BACKGROUND:Photothermal therapy is a novel tumor treatment strategy that uses photothermal agents to transform light energy into heat energy to accomplish non-invasive tumor ablation.The rise of photothermal therapy and nanotechnology has provided a new perspective on breast cancer treatment.OBJECTIVE:To prepare a new type of near-infrared biomimetic nanoprobe that has been modified by breast cancer cell membrane,to investigate the effect of near-infrared fluorescence/ultrasound imaging in vitro,and to observe its targeting ability and photothermal therapy effect on homologous tumor cells in vitro.METHODS:Organic small molecule ITIC-4CI with A-D-A structure was used as photothermal agents;polylactic acid/glycolic acid copolymer as nanocarrier;4T1 cell membrane of mouse breast cancer cells as a surface modifier of nanoparticles;perfluorohexane(PFH)was loaded.A novel near-infrared biomimetic nanoprobe(4T1m/ITIC-4CI/PFH)was prepared by the double emulsion evaporation method and sonication method.The basic characterization of the nanoprobe and the homologous targeting ability were detected.The photothermal properties and photothermal stability of the probe were investigated,and the near-infrared fluorescence/ultrasound imaging effect of the probe under laser irradiation was observed.The CCK-8 assay and calcein/propidium iodide staining were used to assess the efficacy of photothermal therapy.RESULTS AND CONCLUSION:(1)The prepared 4T1m/ITIC-4CI/PFH nanoprobes had uniform size,high stability,and an average particle size of(92.7±2.3)nm.The probe's protein composition was identical to that of the 4T1 cell membrane.The nanoprobe's ability to target homologous 4T1 cells was validated by an in vitro cell uptake assay.(2)The nanoprobe had a red-shift absorption spectrum and tail emission extending to the near-infrared-Ⅱ,which emitted a bright near-infrared-Ⅱ fluorescence signal under laser irradiation.(3)After laser irradiation,the nanoprobe 4T1m/ITIC-4CI/PFH could be turned into microbubbles and enhanced ultrasound imaging.The results of CCK-8 assay and calcein/propidium iodide staining showed that the nanoprobe 4T1m/ITIC-4CI/PFH had an obvious photothermal killing effect on 4T1 cells.(4)The results show that the nanoprobe 4T1m/ITIC-4CI/PFH has the ability to target homologous tumors and enhance near-infrared-Ⅱ fluorescence imaging/ultrasound imaging and photothermal therapy effects.

The United States has established a perfect specialist training system for developmental and behavioral pediatrics (DBP), while the DBP specialist training system in China is still in the early stage of development and has been constantly improved. This article analyzes and compares the current status of DBP specialist training system between the United States and China from the aspects of training pattern, eligibility criteria, training plans and contents, assessment and evaluation, and certification. With reference to the training system in the United States, we can further improve the DBP specialist training system in China by perfecting the training system and related documents, constructing reasonable eligibility criteria, establishing a training pattern guided by post competency, improving the DBP assessment and evaluation system based on competency, and enhancing the certification of DBP physicians.

Objective To explore the effect and mechanism of C-C motif chemokine ligand 2(CCL2)/C-C chemokine receptor type 2(CCR2)signaling pathway mediated by ZXDC in spinal dorsal root ganglion(DRG)on neuropathic pain after chronic compressive injury.Methods A chronic compressive injury(CCI)mouse model was established.The expression of ZXDC and CCL2 in DRG was detected by immunofluorescence,Western blot,and real-time fluorescent quantitative PCR(RT-qPCR).The animals were divided in-to sham group,CCI+AAV-NC group,and CCI+AAV-ZXDC siRNA group.Western blot and immunofluorescence were employed to measure the expression of ZXDC,CCL2,and CCR2 in DRG after CCI,and the expression of pro-inflammatory factor TNF-α and IL-1β mRNA was evaluated by RT-qPCR.At last,the paw withdrawal threshold was used to evaluate the changes in neuropathic pain be-havior.Results ZXDC was localized in large,medium,and small DRG neurons.The expression of ZXDC and CCL2 protein and mRNA were significantly increased 1-3 days after CCI,and decreased 7days after CCI in DRG.The expression of ZXDC and CCL2mRNA was positively correlated(P＜0.05).3 days after CCI,compared with sham group,ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-NC group and CCI+AAV-ZXDC siRNA group were significantly increased,and ZXDC,CCL2,CCR2 protein expression,TNF-α and IL-1 β mRNA in CCI+AAV-ZXDC siRNA group were significantly decreased than those in CCI+AAV-NC group(P＜0.05).Compared with sham group,the paw withdrawal threshold of CCI+AAV-ZXDC siRNA group and CCI+AAV-NC group were significantly decreased at various time points after CCI,and the withdrawal threshold in CCI+AAV-ZXDC siRNA group was significantly increased than that in CCI+AAV-NC group at 7days after CCI(P＜0.05).Conclusion Spinal dorsal root gan-glion ZXDC siRNA can inhibit neuropathic pain after CCI injury by downregulating CCL2/CCR2signaling axis.

