Objective To investigate the feasibility of granzyme B(GB)promoter-controlled ferritin heavy chain(FTH1)reporter gene expression for monitoring the activation status of chimeric antigen receptor T cells(CAR-T)by magnetic resonance imaging(MRI).Methods Cytotoxic T lymphocytes(CTLs)were screened by Ficoll density gradient centrifugation and flow sorting.The GB promoter and FTH1 gene were ligated together with disialoganglioside 2(GD2)CAR,and lentiviral vectors were transfected into CTLs to construct GD2-CAR-T/pGB-FTH1 cells.GD2-CAR-T/pCMV-FTH1,GD2-CAR-T,and T cells served as control cells.CytoTox96@non-radioactive cytotoxicity was used to detect the killing effect of each group of cells after co-culture with human neuroblastoma cells(SK-N-SH).ELISA was employed to detect the coincubation factor as well as the amount of GB secretion.Western blotting,Prussian blue staining and cellular MRI were applied to detect the expression of the FTH1 gene after co-culture.Results CTLs were successfully obtained,and then GD2-CAR-T/pGB-FTH1,GD2-CAR-T/pCMV-FTH1 and GD2-CAR-T cells were constructed.The killing effect,co-incubation factor and GB secretion of the above 3 groups of cells were significantly higher than those of the T cells,and the level of GB expression was highest at day 1,and then decreased in order at day 3 and day 7 after co-culturing with SK-N-SH cells.The relative expression of FTH1 and iron content of the GD2-CAR-T/pGB-FTH1 cells showed the same trend as GB expression,and the MRI signals were gradually increased.There were no significant differences in the relative expression of FTH1,iron content and MRI signals in the GD2-CAR-T/pCMV-FTH1 cells at all time points.No FTH1 expression or iron aggregation was observed in the GD2-CAR-T and T cells groups.Conclusion MRI based on the FTH1 reporter gene driven by the granzyme B promoter can reflect the GB expression level and tumor killing effect of CAR-T cells,which provides a potential real-time visual means to monitor the cell activation status for CAR-T therapy.

Objective:To explore the efficacy and safety of different anti-platelet regimens in the treatment of high-risk non-disabling ischemic cerebrovascular events (HR-NICE) guided by point-of-care testing of CYP2C19 gene. Methods:A single-centre, prospective, randomised, open-label, and blinded endpoint design was uesd in the study. From July 2020 to January 2022, HR-NICE patients were enrolled in the Stroke Green Channel and Department of Neurology of Xuzhou Central Hospital, and all patients were scraped the buccal mucosa for screening for CYP2C19 loss-of-function allele carriers by point-of-care testing . Patients with intermediate metabolism were defined as those who carried 1 loss-of-function allele and patients with poor metabolism were those who carried 2 loss-of-function alleles. This study reduced the test turnaround time to 1 hour by using a fully automated medical polymerase chain reaction analyzer for a point-of-care test of CYP2C19 genotype. CYP2C19 loss-of-function allele carriers were divided according to the random number table method into the conventional treatment group (clopidogrel 75 mg, once a day), the ticagrelor group (ticagrelor 90 mg, twice a day) and the intensive dose group (clopidogrel 150 mg, once a day) separately combined with aspirin (100 mg, once a day) dual antiplatelet for 21 days. Baseline information, Acute Stroke Org 10172 Treatment Trial staging, 90-day modified Rankin Scale score, occurrence of adverse events and severe adverse events were collected for all the 3 groups. The primary efficacy outcome was new stroke within 90 days, and the primary safety outcome was severe or moderate bleeding within 90 days. Results:A total of 716 patients were included: 240 in the conventional treatment group, 240 in the ticagrelor group and 236 in the intensive dose group. There was no statistically significant difference between the 3 groups at baseline (all P>0.05). There were 26 cases (10.8%) with new stroke events in the conventional treatment group, 11 cases (4.6%) in the ticagrelor group and 4 cases (1.7%) in the intensive dose group, with statistically significant differences among the 3 groups (χ 2=19.28, P<0.05), and the differences between the conventional treatment group and the ticagrelor group (χ 2=6.59, P=0.010) and between the conventional treatment group and the intensive dose group (χ 2=16.83, P<0.001) were statistically significant, whereas the difference between the ticagrelor group and the intensive dose group was not statistically significant ( P>0.05). In the 3 groups, there was 1 case (0.4%) of severe bleeding in the conventional treatment group, 6 cases (2.5%) in the ticagrelor group and none in the intensive dose group, which showed statistically significant differences (χ 2=7.23, P<0.05), and there was statistically significant difference between the ticagrelor group and the intensive dose group ( P=0.030). Among the patients with intermediate CYP2C19 metabolism, there were 13 cases (13/158, 8.2%) with 90-day recurrent stroke in the conventional treatment group, 4 cases (4/153, 2.6%) in the ticagrelor group, and 0 case (0/159) in the intensive dose group, with statistically significant difference (χ 2=16.04, P<0.001), and the differences between the intensive dose group and the conventional treatment group were statistically significant (χ 2=13.64, P<0.001), whereas there was no statistically significant difference between the intensive dose group and the ticagrelor group ( P>0.05). In the patients with 90-day recurrent stroke in the intensive dose group, there was 0 case (0/159) with intermediate metabolism and 4 cases (4/77,5.2%) with poor metabolism, with statistically significant differences ( P=0.011), whereas there were no statistically significant differences in the conventional treatment group and the ticagrelor group ( P>0.05). Conclusions:Screening carriers of CYP2C19 loss-of-function alleles by point-of-care testing can quickly and precisely guide the treatment of patients with non-cardiogenic HR-NICE. An intensive clopidogrel dose of 150 mg, once a day combined with aspirin was effective in reducing stroke recurrence with less occurrence of any bleeding and adverse events, and patients with intermediate CYP2C19 metabolism may be the best population to benefit.

