[摘 要] 目的：构建负载STING激动剂DMXAA的锰卟啉金属有机框架纳米颗粒（DPM），探讨其对三阴性乳腺癌（TNBC）细胞4T1及其小鼠移植瘤的治疗效果。方法：通过物理吸附法制备 DPM 纳米颗粒，利用透射电镜、扫描电镜及纳米粒度电位仪表征其形貌与理化性质。常规培养4T1细胞，细胞实验分为对照组、超声辐照组（US组）、DPM治疗组（DPM组）和DPM治疗联合超声辐照组（DPM + US组），用CCK-8法检测细胞活性，免疫荧光法检测高迁移率族蛋白B1（HMGB1）和钙网蛋白（CRT）的表达，WB法检测STING通路相关蛋白的表达。构建4T1细胞移植瘤小鼠模型，分为四组，处理同细胞实验，测量肿瘤体积，免疫荧光法检测移植瘤组织中Ki-67、HMGB1、CRT和缺氧诱导因子-1ɑ（HIF-1ɑ）蛋白的表达，TUNEL法检测细胞凋亡，流式细胞术检测免疫细胞活化情况，对主要器官进行H-E染色，以评估纳米材料的体内安全性。结果：DPM呈梭形，平均粒径（268 ± 3.302）nm，电位（33.1 ± 0.87）mV。细胞实验中，DPM联合超声辐照可明显抑制4T1细胞的增殖（P < 0.001），提高4T1细胞中ROS水平（P < 0.001），诱导4T1细胞CRT表达上调（P < 0.001），HMGB1从细胞核中移至细胞质，激活STING信号通路[p-STING、p-TBK1、p-IRF3蛋白表达均显著增加（均P < 0.001）]。体内实验中，DPM联合超声辐照可显著抑制4T1细胞移植瘤生长（P < 0.001）并促进免疫细胞表型转化（P < 0.001），抑制移植瘤组织中Ki-67、HIF-1α蛋白表达（均P < 0.01），谷胱甘肽（GSH）产生（P < 0.01），促进CRT、HMGB1蛋白表达、ROS产生（P < 0.001），对主要器官结构无明显影响。结论： DPM联合超声辐照可通过激活STING通路显著抑制4T1细胞及其移植瘤的生长，诱导抗肿瘤免疫应答，且对主要器官无明显毒性。

AIM: To compare the control effect of spherical and toric orthokeratology on low-to-moderate myopia with astigmatism(-1.00--1.50 DC)in adolescents.METHODS: The clinical data of 119 cases(119 eyes)of low-to-moderate myopia with astigmatism(-1.00--1.50 DC)adolescents who were treated and fitted with orthokeratology in the ophthalmology department of Sichuan Provincial People's Hospital from June 2021 to January 2022 were retrospectively analyzed. They were divided into spherical group, with 65 cases(65 eyes), and toric group, with 54 cases(54 eyes)according to the type of orthokeratology. The changes of uncorrected visual acuity(UCVA), axial length and corneal astigmatism before and after wearing lenses were recorded to evaluate the therapeutic effect.RESULTS: The UCVA of both the groups significantly improved at 1 and 2 a after wearing lenses(all P<0.01); corneal astigmatism decreased, but there was no significant difference(all P>0.05); the axial length was longer than that before wearing lenses(P<0.01). There were no statistical significant differences in the UCVA and corneal astigmatism between the spherical group and the toric group(Fintergroup=0.829,Pintergroup=0.364; Fintergroup=0.997,Pintergroup=0.320); and there were no statistical significant differences in the axial length growth between the spherical group and the toric group after wearing lenses for 1 a(0.18±0.11 mm vs 0.17±0.14 mm), and 2 a(0.17±0.10 mm vs 0.16±0.10 mm; all P>0.05).CONCLUSION: Both orthokeratology lenses can improve the UCVA, reduce corneal astigmatism, and delay axial length growth of adolescents with low-to-moderate myopia with astigmatism(-1.00--1.50 DC), and there are no significant differences in the control effect of spherical design orthokeratology and the toric design orthokeratology on myopia.

