ObjectiveTo observe the effect of enriched environment (EE) combined with acupuncture at head point (HA) on behavior in rats with autism spectrum disorder. MethodsHealthy female Wistar rats were given peritoneal injection of sodium valproate at 12.5 days of gestation. Twenty-four male offspring rats were randomly selected and then randomly divided into model group (n = 6), EE group (n = 6), HA group (n = 6) and EE combined with HA group (the combined group, n = 6). Six male offspring rats born from female mice injected with the same amount of saline intraperitoneally were as control group. After four weeks of treatment, all the five groups were tested with three-chamber test and marble burying test, and the sociability index, the social novelty index and the number of buried marbles were recorded. The levels of interleukin (IL)-1β and IL-6 in peripheral blood were determined by enzyme-linked immunosorbent assay (ELISA). ResultsAfter treatment, compared with the model group, the sociability index and the social novelty index improved (P < 0.05), the number of buried marbles reduced (P < 0.05), and the levels of IL-6 and IL-1β in peripheral blood decreased in EE group, HA group and the combined group (P < 0.05); while the combined group was the best (P < 0.01). ConclusionBoth EE or acupuncture at HA could improve behavioral symptoms, and reduce the expression of inflammatory factors in rats with autism spectrum disorder. The combination of the two methods showed the best result.

Tropane alkaloids (TAs) are a class of anticholinergic drugs widely used in clinical practice and mainly extracted from plant, among which Atopa belladonna is the main commercial drug source. It is of great industrial value to obtain TAs in large quantities by plant metabolic engineering. In TAs pathway, cytochrome oxidase CYP82M3 catalyze the synthesis of tropinone and then tropinone reductase I (TRI) compete with TRII for tropinone to form tropine leading to the TAs synthesis (drainage). In this study, based on the "increasing flow and drainage" metabolic engineering strategy, two genes, namely HnCYP82M3 and DsTRI from Hyoscyamus niger and Datura stramonium, respectively, were overexpressed in the hair roots of A. belladonna, with a view to promote the TAs accumulation. The HnCYP82M3 gene was cloned from the root of H. niger, and it encoded amino acid with 91.7% sequence identity with AbCYP82M3 from A. belladonna. Overexpression of HnCYP82M3 alone did not affect the content of TAs in hair roots of A. belladonna, indicating that CYP82M3 was not a key enzyme in TAs biosynthesis. Simultaneous overexpression of HnCYP82M3 and DsTRI greatly promoted the accumulation of the three TAs, and the contents of hyoscyamine, anisodamine and scopolamine were 4.97 times, 2.83 times and 2.19 times that of the control, respectively, and the increase amplitude was greater than that of single overexpression of DsTRI. This study showed that the "increasing flow and drainage" strategy of enzyme genes co-expression at branch points was a promising metabolic engineering method to effectively improve the biosynthesis of TAs in A. belladonna, and laid a theoretical and technical foundation for the large-scale industrial acquisition of TAs.

Objective:To investigate the changes in cardiopulmonary exercise testing (CPET) characteristics before and after the outbreak of COVID-19 in patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI).Methods:This is a cross-sectional study that included ACS patients who underwent PCI at the General Hospital of the Northern Theater Command from July 2018 to February 2023. Based on the timeline of the COVID-19 pandemic, patients were divided into two groups: the pre-pandemic group and the during-pandemic group, with January 2020 as the dividing line. Clinical data were collected from both groups, and a comparative analysis was performed on their postoperative CPET outcomes, including peak oxygen uptake (peak VO 2), peak metabolic equivalents (peak MET), and other indicators. Weber′s classification was used to assess cardiac function. In addition, the 7-tiem generalized anxiety disorder scale (GAD-7) and the patient health questionnaire-9 (PHQ-9) were used to assess the patients′ psychological anxiety and depression states, respectively. Multivariate logistic regression was used to analyze the influencing factors of CPET after PCI. Results:A total of 4 310 post-PCI ACS patients were included, with an average age of (58.7±9.1) years, and 3 464 (80.37%) were male. There were 1 698 patients in the pre-pandemic group and 2 612 patients in the during-pandemic group. The main indicator of the CPET, peak VO 2 (15.04±3.93) ml·min -1·kg -1 in the during-pandemic group, was lower than that in the pre-pandemic group (15.52±3.68) ml·min -1·kg -1, and the difference was statistically significant ( P<0.001). Multivariate logistic regression analysis showed that advanced age, female gender, high body mass index, elevated high-sensitivity C-reactive protein, reduced high-density lipoprotein cholesterol, smoking history, history of myocardial infarction, more severe ACS classification, and mild to moderate degree of depression were related to poor cardiopulmonary outcomes ( P<0.05). Conclusion:The COVID-19 pandemic had a negative impact on the cardiopulmonary outcomes of ACS patients after PCI. Reduced physical activity, and increased psychological stress should be given consideration and attention regarding their impact on patients′ cardiopulmonary function.

