OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Depression is increasingly prevalent among adolescents and can profoundly impact their lives. However, the early detection of depression is often hindered by the time-consuming diagnostic process and the absence of objective biomarkers. In this study, we propose a novel approach for depression detection based on an affective brain-computer interface (aBCI) and the resting-state electroencephalogram (EEG). By fusing EEG features associated with both emotional and resting states, our method captures comprehensive depression-related information. The final depression detection model, derived through decision fusion with multiple independent models, further enhances detection efficacy. Our experiments involved 40 adolescents with depression and 40 matched controls. The proposed model achieved an accuracy of 86.54% on cross-validation and 88.20% on the independent test set, demonstrating the efficiency of multimodal fusion. In addition, further analysis revealed distinct brain activity patterns between the two groups across different modalities. These findings hold promise for new directions in depression detection and intervention.
Humans ; Male ; Female ; Adolescent ; Case-Control Studies ; Depression/diagnosis* ; Early Diagnosis ; Rest ; Electroencephalography/methods* ; Brain-Computer Interfaces ; Models, Psychological ; Reproducibility of Results ; Affect/physiology* ; Photic Stimulation/methods* ; Video Recording ; Brain/physiopathology*

Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry* ; Sesquiterpenes/chemical synthesis* ; Molecular Structure ; Humans ; Liver Cirrhosis/genetics* ; Biomimetics ; Plant Extracts/pharmacology*

Objective To investigate the therapeutic effect of gabapentin combined with hemoperfusion on skin pruritus in the patients on maintenance hemodialysis(MHD).Methods A total of 72 patients with MHD complicating moderate to severe skin itching treated in Lianyungang Municipal Oriental Hospital from January 2023 to March 2024 were selected as the study subjects and divided into the observation group and control group by the random number table method,36 cases in each group.On the basis of symptomatic treat-ment,the control group was given hemodialysis 3 times a week and hemoperfusion twice a month;on the basis of the control group,the observation group orally took 1 gabapentin capsule every night,and the patients in the two groups continued to be treated for 12 weeks.The visual analogue scale(VAS)score,Pittsburgh Sleep Quality Index(PSQI)score,molecular toxin level and calcium and phosphorus metabolism were evaluated be-fore treatment,in 4,12 weeks after treatment respectively,and the occurrence of adverse reactions during treatment in the two groups was observed.Results After 4 weeks and 12 weeks of treatment,the VAS and PSQI scores of the observation group were decreased compared with those before treatment,moreover the scores of the observation group were lower than those of the control group in the same period,and the differ-ences were statistically significant(P<0.05);the VAS and PSQI scores after 4 weeks of treatment in the control group were decreased compared with those before treatment,but the difference was not statistically significant(P>0.05);and the VAS and PSQI scores after 12 weeks of treatment in the control group were decreased compared with before treatment,and the difference was statistically significant(P<0.05).After 4 weeks of treatment,the levels of Scr,BUN and β2-MG in the two groups were decreased compared with those before treatment,but the differences were not statistically significant(P>0.05);after 12 weeks of treatment,the levels of Scr,BUN and β2-MG in the two groups were decreased compared with those before treatment and after 4 weeks of treatment,and the differences were statistically significant(P<0.05),but there was no sta-tistically significant difference between the two groups(P>0.05).After 4 weeks of treatment,there was no statistically significant difference in the levels of blood Ca,P and iPTH between the two groups compared with before treatment(P>0.05);after 12 weeks of treatment,except for blood Ca,the levels of blood P and iPTH in the two groups were decreased compared with those before treatment and in 4 weeks of treatment(P<0.05),and the differences were statistically significant(P<0.05),but there was no statistical difference be-tween the two groups(P>0.05).There were no adverse reactions in the control group,and there were 3 cases of drowsiness,1 case of fatigue and 1 case of dizziness at the beginning of treatment in the observation group.The symptoms were mild without treatment and spontaneously relieved in about 1 week.Conclusion Gabap-entin combined with hemoperfusion could quickly and effectively alleviate the itchy symptoms of skin,improve the sleep quality,reduce the uremic toxin levels,and improve the calcium and phosphorus metabolism in MHD patients,with few adverse reactions,and the patients are easy to tolerate.

