This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

Objective:To investigate the efficacy and safety of daratumumab (Dara) - combination regimens for newly diagnosed multiple myeloma (NDMM).Methods:A retrospective case series study was conducted. The clinical data of 34 patients with NDMM receiving treatment regimen including Dara from Qilu Hospital of Shandong University, Yantai Yuhuangding Hospital, Huangdao Branch of Affiliated Hospital of Qingdao University and Taian City Central Hospital between April 2020 and March 2022 were retrospectively collected. The efficacy, survival and adverse reactions of patients were analyzed. Cox proportional risk model was used to analyze the factors affecting overall survival (OS) and minimal residual disease (MRD) turning negative.Results:Among 34 patients with NDMM, there were 19 males and 15 females, with 21 cases aged < 65 years and 13 cases aged ≥65 years. The median follow-up duration [ M ( Q1, Q3)] was 22 months (19 months, 26 months), the median of Dara treatment cycles was 7 (5, 11), and the overall response rate (ORR) reached 97.1% (33/34). There were statistically significant differences in the optimal efficacy of patients stratified by receiving hematopoietic stem cell transplantation or not and receiving different treatment cycles (all P ≤ 0.05), while there were no statistically significant differences in patients stratified by other clinical features (all P > 0.05). The 1-year progression-free survival rate was 79.4% and the 1-year OS rate was 94.1%. Multivariate Cox regression analysis showed that the cycle number of treatment regimens containing Dara was an independent influencing factor of MRD turning negative (6 cycles vs. 2 cycles, HR = 0.267, 95% CI: 0.076-0.935, P = 0.039); age ≥ 65 years was an independent risk factor for OS ( HR = 35.313, 95% CI: 1.709-729.669, P = 0.021). The incidence of hematological adverse reactions grade 3 or above was 20.6% (7/34), and the non-hematological adverse reactions primarily included infection [44.1% (15/34)] and edema of extremity and trunk [41.2% (14/34)]. Conclusions:The Dara-based regimens for NDMM exhibit a high ORR. The remission depth accelerated with the increasing number of treatment cycle, and the adverse reactions are mild.

Objective To illuminate the benefit finding experience of maintenance hemodialysis patients,and to provide a reference for promoting their mental health.Methods From March to May 2023,the purposive sampling was used to select 13 maintenance hemodialysis patients in a tertiary hospital in Shanghai for semi-structured interviews.The data were organized with the help of Nvivo software,and the Colaizzi's seven-step method was used to analyze the data.Results 3 themes were extracted:①the search of meaning,including approved hemodialysis,the desire to live;②gaining a sense of mastery,including adjusting self-psychology,developing healthy living habits,and learning hemodialysis related behavior management;(3)self-enhancement,including excavating external resources and affirming self-worth.Conclusion Maintenance hemodialysis patients have benefit finding experience in many aspects.Medical staff can guide patients to carry out positive psychological construction by strengthening disease knowledge education,building a psychological mutual assistance platform,forming a multidisciplinary nursing team,excavate and provide effective social support resources,and cultivate patients'self-health management,so as to improve the level and ability of benefit finding of patients,experience positive incentives,promote physical and mental health,and improve the quality of life of hemodialysis patients.

Objective:To explore the clinical application of preimplantation genetic testing for monogenic disorders (PGT-M) in an unique case with Spinal muscular atrophy (SMA) type 2+ 0.Methods:A special SMA family presented at the Third Affiliated Hospital of Guangzhou Medical University on October 19, 2020 was selected as the study subject. Multiple ligation-dependent probe amplification (MLPA) and molecular tagging linkage analysis were carried out to identify the SMN1 genotype of the couple and their fetus. Subsequently, next-generation sequencing (NGS), molecular tagging linkage analysis, and chromosomal microarray analysis were employed to determine the haplotypes and validate the result of PGT-M on the 11 embryos derived for the couple. Results:The female partner was identified as a carrier of the rare SMN1[2+ 0] variant, and prenatal diagnosis confirmed the fetus to be affected by SMA. Ultimately, PGT-M has successfully selected four embryos free from the pathogenic SMN1 variants and X chromosome deletion. Conclusion:PGT-M can effectively prevent the transmission of rare genetic variants such as the SMA 2+ 0 subtype in the families. Above finding has provided guidance for genetic counseling and family planning for the couple.

