ObjectiveTo investigate the effect of folic acid-modified crebanine polyethylene glycol-polylactic acid hydroxyacetic acid copolymer（PEG-PLGA） nanoparticles（FA-Cre@PEG-PLGA NPs， hereinafter referred to as NPs） combined with ultrasonic irradiation on subcutaneous tumor of liver cancer in Kunming（KM） mice. MethodsEighty-four healthy male KM mice were utilized to establish a subcutaneous tumor model of mouse hepatocellular carcinoma with H22 cells， then mice were randomly divided into model group， placebo group， hydroxycamptothecin group（8 mg∙kg^-1）， low， medium and high dose crebanine raw material groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose crebanine groups， respectively）， low， medium and high dose NPs groups（2， 2.5， 3 mg∙kg^-1）， and low， medium and high dose NPs combined with ultrasonic irradiation groups（2， 2.5， 3 mg∙kg^-1， hereinafter referred to as the low， medium and high dose combination groups， respectively）. The corresponding doses of drugs were administered via tail vein injection， the model group received no treatment， while the placebo group was injected with an equivalent amount of normal saline. Dosing was conducted for a total of 10 times on alternate days. The body mass of the mice was monitored， and parameters such as body mass change rate， thymus index， spleen index， tumor volume， tumor weight， relative tumor growth rate（T/C）， and tumor inhibition rate（TGI） were calculated. Pathological changes in liver and kidney tissues as well as the tumor were observed by hematoxylin-eosin（HE） staining. Additionally， the levels of aspartate aminotransferase（AST）， alanine aminotransferase（ALT）， blood urea nitrogen（BUN） and creatinine（CREA） in serum of mice were detected by biochemical method. Furthermore， the effect of ultrasound on the distribution of NPs in subcutaneous tumors of mouse hepatocellular carcinoma was observed by in vivo imaging technique. ResultsAmong different treatment methods， the combination of NPs and ultrasound irradiation had the best therapeutic effect. Compared with the model group， the body mass growth rates of mice in the medium and high combination groups decreased， while the thymus index and spleen index increased， but there was no statistically significant difference in serum AST， ALT， BUN and CREA levels， indicating that NPs combined with ultrasound irradiation had little effect on the normal physiological state of the body， oth groups had TGI>40% and T/C<60%， indicating a clear anti-tumor effect. Pathological analysis showed that compared with the NPs groups， the combination groups exhibited varying degrees of necrosis in tumor cells， accompanied by less damage to the liver and kidneys. In vivo imaging of small animals showed that compared with the high dose NPs group， the high dose combination group had stronger tumor targeting ability（P<0.01）. ConclusionNPs combined with ultrasonic irradiation can not only effectively targeted the drug to the tumor site， inhibit the subcutaneous tumor growth of mouse liver cancer， but also decrease damage to liver and kidney tissues.

OBJECTIVE To investigate the targeting effect of folic acid-modified crebanine nanoparticles （FA-Cre@PEG- PLGA NPs， hereinafter referred to as “NPs”） combined with ultrasound irradiation on M109 cells in vitro and in vivo after administration， and explore the anti-tumor mechanism. METHODS CCK-8 assay was used to detect the inhibitory effect of NPs combined with ultrasound irradiation on the proliferation of M109 cells， and the best ultrasound time was selected. Using human lung cancer A549 cells as a control， the targeting of NPs combined with ultrasound irradiation to M109 cells was evaluated by free folic acid blocking assay and cell uptake assay. The effects of NPs combined with ultrasound irradiation on the migration， invasion， apoptosis， cell cycle and reactive oxygen species （ROS） levels of M109 cells were detected by cell scratch test， Transwell chamber test and flow cytometry at 1 h after 958401536@qq.com administration； the changes of mitochondrial membrane potential （MMP） were observed by fluorescence inverted microscope. A mouse subcutaneous tumor model of M109 cells was constructed， and the in vivo tumor targeting of NPs combined with ultrasound irradiation was investigated by small animal in vivo imaging technology. RESULTS NPs combined with ultrasound irradiation could significantly inhibit the proliferation of M109 cells， and the optimal ultrasound time was 1 h after administration. The free folic acid could antagonize the inhibitory effect of NPs on the proliferation of M109 cells， and combined with ultrasound irradiation could partially reverse this antagonism. Compared with A549 cells， the uptake rate of NPs in M109 cells was significantly higher （P＜0.01）， and ultrasound irradiation could promote cellular uptake. NPs combined with ultrasound irradiation could inhibit the migration and invasion of M109 cells and block the cell cycle in the G0/G1 and G2/M phases. Compared with control group， the apoptosis rate of M109 cells and ROS level were increased significantly （P＜0.01）， while the MMP decreased significantly （P＜0.01） in the different concentration （100， 200， 300 μg/mL） groups of M109 cells. Compared with the mice in non-ultrasound group， the fluorescence intensity and tumor-targeting index of the tumor site in the 0 h ultrasound group were significantly enhanced （P＜0.05 or P＜0.01）. CONCLUSIONS NPs combined with ultrasound irradiation have a strong targeting effect on M109 cells in vitro and in vivo， the anti-tumor mechanism includes inhibiting cell migration and invasion， blocking cell cycle， and inducing apoptosis.