Objective To elucidate the effect of Deduhonghua-7 powder and its main components on liver fibrosis induced by carbon tetrachloride(CCl4)by regulating chemokine receptor 1(CCR1)and DNA methyltransferase 1(DNMT1).Methods C57BL/6 mice were randomly divided into blank group,model group,Deduhonghua-7 powder group(0.75 g·kg-1 Deduhonghua-7 powder),Scabiosa Atropurea group(0.75 g·kg-1 Scabiosa Atropurea)and Luteolin-L,-H groups(0.02 and 0.04 g·kg-1 Luteolin,respectively).Except the blank group,the other groups were intrabitoneally injected with 10％CC14 olive oil solution to establish liver fibrosis model,and all groups were given 0.5％CMC-Na dissolved intragastric drug once a day for 4 weeks,and blood and liver tissues were collected after the last administration.The serum CCR1,DNMT1,α-smooth muscle actin(α-smA)and precollagen Ⅲ contents were detected by enzyme linked immunosorbent assay;the CCR1,DNMT1,α-smA,Collagen Ⅰprotein expression were detected by Western blot.Result The contents of serum DNMT1 in blank group,model group,Deduhonghua-7 powder group,Luteotin-L,-H groups and Scabiosa Atropurea group were(4.56±0.69),(6.09±0.59),(5.21±0.33),(4.99±0.68),(5.03±0.45)and(5.17±0.61)pg·mL-1;the contents of CCR1 were(13.38±0.47),(11.20±0.73),(12.97±0.80),(12.89±0.75)(12.88±0.95)and(12.92±0.58)pg·mL-1;the contents of α-smA were(181.80±24.50),(281.30±26.60),(220.90±22.30),(193.70±16.10),(199.30±17.70)and(205.80±14.70)pg·mL-1;the contents of procollagen Ⅲ were(49.29±8.26),(77.56±8.61),(67.56±5.63),(55.47±7.07),(64.93±8.66)and(59.66±8.51)pg·mL-1;the relative expression levels of DNMT1 protein in liver tissues were 0.08±0.03,0.26±0.08,0.13±0.01,0.12±0.05,0.13±0.05 and 0.15±0.03;the CCR1 protein relative expression levels were 0.18±0.03,0.13±0.02,0.21±0.06,0.22±0.07,0.17±0.07 and 0.18±0.06;the α-smA protein relative expression levels were 0.03±0.01,0.27±0.11,0.09±0.05,0.12±0.08,0.09±0.07 and 0.11±0.07;the expression of Colagen Ⅰ protein were 0.09±0.04,0.65±0.22,0.28±0.12,0.26±0.19,0.30±0.22 and 0.25±0.12.The differences of above indicators between the model group and the blank group,between the Deduhonghua-7 powder group,Luteotin-L,-H groups,Scabiosa Atropurea group and the model group were statistically significant(all P＜0.05).Conclusion Luteotein is one of the pharmacodynamic substance bases of Deduhonghua-7 powder to alleviate liver fibrosis induced by CC14.It can inhibit or delay the formation of liver fibrosis through CCR1,DNMT1,α-smA and Collagen Ⅰ proteins.

Primary immune thrombocytopenia(ITP)is an autoimmune disease characterized by thrombocytopenia,and T cell immune dysfunction plays an important role in the formation of ITP.As a thrombopoietin receptor agonist(TPO-RA),eltrombopag can not only directly stimulate megakaryocytes to produce platelets,but also play an immunomodulatory role by inducing regulatory T cell generation and reducing proinflammatory factors.As a second-line treatment drug for adult ITP,eltrombopag is increasingly widely used in clinical practice.This review summarized the latest research progress on the mechanism of action,efficacy,safety,and how to reduce the dosage of eltrombopag in ITP.