BACKGROUND:A novel aggregation induced luminescence fluorescence probe based on the mechanism of intramolecular motility restriction can be used for the detection of disease markers,tumor diagnosis,and bacterial imaging recognition.OBJECTIVE:To prepare a near-infrared Ⅱ nanoprobe called FA-DSPE-PEG-AIE@NPs based on aggregation-induced luminescence,and to explore its potential of targeted fluorescence imaging and photothermal therapy for prostate cancer.METHODS:Lecithin,polyethylene glycol phospholipids,folate polyethylene glycol phospholipids,and aggregation induced luminescent molecule 2TT-oC26B were used as raw materials.The folate-targeted nanoprobe FA-DSPE-PEG-AIE@NPs were prepared by nanoprecipitation method,and basic characterization of the nanoprobe was detected.PC3 human prostate cancer cells and human umbilical vein endothelial cells were selected as experimental objects.The cytotoxicity and phototoxicity of FA-DSPE-PEG-AIE@NPs were detected.PC3 human prostate cancer cells were selected as the experimental objects.Flow cytometry and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.PC3 human prostate cancer cells were injected subcutaneously into the abdomen of BALB/C nude mice to establish a tumor model,and nanoprobes FA-DSPE-PEG-AIE@NPs were injected into the tail vein.The mice were immediately subjected to near-infraced Ⅱ fluorescence imaging.12 hours later,the tumor was irradiated by laser for 5 minutes,and the photothermal treatment effect was observed within 14 days.RESULTS AND CONCLUSION:(1)The nanoprobes FA-DSPE-PEG-AIE@NPs with a mean diameter of(171.0±0.3)nm showed a well-defined spherical morphology.The nanoprobe had a wide absorption spectrum and tail emission extending to the near-infrared Ⅱ which emitted a bright near-infrared Ⅱ fluorescence signal under laser irradiation.(2)The nanoprobes FA-DSPE-PEG-AIE@NPs had low cytotoxicity and high phototoxicity.The results of flow cytometry and calcein/propidium iodide staining showed that nanoprobes FA-DSPE-PEG-AIE@NPs had an obvious photothermal killing effect on human prostate cancer cells.(3)The nanoprobes FA-DSPE-PEG-AIE@NPs successfully achieved near-infrared Ⅱ fluorescence imaging of mouse blood vessels and the maximum enrichment time of the tumor was 12 hours.The vessel widths of the hind leg and single blood vessels of abdomen were estimated to be 0.63 mm and 0.42 mm.The tumor volume of mice was significantly smaller after 14 days of treatment.(4)The results show that nanoprobes FA-DSPE-PEG-AIE@NPs can achieve near-infrared Ⅱ fluorescence imaging and photothermal therapy of prostate cancer effectively,which may provide a new method for early diagnosis and combined treatment of prostate cancer.

Objective To investigate the effect of growth differentiation factor 15(GDF15)on apoptosis and insulin secretion of MIN6 cells under high glucose conditions.Methods The mouse pancreatic islet β cell line(MIN6 cells)were divided into four groups:NG group,NG+rGDF15 group,HG group,and HG+rGDF15 group.The cell morphology among groups were observed,the apoptosis rate,the protein expression levels of Bcl-2 and Bax and the insulin level was detected.Results HG group exhibited significant cellular damage,characterized by upregulated apoptosis-promoting protein Bax and downregulated apoptosis-suppressing protein Bcl-2 expression,accompanied by a marked increase in apoptosis rate and a substantial decrease in insulin secretion(P＜0.01).Administration of recombinant GDF15 protein improved MIN6 cell morphology,significantly reduced Bax protein relative expression,elevated Bcl-2 protein relative expression,markedly decreased apoptosis rate,and enhanced insulin secretion(P＜0.01).Conclusion GDF15 can mitigate high glucose-induced MIN6 cell damage.