Objective To investigate the suitable habitats of Phlebotomus chinensis in Gansu Province, so as provide insights into effective management of mountain-type zoonotic visceral leishmaniasis (MT-ZVL). Methods The geographical coordinates of locations where MT-ZVL cases were reported were retrieved in Gansu Province from 2015 to 2023, and data pertaining to 26 environmental variables were captured, including 19 climatic variables (annual mean temperature, mean diurnal range, isothermality, temperature seasonality, maximum temperature of the warmest month, minimum temperature of the coldest month, temperature annual range, mean temperature of the wettest quarter, mean temperature of the driest quarter, mean temperature of the warmest quarter, mean temperature of the coldest quarter, annual precipitation, precipitation of the wettest month, precipitation of the driest month, precipitation seasonality, precipitation of the wettest quarter, precipitation of the driest quarter, precipitation of the warmest quarter, and precipitation of the coldest quarter), five geographical variables (elevation, annual normalized difference vegetation index, vegetation type, landform type and land use type), and two population and economic variables (population distribution and gross domestic product). Twelve species distribution models were built using the biomod2 package in R project, including surface range envelope (SRE) model, generalized linear model (GLM), generalized additive model (GAM), multivariate adaptive regression splines (MARS) model, generalized boosted model (GBM), classification tree analysis (CTA) model, flexible discriminant analysis (FDA) model, maximum entropy (MaxEnt) model, optimized maximum entropy (MAXNET) model, artificial neural network (ANN) model, random forest (RF) model, and extreme gradient boosting (XGBOOST) model. The performance of 12 models was evaluated using the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS), and Kappa coefficient, and single models with high performance was selected to build the optimal ensemble models. Factors affecting the survival of Ph. chinensis were identified based on climatic, geographical, population and economic variables. In addition, the suitable distribution areas of Ph. chinensis were predicted in Gansu Province under shared socioeconomic pathway 126 (SSP126), SSP370 and SSP585 scenarios based on climatic data during the period from 1991 to 2020, from 2041 to 2060 (2050s), and from 2081 to 2100 (2090s) . Results A total of 11 species distribution models were successfully built for prediction of potential distribution areas of Ph. chinensis in Gansu Province, and the RF model had the highest predictive accuracy (AUC = 0.998). The ensemble model built based on the RF model, XGBOOST model, GLM, and MARS model had an increased predictive accuracy (AUC = 0.999) relative to single models. Among the 26 environmental factors, precipitation of the wettest quarter (12.00%), maximum temperature of the warmest month (11.58%), and annual normalized difference vegetation index (11.29%) had the greatest contributions to suitable habitats distribution of Ph. sinensis. Under the climatic conditions from 1991 to 2020, the potential suitable habitat area for Ph. chinensis in Gansu Province was approximately 5.80 × 10⁴ km², of which the highly suitable area was 1.42 × 10⁴ km², and primarily concentrated in the southernmost region of Gansu Province. By the 2050s, the unsuitable and lowly suitable areas for Ph. chinensis in Gansu Province had decreased by varying degrees compared to that of 1991 to 2020 period, while the moderately and highly suitable areas exhibited expansion and migration. By the 2090s, under the SSP126 scenario, the suitable habitat area for Ph. chinensis increased significantly, and under the SSP585 scenario, the highly suitable areas transformed into extremely suitable areas, also showing substantial growth. Future global warming is conducive to the survival and reproduction of Ph. chinensis. From the 2050s to the 2090s, the highly suitable areas for Ph. chinensis in Gansu Province will be projected to expand northward. Under the SSP126 scenario, the suitable habitat area for Ph. chinensis in Gansu Province is expected to increase by 194.75% and 204.79% in the 2050s and 2090s, respectively, compared to that of the 1991 to 2020 period. Under the SSP370 scenario, the moderately and highly suitable areas will be projected to increase by 164.40% and 209.03% in the 2050s and 2090s, respectively, while under the SSP585 scenario, they are expected to increase by 195.98% and 211.66%, respectively. Conclusions The distribution of potential suitable habitats of Ph. sinensis gradually shifts with climatic changes. Intensified surveillance and management of Ph. sinensis is recommended in central and eastern parts of Gansu Province to support early warning of MT-ZVL.

