BackgroundPatients with chronic schizophrenia often suffer from cognitive impairment. Traditional cognitive rehabilitation training has problems such as a single form and poor compliance， making it urgent to develop new cognitive intervention methods. ObjectiveTo explore the intervention effect of smartphone games on the cognitive function of patients with chronic schizophrenia， and to analyze the differences in cognitive function improvement between patients of different genders， in order to provide references for the cognitive function intervention of these patients. MethodsThis study was a prospective cohort study. A total of 30 patients who were hospitalized in the Psychiatry Department of Chaohu Hospital Affiliated to Anhui Medical University from March to October 2021， met the diagnostic criteria for schizophrenia as defined in the International Classification of Diseases， tenth edition （ICD-10）， and had a disease duration of above 5 years， were selected as the research subjects. All patients received smartphone game intervention for 12 weeks， 5 times a week， each session lasting 1 hour， in addition to conventional antipsychotic drug treatment. At the baseline and at 3， 6， 9， and 12 weeks of the intervention， the cognitive function was evaluated using the Repeatable Battery for the Assessment of Neuropsychological Status （RBANS）， the Positive and Negative Syndrome Scale （PANSS） was used to assess mental symptoms， and the Problematic Mobile Gaming Questionnaire （PMGQ） was used to assess addiction symptoms. ResultsA total of 26 patients （86.67%） completed the study， including 13 females and 13 males. The time effects， group effects， and interaction effect between time and group for the immediate memory factor score of RBANS in the female group and the male group were all statistically significant （F=36.682， 5.712， 3.090， P<0.05 or 0.01）， and the time effects and group effects for the verbal and delayed memory factors as well as the total score in both groups were also statistically significant （F=3.841， 6.149， 15.372， P<0.05 or 0.01）. The time effects and group effects of the total score of PANSS in both groups had no statistical significance （F=2.041， 0.623， P>0.05 for both）， and the interaction effect between time and group was statistically significant （F=5.728， P<0.01）. The time effects， group effects， and interaction effect of the total score of PMGQ in both groups were all without statistical significance （F=2.672， 0.166， 0.642， P>0.05 for both）. ConclusionSmartphone game intervention may help improve the cognitive function of patients with chronic schizophrenia （especially immediate memory， verbal function， and delayed memory）， and the benefits are greater for female patients. The smartphone game intervention did not induce game addiction， but no significant improvement in psychotic symptoms was observed. ［Funded by Excellent Young Talents Support Program of Anhui Provincial Department of Education （number， gxyqZD2022022）； www.chictr.org.cn number， ChiCTR2100044113］

Biohybrid robots are hybrid systems that deeply integrate living biological components （such as cells, tissues, organs, or microorganisms） with artificial synthetic components （including sensors, actuators, control systems, and structural materials）. Focusing on key advancements in cellular/microbial-level and tissue-level biohybrid robots, the applications in two major scenarios: targeted drug delivery in vivo and drug evaluation in vitro were reviewed. International research progress demonstrated that biohybrid robots offered novel solutions for overcoming deep tissue delivery barriers, enhancing biocompatibility, and enabling real-time monitoring. However, their clinical translation still faced critical challenges, including reproducibility, in vivo/in vitro nutrient supply, encapsulation technologies, and safety regulatory frameworks.

Objective To understand the epidemiological characteristics of severe congenital heart dis-ease in Chongqing City during 2007-2023 to provide a basis for its comprehensive prevention and control measures.Methods Based on hospital monitoring data,453 children patients with severe congenital heart dis-ease monitored by the birth defects monitoring institutions in Chongqing city from January 2007 to December 2023 were included in the study.They were grouped by year,perinatal infants gender,maternal permanent res-idence(urban/rural),maternal age,different regions and other categories.The χ2 test was used to analyze the difference in the incidence rate of different categories of severe congenital heart diseases,and the Joinpoint re-gression model was used to analyze the change trend.Results A total of 1 468 005 perinatal neonates were monitored in Chongqing City during 2007-2023 and 453 cases of severe congenital heart disease were found,with an incidence rate of 3.09/10 000,in which the incidence rate of atrioventricular septal defect was 2.16/10 000,the incidence rate of tetralogy of fallot was 0.66/10 000 and the incidence rate of transposition of great ar-teries was 0.27/10 000.The total incidence rate of cities and towns was higher than that in the countryside(χ2=64.08,P<0.001),the urban area was higher than the Chongqing southeast and Chongqing northeast towns cluster(χ2=49.34,P<0.001),the female was higher than the male(χ2=5.63,P=0.018).The inci-dence rates in different ages groups showed the U shape distribution(χ2=31.63,P<0.001).The incidence rate of the pregnant women<20 years old group and pregnant women≥35 years old group was higher,which of the 25-29 years old group was lower.The incidence rate of severe congenital heart disease in Chongqing City during 2007-2023 appeared the turning point,which during 2007-2016 was gradually increased(APC=-15.95),and which during 2016-2023 was gradually decreased(APC=-15.36).Conclusion The incidence rate of severe congenital heart disease in Chongqing city during 2007-2023 was increased first and then de-creased,moreover there were differences in time,region and population.

