Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

The accuracy of orthodontic bracket bonding directly affects the treatment effect,and intelligent orthodontics is gradually advancing clinical practice toward precision.Mixed reality(MR),a new digital holographic imaging simulation technology,enables interactive scenarios between 3D data and the real world,allowing precise identification and localization of dental roots and jaw ana-tomical structures.This study constructs an oral visualization model via multimodal image fusion,establishes a virtual-real registra-tion algorithm combining target detection and point cloud registration for high-dynamic scenarios,and develops an MR-based intelli-gent auxiliary and teaching system for orthodontic bracket bonding.The system achieves clinical training and intraoperative naviga-tion for bracket positioning and bonding,accurately identifies dental root and jaw information,and is of significant importance for improving the precision,intelligence,and digitization of orthodontic clinical practice.

The accuracy of orthodontic bracket bonding directly affects the treatment effect,and intelligent orthodontics is gradually advancing clinical practice toward precision.Mixed reality(MR),a new digital holographic imaging simulation technology,enables interactive scenarios between 3D data and the real world,allowing precise identification and localization of dental roots and jaw ana-tomical structures.This study constructs an oral visualization model via multimodal image fusion,establishes a virtual-real registra-tion algorithm combining target detection and point cloud registration for high-dynamic scenarios,and develops an MR-based intelli-gent auxiliary and teaching system for orthodontic bracket bonding.The system achieves clinical training and intraoperative naviga-tion for bracket positioning and bonding,accurately identifies dental root and jaw information,and is of significant importance for improving the precision,intelligence,and digitization of orthodontic clinical practice.

Objective:To construct fused cancer cell/neutrophil membrane-coated polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNP@FMs) and explore the potential for targeted pancreatic cancer fluorescence imaging and MRI.Methods:Cancer cell membranes fused with neutrophil membranes were encapsulated on the surface of polydopamine nanoparticles chelated with manganese ions (Ⅱ) (PMNPs) to prepare PMNP@FMs. The morphology, structure, and MRI performance of the product were characterized. The cytotoxicity of PMNP@FMs towards human pancreatic cancer cells (PANC-1) and normal human pancreatic ductal epithelial cells (hTERT-HPNE) was evaluated using cell counting kit (CCK)-8, and in vivo toxicity was assessed in healthy mice. PANC-1 pancreatic cancer xenograft nude mouse models were established for in vivo fluorescence imaging and MRI. Data were analyzed using the independent-sample t test, repeated measures analysis of variance and the least significance difference method. Results:PMNP@FMs exhibited a core-shell structure with a diameter of (112.81±8.64) nm, negative surface charge, and good dispersibility. The T 1 relaxivity of PMNPs was 18.81±0.22, which was 4.1 times higher than that of gadopentetate dimeglumine (Gd-DTPA) (4.55±0.24; t=75.54, P<0.001). Co-culture of PMNPs and PMNP@FMs with hTERT-HPNE and PANC-1 cells for 24 h resulted in cell viability above 90% within the concentration range of 0-500 μg/ml. PMNP@FMs did not affect mouse survival and showed no apparent organ damage. In vivo fluorescence imaging and MRI revealed that PMNP@FMs accumulated highly in tumors and reached the peak 24 h post intravenous administration (relative MR signal: 1.35±0.01, fluorescence intensity: (1.20±0.25)×10 10), surpassing the peak observed in the control group (1.22±0.01, (3.87±0.50)×10 9;F values: 11.03-188.01, t values: 18.20, 5.64, all P<0.05), with hepatic metabolism being the primary route of clearance. Conclusion:PMNP@FMs demonstrate a potential for targeted pancreatic cancer fluorescence imaging and MRI, offering promising prospect for precise diagnosis of early-stage pancreatic cancer.

Objective To investigate the clinical application value of MRI Radiomics score(Radscore)combined with clinicopatho-logical features in predicting postoperative progression-free survival(PFS)of patients with endometrial cancer(EC).Methods A total of 127 patients with EC were selected.The radiomic features of the lesions were extracted from T2 WI,diffusion weighted imaging(DWI)and apparent diffusion coefficient(ADC)images.The features were screened by random forest model and Radscore was calcu-lated.Simultaneously,clinical and pathological characteristics of patients were collected and incorporated,and multivariate Cox regression analysis was used to screen the risk factors related to PFS.The MRI Radscore and clinicopathological features were mapped to the nomogram,and the performance of nomogram was evaluated by receiver operating characteristic(ROC)curve and calibration curve.Results Multivariate Cox regression analysis showed that progesterone receptor(PR),human epididymis protein 4(HE4)and MRI Radscore were independent risk factors for predicting PFS in patients with EC(P＜0.05).The area under the curve(AUC)of the predicted PFS at 1,3 and 5 years after surgery were 0.91,0.804 and 0.776,respectively.Calibration curves showed that nomogram had a good fit in predicting PFS in patients with EC 1,3 and 5 years after surgery.Conclusion The nomogram con-structed based on multi-sequence MRI Radscore and clinicopathological features has favorable accuracy and stability in predicting postoperative PFS in individuals diagnosed with EC.