OBJECTIVE To investigate the causes of abnormal rising trends of isolation rate and infection of Staph-ylococcus aureus in the breast surgery department of a specialized cancer hospital.METHODS By means of pro-spective survey in combination with retrospective survey,an epidemiological survey was conducted for 5 patients with hospital-associated S.aureus infection who were treated in breast surgery department of Sun Yat-sen Univer-sity Cancer Center from Jan.2023 to Aug.2023,and the homology was observed.RESULTS The incidence rate of hospital-associated S.aureus infection(ward E 0.08％,ward F 0.38％)of the breast surgery department patients was higher during the period from Jan.2023 to Aug.2023,higher than 0.004％of the whole patients during the same period.The environmental sampling result showed that the colonized rate of S.aureus was 17.39％(4/23)and in nasal cavity 7.41％(2/27)in hands of the healthcare workers,and 28.57％in nasal cavity of logistical per-sonnel.Bundle interventions could reduce the incidence of hospital-associated methicillin-resistant S.aureus(MRSA)infection and the colonized rate in hands of the healthcare workers but had less impact on the colonized rate in the nasal cavity.The result of pulse field gel electrophoresis(PFGE)indicated that there was risk of cross transmission of colonized S.aureus between the hands of healthcare workers and the nasal cavities.The hand hy-giene,measures for contact transmission and environmental disinfection were supposed to be taken as the major links for control of the hospital-associated S.aureus infection.CONCLUSIONS The sporadic community-ac-quired infections and hospital-associated infections are the leading causes of the abnormal rise of the isolation rate and the infection rate of S.aureus in the breast surgery department.The bundle prevention and control measures can block the transmission of infections.

Objective To investigate the mechanism of Wenhe Decoction in the treatment of febrile seizures through network pharmacology based on NLRP3/Caspase-1/GSDMD signaling pathway;To conduct experimental verification.Methods The active components and targets of Wenhe Decoction were retrieved and screened through TCMSP,BATMAN-TCM,PubChem databases and SwissADME platform.The disease targets of febrile seizures were found in GenCards,OMIM and DisGeNET databases.The intersection targets of Wenhe Decoction and the disease and the active components corresponding to the intersection targets were imported into Cytoscape 3.7.2 software to construct the Chinese materia medica-active components-targets network.The intersection targets were submitted to the STRING database to construct a protein-protein interaction network,and then the intersection targets were imported into the Metascape database for GO and KEGG pathway enrichment analysis.The febrile seizures rat model was established,and Wenhe Decoction of 4.05,8.1 and 16.2 g/kg were given respectively by gavage for 21 days.The rats were placed in batches in(45±0.5)℃constant temperature water bath to induce convulsive seizures,and the convulsive latency time and convulsive duration of rats were recorded.The behavioral differences of mice were observed.The morphology of hippocampal tissue were observed by HE and Nissl staining.The ROS content of hippocampal tissue was detected by DHE fluorescent probe technology.The serum ATP,GABA,Glu,Caspase-1,GSDMD,IL-1β and IL-18 contents were detected by ELISA,and the expression of NLRP3 inflammasome-related protein in hippocampal tissue was detected by Western blot.Results Network pharmacology analysis obtained 98 active components of Wenhe Decoction and 1 838 targets.162 targets were obtained by intersecting with disease targets,the core components for the treatment of febrile seizures were β-sitosterol,quercetin,luteolin,trans-squalene,sitosterol,saponin,etc.,and the core targets were EGFR,TNF,JUN,MTOR,etc.,and mainly through the regulation of inflammatory response,apoptosis,mitochondrial function and energy metabolism,mediating anti-inflammatory pathways such as PI3K-Akt signaling pathway and calcium signaling pathway to exert anticonvulsant effects.The experimental results showed that Wenhe Decoction could prolong the convulsive latency and shorten the duration of convulsions in febrile seizures model rats,decrease the level of convulsions,and the pathological damage of hippocampal tissue was improved and damaged neurons were repaired.The serum contents of ROS,Glu,Caspase-1,GSDMD,IL-1β and IL-18 were significantly reduced,and ATP and GABA contents significantly increased.The protein expressions of NLRP3,ASC,pro-Caspase-1,pro-IL-1β and pro-IL-18 in hippocampal tissue significantly decreased.Conclusion Wenhe Decoction may intervene in febrile seizures rats through NLRP3/Caspase-1/GSDMD signaling pathway,inhibit pyroptosis to reduce the occurrence of neuroinflammation,and then affect the balance of neurotransmitters Glu and GABA to play a role in anti-febrile seizures and prevent brain tissue damage.

