Drug administration via hollow microneedles (HMN) have the advantages of painlessness, avoidance of first-pass effect, capability of sustained infusion, and no need for professional personnel operation. In addition, HMN can also be applied in the fields of body fluid extraction and biosensors, showing broad application prospects. However, traditional manufacturing technologies cannot meet the demand for low-cost mass production of HMN, limiting its widespread application. This paper reviews the main manufacturing technologies used for HMN in recent years, which include photolithography and etching, laser etching, sputtering and electroplating, micro-molding, three-dimensional (3D) printing and drawing lithography. It further analyzes the characteristics and limitations of existing manufacturing technologies and points out that the combination of various manufacturing technologies can improve production efficiency to a certain extent. In addition, this paper looks forward to the future trends of HMN manufacturing technology and proposes possible directions for its development. In conclusion, it is expected that this review can provide new ideas and references for follow-up research.
Printing, Three-Dimensional ; Needles ; Humans ; Drug Delivery Systems/methods* ; Equipment Design ; Microinjections/methods*

Objective:To evaluate the clinical utility of left atrial strain parameters and left atrioventricular global longitudinal strain（LAVGLS）in detecting cardiovascular immune-related adverse events（CV-irAEs）among non-small cell lung cancer patients receiving immune checkpoint inhibitors（ICIs）.Methods:A total of 68 patients with non-small cell lung cancer were prospectively enrolled in Tianjin Medical University Cancer Institute and Hospital from October 2023 to October 2024. All patients were treated with ICIs for 6 cycles. Electrocardiogram，cardiac serological markers and echocardiography were examined before medication（T0 stage），4 cycles after medication（T1 stage）and 6 cycles after medication（T2 stage），respectively. According to the guidelines of the American Society of Clinical Oncology，all patients were divided into the CV-irAEs group（ n=14）and the No-CV-irAEs group（ n=54）. AFI software and 4D Auto LAQ software were used to calculate LVGLS，left atrial reservoir longitudinal strain（LASr），LAVGLS and a series of left atrial parameters. Cox proportional hazards regression model was applied to find the risk factors for the occurrence of CV-irAEs. ROC curve was applied to analyze the diagnostic efficiency of these parameters for CV-irAEs. Results:Fourteen patients（20.6%）developed CV-irAEs after T2 stage. After ICIs treatment，LVGLS，LASr and LAVGLS decreased in both groups，LVGLS，LASr and LAVGLS decreased more significantly in the CV-irAEs group than those in the No-CV-irAEs group（ P=0.038，0.047，0.005）. Left ventricular ejection fraction（LVEF）decreased in the CV-irAEs group at the same time（ P=0.003）. Cox multivariate analysis showed that ΔLAVGLS（the difference between stage T0 and stage T2）was a risk factor for CV-irAEs（ HR：1.395， P=0.019）. ROC curve analysis showed the area under the curve of LVGLS，LASr，LAVGLS，ΔLVGLS，ΔLASr，ΔLAVGLS，and LVEF at the T2 stage for diagnosis of CV-irAEs were 0.68，0.67，0.75，0.79，0.73，0.82，and 0.72，respectively. Conclusions:Decline of LAVGLS is a risk factor for CV-irAEs in patients with non-small cell lung cancer receiving ICIs and can be used for early detection of CV-irAEs. LASr has potential diagnostic value for CV-irAEs，but it is less valuable than LVGLS and LAVGLS.