Using a novel(OH)n-C60@SiO2@Tm2O3@Ca5(PO4)3(OH)quaternary nano-particles/cross-linked chitosan coated open-tubular capillary column(QNPsC-OTCC)as the analytical column,a new method for highly selective determination of taurine(TAU)in functional drinks using pre-column derivatization capillary electrochromatography coupled with electrochemiluminescence(CEC-ECL)detection was established.In the experiments,it was found that adding hexamethylenetetramine as a co-catalyst in N-methylation derivative reaction could quantitatively convert TAU into a single derivative product that cuold be detected by ECL.With the help of Ru(bpy)32+reagent,the ECL peak intensity of TAU derivative was increased by more than 1000 times compared to the original TAU.In addition,a Ru-containing d-f cyano-bridged heterometallic coordination polymer modified platinum electrode was used instead of a bare platinum electrode as working electrode for ECL detection,which resulted in a further increase of the peak response of TAU derivatives about 5.7 times.Under optimized analytical conditions,by using betastatin hydrochloride(BSH)as the internal standard and simultaneously derivatized with TAU,the relative ratio of peak intensity of TAU and BSH derivatives showed a linear relationship with the initial TAU concentration in a two-segment ranges of 0.2-6.0 mmol/L and 6.0-10 mmol/L.The limit of detection of TAU was 0.09 mmol/L(S/N=3).The developed method was applied to determination of TAU contents in four commercial functional drink samples,and the relative standard deviations(RSDs)for relative intensity ratio were less than 0.9％,and the recoveries were in the range of 95.0％～102.0％,indicating good practicability of the method.

Objective To investigate the relationship between serum kininogen-1(KNG1)and tissue inhib-itor of metalloproteinases-3(TIMP3)levels and coronary artery lesions(CAL)in children with Kawasaki dis-ease(KD)at the acute phase.Methods A total of 132 children with KD at the acute phase admitted to the hospital from October 2020 to February 2024 were selected as the KD group,and were divided into CAL group(66 cases)and non CAL group(66 cases)according to whether they were combined with CAL.In addition,66 healthy children during the same period were selected as the control group.Serum KNG1 and TIMP3 levels were measured using enzyme-linked immunosorbent assay.A multivariate unconditional Logistic regression model with CAL as the dependent variable was established to identify independent factors influencing CAL in children with KD at the acute phase.Receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of serum N-terminal pro-brain natriuretic peptide(NT-proBNP),KNG1,and TIMP3 levels for CAL in children with KD at the acute phase.Results Compared to the control group,serum KNG1 level was elevated in the KD group(P<0.05),and TIMP3 level was reduced(P<0.05).In the CAL group,serum KNG1 level was higher(P<0.05),and TIMP3 level was lower compared to the non CAL group(P<0.05).Independent risk factors for CAL in children with KD at the acute phase included immunoglobulin resistance(OR=5.618,95%CI:1.203-26.248),increased NT-proBNP level(OR=1.003,95%CI:1.000-1.005),and increased KNG1 level(OR=1.648,95%CI:1.251-2.173),while increased TIMP3 level was identified as an independent protective factor(OR=0.966,95%CI:0.949-0.983,P<0.05).The combination of serum NT-proBNP,KNG1,and TIMP3 levels yielded an area under the curve of 0.930 for predicting CAL in children with KD at the acute phase,which was larger than 0.785,0.801,0.792 of NT-proBNP,KNG1,and TIMP3 a-lone(P<0.05).Conclusion increased level of serum KNG1 and decreased level of TIMP3 are independently associated with the occurrence of CAL in children with KD at the acute phase.The combined prediction of ser-um NT-proBNP,KNG1,and TIMP3 levels has high value in predicting CAL in children with KD at the acute phase.