Objective To investigate the correlation between traditional Chinese medicine(TCM)syndrome elements and risk factors in patients with type Ⅱ cardio-renal syndrome(CRS).Methods A retrospective analysis was conducted on the medical records of 116 patients with type Ⅱ CRS.The distribution of TCM syndrome elements was analyzed,and the correlation between the syndrome elements and risk factors of gender,age,smoking history,alcohol consumption history,coronary heart disease,hypertension,diabetes,and anemia were evaluated.Results(1)The analysis of syndrome elements of 116 patients with type Ⅱ CRS showed that the main disease-location elements were heart(96 cases,82.76%),lung(89 cases,76.72%),kidney(81 cases,69.83%),spleen(71 cases,61.21%),and liver(25 cases,21.56%);the main disease-nature elements were qi deficiency(113 cases,97.41%),blood deficiency(96 cases,82.76%),yang deficiency(95 cases,81.89%),phlegm(94 cases,81.03%),yin deficiency(90 cases,77.59%),dampness(61 cases,52.59%),water retention(55 cases,47.41%),and blood stasis(47 cases,40.52%).(2)The analysis of age groups of 116 patients with type Ⅱ CRS showed that the majority of the patients were middle-aged and elderly individuals over 60 years old,and the age groups covered＜60 years old(4 cases,3.45%),61-70 years old(10 cases,8.62%),71-80 years old(28 cases,24.14%),81-90 years old(64 cases,55.17%),and>90 years old(10 cases,8.62%).(3)The analysis of gender of 116 patients with type Ⅱ CRS showed that 46 cases(39.66%)were male,and 70 cases(60.34%)were female,the female outnumbering the male.(4)The exploration of correlation between TCM syndrome elements and risk factors with Logistic regression analysis showed that blood deficiency was positively correlated with alcohol consumption,hypertension,and anemia(P＜0.05 or P＜0.01),yang deficiency was positively correlated with anemia(P＜0.05),yin deficiency was positively correlated with smoking and diabetes(P＜0.05),dampness was positively correlated with smoking and anemia(P＜0.01),water retention was positively correlated with gender and protein abnormalities(P＜0.05 or P＜0.01),and blood stasis was positively correlated with hypertension(P＜0.05).Conclusion The illness of type Ⅱ CRS is located in the heart,involving the five organs,and is closely related to the lungs and kidneys.The general pathogenesis of type Ⅱ CRS is characterized by being deficiency of qi and yang in the root cause,and having the symptom manifestations of phlegm and blood stasis.In type Ⅱ CRS patients,men are more likely to suffer water retention,smokers are more likely to suffer yin deficiency and dampness,drinkers are more likely to suffer blood deficiency,individuals with hypertension are more likely to suffer blood deficiency and blood stasis,individuals with diabetes are more likely to suffer yin deficiency,individuals with anemia are more likely to suffer blood deficiency,yang deficiency and dampness,and individuals with protein abnormalities are more likely to suffer water retention.

Objective To apply a multidimensional neonatal nutritional risk screening scale for hospitalized premature infants to explore its predictive value for extrauterine growth restriction(EUGR)at the time of discharge.Methods A total of 104 premature infants hospitalized in the Neonatal Department of the Second Affiliated Hospital of Kunming Medical University from January 2023 to September 2023 were selected as research subjects.Nutritional risk screening was conducted within 24 hours of admission and weekly thereafter using the multidimensional neonatal nutritional risk screening scale.Scoring was based on four dimensions(birth status,weight changes,nutritional intake methods,and disease diagnosis),with a total score of ≥ 8 indicating high risk;≥4 and＜8 indicating moderate risk;and＜4 indicating low risk.EUGR at the time of discharge was the primary clinical outcome indicator.Receiver operating characteristic(ROC)curves were constructed to explore the predictive value of neonatal nutritional risk screening for EUGR in premature infants.Results At discharge,40 premature infants(38.5％)experienced EUGR.The nutritional risk screening scores of the EUGR group on day 7 of hospitalization were higher than those of the non-EUGR group(P＜0.05).The rate of high nutritional risk on day 7 of hospitalization was highest(7.9％in the non-EUGR group,22％in the EUGR group,and 13.5％overall).On both day 1 and day 7 of hospitalization,the rate of high nutritional risk in the EUGR group was higher than that in the non-EUGR group(P＜0.05).There were significant differences in the nutritional risk screening scores on day 7,birth weight Z-scores,discharge corrected gestational age weight Z-scores,and serum albumin levels between the EUGR and non-EUGR groups(P＜0.05).ROC curves were plotted,yielding AUCs of 0.625(95％CI 0.514,0.736),0.652(95％CI 0.544,0.760),0.674(95％CI 0.561,0.786),and 0.641(95％CI 0.531,0.750),indicating certain predictive value.A combined predictive ROC model yielded an AUC of 0.786(95％CI 0.692,0.880)for EUGR,which was higher than the AUCs for individual indicators(P＜0.001).Conclusion The occurrence of EUGR is relatively common among hospitalized premature infants.The nutritional risk is highest during the first week of hospitalization.The multidimensional neonatal nutritional risk screening scale can dynamically assess nutritional risk during hospitalization and may serve as one of the early warning indicators for EUGR in premature infants.The predictive efficacy for EUGR is enhanced when combined with birth weight Z-scores,discharge weight Z-scores,and serum albumin,providing a basis for individualized nutritional management of premature infants.