Objective To evaluate the current status in the implementation of GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators, identify issues in the application of its technical indicators, and provide a basis for the in-depth implementation and further revision of the standard. Methods In accordance with the Standardization Law of the People’s Republic of China and the Guidelines for Health Standards Tracking Evaluation (WS/T 536-2017), a combination of cluster sampling and stratified sampling methods was employed to select professionals involved in proton accelerator radiotherapy devices and facilities in three provinces (or municipalities directly under the central government) as the subjects of the survey. A questionnaire was developed to collect basic information about the subjects and their understanding and application of the technical indicators in the standard. A standard evaluation indicator system with a total score of 100 points was established to score the implementation of the standard (40 points), the technical content (30 points), and the effectiveness of the implementation (30 points). Results A total of 169 professionals from 107 institutions participated in the survey, with 79.88% of the respondents having at least 5 years of experience in radiation therapy and 74.56% holding intermediate or higher professional titles. The score of standard implementation was 18.3 points. The awareness rate exceeded 80%, indicating a high level of awareness about the standard. However, the scores for the dissemination and application of the standard were relatively low, accounting for 28% and 32% of their respective full marks. The technical content of the standard and the effectiveness of its implementation scored 27.0 and 26.6 points, respectively. The overall score in the evaluation of standard implementation was 72 points, with scores of 68.6, 72.3, and 75.0 for Beijing City, Shanghai City, and Jiangsu Province, respectively. Conclusion GBZ/T 201.5-2015 Radiation shielding requirements for radiotherapy rooms-Part 5: Radiotherapy room of proton accelerators is scientific and operable, and it is well-coordinated with relevant laws and standards. However, considering the development in FLASH technology and multi-chamber radiotherapy room, it is necessary to revise and improve the standard.

Hepatocellular carcinoma （HCC）， as the sixth most common malignant tumor worldwide， poses a serious threat to human health due to its insidious onset and high mortality rate. This article reviews the molecular mechanisms and intervention strategies of gut microbiota （GM） homeostasis in the development and progression of HCC， in order to provide new ideas for the intervention and treatment of HCC. Studies have shown that GM dysbiosis， intestinal leakage， microbial-associated molecular pattern， bacterial translocation， and metabolic products play key roles in the progression of HCC. GM imbalance may lead to immune escape， thereby promoting tumor cell proliferation and metastasis. This article elaborates on the association between GM and HCC， deeply analyzes the mechanism of action of GM in the development and progression of HCC， investigates the role of bile acid-related metabolites， short-chain fatty acid-related metabolites， and other metabolites in HCC， and explores the strategies for targeting GM in the treatment of HCC， including probiotics， prebiotics， antibiotics， Toll-like receptor 4 antagonists， and fecal microbiota transplantation. This article emphasizes that maintaining the integrity of the intestinal barrier and GM homeostasis is of great significance in the prevention and treatment of HCC， which provides a direction for developing new diagnosis and treatment strategies.

