Objective To explore the effect and mechanism of quercetin on osteogenic differentiation of bone marrow mesenchymal stem cells(BMSCs).Methods BMSCs were divided into a blank control group(Control)and quercetin(Quercetin)low-dose group(4.8 mL/kg),medium-dose group(9.6 mL/kg),and high-dose group(19.2 mL/kg)intervened with drug-containing serum,while the positive control group was treated with osteogenic differentiation medium,respectively.The cell cycle was analysed by flow cytometry,cell proliferation was detected by MTT assay,cell activity was determined by Alkaline phosphatase(ALP)assay kit,and calcified nodule formation was observed by alizarin red staining.The expression of β-catenin and the key factors of osteogenic differentiation,runt-related transcription factor 2(RUNX2)and osteocalcin(OCN),were detected by qPCR and Western blot,respectively.Results Compared with the control group,quercetin-containing serum significantly promoted the proliferation of BMSCs(P=0.000205,P=0.000063)and enhanced the formation of calcium nodules,and increased osteogenic and ALP activity after osteogenic differentiation.The results of qPCR and Western blot showed that the quercetin group significantly up-regulated the mRNA and protein expression of β-catenin(P<0.0001),RUNX2(P<0.0001)and OCN(P<0.0001)during osteogenic differentiation.Conclusion Quercetin can effectively promote the osteogenic differentiation of BMSCs,and its mechanism is achieved by activating the Wnt/β-catenin signaling pathway and up-regulating the expression of the osteogenesis-related transcription factor RUNX2.

Objective To study the differences in the blood cell analysis of male officers and soldiers be-tween in the high altitude area station and low altitude area station in summer.Methods A total of 239 male officers and soldiers in the high altitude area(Amdo Xizang,average altitude 4 800 m)and 336 male officers and soldiers in the low altitude area(Nanjing,Jiangsu,average altitude 30 m)from July 18 to 24,2022 were selected as the study subjects and the differences in blood cell analysis parameters of male officers and soldiers stationed between at high altitude and low altitude areas were retrospectively analyzed.Results The eosino-phils percentage(EDS％),eosinophils count(EOS)in the high altitude group were significantly lower than thosein the low altitude group(P＜0.05),and the basophillic granulocyte percentage(BASO％),basophillic granulo-cyte count(BASO)and monocyte percentage(MONO％)were significantly higher than those in the low alti-tude group,and the differences were statistically significant(P＜0.05),but which in the both groups were in the normal reference ranges.The red blood cell count(RBC)hemoglobin(Hb)and hematocrit(HCT)in the high altitude group were significantly higher than those in the low altitude group(P＜0.05),moreover Hb and HCT in the high altitude group were in the upper limit of the medical reference range.The mean corpus-cular volume(MCV),mean corpuscular hemoglobin(MCH),mean corpuscular hemoglobin concentration(MCHC)and red blood cell distribution width-standard diviation(RDW-SD)in the high altitude group were lower than those in the low-altitude group(P＜0.05),but the both groups were in the normal reference ran-ges;there was no statistically significant difference in the erythrocyte distribution width coefficient of variation(RDW-CV)between the two groups(P＞0.05).The platelet(PLT)and thrombocytocrit(PCT)in the high altitude group were higher than those in the low altitude group,the platelet distribution width(PDW),mean platelet volume(MPV)and platelet large cell ratio(P-LCR)were lower than those in the low altitude group,and the differences were statistically significant(P＜0.05);PDW in the low-altitude group was at the upper limit of the medical reference range,and the other platelet-related indexes were in the normal range.Conclusion There are obvious differences in the blood cell analysis indicators of male officers and soldiers be-tween the high altitude area and low altitude area.

Purpose/Significance To analyze the technical situation of patent owners in the field of clinical decision support system(CDSS)in China as a whole,so as to provide references for CDSS related technical research.Method/Process Firstly,the CDSS patent data are analyzed from the aspects of application trend,patent disclosure,technology field distribution,etc.,then the patentees are di-vided into different categories,and their technical concerns are analyzed by word frequency and interword vector.Finally,the technology correlation and patent exclusives are analyzed based on the active patentees.Result/Conclusion The number of CDSS patent disclosure shows an overall increasing trend.This field has not formed a technological monopoly in China.Government departments and research in-stitutions should pay attention to the possible financial risks.