Objective To investigate the predictive value of preoperative ultrasound in combination with neutrophil-to-lymphocyte ratio(NLR),calcitonin(Ctn),and carcinoembryonic antigen(CEA)for cervical lymph node metastasis in patients with papillary thyroid carcinoma.Methods A total of 103 patients diagnosed with papillary thyroid carcinoma(PTC)who were admitted to the hospital between October 2021 and October 2024 were selected as the case group.Among them,34 patients with cervical lymph node metastasis confirmed by surgical and pathological examination were assigned to the metastatic group,and 69 patients without cervical lymph node metas-tasis were assigned to the non-metastatic group.Additionally,103 patients with benign thyroid nodules admitted during the same period were enrolled as the control group.Clinical data,ultrasonographic features,and serum levels of NLR,Ctn,and CEA were compared between the metastatic and non-metastatic groups.The predictive value of ultrasonographic features and the combined detection of NLR,Ctn,and CEA levels for cervical lymph node metastasis in PTC was evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared to the control group,the case group exhibited a higher proportion of patients with microcalcification and grade 3 blood flow,as well as elevated levels of NLR,Ctn,and CEA(P<0.05).Similarly,compared to the non-metastatic group,the metastatic group showed a higher proportion of patients with microcalcification and grade 3 blood flow,along with increased levels of NLR,Ctn,and CEA(P<0.05).The metastatic group tested positive,whereas the non-metastatic group tested negative.The area under the curve(AUC)for ultrasound features(micro-calcification,blood flow classification)combined with NLR,Ctn,and CEA levels in diagnosing cervical lymph node metastasis in papillary thyroid carcinoma was higher than that of individual indicators(P<0.05).Conclusions Preoperative ultrasound combined with the assessment of NLR,Ctn,and CEA levels demonstrates significant predictive value for cervical lymph node metastasis in papillary thyroid carcinoma.

Objective To investigate the predictive value of preoperative ultrasound in combination with neutrophil-to-lymphocyte ratio(NLR),calcitonin(Ctn),and carcinoembryonic antigen(CEA)for cervical lymph node metastasis in patients with papillary thyroid carcinoma.Methods A total of 103 patients diagnosed with papillary thyroid carcinoma(PTC)who were admitted to the hospital between October 2021 and October 2024 were selected as the case group.Among them,34 patients with cervical lymph node metastasis confirmed by surgical and pathological examination were assigned to the metastatic group,and 69 patients without cervical lymph node metas-tasis were assigned to the non-metastatic group.Additionally,103 patients with benign thyroid nodules admitted during the same period were enrolled as the control group.Clinical data,ultrasonographic features,and serum levels of NLR,Ctn,and CEA were compared between the metastatic and non-metastatic groups.The predictive value of ultrasonographic features and the combined detection of NLR,Ctn,and CEA levels for cervical lymph node metastasis in PTC was evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared to the control group,the case group exhibited a higher proportion of patients with microcalcification and grade 3 blood flow,as well as elevated levels of NLR,Ctn,and CEA(P<0.05).Similarly,compared to the non-metastatic group,the metastatic group showed a higher proportion of patients with microcalcification and grade 3 blood flow,along with increased levels of NLR,Ctn,and CEA(P<0.05).The metastatic group tested positive,whereas the non-metastatic group tested negative.The area under the curve(AUC)for ultrasound features(micro-calcification,blood flow classification)combined with NLR,Ctn,and CEA levels in diagnosing cervical lymph node metastasis in papillary thyroid carcinoma was higher than that of individual indicators(P<0.05).Conclusions Preoperative ultrasound combined with the assessment of NLR,Ctn,and CEA levels demonstrates significant predictive value for cervical lymph node metastasis in papillary thyroid carcinoma.

Objective:To evaluate the clinical utility of left atrial strain parameters and left atrioventricular global longitudinal strain（LAVGLS）in detecting cardiovascular immune-related adverse events（CV-irAEs）among non-small cell lung cancer patients receiving immune checkpoint inhibitors（ICIs）.Methods:A total of 68 patients with non-small cell lung cancer were prospectively enrolled in Tianjin Medical University Cancer Institute and Hospital from October 2023 to October 2024. All patients were treated with ICIs for 6 cycles. Electrocardiogram，cardiac serological markers and echocardiography were examined before medication（T0 stage），4 cycles after medication（T1 stage）and 6 cycles after medication（T2 stage），respectively. According to the guidelines of the American Society of Clinical Oncology，all patients were divided into the CV-irAEs group（ n=14）and the No-CV-irAEs group（ n=54）. AFI software and 4D Auto LAQ software were used to calculate LVGLS，left atrial reservoir longitudinal strain（LASr），LAVGLS and a series of left atrial parameters. Cox proportional hazards regression model was applied to find the risk factors for the occurrence of CV-irAEs. ROC curve was applied to analyze the diagnostic efficiency of these parameters for CV-irAEs. Results:Fourteen patients（20.6%）developed CV-irAEs after T2 stage. After ICIs treatment，LVGLS，LASr and LAVGLS decreased in both groups，LVGLS，LASr and LAVGLS decreased more significantly in the CV-irAEs group than those in the No-CV-irAEs group（ P=0.038，0.047，0.005）. Left ventricular ejection fraction（LVEF）decreased in the CV-irAEs group at the same time（ P=0.003）. Cox multivariate analysis showed that ΔLAVGLS（the difference between stage T0 and stage T2）was a risk factor for CV-irAEs（ HR：1.395， P=0.019）. ROC curve analysis showed the area under the curve of LVGLS，LASr，LAVGLS，ΔLVGLS，ΔLASr，ΔLAVGLS，and LVEF at the T2 stage for diagnosis of CV-irAEs were 0.68，0.67，0.75，0.79，0.73，0.82，and 0.72，respectively. Conclusions:Decline of LAVGLS is a risk factor for CV-irAEs in patients with non-small cell lung cancer receiving ICIs and can be used for early detection of CV-irAEs. LASr has potential diagnostic value for CV-irAEs，but it is less valuable than LVGLS and LAVGLS.

