Definitive treatment of lung cancer with radiotherapy is challenging, as respiratory motion and anatomical changes can increase the risk of severe off-target effects during radiotherapy. Online adaptive radiotherapy (ART) is an evolving approach that enables timely modification of a treatment plan during the interfraction of radiotherapy, in response to physiologic or anatomic variations, aiming to improve the dose distribution for precise targeting and delivery in lung cancer patients. The effectiveness of online ART depends on the seamless integration of multiple components: sufficient quality of linear accelerator-integrated imaging guidance, deformable image registration, automatic recontouring, and efficient quality assurance and workflow. This review summarizes the present status of online ART for lung cancer, including key technologies, as well as the challenges and areas of active research in this field.
Humans ; Lung Neoplasms/radiotherapy* ; Radiotherapy Planning, Computer-Assisted/methods*

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective:To analyze the clinical features and prognosis of acute B lymphoblastic leukemia (B-ALL) children carrying a TCF3: : PBX1 fusion gene and to evaluate the prognostic value of this gene.Methods:Retrospective cohort study.A total of 2 164 B-ALL children aged 0-18 years diagnosed and treated at 19 pediatric centers from October 2016 to June 2022 were enrolled.They were divided into the positive group and the negative group according to whether they carried a TCF3: : PBX1 fusion gene.The clinical characteristics, treatment response, adverse reactions, and prognosis of the 2 groups of patients were analyzed.The rank sum and Kruskal-Wallis tests were used to compare two and more than two groups of numerical variables, respectively.Fisher′s exact test was used to compare categorical variables.Results:Among the 2 164 patients, 116 (5.4%) were TCF3: : PBX1 positive, of which 70 patients were female, accounting for 60.3%.There were 840 female patients in the TCF3: : PBX1-negative group, accounting for 41.0%.There was a significant difference in the ratio of females between the TCF3: : PBX1-positive and TCF3: : PBX1-negative groups ( P<0.001).No significant difference was observed in age of onset between the two groups( P>0.05).The proportion of bone marrow naive cells [54.00 (14.00, 76.50)% vs.29.00 (3.00, 68.00)%], white blood cell counts [25.30 (10.46, 60.94)×10 9/L vs.9.03 (4.38, 30.73)×10 9/L] and hemoglobin counts [82.00(63.00, 101.00) g/L vs.74.00(60.00, 90.00) g/L] in the TCF3: : PBX1-positive group were significantly higher than those in the negative group at the onset (all P<0.05).In terms of treatment response, the proportion of peripheral blood naive cells on Day 8 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group [2.00 (0, 9.00)% vs.0 (0, 2.00)%, P<0.001].The proportion of minimal residual disease <0.1% on Day 15 in the TCF3: : PBX1-positive group was significantly higher than that in the negative group ( P=0.038).There were no significant differences in cumulative recurrence rate, treatment-related mortality (TRM), and overall survival (OS) between the TCF3: : PBX1-positive group and TCF3: : PBX1-negative group (all P>0.05).The cumulative recurrence risk of TCF3: : PBX1-positive patients was 9.646 times higher than that of ETV6: : RUNX1-positive patients with better prognosis( HR=9.646, 95% CI: 1.026-90.700, P=0.047).There were no significant differences in TRM and OS between TCF3: : PBX1-positive and ETV6: : RUNX1-positive patients (all P>0.05).A significant enrichment of PAX5 mutations was detected in TCF3: : PBX1-positive patients.Among the 7 high-risk TCF3: : PBX1-positive patients in a single center, 4 patients had PAX5 mutations, and this proportion was significantly higher than that in other patients ( P<0.001). Conclusions:B-ALL children carrying a TCF3: : PBX1 fusion gene have a high remission rate and good long-term prognosis after intensive chemotherapy.It is suggesting that TCF3: : PBX1-positive B-ALL patients should be rated at intermediate risk to receive intensive chemotherapy.

Objective To explore the characteristics of blood vitamins A, B2, B6, B12, D, E, K1, K2 and folic acid and their correlation with severity in patients with metabolic-related fatty liver disease (MAFLD). Methods　From September to December 2022, a total of 473 cases of residents were recruited through community MAFLD screening activities and their health information was obtained through questionnaire survey and physical examination. The severity of hepatic steatosis was determined with FibroScan, and vitamin concentrations were determined with liquid chromatography-tandem mass spectrometry. Two independent samples' t-tests were used to assess the differences between the two groups, and univariate chi-square tests and multivariate logistic regression analysis were used to explore the related factors of MAFLD. Results　Of the 473 inhabitants, 195 (41.23%, 195/473) met the diagnostic criteria for MAFLD, including mild 43 (22.05%, 43/195) cases of fatty liver, 88 (45.13%, 88/195) cases of moderate fatty liver, and 64 (32.82%, 64/195) cases of severe fatty liver. Using healthy residents collected during the same period as controls, the overall mean of vitamins A, E, K1, and K2 in the MAFLD group was higher than that of the healthy group, with a statistical difference (P<0.05). Furthermore, the concentrations of vitamins A, E, K1 and K2 increased with the severity of fatty liver [R=0.149, P=0.004; R=0.245, P<0.001; R=0.110, P=0.032; R=0.129，P=0.012]. There were statistically significant differences (P<0.05) in the blood levels of vitamin A and E between patients with moderate or severe fatty liver and the healthy population. The blood vitamins K1 and K2 in severe fatty liver patients were also different from those of healthy people (P<0.05). However, there was no significance between folic acid, vitamin D, B2, B6, B12, and MAFLD (P>0.05). Through univariate chi-square analysis and multivariate logistic regression analysis, it was found that male [Wald=5.789, P=0.034，OR=1.598(1.037-2.463)] and vitamin E≥8.13 μg/mL[Wald=14.632，P<0.001，OR=2.378(1.522-3.674)] were risk factors for moderate and severe MAFLD. Conclusions The concentrations of vitamin A, E, and K in the blood are increased in patients with MAFLD compared to the healthy population, and they are positively correlated with the severity of MAFLD. ale gender and high levels of vitamin E may be related to moderate to severe MAFLD.

