Objective:To investigate the efficacy and safety of daratumumab based regimens in relapse and/or refractory multiple myeloma(RRMM)in the real world,as well as the impact of daratumumab on stem cell collection and engraftment.Methods:The clinical data of patients with RRMM who received daratumumab in hematology department of the First Affiliated Hospital of Xiamen University from February 2019 to March 2023 and had evaluable efficacy were retrospective analysis.Results:All 43 RRMM patients were treated with daratumumab-based combination regimens,including Dd,DVd,DRd,Dkd,DId,and Dara-DECP.With median follow-up time 10.1(2.1-36.6)months,the best overall response rate(ORR)was 74.4％and a best complete response rate(CR)was 25.6％.1-year overall survival rate(OS)was 84.5％.The most common severe hematologic adverse events(Grade＞3)are 3/4 grade leukopenia(18.6％),and the most common severe non-hematologic adverse events were infusion-related reactions(IRRs,20.9％)and infections(7.0％).Multivariate prognostic analysis showed that extramedullary infiltration was an independent adverse prognostic factor affecting OS(P=0.004).The use of daratumumab has no effect on stem cell collection,or engraftment.Conclusion:Daratumumab is safe and effective in RRMM.

Objective:In order to construct a multisectoral cooperation evaluation index system for chronic disease prevention and control in the Healthy China strategy,so as to provide a reference for the evaluation and improvement of multisectoral cooperation work.Methods:The initial indicator system was constructed based on D'Amour's cooperative structure model.Fifteen public health experts were selected to refine the evaluation indicators through two rounds of expert consultation using the Delphi method.Then weights of indicators were assigned according to AHP.Results:Experts'positive coefficient,level of authority and coordination of opinions were confirmed.The finalized evaluation index system for multisectoral cooperation in chronic disease prevention and control contains 5 first-level indicators,12 second-level indicators and 34 third-level indicators.According to the weight,the indicators in first level were Shared Goals and Vision(0.222 8),Internalization(0.158 7),Formalization(0.252 3),Governance(0.154 5)and Cooperation effects(0.211 8).Conclusions:The evaluation index system applicable to multisectoral cooperation in the prevention and control of chronic diseases in counties(cities/districts)is preliminarily established,which is highly scientific and operable,and lays the foundation for the next step of application and promotion.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.

The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aβ_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aβ_(25-35), 200 μmol·L~(-1), 0.15 μL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aβ_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aβ_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.
Mice ; Animals ; Male ; Semen/metabolism* ; Gastrointestinal Microbiome ; Network Pharmacology ; Linoleic Acid ; Molecular Docking Simulation ; Alzheimer Disease/genetics* ; Brain Injuries

Objective:To investigate the awareness of diabetes knowledge among the health examination population and its influencing factors.Methods:A cross-sectional study. From september to november 2022, the subjects of six health examination centers located in six different cities (Beijing, Shanghai, Tianjin, Chongqing, Xiamen, Hangzhou) in China were investigated in the form of questionnaires to investigate the awareness of diabetes core information and the level of trust to different information sources of diabetes knowledge. According to the questionnaire results, the subjects were divided into a high awareness group of diabetes core information and a low awareness group. Logistic regression was used to analyze the influencing factors of diabetes core information awareness; the t-test was used to compare the trust degree of the two groups to different information sources. Results:A total of 9 315 people were included in the six centers, including 4 932 men (52.90%) with an average age of (39.36±12.64) years and 4 383 women (47.10%) with a mean age of (37.47±11.85) years. Only 36% of the people had high awareness of diabetes core information; variables such as gender, age, education level, physical examination frequency in the past three years, package price of this physical examination, self-evaluation of diabetes knowledge, diabetes status, and city of residence were variables that affect the level of awareness of core information related to diabetes (all P<0.05). Compared with the low awareness group of diabetes core information, the high awareness group trusted professional medical staff ( t=-9.597, P<0.05) and community health promotion more ( t=-5.014, P<0.05), but did not trust the emerging popular science propaganda means, such as WeChat official accounts/WeChat groups/QQ groups, Internet web page, Tiktok/Kwai and other short video APPs. Conclusion:The awareness rate of diabetes knowledge among the health examination population is low, and it is affected by many factors; Health education on diabetes knowledge should be carried out for people undergoing physical examination.