The neural stimulator is a core component of animal robots. While the control effect of animal robots is influenced by various factors, the performance of the neural stimulator plays a decisive role in regulating animal robots. In order to optimize animal robots, embedded neural stimulators had been developed using flexible printed circuit board technology. This innovation not only enabled the stimulator to generate parameter-adjustable biphasic current pulses through control signals, but also optimized its carrying mode, material, and size, overcoming the disadvantages of traditional backpack or head-inserted stimulators, which have poor concealment and are prone to infection. Static, in vitro, and in vivo performance tests of the stimulator demonstrated that it not only had precise pulse waveform output capability, but also was lightweight and small in size. It had excellent in vivo performance in both laboratory and outdoor environments. Our study has high practical significance for the application of animal robots.
Animals ; Robotics

Objective: To explore the possible mechanism of moxibustion in myocardial protection of rats undergoing long-term fatigue exercise based on observing the classical pyroptosis pathway mediated by nuclear factor kappa-B (NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)/cysteinyl aspartate specific proteinase 1 (Caspase-1).Methods: A total of 50 specific-pathogen-free male Sprague-Dawley rats were bought. Ten unqualified rats were excluded, and the remaining 40 rats were divided into a normal group, a normal + Shenque (CV8) group, a model group, a model + non-meridian non-point group, and a model + Shenque (CV8) group according to the random number table method, with 8 rats in each group. Except for rats in the normal group and the normal + Shenque (CV8) group, rats in the other three groups were trained with an incline running table exercise protocol to create a long-term fatigue exercise model, 1 h/time, once a day for 5 d with 2 d off, for a total of 8 weeks. Rats in the normal group received no modeling or intervention. Rats in the normal + Shenque (CV8) group were not modeled but received mild moxibustion at Shenque (CV8); those in the model group were modeled only without intervention; those in the model + non-meridian non-point group received moxibustion at non-meridian and non-point spots after the modeling; those in the model + Shenque (CV8) group received moxibustion at Shenque (CV8) after modeling. The above moxibustion interventions were performed for 15 min/time once daily, for 5 d with 2 d off per week and a total of 8 weeks. Blood was collected from the femoral artery 4 h after the last exercise, and the serum interleukin (IL)-1β and IL-18 levels were measured. The NF-κB, NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), Caspase-1, and gasdermin D (GSDMD) expression levels were detected by Western blotting. Myocardial morphology and pyroptosis were observed by hematoxylin-eosin (HE) staining and electron microscopy. Results: The HE staining results showed that the myocardial cells in the model group and the model + non-meridian non-point group were disorganized with blurred transverse lines, widened interstitial spaces, interstitial edema, and inflammatory cell infiltration. The structure of myocardial cells in the model + Shenque (CV8) group was clearly visible, with slightly widened interstitial spaces and occasional infiltration of inflammatory cells in the interstitium. Compared with the normal group, the serum IL-1β and IL-18 levels were increased, and myocardial NF-κB, NLRP3, ASC, Caspase-1, and GSDMD expression levels were elevated in the model group and the model + non-meridian non-point group (P<0.01). Compared with the model group, the above indicators did not change significantly in the model + non-meridian non-point group, while all the above indicators were decreased in the model + Shenque (CV8) group (P<0.01). Compared with the model + non-meridian non-point group, all the above biochemical indicators were decreased in the model + Shenque (CV8) group (P<0.01). Transmission electron microscopy showed that the mitochondria number was increased in the model group and the model + non-meridian non-point group, some of the mitochondrial lumen was irregularly enlarged, the cell membrane structure was unclear, and chromatin was aggregated. The mitochondria number was increased, the swelling was reduced, and the nuclear membrane structure was more intact in the model + Shenque (CV8) group. Conclusion: Moxibustion at Shenque (CV8) regulates the NF-κB/NLRP3/Caspase-1 pathway and reduces the pyroptosisin the myocardium of rats with long-term fatigue exercise, thus reducing the myocardial injury caused by long-term fatigue exercise.

Objectives:To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients.Results:1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion:Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.