OBJECTIVE To investigate the effects of ligustilide on chemotherapy resistance of cervical cancer cells based on Hippo-Yes-associated protein （YAP） signaling pathway. METHODS Human cervical cancer cisplatin-resistant cells HeLa/DDP were divided into control group， cisplatin group （10 μmol/L cisplatin）， cisplatin+ligustilide low-， medium- and high-concentration groups （10 μmol/L cisplatin+25， 50， 100 μmol/L ligustilide）. The proliferation， apoptosis， migration and invasion of HeLa/DDP cells were all detected in each group. The mRNA expressions of YAP and transcriptional coactivator with PDZ binding motif （TAZ） as well as the protein expressions of YAP， TAZ， matrix metalloproteinase 2 （MMP2）， Ki67， cleaved-caspase-3 and caspase-3 were determined in HeLa/DDP cells. RESULTS Compared with control group， the inhibitory rate， apoptotic rate and cleaved- caspase-3/caspase-3 of cisplatin group were increased significantly； scratch healing rate， the number of invasive cells， the mRNA expressions of YAP and TAZ， and the protein expressions of YAP， TAZ， MMP2 and Ki67 were decreased significantly in cisplatin group （P＜0.05）. Compared with cisplatin group， the inhibitory rate of cell proliferation， apoptotic rate and cleaved-caspase-3/ caspase-3 were further increased in cisplatin+ligustilide low-， medium- and high-concentration groups， while scratch healing rate， the number of invasive cells， the mRNA expressions of YAP and TAZ， and the protein expressions of YAP， TAZ， MMP2 and Ki67 were further decreased， in a dose-dependent manner （P＜0.05）. CONCLUSIONS Ligustilide can increase the sensitivity of drug-resistant cervical cancer cells to cisplatin by inhibiting Hippo-YAP signaling pathway.

Currently, there are practical and technical difficulties in the construction of clinical questions in the development of clinical practice guidelines. Clinicians or guideline developers seldom construct clinical questions based the actual case scenario, leading to some information loss between structured and actual clinical connotation. To overcome this challenge, we proposed a case-guided questions construction approach, and carried out case research and verification in the formulation of the guideline. We found that this method could more efficiently and scientifically assist the formulation of clinical questions, and provide reference for clinicians or guideline developers.

The long-term presence of non-steroidal anti-inflammatory drugs (NSAIDs) in the environmental water samples not only affects the life safety of aquatic organisms and disturbs the ecoenvironment, but also poses a serious threat to human health. In this study, amino-functionalized Fe3O4 nanoparticles (Fe3O4-NH2) were firstly prepared by solvothermal method. Subsequently, polyethyleneimine (PEI) with a branched chain structure was successfully grafted onto Fe3O4 nanoparticles by Schiff base reaction in aqueous solution at room temperature using glutaraldehyde as a cross-linking agent, and a recyclable PEI-grafted magnetic nano-sorbent (Fe3O4@PEI) was synthesized and applied for the detection of NSAIDs in the environmental water samples. The compositional properties of Fe3O4@PEI were investigated by different characterization methods and the parameters affecting the extraction of NSAIDs were optimized. Due to high adsorption of Fe3O4@PEI for NSAIDs, the quantitative analysis of four NSAIDs in the environmental water samples, ketoprofen, naproxen, diclofenac and tolfenamic acid, was performed in combination with high-performance liquid chromatography. A good linear relationship between the chromatographic peak area and concentration was observed in the range of 1−500 µg/mL. The recoveries of the samples at three different spiked levels ranged from 85.6% to 107.8%; the intra-day precision was less than 7.8% (n=6); and the inter-day precision was less than 9.5% (n=3). The method is simple, rapid, accurate and reliable, and can be used for the analysis of NSAIDs in the environmental water samples．