Objective To explore the otherness of orthotopic injection of cell suspensions and transplantation of tumor tissue blocks to establish orthotopic implantation models of hepatocellular carcinoma in mice,and to provide a technical reference for the establishment of an orthotopic implantation model.Methods Healthy KM mice were divided into four groups:group A,direct injection of H22 cells;group B,direct injection of H22 ascitic cells;group C,transplantation of tissues;and group D,direct injection of saline.Activity and weight changes were observed regularly in each group and survival times were recorded.Liver tumor formation,tumor size,abdominal organ adhesion degree,and metastasis were observed in all groups.B-ultrasound imaging was performed,concentrations of alpha fetoprotein(AFP)and abnormal prothrombin(DCP)were detected,and liver histopathological changes were detected by hematoxylin and eosin staining.Results Mice molding operation time in groups A,B,and C were(3.36±0.44)min,(3.30±0.41)min,and(5.68±0.65)min,respectively.After modeling for 25 days,the rates of model formation in groups A,B,and C were all 100.0%.Severe abdominal adhesions occurred in 40.0%of mice in group A and 60.0%in group B,but in no mice in group C or D.Ascites occurred in 40.0%,100.0%,and 0.0%and abdominal wall tumors in 30.0%,60.0%,and 0.0%of mice in groups A,B,and C,respectively,while 40.0%of mice in group B also had liver metastasis.B-ultrasound imaging,detection of serum AFP and DCP levels,and histopathological result showed smooth liver margins,uneven echo and slightly lower echo mass,maintained high AFP and DCP secretion,and large numbers of inflammatory cells and tumor cells in mice in groups A,B,and C.Conclusions At day 25,all three methods can thus be used to establish orthotopic transplantation models of HCC.Among these,inj ection of cell suspensions demonstrated the advantage of simplicity in operation and the presence of multiple metastatic nodules within the liver,compared to transplantation of tumor tissue.Conversely,transplantation of tumor tissue showed the advantage of causing less impact on the abdomen and other organs when compared to inj ection of cell suspensions.

Objective:To explore the application value and treatment effects of multiple free anterolateral perforator flaps of calf for reconstruction of multiple digital wounds in single hand.Methods:From August 2020 to March 2022, 12 patients with soft tissue defects in 35 digits were treated in Department of Hand Surgery, Suzhou Ruihua Orthopaedic Hospital. Ten patients were male and 2 were female, aged 25 to 58 years old. Of the patients, 1 had soft tissue defects in 5 digits, 3 in 4 digits, 2 in 3 digits and 6 in 2 digits. The size of defects was from 1.2 cm ×1.2 cm to 7.0 cm×3.5 cm after debridement. The vascular perforators discovered from intraoperative explorations were found originating from the superficial peroneal artery in 24 flaps, from the peroneal artery in 7 flaps and from the anterior tibial artery in 4 flaps. During surgery, the perforator artery and accompanying veins of the flaps were anastomosed with the proper digital artery and palmar or dorsal subcutaneous veins in the recipient site, respectively. The size of the flaps was from 1.5 cm×1.5 cm to 7.5 cm×4.0 cm. No nerve was affected in the surgery. The wound at donor sites in the calf was sutured directly. Regular postoperative follow-ups were conducted at outpatient clinics. The comprehensive evaluation scale of flap was used to assess the conditions of the donor and recipient sites.Results:In this study, all 35 soft tissue defects of digits in 12 patients were reconstructed by the anterolateral perforator flaps of calf. All the 35 flaps survived after surgery, with a 100% of survival rate. The patients were instructed to carry out early functional training after surgery. Follow-up lasted 6 to 24 months, with an average of 11 months. Twenty-five flaps were found in slightly swollen, and further flap thinning surgery were carried out 3 months after the primary surgery, while the rest of the flaps had good appearance and texture. At 6 months after surgery, all flaps recovered a partial deep and shallow sensory and sense of touch. All wound at donor sites in calf had one-stage healing without dysfunction. The comprehensive evaluation scale was excellent in 28 flaps and good in 7 flaps. The excellent and good rate was 100%.Conclusion:It is an effective method to use multiple free anterolateral perforator flaps of calf to reconstruct multiple digit defects in single hand. The flaps can be conveniently harvested and the multiple digital defects in single hand can be reconstructed in primary surgery with small damages to the donor sites and together with satisfactory clinical outcomes.