Objective To study the effects of Guizhi Shaoyao Zhimu Decoction on factors related to bone destruction and bone protection in rats with collagen-induced arthritis(CIA)based on osteopro-tegerin(OPG)/receptor activator of NF-κB ligand(RANKL)/receptor activator of NF-κB(RANK)signaling pathway.Methods According to the body weight,60 female Wistar rats were randomly di-vided into the following six groups:the normal group,the model group,the Triperygium wilfordii mul-tiglucoside group(0.01 g/kg),the Guizhi Shaoyao Zhimu Decoction low-dose group(8.6 g/kg),the Guizhi Shaoyao Zhimu Decoction medium-dose group(17.2 g/kg),and the Guizhi Shaoyao Zhimu Decoction high-dose group(34.4 g/kg)(n=10 rats per group).The rats in all groups except for the normal group were given 100 μg bovine type Ⅱ collagen on the 1st and 8th days to establish the CIA model,and was injected into the left foot sole and tail root of the rats.After the successful modeling,the rats were treated by gavage for 4 weeks.The general state,body weight,and arthritis index(AI)score of rats were recorded,and the contents of RANKL and OPG in rat serum were determined by enzyme-linked immunosorbent assay.The mRNA and protein expressions of RANKL,RANK,and OPG in the ankle joint were determined through real-time PCR and Western blotting,respectively.Results Com-pared with the normal group,the general state of the model group was poor,the toe swelling was obvious,the AI score was increased,the serum RANKL content was increased,the serum OPG content was de-creased,and the mRNA and protein expressions of RANKL and RANK in the ankle joint were increased(P＜0.05).Compared with the model group,the degree of toe swelling and the AI score of rats in the Guizhi Shaoyao Zhimu Decoction low-,medium-,and high-dose groups were decreased,the serum RANKL content was decreased,the serum OPG content was increased,the mRNA and protein expres-sions of RANKL and RANK in the ankle joint were decreased,the mRNA and protein expressions of OPG were increased,and the RANKL/OPG ratio of the ankle joint was decreased(P＜0.05).Conclusion Guizhi Shaoyao Zhimu Decoction can improve the destruction of joint bone in CIA rats,and its mecha-nism of action may be related to reducing RANKL level,reducing RANKL/OPG ratio,and regulating bone balance.

[摘 要] 目的：探究益气活血汤对恶性肿瘤患者癌痛及癌因性疲乏（CRF）的疗效。方法: 选取2020年1月至2022年12月间安徽省中医药大学第二附属医院收治的82例确诊发生CRF的恶性肿瘤患者（气血亏虚证），采用随机数字表余数分组法将其分为对照组与观察组，每组各41例。对照组患者采用常规止痛、止吐、化痰等对症治疗及健康、心理指导，观察组患者在对照组干预的基础上联合益气活血汤治疗，4周为1个疗程。治疗前及治疗4周后，对两组患者进行中医证候积分评估，以积分变化评估中医临床疗效；采用修订版Piper疲乏量表（RPFS）评估CRF的改善情况；采用数字疼痛分级法（NRS）评分比较癌痛情况；检测患者外周血纤维蛋白原（FIB）、D-二聚体（D-D）评价凝血功能差异，检测患者肝、肾功能指标以评估益气活血汤治疗的安全性。结果：治疗前，两组患者在中医证候积分、RPFS评分、NRS评分及外周血FIB、D-D方面的差异均无显著统计学意义（均P>0.05）。治疗4周后，两组患者在神疲乏力、面色淡白或萎黄、自汗、失眠健忘、手足麻木的证候评分及总积分均较治疗前明显降低（均P<0.05），且观察组各项评分均低于对照组（均P<0.05），中医临床疗效明显高于对照组（P<0.05）；两组患者RPFS各维度评分及总分均较治疗前降低（均P<0.05），观察组行为、情感、感觉维度RPFS评分及总分均低于对照组（均P<0.05），观察组CRF的改善明显优于对照组（P<0.05）；两组患者NRS评分及外周血FIB、D-D指标均较治疗前降低（均P<0.05），且观察组均低于对照组（均P<0.05）。两组患者治疗期间均未发生肝功能、肾功能等明显异常，说明益气活血汤安全性良好。结论：益气活血汤可纠正气血亏虚之证，改善机体凝血功能，促进恶性肿瘤患者CRF及癌痛的减轻，临床应用价值较高。

Primary biliary cholangitis (PBC) is a progressive cholestatic liver disease targeting biliary epithelial cells, and the concept of "treating diseases by intervening with the gut" has become a research hotspot in recent years. In the future, probiotics may be used to improve the abundance and distribution of intestinal flora, reshape the intestinal microenvironment, and intervene against the progression of PBC. This article reviews the gut microbiota and the clinical application of probiotics, so as to provide ideas for finding new treatment strategies for PBC.