ObjectiveIn order to improve the recognition accuracy of named entities in medical record texts and realize the effective mining and utilization of medical record knowledge， a Bert-Radical-Lexicon（BRL） neural network model is constructed to recognize medical record entities with respect to the characteristics of medical record texts. MethodWe selected 408 medical records related to hypertension from the the Complete Library of Famous Medical Records of Chinese Dynasties and constructed a dataset consisting of 1 672 medical records by manually labeling. Then， we randomly divided the dataset into three subsets， including the training set（1 004 cases）， the testing set （334 cases） and the validation set（334 cases）. Based on this dataset， we built a BRL model that fused various text features of medical records， as well as its variants BRL-B， BRL-L and BRL-R， and a baseline model Base for experiments. During the model training phase， we trained the above models using the training set to reduce the risk of overfitting. We continuously monitored the performance of each model on the validation set during training and saved the model with the best performance. Finally， we evaluated the performance of these models on the testing set. ResultCompared with other models， the BRL model had the best performance in the medical records named entity recognition task， with an overall recognition precision of 90.09%， a recall of 90.61%， and the harmonic mean of the precision and recall（F1） of 90.35% for eight types of entities， including disease， symptom， tongue manifestation， pulse condition， syndrome， method of treatment， prescription and traditional Chinese medicine（TCM）. Compared with the Base model， the BRL model improved the overall F1 value of entity recognition by 5.22%， and the F1 value of pulse condition entity increased by 6.92%， which was the largest increase. ConclusionBy incorporating a variety of medical record text features in the embedding layer， the BRL neural network model has stronger named entity recognition ability， and thus extracts more accurate and reliable TCM clinical information.

Missed diagnosis can often be noted in mild traumatic brain injury (mTBI), resulting from atypical symptoms, diverse performances and subjectively dependent report. Blood biomarkers can not only reflect the pathophysiological process of mTBI to a certain extent, but also have important clinical value in assessing brain injury severity and predicting adverse outcomes. This article systematically describes the research progress of blood biomarkers that can assist mTBI diagnosis, distinguish CT manifestations and predict prognoses in recent years, aiming to provide references for clinical application of blood biomarkers in mTBI.

Objective To compare the outcomes of transvaginal natural orifice transluminal endoscopic surgery(vNOTES)and laparoendoscopic single-site surgery(LESS)for total uterine excision in obese patients with benign uterine lesions,and to investigate the utility of vNOTES in this patient population.Methods A total of 100 obese patients(BMI>28.0 kg/m2)diagnosed with benign uterine lesions requiring total uterine and bilateral salpingectomy between January 2022 and January 2023 were included in this study.They were randomly assigned to two groups:the LESS group(n=51)and the vNOTES group(n=49).Patient demographics,surgical duration,intraoperative blood loss,changes in hemoglobin levels,pain scores,time to first flatus postoperatively,length of hospital stay,pelvic floor function,sexual quality of life,and postoperative complications were compared between the two groups.Results The two groups did not show any statistically significant differences in terms of blood loss,pre-and postoperative hemoglobin changes,pelvic floor function,sexual quality of life,or postoperative complications(P>0.05).However,the vNOTES group exhibited shorter surgical durations,time to first flatus postoperatively,and length of hospital stay compared to the LESS group(P<0.05).Additionally,the vNOTES group demonstrated lower intraoperative pain scores than the LESS group.(P<0.05).Conclusions In obese patients with benign uterine lesions,vNOTES total uterine excision surgery demonstrated shorter surgical durations and postoperative hospital stays,lower postoperative pain scores,and better adherence to the principles of en-hanced recovery after surgery(ERAS),indicating its potential for broader application.

Objective:To establish the qualitative and quantitative methods of Lomatogonium carinthiacum(Wulf.)Reichb.in the prescription of Mongolian medicine Polypill Zhuanglun-5 decoction,and solve the phe-nomenon of Lomatogonium carinthiacum(Wulf.)Reichb.being replaced.Methods:Microscopic identification method was used to observe the pollen grains in the powder;The reference substance of swertiamarin and Lomato-gonium carinthiacum(Wulf.)Reichb.were used as the control,and the ethyl acetate methanol water formic acid(12∶2∶2∶0.5)was used as the developing agent for TLC identification;HPLC was used under the condin-tion including Agilent Eclipse Plus C18(250 mm × 4.6 mm,5 μm)as chromatographic column and 0.2％phosphoric acid solution(A)-acetonitrile(B)as mobile phase with gradient elution at 238 nm of detection wavelength were used.Contents of Zhuanglun-5 decoction from different manufacturers were determined with swertiamarin as reference substance.Results:Among the 12 batches of Zhuanglun-5 decoction,8 batches were Lomatogonium carinthiacum(Wulf.)Reichb.,2 batches were Viola yedoensis,and 2 batches were other medicinal materials.The content of swertiamarin in 8 batches of Zhuanglun-5 decoction ranged from 0.2 to 11.7 mg·g-1.Conclusion:The established identification method is simple and effective,and the content determination method is stable and has strong specificity.It can provide technical support for the supervision of the preparation,and has a reference effect for the improvement of traditional Chinese and Mongolian pharmaceuti-cal preparation standards.