Humans ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Multiprotein Complexes/metabolism* ; Neural Stem Cells/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rapamycin-Insensitive Companion of mTOR Protein/metabolism* ; TOR Serine-Threonine Kinases/metabolism*

Animals ; Chloroquine/pharmacology* ; Longevity ; Rats

Objective:To construct a perioperative nursing planning for patients with esophageal cancer based on the concept of enhanced recovery after surgery (ERAS) , so as to provide a basis for the development of ERAS nursing for patients with esophageal cancer during perioperative period.Methods:From November 2019 to September 2020, a perioperative ERAS nursing planning for patients with esophageal cancer was constructed through literature retrieval, field observation, Delphi expert consultation, and analytic hierarchy process.Results:A total of two rounds of expert consultations were conducted. The valid recovery rates of the questionnaire were 95.24% (20/21) and 100.00% (20/20) , and the expert authority coefficients were 0.89 and 0.93. The Kendall harmony coefficients were 0.25 and 0.34 ( P<0.01) . The perioperative enhanced recovery nursing planning for patients with esophageal cancer included 5 first-level indicators, 17 second-level indicators and 49 third-level indicators. Conclusions:The perioperative enhanced recovery nursing planning for patients with esophageal cancer is scientific and reliable, and can effectively standardize and guide the development of clinical nursing work.

Objective:To improve the standardized training effects of the first year graduate new nurses by the mini clinical evaluation exercise (Mini-CEX) .Methods:By cluster sampling, a total of 91 new nurses hired in 2017 of Xinqiao Hospital Affiliated to Army Medical University were in control group; and 120 new nurses hired in 2018 were in experimental group. Control group carried out routine training method. On the basis of that, experimental group implemented the Mini-CEX based clinical nursing core competence training and operational skill training once a month after changing routine teaching rounds and operational training, lasting 12 times. The scores of Mini-CEX for the first and twelfth time of experimental group were compared by paired sample t-test, the theoretical achievements and skill performances of new nurses between two groups were compared by independent sample t-test. Results:The scores of Mini-CEX of clinical nursing core competence training and operational skill training in experimental group for the twelfth time were (6.27±0.46) and (6.73±1.10) respectively, higher than those for the first time with statistical differences ( t=-8.48, -7.64; P<0.01) . Among new nurses in standardized training of the first year, the theoretical achievements and skill performances of department in experimental group were (87.70±11.32) and (92.90±8.22) , those of hospital were (85.50±11.83) and (89.67±8.99) respectively, higher than those in control group with statistical differences ( t=-2.71, -2.09, -2.24, -3.22; P<0.05) . Conclusions:Mini-CEX has significant effects in training for the first year among new nurses .

Objective To investigate the compound rhubarb gallnut gargle combined periodontal treatment effect on inflammatory factors in patients with chronic periodontitis.Methods 76 patients with chronic periodontitis from June 2014 to May 2015 in our hospital were selected and randomly divided into two groups,given periodontal treatment as control group,compound rhubarb gallnut gargle combined periodontal treatment as observation group,38 cases in each group,two groups were detected after treatment of gingival crevicular fluid levels of inflammation.Results After treatment,the gingival crevicular fluid of tumor necrosis factor-α(alpha TNF-α),high sensitive C-reactive protein(hs-CRP)and interleukin three(IL-6,IL-1 beta and IL-8)of two groups were significantly lower than those before treatment,and the observation group of inflammatory cytokine levels were significantly lower than the control group,the difference was statistically significant(P<0.05).The gingival index(GI)and gingival bleeding index(SBI)of the two groups were were lower than those before treatment,and the GI and SBI in the observation group were lower than those in the control group,the difference was statistically significant(P<0.05).Conclusion In the treatment of chronic periodontitis,compound rhubarb gallnut gargle combined periodontal basic treatment effect,can significantly reduce the level of inflammation.