Objective To investigate the relationship between serum microRNA-101-3p(miR-101-3p),pol-ypeptide N-acetylgalactosaminyltransferase 1(GALNT1)and the efficacy and prognosis of neoadjuvant chem-otherapy(NAC)in breast cancer.Methods A total of 203 breast cancer patients who underwent NAC in this hospital from January 2017 to August 2019 were selected as breast cancer group.They were divided into the ineffective group and the effective group according to the therapeutic effect of NAC,and divided into the death group and the survival group according to the 5-year survival situation.Additionally,203 healthy women who underwent routine physical examination during the same period were selected as the control group.The clini-cal data and the levels of serum miR-101-3p and GALNT1 were detected and compared.The binding sites of miR-101-3p and GALNT1 were predicted through the online database.Pearson correlation analysis was per-formed to assess the correlation between serum miR-101-3p and GALNT1 expression in breast cancer pa-tients.The relationship between serum miR-101-3p,GALNT1 and the efficacy and prognosis of NAC in breast cancer patients were analyzed by multivariate unconditional Logistic regression and Cox regression.The pre-dictive value of serum miR-101-3p and GALNT1 for the ineffectiveness and mortalit of NAC treatment in breast cancer patients were analyzed by receiver operating characteristic(ROC)curve.Results Compared with the control group,the expression level of serum miR-101-3p in the breast cancer group decreased,and the level of GALNT1 increased,and the differences were statistically significant(P＜0.05).Serum miR-101-3p in patients with breast cancer was negatively correlated with GALNT1(P＜0.05).High expression of Ki-67,≥4 axillary lymph node metastases after surgery and high expression of GALNT1 were independent risk factors for ineffective NAC treatment in breast cancer patients(P＜0.05),and high expression of miR-101-3p was an independent protective factor(P＜0.05).TNM stage Ⅲ,postoperative axillary lymph node metastasis ≥10,and high expression of GALNT1 were independent risk factors for ineffective NAC treatment in breast cancer patients(P＜0.05),while high expression of miR-101-3p was an independent protective fac-tor(P＜0.05).The predictive efficacy of combined detection of serum miR-101-3p and GALNT1 for ineffec-tive NAC treatment and death in breast cancer patients was higher than that predicted by either of them alone(both P＜0.05).Conclusion Low serum miR-101-3p and high GALNT1 expression in breast cancer patients are closely related to NAC efficacy and prognosis.The combination of the two has a high predictive value for both the efficacy and prognosis of NAC.

Lung cancer poses a serious threat to global public health security.Chemotherapy,as the main strategy for cancer treatment,faces challenges such as high toxicity and drug resistance.Anticancer peptides have the potential of being developed into new anticancer drugs due to their advantages of broad-spectrum anticancer activity,rapid action,and difficulty in generating drug resistance,but they also face shortcomings such as weak activity and strong toxic side effects.The weakly acidic microenvironment of tumors(pH 6.5-6.8)provides a good idea for the design of anticancer peptides of high-efficiency and low-toxicity.Previously,we designed the acid-sensitive antibacterial peptide pHly-1 using the wolf spider(Lycosa singoriensis)toxin Lycosin-Ⅰ as a template.In this study,we found that pHly-1 also had acid-sensitive anticancer activity.Further alanine scanning analysis of pHly-1 was carried out,and we ob-tained a mutant pHTP-2 with better acid sensitivity,whose IC50(half maximal inhibitory concentration)against A549 cells was 15.68 μmol/L at pH 6.6 and was greater than 100 μmol/L at pH 7.4.At pH 6.6,pHTP-2 could act on various lung cancer cell lines and induce the death of A549 cells by rapid ly-sis;at pH 7.4,500 μmol/L pHTP-2 had weak toxicity to red blood cells(the hemolysis rate was ap-proximately 38％)and primary myocardial cells(the inhibition rate was 49.7％,with P＜0.05).Analy-sis of its charge,particle size,morphology,and secondary structure showed that at pH 6.6,the histidine in the sequence of pHTP-2 was protonated,increasing the positive charge(P＜0.01),decreasing the hy-drated particle size(P＜0.05)and forming an α-helical structure to induce membrane lysis of A549 cells.At pH 7.4,it was deprotonated,the positive charge decreases,a β-sheet structure was formed and self-aggregation occurred,limiting its effect on the A549 cell membrane and showing weak activity.In summary,pHTP-2 could respond to the weakly acidic microenvironment of tumors to exert selective cyto-toxic activity,effectively overcoming the shortcomings of anticancer peptides such as low efficiency and high toxicity.Our findings suggest that it is a high-quality lead molecule for anticancer drugs.

