Gene therapy, harnessing the power of CRISPR-Cas9 and/or DNAzyme systems, stands as a pivotal approach in cancer therapy, enabling the meticulous manipulation of genes pivotal to tumorigenesis and immunity. However, the pursuit of precise gene therapy encounters formidable hurdles. Herein, a near-infrared upconversion theranostic nanomachine is devised and tailors for CRISPR-Cas9/DNAzyme systems mediate precise gene therapy. An ingenious logic DNAzyme system consists of Chain 1 (C1)/Chain 2 (C2) and endogenous lncRNA is designed. We employ manganese modified upconversion nanoparticles for carrying ultraviolet-responsive C1-PC linker-C2 (C₂P) chain and Cas9 ribonucleoprotein (RNP), with outermost coats with hyaluronic acid. Upon reaching tumor microenvironment (TME), the released Mn²⁺ ions orchestrate a trifecta: facilitating endosomal escape, activating cGAS-STING signaling, and enabling T1-magnetic resonance imaging. Under near-infrared irradiation, Cas9 RNP/C₂P complex dissociates, releasing Cas9 RNP into the nucleus to perform gene editing of Ptpn2, while C1/C2 chains self-assemble with endogenous lncRNA to form a functional DNAzyme system, targeting PD-L1 mRNA for gene silencing. This strategy remodels the TME by activating cGAS-STING signaling and dual immune checkpoints blockade, thus realizing tumor elimination. Our theranostic nanomachine armed with the CRISPR-Cas9/DNAzyme logic systems, represents a resourceful and promising strategy for advancing cancer systemic immunotherapy and precise gene therapy.

Objective:To explore the clinical efficiency of cognitive behavioral training combined with methylphenidate hydrochloride sustained-release tablets on children with attention-deficit hyperactivity disorder (ADHD).Methods:118 children with ADHD in Northwest Women' s and Children' s Hospital were selected from June 2022 to July 2023. Based on the principle of baseline feature matching between groups, they were randomly divided into MPH group and combined group by coin tossing method, with 59 cases in each group. Children in the MPH group were treated with MPH sustained-release tablets orally (The initial dose was 18mg each time, whole tablet was swallowed in the morning, dose adjustment was increased by 18 mg each time, once a week, and maximum dose was not more than 54 mg), while the children in the combined group were combined with cognitive behavior training on the basis of the treatment in the MPH group. Children in both groups were continuously treated for 3 months. The clinical efficacy, scores of dimensions of Swanson Nolan and Pelham, rating scale-version IV (SNAP-IV) parent edition, scores of Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), scores of Wisconsin Card Sorting Test (WCST) and serological indicators [dopamine, 25 (OH)D 3, cortisol, brain-derived neurotrophic factor (BDNF)] before and after treatment and incidence of adverse reactions were compared between groups. Results:After 3 months of treatment, the combined group [93.2%(55/59)] had higher total effective rate than the MPH group [79.7% (47/59)] ( χ2=4.63, P=0.031). The scores of three dimensions, including attention deficit, hyperactivity-impulsion and oppositional defiance in both groups were lower than those before treatment, and the scores in combined group were lower than those in MPH group, the differences were statistically significant [(1.27±0.19) points vs (1.65±0.23) points, (1.35±0.25) points vs (1.78±0.27) points, (1.55±0.13) points vs (1.86±0.22) points, t=9.78, 8.98, 9.32,respectively, all P<0.001]. The control quotient score and attention quotient score were higher than those before treatment, and the scores in combined group were higher than those in MPH group, the differences were statistically significant [(99±6) points vs (91±3) points, (98±5) points vs. (92±3) points, t=8.47, 7.46,respectively, all P<0.001]. The total response count, completed categories count and correct response count were all higher than those before treatment, and the scores were higher in combination group than those in MPH group, the differences were statistically significant [(116±16) points vs(105±14) points, (4.57±0.35) points vs (4.15±0.25) points, (83±12) points vs (72±10) points, t=4.07, 7.50, 5.48, respectively, all P<0.001). Perspective response count was lower than that before treatment, and the score in combined group was lower than that in MPH group, the difference was statistically significant [(15.6±1.8) points vs (18.2±2.0) points, t=7.35, P<0.001]. Serum levels of dopamine, 25(OH)D 3 and BDNF were higher than those before treatment, and the levels in combined group were all higher than those in MPH group, the differences were statistically significant [(16.2±2.8) pmol/L vs (13.8±2.4) pmol/L, (78±10) nmol/L vs. (70±9) nmol/L, (1 060±135) pmol/L vs (986±126) pmol/L, t=5.00, 4.59, 3.08, respectively, all P<0.05]. Serum cortisol level was lower than that before treatment, and the level in combined group was lower than that in MPH group, the difference was statistically significant [(255±27) nmol/L vs (271±28) nmol/L, t=3.16, P=0.002]. There was no statistical significance difference in the incidence rate of adverse reactions between combined group and MPH group during treatment [6.8% (4/59) vs 5.1% (3/59)] ( χ2=0.00, P=1.000). Conclusion:Cognitive behavioral training combined with MPH sustained-release tablets in the treatment of children with ADHD can significantly enhance the efficacy, improve the ADHD symptoms and cognitive function, and increase the levels of serum dopamine and 25 (OH)D 3, and have good safety.