Objective: To assess the nutritional status of primary and secondary school students in Beijing City and to analyze the related factors, so as to provide a scientific basis for improving the nutritional status of primary and secondary school students in a targeted manner. Methods: Based on the 2021 Beijing Student Common Diseases and Health Influencing Factors Surveillance Project, a stratified random cluster sampling method was used to conduct a physical examination and questionnaire survey on 25 487 primary and secondary school students from September to November 2021. The Chi square test was used for comparison of nutritional status detection rates, and disordered multi classification Logistic regression analysis was used to explore the factors associated with students nutritional status. Results: The detection rates of malnutrition, overweight and obesity among primary and secondary school students in Beijing City were 4.7%, 18.0% and 23.8% respectively. The detection rates of malnutrition, overweight and obesity were higher among male students (5.1%, 20.4%, 29.7%) than female students (4.2%, 15.5%, 17.4%) ( χ 2= 12.23, 101.71, 526.99, P <0.01). The detection rate of obesity was higher in the suburbs than urban areas(26.6%, 19.8%), and the detection rate of malnutrition was lower in the suburbs than urban areas (4.2%,5.5%)( χ 2=157.25, 23.61, P <0.01). The results of disordered multi classification Logistic regression showed that the related factors for malnutrition, overweight and obesity were gender, residence, moderate to vigorous exercise ≥60 min per day and lack of sleep( OR =1.70, 1.88,2.48; 1.14, 0.87, 0.67; 0.85, 0.92, 0.81 ; 0.83, 1.08, 1.07); frequency of fried food intake daily was a related factor for overweight ( OR =0.70); whether eating breakfast daily or not was a related factor for overweight and obesity ( OR =0.91, 0.84); academic level (middle and high school) was a related factor for malnutrition and obesity ( OR =1.38, 1.37; 0.77, 1.40)( P <0.05). Conclusions The problem of overweight and obesity among primary and secondary school students in Beijing City continues to be serious, especially among boys and suburban areas. It is recommended that society, schools, families and individuals should work together to improve the nutritional status of primary and secondary school students by adopting a graded and classified approach.