Objective:To analyze the distribution of TCM syndrome elements and syndromes in patients with hypertension with insomnia (HWI) in the real world.Methods:A cross-sectional study and retrospectively enrolled. The positive symptoms and TCM syndrome type entries of 359 patients with HWI who were collected from Henan Integrated Medicine Hospital,Henan Provincial People's Hospital,the First Affiliated Hospital of Henan University of Chinese Medicine from December 2020 to August 2022 were retrospectively studied. Based on factor analysis dimension reduction and systematic cluster analysis, the TCM syndrome elements and potential syndrome types of patients were summarized. The Latern 5.0 software was used to establish a latent structure model and comprehensive clustering based on the mountain climbing method (LTM-EAST) algorithm, and analyze and judge the common syndrome types, providing a basis for proposing the clinical common syndrome types of this disease.Results:Factor analysis extracted 14 common factors, and the cumulative contribution rate was 63.254%. Among the 36 symptom variables with frequency ≥ 70, more than half of the patients with hypertension and insomnia were upset, irritable, less sleepy, dreamy, dizzy, palpitations, stuffy chest, dry mouth, easy to wake up, and tired. The tongue color was mainly light red tongue and red tongue. The tongue is mainly thin and greasy. The first three pulse conditions are string pulse, number pulse and slippery pulse. The disease location and syndrome elements of hypertension with insomnia were mainly liver (52.09%), heart (33.43%), spleen (26.46%) and kidney (23.68%); The disease syndrome elements are mainly phlegm dampness (34.54%), yin deficiency (29.25%), heat (fire) (25.35%), and qi stagnation (25.07%). Ten syndrome types are obtained by frequency statistics, nine syndrome types are obtained by factor clustering, and seven syndrome types are inferred by implicit structure clustering. Among the syndrome types inferred by the above three methods, there are seven syndrome types that recur at least twice, which can be identified as the common syndrome type of hypertension with insomnia.Conclusions:The common clinical symptoms of HWI are upset and irritable, less sleep, more dreams, dizziness, palpitations, stuffy chest, dry mouth, easy to wake up, mental fatigue and body tiredness. The disease location and syndrome elements are mainly in liver, heart, spleen and kidney. The disease mainly involves phlegm dampness, yin deficiency, heat and qi stagnation. The common clinical syndrome types are liver depression transforming fire type, yin deficiency and yang hyperactivity type, phlegm dampness intrinsic type, yin deficiency and internal heat type, heart and gallbladder qi deficiency type, heart and spleen deficiency type, and heart kidney disjunction type.

Objective: To investigate child injury prevention practice and associated factors among parents of primary school students. Methods: Parents of 2 577 students were selected from three primary schools in three administrative regions of Shanghai by multi stage sampling method between May and June in 2021. Questionnaire survey was administered to parents based on the Index System for Assessing Parent s Ability on Child Injury Prevention, which was developed previously by the present research group. Results were converted into standardized scores for descriptive analysis, and the original scores were analyzed by multiple linear regression model. Results: The standardized scores of parents on environment safety, product safety, behaviors and skills and psychological safety were (0.91±0.08)(0.93±0.08)(0.97±0.04)(0.95±0.05), respectively. The standardized score of general ability was (0.95±0.04). The standardized scores on knowledge, attitude and practice of injury prevention were (0.99±0.03)( 0.97± 0.05)(0.89±0.10), respectively. Mothers performances were generally better than fathers . Parents with higher education performed better than those with lower education. Parents with "being a parent" in mind performed better on child injury prevention. Conclusion There is a gap between practice with the knowledge as well as attitude towards child injury prevention among parents of primary school students. Parenting role, educational background and parental awareness of the importance of parental role are primary factors that affect child injury prevention practice.