Objective: To investigate the effects of β-caryophyllene(BCP) on the browning of white adipose tissue in obese mice and the related mechanisms. Methods: An obese mouse model was establishedviaintraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution [14.4 mg/(kg·d)] in male Kunming mice. Obesity model mice were randomly divided into a model group(Model group) and a BCP administration group(BCP-50 group); normal diet mice were set up as a control group(Control group), with 8 mice in each group. BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group, while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks. The oral glucose tolerance test was performed at the end of 4-week administration, and mice were executed after overnight fasting at the end of the experiment, and blood samples and adipose tissues were rapidly collected for subsequent experimental tests. The kit was used to detect serological-related indexes; hematoxylin-eosin staining was conducted to observe the morphology of adipose tissue; immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1) in adipose tissue; Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α), peroxisome proliferator-activated receptor γ(PPARγ), UCP1 and cannabinoid receptor 2(CNR2) proteins in epididymal white adipose(eWAT). Results: Compared with the model group, the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05), food intake was decreased(P<0.01), insulin resistance was improved(P<0.000 1), and the serum content of low-density lipoprotein cholesterol(LDL-C) and nonesterified fatty acid(NEFA) in the obese mice was significantly reduced(P<0.000 1 andP<0.01). Total cholesterol(TC), triglyceride(TG), and high-density lipoprotein cholesterol(HDL-C) contents did not change significantly. In addition, the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05); the adipocytes in eWAT and BAT were reduced; and the expression of the UCP1 protein was significantly elevated(P<0.01 andP<0.05). In addition to UCP1, the expression levels of PGC1α, PPARγ, and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05, andP<0.001). Conclusion β-caryophyllene promotes white adipose tissue browning through up-regulating PPARγ/PGC-1α/UCP1 pathway expression, thus improving obesity.

Objective:To investigate the incidence and risk factors of deep vein thrombosis(DVT)in patients with rheumatoid arthritis(RA).Methods:The clinical data of RA patients who were hospi-talized in the Department of Rheumatology and Immunology of Aerospace Center Hospital from May 2015 to September 2021 was retrospectively analyzed,including demographic characteristics,concomitant diseases,laboratory examinations(blood routine,biochemistry,coagulation,inflammatory markers,rheumatoid factor,antiphospholipid antibodies and lupus anticoagulant,etc.)and treatment regimens.The patients were compared according to the presence or absence of DVT,and the t test,Mann-Whitney U test or Chi-square test were applied to screen for relevant factors for DVT,followed by Logistic regres-sion analysis to determine risk factors for DVT in patients with RA.Results:The incidence of DVT in the RA patients was 9.6％(31/322);the median age of RA in DVT group was significantly older than that in non-DVT group[64(54,71)years vs.50(25,75)years,P＜0.001];the level of disease activity score using 28 joints(DAS28)-erythrocyte sedimentation rate(ESR)in DVT group was higher than that in non-DVT group[5.2(4.5,6.7)vs.4.5(4.5,5.0),P＜0.001];the incidence of hypertension,chronic kidney disease,fracture or surgery history within 3 months,and varicose veins of the lower ex-tremities in DVT group was higher than that in non-DVT group(P＜0.001).The levels of hemoglobin and albumin in DVT group were significantly lower than that in non-DVT group(P=0.009,P=0.004),while the D-dimer level and rheumatoid factor positive rate in DVT group were significantly higher than that in non-DVT group(P＜0.001).The use rate of glucocorticoid in DVT group was higher than that in non-DVT group(P=0.009).Logistic regression analysis showed that the age(OR=1.093,P＜0.001),chronic kidney disease(OR=7.955,P=0.005),fracture or surgery history with-in 3 months(OR=34.658,P=0.002),DAS28-ESR(OR=1.475,P=0.009),and the use of glu-cocorticoid(OR=5.916,P=0.003)were independent risk factors for DVT in RA patients.Conclu-sion:The incidence of DVT in hospitalized RA patients was significantly increased,in addition to tradi-tional factors,such as age and chronic kidney disease,increased DAS28-ESR level and the use of glu-cocorticoid were also independent risk factors for DVT.

BACKGROUND:It has been demonstrated that osteoclast activation plays an important role in skeletal system-related diseases.The mechanism of regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA has not been fully elucidated. OBJECTIVE:To review and summarize relevant literature in and outside China,and to review the regulation of osteoclast activation by different non-coding RNAs in extracellular vesicles in different diseases,so as to provide a certain direction for subsequent research. METHODS:"Non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclasts,extracellular vesicles,exosome,microparticle,apoptotic bodies"were used as search terms to search the databases of CNKI,WanFang,and VIP."Extracellular vesicles,exosome,microparticle,apoptotic bodies,non-coding RNA,miRNA,lncRNA,circRNA,snoRNA,osteoclast"were used as search terms to search PubMed.Finally,71 articles were included. RESULTS AND CONCLUSION:(1)The activation of osteoclasts is affected by many factors,among which the specific mechanism of non-coding RNA regulating osteoclast activation is not clear.(2)Extracellular vesicles can be secreted by osteoblasts,bone marrow mesenchymal stem cells,tumor cells and other cells.As a carrier of intercellular communication,extracellular vesicles can carry non-coding RNA to regulate osteoclast activation.(3)In the current studies on the regulation of osteoclast activation by extracellular vesicles carrying non-coding RNA,most of the diseases are osteoporosis,followed by tumor bone metastasis,and most types of non-coding RNA are miRNA.(4)There are relatively few studies on the regulation of extracellular vesicles carrying lncRNA and circRNA and snoRNA on osteoclast activation,and the regulatory mechanism is mainly ceRNA mechanism.(5)In conclusion,an in-depth study of the regulatory mechanism of extracellular vesicles carrying non-coding RNA on osteoclast activation is helpful to find key targets for the treatment of skeletal system-related diseases.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.