Objective To analyze the involvement of pharmacists in the pharmaceutical care of olfacatumumab in the treatment of elderly patients with refractory anti-metabotropic glutamate receptor 5(mGluR5)encephalitis and to provide a reference for the treatment and pharmaceutical care of patients with refractory autoimmune encephalitis(AE).Methods An 81-year-old patient with anti-mGluR5 encephalitis who had poor first-line immunotherapy effect.The key points of pharmaceutical care were determined according to the patient's condition and the characteristics of therapeutic drugs.The drug selection,administration mode,drug interaction,adverse reactions,and precautions of ofatumumab were put forward.At the same time,the patients and their families were given medication guidance and discharge education,and regular follow-up was carried out.Results With the cooperation of doctors,the patient was provided with whole-process pharmaceutical care,and the patient's condition was improved,and the patient's condition was good so far.Conclusion Clinical pharmacists pay attention to the effectiveness and safety of the treatment with ofatumumab by carrying out individualized pharmaceutical care for this patient,which fully reflects the value of clinical pharmacists and provides a reference for the treatment and pharmaceutical care of refractory AE patients.

To investigate the in vitro inhibitory mechanism of Nymphaea candida total flavonoids(NCTF)against Staphylococcus aureus(S.aureus)and its safety in mice,this study first deter-mined the antibacterial effect of NCTF on the clinically isolated strain S.aureus-C1.Subsequently,the inhibitory mechanism of NCTF on S.aureus-C1 was explored by measuring its effects on bac-terial growth curves,microstructure,intracellular AKP and LDH levels,and biofilm formation.Safety evaluation included determination of LD50 and MDT in mice,as well as analysis of serum biochemical parameters,organ indices,and histopathological observations.Results showed that NCTF effectively inhibited S.aureus-C1 proliferation,with an inhibition zone diameter of(18.98±0.67)mm and a MIC of 6.25 g/L.A concentration of 2×MIC nearly completely suppressed bacte-rial growth.Scanning electron microscopy revealed structural damage to bacterial cells,including collapse and shrinkage.AKP and LDH assays indicated significantly increased AKP activity(P＜0.05)and decreased intracellular LDH activity(P＜0.05)in the supernatant of drug-treated groups,demonstrating NCTF-induced disruption of cell walls and membranes leading to leakage of AKP and LDH.Crystal violet staining of biofilms showed significant inhibition rates of(43.77±9.16)％and(61.71±9.82)％at 2 × MIC and 4 × MIC concentrations,respectively(P＜0.05).Safe-ty assessments indicated low toxicity of NCTF in mice,with transient effects that returned to nor-mal levels within a short period.These findings demonstrate that NCTF exhibits potent antibacte-rial activity against S.aureus-C1 by damaging bacterial cell structures,increasing cell wall/mem-brane permeability,reducing biofilm formation,and displaying low toxicity.This study provides scientific evidence for clinical drug screening against bovine mastitis and the development of Nym-phaea candida resources.

To investigate the in vitro inhibitory mechanism of Nymphaea candida total flavonoids(NCTF)against Staphylococcus aureus(S.aureus)and its safety in mice,this study first deter-mined the antibacterial effect of NCTF on the clinically isolated strain S.aureus-C1.Subsequently,the inhibitory mechanism of NCTF on S.aureus-C1 was explored by measuring its effects on bac-terial growth curves,microstructure,intracellular AKP and LDH levels,and biofilm formation.Safety evaluation included determination of LD50 and MDT in mice,as well as analysis of serum biochemical parameters,organ indices,and histopathological observations.Results showed that NCTF effectively inhibited S.aureus-C1 proliferation,with an inhibition zone diameter of(18.98±0.67)mm and a MIC of 6.25 g/L.A concentration of 2×MIC nearly completely suppressed bacte-rial growth.Scanning electron microscopy revealed structural damage to bacterial cells,including collapse and shrinkage.AKP and LDH assays indicated significantly increased AKP activity(P＜0.05)and decreased intracellular LDH activity(P＜0.05)in the supernatant of drug-treated groups,demonstrating NCTF-induced disruption of cell walls and membranes leading to leakage of AKP and LDH.Crystal violet staining of biofilms showed significant inhibition rates of(43.77±9.16)％and(61.71±9.82)％at 2 × MIC and 4 × MIC concentrations,respectively(P＜0.05).Safe-ty assessments indicated low toxicity of NCTF in mice,with transient effects that returned to nor-mal levels within a short period.These findings demonstrate that NCTF exhibits potent antibacte-rial activity against S.aureus-C1 by damaging bacterial cell structures,increasing cell wall/mem-brane permeability,reducing biofilm formation,and displaying low toxicity.This study provides scientific evidence for clinical drug screening against bovine mastitis and the development of Nym-phaea candida resources.