Endometriosis（EMs） is a common chronic inflammatory gynecological disease，affecting about 5%-10% of women of childbearing age worldwide，and has always been a major challenge in clinical treatment. Huposan， derived from the Experiential Prescriptions for Universal Relief （《普济本事方》）， has the effects of moving qi， activating blood，expelling blood stasis， and relieving pain. It is often used to treat EMs clinically and has achieved good curative effect. The relevant studies on the treatment of EMs by Huposan were retrieved from databases， such as CNKI，PubMed，Wanfang Data， and VIP for summarizing the mechanisms of action and clinical application of Huposan in the treatment of EMs， aiming to provide ideas and references for the basic research and clinical application of Huposan. As revealed by basic experiments，Huposan could exert therapeutic effects on EMs through resisting cell adhesion by reducing intercellular adhesion molecule 1（ICAM-1）content，decreasing concentrations of matrix metalloproteinase（MMP）-2 and MMP-9 against ectopic endometrial invasion，inhibiting vascular endothelial growth factor（VEGF）expression for antiangiogenesis，inhibiting the expression of tumor necrosis factor-α（TNF-α）， interleukin （IL）-6， and IL-1，reversing helper T cell（Th）1/Th2 balance shifts to regulate the body's immune mechanism，and reducing the serum levels of nitric oxide（NO）and nitric oxide synthase（NOS）. In clinic practice，Huposan has the effects of reducing ectopic lesions，relieving pain symptoms，reducing serum carbohydrate antigen 125（CA125）content，improving hormone levels，regulating endocrine and immune factors，and reducing postoperative recurrence rate. Huposan plays a therapeutic role in EMs through multiple targets and mechanisms，which is worthy of further exploration and clinical promotion.

OBJECTIVE To study the chemical constituents in S henfu injection and the anti-inflammatory activities of its polyacetylene compounds. METHODS Shenfu injection was separated and purified by macroporous adsorption resin ，medium pressure liquid chromatography ，preparative thin layer chromatography and reversed-phase semi-preparative high-performance liquid chromatography，and the compound structure was identified according to the physicochemical properties and spectral data. RAW 264.7 cell inflammation model was used to evaluate the anti-inflammatory activities of polyacetylene compounds . The effects of active polyacetylene compounds on the expressions of cyclooxygenase- 2（COX-2）protein were evaluated by Western blot assay. RESULTS Twelves compounds were isolated and identified from Shenfu injection ，including 8 ginsenoside compounds ，i.e. ginsenoside Rg 1（1），ginsenoside Re （2），ginsenoside Rb 1（3），ginsenoside Rk 1（4），20（R）-ginsenoside Rh 1（5），20（S）-ginsenoside Rg3 （6），notoginsenoside R 1（7），panaxatriol（8）；4 polyacetylene compounds ，i.e.（3R，9R，10R）-panaxytriol（9），panaxydol（10）， heptadeca-1，8-dien-4，6-diyne-3，10-diol（11）and panaxynol （12）. Among 4 polyacetylene compounds ，only compound 10 had anti-inflammatory activity. Compound 10 was not toxic to normal RAW 264.7 cells；when the concentration of compound 10 ranged 12.5-50.0 μmol/L，it could significantly reverse the lipopolysaccharide-induced NO content increase in cell supernatant （P＜0.05 or P＜0.01）；when the concentration of co mpound 10 was 50.0 μmol/L，it could significantly reverse the lipopolysaccharide-induced protein expression increase of COX- 2 in cells （P＜0.05）. CONCLUSIONS Compounds 4，7，10-12 are identified and reported in Shenfu injection for the first time ，and panaxydol possesses a certain anti-inflammatory effect.