Objective:To explore patterns of traditional Chinese medicine (TCM) use among patients with inflammatory bowel disease (IBD) in Jiangsu Province, China from 2019 to 2023.Methods:Using data from the IBD health data platform of the National Healthcare Big Data (Eastern) Center, a retrospective cohort study was conducted. We performed descriptive analyses on hospitalised patients diagnosed with IBD between 2019 and 2023, who received TCM treatment.Results:The study included 11 095 case records from 4 760 patients, with TCM diagnoses primarily indicating diarrhoea and abdominal pain. Ulcerative colitis (UC) accounted for 4 782 hospitalizations (3 103 patients), while Crohn's disease (CD) accounted for 6 313 hospitalizations (1 657 patients). Patient demographics showed a trend towards younger age and a higher proportion of males. Treatment utilisation was highest in southern Jiangsu compared with the central and northern regions. In terms of disease burden, all treatment costs showed a downward trend. In terms of external TCM therapies, UC patients tend to prefer plasters and enemas, while CD patients are more inclined to use acupuncture. Regarding herbal medicine, licorice, white atractylodes, and white peony root are commonly used single herbs for IBD patients.Conclusions:The number of IBD patients treated with TCM in Jiangsu Province has steadily increased from 2019 to 2023. It is important to identify effective TCM treatment methods to reduce the burden of patients.

OBJECTIVE T o carry out the health economics evaluation and cost-benefit analysis of the type b Hae-mophilus influenzae(Hib)vaccination for the children who were hospitalized due to Hib infection so as to provide evidence for public health policies.METHODS The children who were diagnosed with Hib-related respiratory tract infections or meningitis and were hospitalized in respiratory medicine department,infection management depart-ment,emergency rooms and neurology department of Jiangxi Provincial Children's Hospital from Jan.1,2021 to Dec.31,2023 were recruited as the research subjects.Based on a 1∶1 matching condition,the matching variables included four items such as the same age for the admission to the hospital,same gender,same department and same grade of disease severity.The children for whom the primary immunization of Hib vaccination(including Hib monovalent vaccine and Hib-containing combination vaccine)were completed and the integrity of vaccination infor-mation could be checked out were assigned as the intervention group,while the children for whom the primary im-munization of Hib vaccination was not completed were chosen as the control group.The clinical data,vaccination data and the data such as length of hospital stay and hospitalization cost were collected from the children.The cost-benefit of the Hib vaccination among the children with Hib infection was observed.RESULTS A total of 622 hospi-talized children who were detected with Hib-positive respiratory tract infections or meningitis were enrolled in the study,and 73 children(20 children from infection management department,27 children from respiratory medi-cine department,26 children from emergency rooms)were finally included in the intervention group after matc-hing and multiple rounds of screening,73 children were chosen as the control group based on a 1∶1 matching con-dition.The male children accounted for 57.53％(42 cases)in both groups,and the female children accounted for 42.47％(31 cases)in both groups.With the respect to the length of hospital stay,it was 7.00(5.00,8.00)days in the intervention group,7.00(6.00,8.00)days in the control group(Z=-0.341,P=0.733).In terms of the hospitalization cost,it was 7 756.17(6 617.92,10 617.69)yuan in the intervention group,9 040.65(8 033.76,10 935.84)yuan in the control group(Z=-2.795,P=0.005).The cost of Hib vaccination was 343.03 yuan per capita in the intervention group,and the benefit-cost ratio(BCR)was 1∶3.74(343.03 yuan/1 284.48 yuan).CONCLUSIONS The Hib vaccination can save the hospitalization cost and has high cost effectiveness.It is sugges-ted that the Hib vaccination should be promoted and the coverage rate of Hib vaccination should be raised among the age-eligible children.