Objective: To understand the trend of changes of hygiene status in the teaching environment among primary and secondary schools in Beijing City during 2016-2020, so as to provide basis for further improving the teaching environment and campus hygiene conditions in primary and secondary schools. Methods: A proportional systematic sampling method covered over 50% of schools selected annually in Beijing from 2016 to 2019, and 34% were selected in 2020. Two representative classrooms were selected from each selected school for testing based on their structure and other factors, with 6 196 classrooms supervised, from 2016 to 2020,1 330,1 312,1 384,1 322,848 classrooms were monitored for each year. Results: From 2016 to 2020, the overall lighting qualification rate of classrooms (lighting coefficient 72.8%, window to floor area ratio 41.8%, rear wall reflectance ratio 42.2%, blackboard reflection ratio 37.4%), the overall qualification rate of average blackboard illumination and uniformity (50.6%, 34.9 %), and the overall qualification rate of desk and chair allocation (58.6%) were all below 80%. The overall qualification rate of per capita classroom area (87.5%), blackboard size (83.2%), average desk illumination ( 80.1% ), average desk illumination and uniformity (82.9%), the distance between lamp and desk (99.1%), carbon dioxide ( 86.6% ), temperature (84.9%), and noise (96.6%) were all above 80%. The following indicators, blackboard size, the distance between lamp and desk, average blackboard illumination, lighting coefficient, blackboard reflectance, rear wall reflectance, carbon dioxide, temperature, and noise ( χ 2=78.38, 9.71, 11.76, 320.59, 37.63, 58.45, 236.45, 1 347.56, 101.97), had statistically significance between years. Among those indicators, the qualified rates of blackboard size, blackboard reflectance, lighting coefficient, and noise had been increasing year by year ( χ 2 trend =69.98, 15.82, 240.02, 5.77) ( P <0.05). The qualified rates of per capita classroom area, window to floor area ratio, and blackboard reflection ratio in primary schools (81.6%, 39.8%, 36.3%) were all lower than those in secondary schools (94.9%, 44.5%, 40.3%) ( χ 2=246.32, 12.03, 10.51, P <0.05). The qualified rates of blackboard size, average blackboard illumination, average blackboard illumination and uniformity, and desk and chair allocation (89.3%, 55.6% , 36.0%, and 60.2%) were all higher than those in secondary schools (75.4%, 44.1%, 33.3%, and 56.5%) ( χ 2=209.33, 78.41, 4.44, 8.22) ( P <0.05). The qualified rates of average desk illumination and uniformity, average blackboard illumination, rear wall reflectance ratio, desk and chair allocation, carbon dioxide, temperature, and noise indicators in urban area (82.9%, 84.1% , 51.9%, 45.0%, 60.9%, 91.2%, 89.5%, 97.8%) were all higher than those in suburban area (77.3%, 81.7%, 49.2%, 39.5%, 56.3%, 82.3%, 80.4%, 95.5%) ( χ 2=31.16, 6.28, 4.36, 16.40, 13.39, 105.29, 98.23, 24.66， P <0.05). The qualified rates of the distance between lamp and desk, lighting coefficient, window to floor area ratio, blackboard size, blackboard reflection ratio, average blackboard illumination and uniformity, and per capita classroom area in urban areas (98.8%, 65.2%, 34.3%, 76.7%, 35.9%, 30.1%, 84.6%) were all lower than those in suburban areas (99.4%, 81.4%, 49.8%, 89.7%, 40.2%, 39.6%, 90.3%) ( χ 2=6.80, 171.67, 132.43, 188.46 , 12.45, 60.28, 44.82) ( P <0.05). Conclusions The main problems in the teaching environment of schools in Beijing are classroom lighting, as well as desk and chair allocation. The findings suggest technical rationality and operability of relevant standard should be considered when under revision, and standard training and supervision management should be strengthened, with the aim of teaching environment improvement.

OBJECTIVE To investigate the improvement effects of limonin on intestinal injury and intestinal flora disturbance in rats with ulcerative colitis （UC） and its mechanism. METHODS UC rat models were established， and 70 rats with successful modeling were randomly divided into model group， limonin low-， medium-， and high-dose groups （12.5， 25， 50 mg/kg）， and sulfasalazine group （positive control group，500 mg/kg）， with 14 rats in each group. Another 14 rats were selected as the control group. After modeling， each group was given the corresponding drug or equal amount of normal saline， once a day， for 2 weeks. Twenty-four hours after the last administration， the general condition of rats was observed and the body weight was measured， and colon tissue was collected for colonic mucosal damage index （CMDI） scoring； the levels of interleukin-1β （IL-1β）， IL-6 and tumor necrosis factor-α （TNF-α） in colon tissue were detected； the pathological changes of colon tissue were observed； the protein expressions of Claudin-1， Occludin， ZO-1， high mobility group protein B1 （HMGB1） and receptor for advanced glycation end products （RAGE） in colon tissue were detected； fecal 16S rRNA sequencing was used to detect the relative abundance of zhangxiaxia5287@163.com intestinal microbiota in rats. RESULTS Compared with the control group， the rats in the model group were in poor mental state， with darker fur， irritable mood， disordered arrangement of colon glands， inflammatory cell infiltration， cell necrosis and edema； CMDI score， the levels of IL-1β， IL-6 and TNF-α， protein expressions of HMGB1 and RAGE in colon tissue， the relative abundance of Proteobacteria and Bacteroidetes were significantly increased （P＜0.05）； body weight， the protein expressions of Claudin-1， Occludin and ZO-1 in colon tissue， the relative abundance of Firmicutes in the intestine were significantly decreased （P＜0.05）. Compared with the model group， general situation and pathological damage of colonic tissue in limonin groups were improved， the levels of the above indicators were significantly reversed （P＜0.05）， and in a dose-dependent manner （P＜0.05）； there was no significant difference in various indexes between sulfasalazine group and limonin high-dose group （P＞0.05）. CONCLUSIONS Limonin can improve intestinal injury and intestinal flora disturbance in UC model rats， the mechanism of which may be associated with the down-regulation of HMGB1/RAGE signaling pathway.