Objective To analyze the involvement of pharmacists in the pharmaceutical care of olfacatumumab in the treatment of elderly patients with refractory anti-metabotropic glutamate receptor 5(mGluR5)encephalitis and to provide a reference for the treatment and pharmaceutical care of patients with refractory autoimmune encephalitis(AE).Methods An 81-year-old patient with anti-mGluR5 encephalitis who had poor first-line immunotherapy effect.The key points of pharmaceutical care were determined according to the patient's condition and the characteristics of therapeutic drugs.The drug selection,administration mode,drug interaction,adverse reactions,and precautions of ofatumumab were put forward.At the same time,the patients and their families were given medication guidance and discharge education,and regular follow-up was carried out.Results With the cooperation of doctors,the patient was provided with whole-process pharmaceutical care,and the patient's condition was improved,and the patient's condition was good so far.Conclusion Clinical pharmacists pay attention to the effectiveness and safety of the treatment with ofatumumab by carrying out individualized pharmaceutical care for this patient,which fully reflects the value of clinical pharmacists and provides a reference for the treatment and pharmaceutical care of refractory AE patients.

Objective:To explore the clinical efficiency of cognitive behavioral training combined with methylphenidate hydrochloride sustained-release tablets on children with attention-deficit hyperactivity disorder (ADHD).Methods:118 children with ADHD in Northwest Women' s and Children' s Hospital were selected from June 2022 to July 2023. Based on the principle of baseline feature matching between groups, they were randomly divided into MPH group and combined group by coin tossing method, with 59 cases in each group. Children in the MPH group were treated with MPH sustained-release tablets orally (The initial dose was 18mg each time, whole tablet was swallowed in the morning, dose adjustment was increased by 18 mg each time, once a week, and maximum dose was not more than 54 mg), while the children in the combined group were combined with cognitive behavior training on the basis of the treatment in the MPH group. Children in both groups were continuously treated for 3 months. The clinical efficacy, scores of dimensions of Swanson Nolan and Pelham, rating scale-version IV (SNAP-IV) parent edition, scores of Integrated Visual and Auditory Continuous Performance Test (IVA-CPT), scores of Wisconsin Card Sorting Test (WCST) and serological indicators [dopamine, 25 (OH)D 3, cortisol, brain-derived neurotrophic factor (BDNF)] before and after treatment and incidence of adverse reactions were compared between groups. Results:After 3 months of treatment, the combined group [93.2%(55/59)] had higher total effective rate than the MPH group [79.7% (47/59)] ( χ2=4.63, P=0.031). The scores of three dimensions, including attention deficit, hyperactivity-impulsion and oppositional defiance in both groups were lower than those before treatment, and the scores in combined group were lower than those in MPH group, the differences were statistically significant [(1.27±0.19) points vs (1.65±0.23) points, (1.35±0.25) points vs (1.78±0.27) points, (1.55±0.13) points vs (1.86±0.22) points, t=9.78, 8.98, 9.32,respectively, all P<0.001]. The control quotient score and attention quotient score were higher than those before treatment, and the scores in combined group were higher than those in MPH group, the differences were statistically significant [(99±6) points vs (91±3) points, (98±5) points vs. (92±3) points, t=8.47, 7.46,respectively, all P<0.001]. The total response count, completed categories count and correct response count were all higher than those before treatment, and the scores were higher in combination group than those in MPH group, the differences were statistically significant [(116±16) points vs(105±14) points, (4.57±0.35) points vs (4.15±0.25) points, (83±12) points vs (72±10) points, t=4.07, 7.50, 5.48, respectively, all P<0.001). Perspective response count was lower than that before treatment, and the score in combined group was lower than that in MPH group, the difference was statistically significant [(15.6±1.8) points vs (18.2±2.0) points, t=7.35, P<0.001]. Serum levels of dopamine, 25(OH)D 3 and BDNF were higher than those before treatment, and the levels in combined group were all higher than those in MPH group, the differences were statistically significant [(16.2±2.8) pmol/L vs (13.8±2.4) pmol/L, (78±10) nmol/L vs. (70±9) nmol/L, (1 060±135) pmol/L vs (986±126) pmol/L, t=5.00, 4.59, 3.08, respectively, all P<0.05]. Serum cortisol level was lower than that before treatment, and the level in combined group was lower than that in MPH group, the difference was statistically significant [(255±27) nmol/L vs (271±28) nmol/L, t=3.16, P=0.002]. There was no statistical significance difference in the incidence rate of adverse reactions between combined group and MPH group during treatment [6.8% (4/59) vs 5.1% (3/59)] ( χ2=0.00, P=1.000). Conclusion:Cognitive behavioral training combined with MPH sustained-release tablets in the treatment of children with ADHD can significantly enhance the efficacy, improve the ADHD symptoms and cognitive function, and increase the levels of serum dopamine and 25 (OH)D 3, and have good safety.

