6.6 cm, mean distance between tumor and esophageal resection margin was 1.5 cm, and proportions of tumor invasion into the dentate line, nerves, and vessels were 80.0% (24/30), 86.7%(26/30), and 93.3% (28/30), respectively. The mean number of lymph nodes resected was 20.4±8.9. The pathological stage was mainly T4 (n=18, 60.0%) and N3 (n=21, 70.0%), the median Ki67 was 52.7%, and the rates of positivity for HER2, EGFR, VEGFR, E-cadherin and PD-L1 were 40.0% (12/30), 46.7% (14/30), 80.0% (24/30), 86.7% (26/30) and 16.7% (5/30), respectively. At the cellular level, cancer cells were mainly distributed in small focal areas, as cell masses, or as tumor thrombi; large numbers of widely distributed atypic cells were seldom observed. At the tissue level, cancer cells were located in the mucosal layer in seven patients (23.3%), in the submucosal layer in 18 (60.0%), and in the muscular layer in five (16.7%); no cancer cells were identified in the outer membrane. Five of the seven tumors were located in the lamina propria, two in the muscularis mucosae, and none in the mucosal epithelium. Conclusion: Patients with skip metastasis at the esophageal resection margin at radical gastrectomy have unfavorable tumor biology and a high proliferation index, are at a late pathological stage, and the residual cancer is mostly located in the submucosa.
Humans ; Male ; Middle Aged ; Aged ; Female ; Margins of Excision ; Adenocarcinoma/pathology* ; Carcinoma, Signet Ring Cell/pathology* ; Lymph Nodes/pathology* ; Adenocarcinoma, Mucinous/pathology* ; Stomach Neoplasms/pathology* ; Gastrectomy ; Neoplasm Staging ; Retrospective Studies