Objective To investigate the predictive value of a nomogram model constructed with clinical variables and multiparametric magnetic resonance imaging(MRI)radiomics features in prognosis of patients undergoing chemotherapy for breast cancer.Methods A total of 150 breast cancer patients who received chemotherapy in Qingdao Central Hospital from January 2020 to December 2021 were enrolled for the study.All patients underwent breast MRI examination before chemotherapy,and the optimal radiomics features were extracted from the tumor regions of interest on multiparametric MRI image which were manually outlined using segmentation software.After 2-year follow-up,the patients were divided into good prognosis group and poor prognosis group according to whether there were disease recurrence,metastasis and death,and they were divided into training set(n=105)and test set(n=45)in a ratio of 7:3.The clinical data and multiparametric MRI radiomics features were collected,and the factors affecting the prognosis of breast cancer patients receiving chemotherapy were analyzed by univariate and multivariate Logistic regression analyses.Three models,namely clinical model,radiomics model,and clinical-multiparametric MRI radiomics-based nomogram model were constructed,and their predictive value in the prognosis of breast cancer patients treated with chemotherapy was analyzed with receiver operating characteristic curves.Results Out of 150 cases of breast cancer treated with chemotherapy,52 cases were included in poor prognosis group,with 33 cases of recurrence and/or metastases and 19 cases of deaths.Logistic regression analysis identified TNM stage,estrogen receptor and progesterone receptor as clinical predictors for prognosis of breast cancer patients treated with chemotherapy(P<0.05).There were 69 and 36 patients with good and poor prognoses in training set,and 29 and 16 patients with good and poor prognoses in test set.Through least absolute shrinkage and selection operator algorithm,16 radiomics features related to the prognosis of breast cancer patients treated with chemotherapy were screened out from TIRM,DWI,and DCE-MRI sequences,and their radiomics scores were calculated.Compared with patients with poor prognosis,those with good prognosis in training set and test set had higher radiomics scores(P<0.05).ROC curve analysis showed that the area under the curve of radiomics model,clinical model,and nomogram model were 0.853,0.741,0.923 in training set(P<0.05),and 0.797,0.749,0.896 in test set(P<0.05),respectively.Conclusion Based on pre-chemotherapy radiomics scores,TNM stage,estrogen receptor and progesterone receptor are identified as independent predictors for prognosis of breast cancer patients treated with chemotherapy,and the clinical-multiparametric MRI radiomics-based nomogram can effectively improve the predictive efficacy of prognosis in breast cancer patients treated with chemotherapy.

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 present a method of modeling 3D-printed guide templates (3DPGTs) strictly based on pre-plans for the interstitial implantation brachytherapy of cervical cancer, and elucidate the advantages of 3DPGTs in the interstitial implantation brachytherapy of cervical cancer.Methods:This study retrospectively selected six cases of locally advanced cervical cancer treated with interstitial implantation brachytherapy using 3DPGTs. Based on the CT images of 3DPGTs and pre-plans, the mechanical precision of 3DPGTs was verified through image registration. The dosimetric differences were compared between the 3DPGT treatment plan and the pre-plan/the freehand implantation plan. The dosimetric parameters included the volume and D90 for the high-risk clinical target volume (HR-CTV), and the D2 cm 3, D1 cm 3, and D0.1 cm 3 for the bladder, rectum, intestine, and sigmoid. Results:The 3DPGTs modeled using the method strictly based on pre-plans exhibited relatively high mechanical precision, with deviations all below 1 mm. Regarding the D90 of the HR-CTV, the 3DPGT treatment plan resulted in a dose of (713.37±143.26) cGy, reduced by 6.95% ( z= -1.98, P<0.05) compared to the (766.62±145.97) cGy in the pre-plan, and increased by 107.6% ( z= -1.89, P<0.05) compared to the (343.56±188.72) cGy in the freehand implantation plan. For dosimetric parameters of organs at risk (OARs), no statistical differences were observed ( P>0.05) between the 3DPGT treatment plan and the pre-plan/the freehand implantation plan. Conclusions:The method of modeling 3DPGTs for cervical cancer proposed in this study demonstrates high accuracy. Hence, the dose for the HR-CTV can be substantially increased under the condition that the OARs are protected from over-irradiation.