Objective:To construct a core competency indicator system for oncology advanced practice nurses.Methods:This study is a cross-sectional study. A preliminary draft of the core competency indicator system for oncology advanced practice nurses was developed through literature review and expert group coordination from June to November 2022. The core competency indicator system for oncology advanced practice nurses was established using the Delphi method for expert consultation and the analytic hierarchy process.Results:A total of 54 experts from 11 hospitals and four medical schools in 10 provinces and municipalities directly under the central government across the country were included in two rounds of expert consultation. The effective response rates of the questionnaire were all 100%, with an expert authority coefficient of 0.90, Kendall coordination coefficients of 0.089 to 0.179 and 0.101 to 0.176 ( P<0.01). The final established core competency indicator system for oncology advanced practice nurses included seven primary indicators and 69 secondary indicators. Conclusions:The core competency indicator system for oncology advanced practice nurses is comprehensive and has the characteristics of specialized oncology nursing, and the construction process is scientific and reliable, laying the foundation for future training of oncology advanced practice nurses.

Objective To explore the relationship between the expression levels of microRNA-155(miR-155)and suppressor of cytokine signaling 1(SOCS1)in the colonic mucosal tissue of patients with ulcerative co-litis(UC)and the severity of the disease.Methods A total of 130 UC patients admitted to the Second Affiliated Hospital of Hebei North University from September 2021 to June 2023 were selected.According to the modified Mayo score system,the patients were assigned into an active stage group(n=85)and a remission stage group(n=45).According to the modified Truelove and Witts classification criteria,the UC patients at the active stage were as-signed into a mild group(n=35),a moderate group(n=30),and a severe group(n=20).A total of 90 healthy individuals who underwent colonoscopy for physical examination or those who had normal colonoscopy re-sults after single polypectomy and excluded other diseases were selected as the control group.The colonic mucosal tissues of UC patients with obvious lesions and the colonic mucosal tissue 20 cm away from the anus of the control group were collected.The levels of miR-155 and SOCS1 mRNA in tissues were determined by fluorescence quanti-tative PCR,and the expression of SOCS1 protein in tissues was determined by immunohistochemistry.The corre-lations of the levels of miR-155 and SOCS1 mRNA in the colonic mucosal tissue with the modified Mayo score of UC patients were analyzed.The values of the levels of miR-155 and SOCS1 mRNA in predicting the occurrence of severe illness in the UC patients at the active stage were evaluated.Results Compared with the control group and the remission stage group,the active stage group showed up-regulated expression level of miR-155,down-regula-ted level of SOCS1 mRNA,and decreased positive rate of SOCS1 protein in the colonic mucosal tissue(all P＜0.001).The expression level of miR-155 and modified Mayo score in colonic mucosal tissues of UC patients at the active stage increased,while the mRNA level of SOCS1 was down-regulated as the disease evolved from being mild to severe(all P＜0.001).The modified Mayo score was positively correlated with the miR-155 level and neg-ative correlated with the mRNA level of SOCS1 in colonic mucosal tissues of UC patients(all P＜0.001).The high miR-155 level(OR=2.762,95％CI=1.284-5.944,P=0.009),low mRNA level of SOCS1(OR=2.617,95％CI=1.302-5.258,P=0.007),and modified Mayo score≥ 12 points(OR=3.232,95％CI=1.450-7.204,P=0.004)were all risk factors for severe disease in the UC patients at the active stage.The ar-ea under curve of miR-155 combined with SOCS1 mRNA in predicting severe illness in the UC patients at the ac-tive stage was 0.920.Conclusions The expression levels of miR-155 and SOCS1 mRNA were correlated with the disease severity in the UC patients at the active stage.The combination of the two indicators demonstrates good performance in predicting the occurrence of severe illness in UC patients at the active stage.