This study aims to explore the molecular mechanism of Ganoderma against gastric cancer based on network pharmacology, molecular docking, and cell experiment. The active components and targets of Ganoderma were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and gastric cancer-related targets from GeneCards and Online Mendelian Inheritance in Man(OMIM). The protein-protein interaction(PPI) network of the common targets was constructed with STRING, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis of the common genes based on Bioconductor and R language. The medicinal-disease-component-target network and medicinal-disease-component-target-pathway network were established by Cytoscape. Molecular docking was performed between β-sitosterol(the key component in Ganoderma) and the top 15 targets in the PPI network. Cell experiment was performed to verify the findings. A total of 14 active components and 28 targets of Ganoderma were retrieved, and the medicinal and the disease shared 25 targets, including caspase-3(CASP3), caspase-8(CASP8), caspase-9(CASP9), and B-cell lymphoma-2(BCL2). The common targets involved 72 signaling pathways and apoptosis and p53 signaling pathway may play a crucial role in the effect of Ganoderma against gastric cancer. β-sitosterol had strong binding activity to the top 15 targets in the PPI network. The in vitro cell experiment demonstrated that β-sitosterol inhibited gastric cancer AGS cell proliferation by inducing cell apoptosis and cell cycle arrest in the S phase, which might be related to the regulation of the p53 pathway. This study shows the multi-component, multi-target, and multi-pathway characteristics of Ganoderma against gastric cancer, which lays a scientific basis for further research on the molecular mechanism.
Ganoderma ; Humans ; Medicine, Chinese Traditional ; Molecular Docking Simulation ; Network Pharmacology ; Stomach Neoplasms/genetics*

The UHPLC-LTQ-orbitrap-MS metabolomics technique was used to determine the effect of deapio-platycodin D (DPD) on endogenous metabolites in lung tissues of mice with ammonia-induced cough, and to identify the metabolic regulatory pathways of DPD in its antitussive and expectorant activities. This work was approved by the Animal Ethics Committee of Jiangxi University of Chinese Medicine (Approval No. JZLLSC-20190235). Metabolites were identified by UHPLC-LTQ-orbitrap-MS method and the metabolic pathways related to differentially-expressed metabolites were analyzed by the MetaboAnalyst platform. DPD significantly prolonged (P < 0.05) cough latency, reduced the number of coughs, and significantly increased (P < 0.05) phenol red excretion in ammonia-induced cough mice. Twenty-five metabolites related to cough and 38 metabolites related to sputum excretion were identified by UHPLC-LTQ-orbitrap-MS. Changes in the metabolism of linoleic acid, arachidonic acid, glycerophospholipid, alanine, aspartic acid and glutamic acid, pentose and glucuronate interconversions, and lysine degradation were evident with DPD treatment of ammonia-induced cough mice. Changes in the metabolism of linoleic acid, taurine and hypotaurine, glycerophospholipid, purines and pyrimidines, arachidonic acid and the biosynthesis of unsaturated fatty acids after DPD treatment were related to phenol red excretion. Linoleic acid metabolism, arachidonic acid metabolism and glycerophospholipid metabolism are common regulatory pathways by which DPD appears to exert its antitussive and expectorant activity. These metabolic pathways are closely related to anti-inflammatory pathways, immune function regulation, neurotransmitter release, cell signal transduction, energy metabolism and apoptosis. This study clarifies the antitussive and expectorant activity and mechanism of DPD.

Objective: To understand nutrient intake and dietary structure among migrant children in primary schools in Hongshan District of Wuhan, so as to carry out dietary nutrition intervention and evaluate the effectiveness of the intervention. Methods: Stratified random sampling was used to select children in grade 3-6 who were randomly assigned to the intervention group (n=218) and the control group (n=222) from primary schools with a large number of migrant children in Hongshan District of Wuhan. After the baseline survey, the intervention group was given a two month diet intervention with "nutrition class" and knowledge lecture, and the caregivers of the intervention group were also given an intervention. Results: At baseline, both groups had inadequate nutrient intake, with adequate intake rate of calcium, selenium, vitamin B 1 and vitamin B 2 less than 5%; children were lack of dietary diversity with adequate intake of vegitable, milk and milk product less than 5%. After intervention, the intake of energy, three main macronutrients, calcium, vitamin A, and vitamin C in the intervention group were higher than that of before intervention, as well as than the control group, differences were statistically significant (Z=2.22-8.65，2.62-8.46，P<0.05). In terms of dietary structure, adequate intake rate of cereals and miscellaneous beans increased from 55.5% to 68.8%, livestock and poultry meat increased from 45.9% to 56.4%, which were higher than that of the control group (56.3% and 44.6%) (χ 2=5.29-13.25，4.39-14.13，P<0.05). Conclusion Inadequate nutrient intake and unreasonable dietary structure of migrant children can be improved through short term dietary intervention including nutrition education to both parents and children.

Two phloroglucinol compounds(1-2) were isolated and purified from 95% ethanol extract of Dryopteris fragrans through various column chromatographies on silica gel, Sephadex LH-20, medium pressure column chromatography, and preparative HPLC. Their structures were elucidated as 2',4',6'-trihydroxy-5'-methyl acetate-3'-methyl-1'-butyrophenone(1) and aspidinol B(2) based on their chemical and physicochemical methods and spectroscopic data. Compound 1 is a new phloroglucinol compound named "dryofraginol".
Chromatography, High Pressure Liquid ; Dryopteris ; Ethanol ; Phloroglucinol ; Plant Extracts