Objective:To investigate the effects of microRNA (miR) -125b on the proliferation and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway of hepatocellular carcinoma (HCC) cell by targeting Polo like kinases (PLK4).Methods:The tumor tissues and adjacent tissues of 65 patients with HCC were collected from March 2022 to March 2023 in Tianjin Medical University Cancer Hospital, including 33 males and 32 females, aged (60.1±5.6) years. The expressions of miR-125a and miR-125b in liver cancer, adjacent tissues and liver cancer cells were detected by fluorescence quantitative polymerase chain reaction. Low expression liver cancer cell was selected to transfect negative control (NC) sequences of miR, miR-125a and miR-125b. Subsequently, miR-NC and NC plasmid, miR-125b sequence and NC plasmid, and miR-125b sequence and PLK4 plasmid were co-transfected. Cell proliferation was detected by cell counting assay, the expression of PLK4, phosphorylated PI3K (p-PI3K) and phosphorylated Akt (p-Akt) was detected by Western blot, and miR-125b-targeting PLK4 were detected by bioinformatics analysis and dual luciferase reporter gene.Results:The relative expressions of miR-125a and miR-125b in HCC patients were (0.62±0.08) and (0.58±0.07), respectively, lower than those in adjacent tissues (1.00±0.12) and (1.00±0.13), and the differences were statistically significant ( t=21.24, 22.93, P=0.005, P<0.001). HepG2 cells with low expression of miR-125a and miR-125b and miR-125b targeting PI3K/Akt were selected for transfection. Bioinformatic analysis and dual luciferase reporter gene assay confirmed that miR-125b binds to PLK4. Overexpression of miR-125b could inhibit the proliferation of HepG2 cells and the expression of p-PI3K and p-Akt, while overexpression of PLK4 could partially reverse the proliferation inhibition caused by miR-125b and the expression of p-PI3K and p-Akt, (0.91±0.07) vs(0.41±0.04), (0.97±0.08) vs (0.32±0.03)( t=13.87, 17.01, both P<0.001). Conclusion:The inhibitory effect of miR-125b on HepG2 cell proliferation and PI3K/Akt signaling pathway is partly mediated by targeted inhibition of PLK4.

Objective To evaluate the clinical efficacy of traditional Chinese medicine turbid phlegm obstructing lung decoction on patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD)and its influence on laboratory indexes.Methods A total of 191 patients with AECOPD who were hospitalized in the First People's Hospital of Changde from January 2021 to December 2022 were selected.Patients were divided into observation group(96 cases)and control group(95 cases)according to their treatment intention.The control group received conventional treatment of western medicine,and the observation group received oral administration of traditional Chinese medicine turbid phlegm obstructing lung decoction for one week.TCM symptom scores,COPD assessment test(CAT),lung function,laboratory indicators and efficacy were compared between two groups.Results The total effective rate of observation group was significantly higher than that of control group(χ2=4.573,P=0.030).After treatment,TCM symptom score,CAT score,hypersensitive C-reaction protein(hsCRP)and interleukin-6(IL-6)of patients in both groups were significantly lower than before treatment,percentage of forced vital capacity to predicted value(FVC%)and percentage of forced expiratory volume in one second to predicted value(FEV1%)were significantly higher than before treatment(P<0.05),arterial partial pressure of carbon dioxide(PaCO2)of observation group was lower than before treatment,and arterial partial pressure of oxygen(PaO2)was higher than before treatment(P<0.05).The TCM symptom score,CAT score,hsCRP and IL-6 of observation group were significantly lower than those of control group,while FVC%,FEV1%and PaO2 were significantly higher than those of control group(P<0.05).Conclusion On the basis of western medicine treatment,traditional Chinese medicine turbid phlegm obstructing lung decoction can more effectively improve clinical symptoms of AECOPD patients,relieve the inflammation in the body,contribute to the recovery of lung function and improve the quality of life of patients.