Pancreatic cancer has emerged as one of the most challenging malignancies worldwide,with its high resistance to chemotherapy being the primary cause of treatment failure.Therefore,enhancing the chemosensitivity of pancreatic cancer has become a major focus of current research.In this study,we in-vestigated how Bufotaline,a bufadienolide extracted from the traditional Chinese medicine toad venom,exhibits its antitumor activity.Specifically,we explored the potential of Bufotaline to enhance the chemo-sensitivity of pancreatic cancer cells to Adriamycin and elucidated its underlying molecular mechanisms.Using CCK-8 and colony formation assays,we demonstrated that Bufotaline enhances the inhibitory effect of Adriamycin on the survival of pancreatic cancer cell lines Patu-8988T,Aspc-1,and Patu-8988S.No-tably,Bufotaline treatment reduced the IC50 of Adriamycin in drug-resistant pancreatic cancer cells to lev-els comparable to those in non-resistant cells.Results from Western blot,immunofluorescence,comet as-say,and TUNEL assays revealed that Bufotaline promotes Adriamycin-induced DNA damage in pancreatic cancer cells.RNA-seq analysis of Patu-8988T cells treated with Adriamycin alone or in combination with Bufotaline showed significant changes in gene expression,and qRT-PCR analysis further confirmed that Bu-fotaline downregulates the expression of DNA damage repair proteins NBS1 and RAD50.Moreover,Western blot analysis revealed that Bufotaline reduces the levels of DNA damage response repair proteins,and Im-munofluorescence experiments indicated that Bufotaline inhibits the activation of the ATM/CHK2 signaling pathway.Finally,in a subcutaneous xenograft mouse model,the combination of Adriamycin and Bufotaline treatment significantly suppressed pancreatic cancer cell growth.In conclusion,Bufotaline enhances Adria-mycin-induced chemosensitivity in pancreatic cancer cells;the combination of Adriamycin and Bufotaline downregulates the expression of DNA damage response repair proteins NBS1 and RAD50,and inhibits the ATM/CHK2-mediated DDR signaling pathway,thereby delaying DNA damage repair.

Objective:To explore the effect of CO2 fractional laser combined with glucocorticoid(GC)on T follicular helper cell(Tfh)and B cell subsets in patients with advanced vitiligo(VL).Methods:Patients with advanced VL(128 cases)who were treated in Affiliated Hospital of Hebei University of Engineering from August 2019 to March 2022 were selected as research objects,and divided into group A(64 cases,CO2 fractional laser combined with GC)and group B(64 cases,CO2 fractional laser)according to different treatment methods,clinical efficacy and safety of the two groups were compared.Another healthy subjects(64 cases)were selected as control group.Collected clinical data of the three groups of subjects for comparative analysis.Randomized walking model was used to evaluate the effect of CO2 fractional laser combined with GC on immune function and inflammatory response in patients with advanced VL.Results:Compared with group B,group A had a higher clinical total effective rate(P<0.05)and a lower probability of adverse reactions(P<0.05).After treatment,compared with control group,proportion of Tfh2 and Tfh17 in group A had no significant difference(P>0.05),while proportion of Tfh2 and Tfh17 in group B still had significant difference(P<0.05);compared with group B,proportion of Tfh2 in group A after treatment was higher(P<0.05),while proportion of Tfh17 type was lower(P<0.05).After treat-ment,compared with control group,proportion of memory transformed B cell in group B was still significantly different(P<0.05).After treatment,compared with control group,levels of IgA,IgE and IgM in group B were still significantly different(P<0.05);compared with group B,level of IgM in group A was higher after treatment(P<0.05).After treatment,compared with control group,levels of IL-21 and IL-1β in group B were still significantly different(P<0.05);compared with group B,level of IL-10 in group A after treatment was higher(P<0.05),while levels of IL-21 and IL-1β were lower(P<0.05).Evaluation results of random walking model showed that the improvement of immune function and inflammatory reaction in group A was better than that in group B.Conclusion:CO2 fractional laser combined with GC can improve the immune function and inflammatory reaction of patients with advanced VL better after treatment,and the probability of adverse reactions is lower.