Purpose/Significance To identify research frontiers in the field,so as to assist scientific researchers to effectively select and track key research topics,and help research management decision-makers to dynamically adjust policy orientation.Method/Process Taking 37 927 pieces of high-impact journal document references and highly cited document references from the WOS database which published in the period of 2012-2022 as the data samples,BERTopic is used to extract topics,a multi-dimensional indicator re-search frontier recognition model is constructed,and different types of research frontiers in the field are identified from multiple dimen-sions.Result/Conclusion The proposed model identifies 9 hot research frontier topics,14 emerging research frontier topics,13 potential research frontier topics and 1 declining research topic in the field of oncology,which is effective.

In order to detect the environmental data of isolated cabin under various environmental conditions,a negative pressure cabin environment detector for aviation was developed,which was composed of a shell,a differential pressure transmitter,a pressure sensor,a carbon dioxide concentration sensor,an oxygen concentration sensor,a temperature and humidity sensor,a data processing module,a liquid crystal display(LCD)screen and USB data interface.It could environmental data such as carbon dioxide concentration,oxygen concentration,temperature,humidity,pressure difference between cabin and outside the cabin and air pressure outside the cabin in real time,the data processing module collected and processed the data,the data and data change curves was displayed in real time by the LCD screen,and the detection data was extracted through the USB data interface.When used in aviation environment,the detector could work continuously without fault for no less than 300 hours,and the average fault repair time was about 30 minutes,with good performance and high detection accuracy,which can provide convenience for the environmental data detection of negative pressure cabins,and is worthy of popularization.

Objective To investigate the predictive value of artificial intelligence(AI)-assisted high-resolution computed tomo-graphy(HRCT)in degree of invasion of early lung adenocarcinoma with subsolid nodules(SSN).Methods Ninety patients(a total of 90 SSN)with pulmonary SSN on AI-assisted HRCT scans were selected as the study subjects.According to the degree of invasion in pathology,the cases were divided into invasive adenocarcinoma(IAC)group(48 cases)and non-invasive adenocarcinoma(non-IAC)group(42 cases).The differences in general information,pulmonary SSN morphological characteristics,and related parameters were compared between the two groups.The influencing factors were analyzed using a multiple logistic regression model,and a nomo-gram prediction model was constructed.The diagnostic efficacy of the model was evaluated using receiver operating characteristic(ROC)curves,calibration curves,and clinical decision curves.Results Between the two groups,there were statistically significant differences in age,nodular nature,shape,tumor-lung interface,vacuole sign,burr sign,air-bronchial sign,vascular bunching sign and pleural indentation sign.Compared with the non-IAC group,the CT maximum value,energy,variance of CT value,CT average value,maximum surface area,mean long and short diameter,3D long diameter,surface area,volume,mass and entropy of the IAC group significantly increased,while the CT minimum value,compactness and sphericity of the IAC group significantly decreased.The results of multiple logistic regression model showed that burr sign,vascular bunching sign,tumor-lung interface,mass,pleural indentation sign,and CT average value were independent risk factors affecting the development of SSN into early IAC.Finally,a nomogram pre-diction model was constructed based on risk factors,and the results of ROC curves,calibration curves and clinical decision curves showed that the predictive model had good diagnostic efficacy.Conclusion HRCT imaging features assisted by AI have a high pre-dictive value for the degree of invasion in early lung adenocarcinoma with SSN,and focusing on the burr sign,vascular bunching sign,tumor-lung interface,mass,pleural indentation sign,and CT average value can improve clinical treatment and prognosis for patients.