Objective:To explore the application effect of rehabilitation nursing based on gratitude extension-construction theory in postoperative patients with endometrial cancer.Methods:Using the convenient sampling method, a total of 80 patients with endometrial cancer who were admitted to the Affiliated Hospital of Jining Medical University from January 2019 to December 2021 were selected as the research objects. The patients were divided into the observation group (42 cases) and the control group (38 cases) using the random number table method. The control group received routine nursing interventions, while the observation group received rehabilitation nursing interventions based on gratitude extension-construction theory. Psychological distress, gratitude, fear of cancer recurrence, quality of life and pelvic floor function were compared between the two groups before and after intervention.Results:After intervention, the scores of psychological distress, cancer recurrence and Pelvic Floor Distress Inventory score in the observation group were lower than those in the control group, and the scores of gratitude and quality of life in the observation group were higher than those in the control group, and the differences were statistically significant ( P<0.05) . Conclusions:Rehabilitation nursing based on gratitude extension-construction theory can increase the gratitude level of patients undergoing endometrial cancer surgery, promote the recovery of pelvic floor function, reduce psychological pain and cancer recurrence concerns and improve their quality of life.

OBJECTIVE To analyze the influential factors of cardioto xicity in patients with positive breast cancer of human epidermal growth factor receptor 2（HER-2）treated by trastuzumab combined with chemotherapy. METHODS From April 2017 to January 2021，200 HER-2 positive breast cancer patients receiving pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab were collected from our hospital. According to the presence or absence of cardiotoxicity ，the patients were divided into cardiotoxicity group and non-cardiotoxicity group. The clinical data and echocardiographic results of the patients were collected，and the influential factors of cardiotoxicity were analyzed. RESULTS Among 200 patients，43 patients suffered from cardiotoxicity with the incidence of 21.5％. The proportion of patients with cardiotoxicity during pirarubicin+cyclophosphamide therapy accounted for 5.5％（11/200），and the proportion of patients with cardiotoxicity during sequential paclitaxel+trastuzumab therapy accounted for 20.5％（41/200）；the latter was significantly higher than the former （P＜0.01）. At the same time ，the decrease of left ventricular ejection fraction during sequential therapy of paclitaxel and trastuzumab was significantly higher than that during pirarubicin+cyclophosphamide therapy [ 14％（12％，17％）vs. 7％（3％，10％），P＜0.001]. Compared with patients without cardiotoxicity ，the proportion of patients with cardiotoxicity with a history of hyperlipidemia was significantly higher （P＜ 0.01），while the proportion of patients receiving dexrazoxane was significantly lower （P＜0.01）. Results of binary Logistic regression analysis showed that the history of hyperlipidemia [OR ＝3.672，95％ CI（1.499，8.992），P＝0.004] and the use of dextrazoxane [OR ＝0.154，95％ CI（0.072，0.330）， P＜0.001] were associated with the occurrence of cardiotoxicity. CONCLUSIONS Hyperlipidemia is an independent risk factor for cardiotoxicity induced by pirarubicin + cyclophosphamide combined with sequential paclitaxel+trastuzumab in HER 2 positive breast cancer patients ，while the use of dextrazoxane is a protective factor.

A 66-year-old female patient regularly received nifedipine sustained release tablets 20 mg twice daily and captopril 25 mg once daily by mouth for 2 years due to hypertension. Low blood glucose (3.0 mmol/L) appeared in recent 1 year, frequent hypoglycemic coma occurred in recent 4 months. Laboratory tests showed minimum fasting glucose 1.6 mmol/L, insulin 12 mU/L, C-peptide 1.78 nmol/L, and positive anti-insulin antibody. Insulin autoimmune syndrome was considered, which might be associated with captopril. Then captopril was stopped, nifedipine sustained-release tablets was continued, irbesartan hydrochlorothiazide was added, and prednisone 30 mg orally once daily was given at the same time. In addition, the patient was asked to adjust diet, including low carbohydrate and eating less and often. After stopping captopril for 3 days, her blood glucose was between 4.3 to 11.2 mmol/L, and hypoglycemia did not recur.