Autophagy is a lysosome-mediated catabolic process that captures and degrades dysfunctional organelles and useless proteins during cellular stress process， which plays a dual role in cervical cancer. In the early stage of cervical cancer， autophagy inhibits the occurrence and development of cervical cancer by prohibiting the accumulation of oncogenic p62 protein. In the advanced stage of cervical cancer， inhibition of autophagy of cancer cells enhances the sensitivity of cancer cells to chemotherapeutic drugs， thus inhibiting their proliferation. In recent years， the research on Chinese medicine monomers regulating autophagy in the treatment of cervical cancer has attracted extensive attention from scholars at home and abroad. Chinese medicine monomers regulate the autophagy of cervical cancer cells through multiple pathways and multiple targets， so as to increase the apoptosis rate and reduce the resistance of cancer cells to chemotherapeutic drugs. Therefore， this paper reviewed the mechanism of Chinese medicine monomers in inhibiting cervical cancer through autophagy， expecting to find new breakthroughs in the discovery and development of preventive and therapeutic drugs for cervical cancer. By reviewing the literature， it was found that in the early stage of cervical cancer， Chinese medicine monomers activated autophagy to promote apoptosis of cancer cells， and the main mechanism was to increase lysosomal membrane permeability and chemotherapeutic sensitivity and activate intact autophagy flow. In the advanced stage of cervical cancer， inhibition of autophagy reduced the sensitivity of cancer cells to chemotherapy drugs by inhibiting the formation of autophagosomes and autolysosomes. The treatment of cervical cancer by Chinese medicine monomers regulating autophagy has achieved certain effect， but there are few clinical experimental studies and lack of reliable clinical theoretical basis. Therefore， it is essential to carry out more clinical experimental studies on Chinese medicine monomers regulating autophagy to treat cervical cancer， thus finding more reliable theoretical basis for the treatment of tumors.

Objective: To construct and determine the weight of Index System for Assessing Parent s Ability on Child Injury Prevention, and to provide the basis for childhood injury intervention in family. Methods: Twenty four experts majored in related fields were invited to participate in Delphi consultation. The final index system was constructed according to the consulting results and the weight of primary and secondary indicators were calculated. Results: The final index system consisted of 5 subscales corresponding to 5 age groups: 0,1-2,3-5,6-11 and 12-17 years old. Each scale included 4 primary indicators and 11 secondary indicators. The weight of primary indicators obtained by analytic hierarchy process is 0.28 for "environment", 0.16 for "product", 0.31 for "behaviors and skills", and 0.25 for "psychology". The highest weight of secondary indicators for "environment", "product" and "behaviors and skills" was "water area", while the top secondary indicators for "psychology" included "parental style""emotional control" "family atmosphere", with all indicators weighted higher than 0.2. Conclusion The Index System for Assessing Parent s Ability on Child Injury Prevention by Delphi consultation is comprehensive in content, and with the focus on parental behaviors and skills on injury prevention.

Objective:To correlate peripheral blood hypersensitive C-reactive protein (hs-CRP) with cognitive function in patients with depression.Methods:Seventy-five patients with depression who received treatment in the Second People's Hospital of Lishui from January 2019 to May 2020 were included in the depression group. An additional 50 healthy controls were included in the control group. The MATRICS Consensus Cognitive Battery (MCCB) was used to evaluate participates' cognitive function. Serum hs-CRP level was determined using enzyme-linked immunosorbent assay.Results:Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in the depression group were significantly lower than those in the control group ( t = 10.774, 2.774, 9.840, 5.064, 7.915, all P < 0.01). Serum hs-CRP level in the depression group was significantly higher than that in the control group [(13.05 ± 2.94) mL vs. (1.13 ± 0.18) mL, t = 28.595, P < 0.01]. Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in patients with moderate and severe depression were significantly lower than those in patients with mild depression. Serum hs-CRP level in patients with moderate and severe depression was (10.41 ± 2.21) mg/L and (25.71 ± 4.04) mg/L, respectively, which was significantly higher than that in patients with mild depression [(3.03 ± 0.49) mg/L, t = 3.015, 3.370; 3.903, 3.441; 3.541, 3.604; 4.503, 4.661; 4.001, 3.980; 4.035, 3.669, all P < 0.01]. Speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores in patients with severe depression were significantly lower than those in patients with moderate depression ( t = 8.331, 5.227, 10.031, 6.003, 9.416, all P < 0.01). Serum hs-CRP level in patients with severe depression was significantly higher than that in patients with moderate depression [(25.71 ± 4.04) mg/L vs. (10.41 ± 2.21) mg/L, t = 11.005, P < 0.01]. Pearson correlation analysis showed that serum hs-CRP level in patients with depression was remarkably negatively correlated with speed of processing, working memory, verbal learning, visual learning and reasoning/problem-solving scores (all P < 0.01). Conclusion:Serum hs-CRP level in patients with depression is greatly increased, can reflect the severity of depression and is related to cognitive function.