Objective:To analyze the patterns of antibacterial agents in Chinese children surveyed by the China multi-center monitoring network for the application of antibacterial agents in children and neonates in 2019 by using World Health Organization (WHO) Access, Watch, Reserve and Not-recommended (AWaRe) and typical anatomical/therapeutic/chemical (ATC) in this study.Methods:The cross-sectional method was adopted.A multi-center cross-sectional survey was conducted on one day from September to December 2019.The information of all inpatients taking antibiotics was uploaded to the network-based data collection system (https: //garpec-31.mobilemd.cn/login.aspx? relogin=true). This study covered 13 hospitals from 10 provinces and cities in China.All hospitalized children in the Respiratory Department, Infectious Disease Department, General Surgery Department, Pediatric Intensive Care Units, Neonatal Intensive Care Units and Neonatology joined in this survey.The clinically used antibacterial agents were classified by AWaRe and ATC, and the AWaRe and ATC distributions of antibacterial agents prescribed for Chinese children and neonates were described.Results:Of the 2 644 antibiotic prescriptions included from 13 hospitals, 2 134 (80.71%) were for children and 510 (19.29%) were for neonates.Of all antibiotic prescriptions, there were 368 (13.92%) Access antibiotics prescriptions, 1 973 (74.62%) Watch prescriptions, 60 (2.27%) Reserve prescriptions and 243 (9.19%) Not-recommended prescriptions.The top-five antibiotics prescribed for children and neonates were third-generation cephalosporins (1 056, 39.94%), macrolides (492, 18.61%), carbapenems (275, 10.40%), beta lactam-beta lactamase inhibitors (246, 9.30%), and second-generation cephalosporins (136, 5.14%). The use ratios of Access, Watch, Reserve and Not-recommended antibiotics in each center ranged from 0 to 30.00%, 36.67% to 97.20%, 0 to 17.02% and 0 to 33.33%, respectively.In 1 360 antibiotic prescriptions for children and neonates with pneumonia, there were 152 (11.18%) Access antibiotics, 1 051 (77.28%) Watch antibiotics, 37 (2.72%) Reserve antibiotics, and 120 (8.82%) Not-recommended antibiotics.The top-five antibiotics prescribed for children with pneumonia were third-generation cephalosporins (522, 38.38%), macrolides (388, 28.53%), beta lactam-beta lactamase inhibitors (141, 10.37%), carbapenems (117, 8.6%) and penicillins (49, 3.60%).Conclusions:Watch antibiotics and broad spectrum antibiotics such as third-generation cephalosporins and macrolides prone to induce resistance are the main antibacterial agents used in Chinese children and neonates with pneumonia.Broad-spectrum antibiotics may be overused in Chinese children and neonates.

Objective:To explore the relationship between the expression of human epidermal growth factor receptor 2 (HER2) in core needle biopsy (CNB) specimens before neoadjuvant chemotherapy (NAC) and post NAC Residual Cancer Burden (RCB) classification in breast cancer.Methods:This retrospective study included 150 patients with CNB proven invasive breast carcinoma in the Fourth Hospital of Hebei Medical University from January 2013 to January 2014. Immunohistochemistry (IHC) or fluorescence in situ hybridization (FISH) was used to detect the expression of HER2 in the CNB specimens. RCB was used to assess the chemotherapy response of patients. SPSS 21.00 and GraphPad Prism 8.0.1 were used for data statistics; Chi square test and Fisher′s exact test for correlation analysis, and Cox regression for survival analysis. P<0.05 was considered statistically significant. Results:Among the 150 patients, there were 38 RCB-0, 12 RCB-Ⅰ, 61 RCB-Ⅱ and 39 RCB-Ⅲ post NAC. RCB-0 meant pathological complete response (PCR). Statistical analysis found that the pre NAC HER2 expression was related to PCR and RCB classification after surgery ( r 1=?0.217, r 2=?0.282; P<0.05). Further analysis demonstrated that in the HER2-positive group, PCR was associated with prolonged OS and DFS ( HR=2.939, 2.359; P<0.05); the differences of OS and DFS in RCB classifications were more significant ( P<0.05) in the HER2 positive than HER2 negative groups. Conclusion:There is a correlation between pre NAC HER2 expression and PCR and RCB classification after treatment. In HER2-positive patients, the prognostic stratification of RCB classification is more obvious, suggesting that pre NAC HER2 overexpression combined with RCB classification after surgery can more accurately predict the prognosis.