Despite being a common therapy for hepatocellular carcinoma (HCC), insufficient thermal ablation can leave behind tumor residues that can cause recurrence. This is believed to augment M2 inflammatory macrophages that usually play a pro-tumorigenic role. To address this problem, we designed d-mannose-chelated iron oxide nanoparticles (man-IONPs) to polarize M2-like macrophages into the antitumor M1 phenotype. In vitro and in vivo experiments demonstrated that man-IONPs specifically targeted M2-like macrophages and accumulated in peri-ablation zones after macrophage infiltration was augmented under insufficient microwave ablation (MWA). The nanoparticles simultaneously induced polarization of pro-tumorigenic M2 macrophages into antitumor M1 phenotypes, enabling the transformation of the immunosuppressive microenvironment into an immunoactivating one. Post-MWA macrophage polarization exerted robust inhibitory effects on HCC progression in a well-established orthotopic liver cancer mouse model. Thus, combining thermal ablation with man-IONPs can salvage residual tumors after insufficient MWA. These results have strong potential for clinical translation.

Objective:To investigate the effect of L-asparaginase on the proliferation, cell cycle, and apoptosis of Burkitt lymphoma cell lines and explore the molecular mechanism.Methods:The effect of L-asparaginase on the cell proliferation of Burkitt lymphoma cell lines was detected using the CCK-8 method. The apoptosis rate and cell cycle were detected using flow cytometry. The expression of related molecules in cell cycle, apoptosis, autophagy, and PI3K/Akt/mTOR signaling pathway was detected and analyzed using qPCR and Western blot assay.Results:L-asparaginase significantly inhibited the proliferation of Burkitt lymphoma cell lines and caused cell cycle arrest at G 0/G 1 phage. L-asparaginase induced cell apoptosis and autophagy in Burkitt lymphoma cell lines. Further results showed that L-asparaginase inhibited the expression of c-Myc and also inhibited the expression of p-PI3K, p-Akt-S473, p-mTOR, p-70S6K, and p-4E-BP1. Combining PI3K inhibitor LY294002 with L-asparaginase further induced apoptosis. Additionally, L-Asp inhibited STAT and ERK signaling pathways. Conclusion:L-asparaginase inhibited Burkitt lymphoma cell proliferation, arrested cell cycle, activated autophagy, and induced apoptosis by inhibiting the PI3K/Akt/mTOR signaling pathway.

Objectives:To explore health-related quality of life (HRQoL) and identify its associated variables in Chinese patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) .Methods:In this cross-sectional study, anonymous questionnaires were distributed to adult patients with MPNs to assess symptom burden measured by MPN-10 and HRQoL measured by Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) .Results:The data from 1405 respondents with MPNs, including 645 (45.9%) with essential thrombocythemia (ET) , 297 (21.1%) with polycythemia vera (PV) , and 463 (33.0%) with myelofibrosis (MF) , were analyzed. 646 (46.0%) respondents were male. The median age was 56 (range, 18-99) years. The mean MPN-10 scores were 13.0±12.7, 15.0±14.7, and 21.0±16.6 ( P<0.001) , and the physical component summary (PCS) and mental component summary (MCS) scores were 48.0±8.5, 47.0±9.0, and 42.0±10.0 ( P<0.001) and 51.0±11.0, 50.0±10.8, and 49.0±11.1 ( P=0.002) for respondents with ET, PV, and MF, respectively. Respondents with MF reported the lowest score of physical functioning, role functioning, emotional functioning, cognitive functioning, social function, and global health status (all P<0.01) and the highest score of fatigue, pain, dyspnea, appetite loss, diarrhea, and financial problems (all P<0.05) in EORTC QLQ-C30. Multivariate analyses revealed that higher MPN-10 scores were significantly associated with lower PCS (-0.220 to -0.277, P<0.001) and MCS (-0.244 to -0.329, P<0.001) scores; increasing age (-1.923 to -4.869; all P<0.05) , lower PCS score. Additionally, comorbidity (ies) , symptom at diagnosis, splenomegaly, anemia, unknown driver gene, and higher annual out-of-pocket cost were significantly associated with lower PCS and/or MCS scores. However, age ≥ 60 years, urban household registration, concomitant medication, and receiving ruxolitinib therapy in respondents with MF were associated with higher MCS scores. Weak correlations were found between MPN-10 score (except the subscale of appetite loss and constipation) and EORTC QLQ-C30 score in majority of subscales in respondents with ET (| r| = 0.193-0.457, all P<0.001) , PV (| r| = 0.192-0.529, all P<0.01) , and MF (| r| = 0.180-0.488, all P<0.001) , respectively. Conclusions:HRQoL in patients with MPN was significantly reduced, especially in patients with MF. Sociodemographic and clinical variables were significantly associated with the HRQoL in patients with MPNs.