Objective:To investigate the effect of combination of infrared thermography (IRT) and high frequency colour Doppler ultrasound (HFCDU) in location of superficial fascia perforating vessels and to guide the design and harvest of super-thin anterolateral thigh flap (ALTF) .Methods:A total of 15 patients who received medical treatment in the Department of Orthopaedics, Zhoushan Hospital and Department of Foot and Ankle Surgery, Wuxi No.9 People’s Hospital from January 2022 to July 2023 were selected to participate the study. The patients were 11 males and 4 females, aged 26 to 64 years with an average age of 48.3 years. A total of 14 wounds of foot, 1 of hand, 1 of forearm and 1 of ankle were reconstructed with 17 free super-thin ALTFs. The sizes of soft tissue defect were 5 cm×3 cm-23 cm×7 cm. The flaps were 6 cm×4 cm to 25 cm×8 cm in size. The donor sites were directly pulled together and sutured. Before surgery, HFCDU was applied to locate the perforator vessels across deep fascia into superficial fascia of the ALTF. IRT was further employed to locate the superficial perforator vessels on the superficial fascia in operating room. The running course of a perforating branch in the superficial fascia was determined by the running courses of the perforating branch located by the two location methods. Super-thin ALTFs were harvested and the precise locations of the perforating vessels were verified in surgery. SPSS 23.0 software was used for data analysis. Rank sum test was performed on the location data of superficial fascial perforating branches found by IRT and the data in surgery. P<0.05 was considered a statistically significant difference. All patients were included in the postoperative follow-up by means of visit of outpatient clinic and via WeChat reviews, where the survival and functional recovery of the flaps were observed. Results:A total of 30 perforating vessels had been located by HFCDU and 30 by IRT, and a total of 31 perforating vessels were found in superficial fascia in surgery. The true positive rate was 93.3%, with a false positive rate at 6.7% and a false negative rate at 9.7%. The rank sum test calculated P=0.853 for the number of perforating vessels located by the IRT and those found from surgery. There was no significant difference between the 2 detecting methods. No postoperative complication occurred in all 14 flaps. Partial necrosis occurred in 1 flap but healed after dressing changes. Venous occlusion had occurred in 1 flap, it was rectified after surgical exploration. Superficial infection happened in 1 flap and it was improved after anti-infection treatment. Postoperative follow-up was conducted for 3-12 months. The flaps were in good texture with satisfactory appearance and function of limbs. All donor sites healed well without scar hyperplasia. Conclusion:IRT combined with HFCDU is a reliable method in location of perforator vessels of ALTF, and it is an ideal technique in the exploration of perforator vessels and in the harvest of a super-thin flap.

ObjectiveTo present the exploration and application of a prospective follow-up research method for acute infectious disease surveillance based on natural community populations， using COVID-19 infection as an example， and to provide a reference for improving the infectious disease surveillance and early warning system. MethodsA multi-stage probability proportional sampling method was employed to sample residents from all communities of 16 administrative districts in Shanghai， with households as the units. A cohort for acute infectious diseases based on natural community populations was established. The baseline survey was conducted for all cohort subjects， and COVID-19 antigen test kits were distributed. From December 21， 2022 to September 30， 2023， prospective follow-up monitoring of COVID-19 antigen and nucleic acid was carried out on the study subjects on a weekly basis. The baseline characteristics and follow-up information of the cohort subjects were described. ResultsThe cohort for acute infectious diseases included a total of 12 881 subjects， comprising 6 098 males （47.3%） and 6 783 females （52.7%）. The baseline survey revealed that 35.2% （4 540/12 881） of the subjects had a history of COVID-19 infection. During the follow-up period from December 21， 2022 to September 30， 2023， the average incidence density in the cohort was 0.61/person-year， with a higher incidence density in females （0.63/person-year） compared to males （0.59/person-year）. Individuals aged 60 and above （0.64/person-year） and those with underlying health conditions （0.67/person-year） had a higher incidence density. Healthcare workers showed a notably higher incidence density （0.84/person-year） than that in other occupational groups. As of September 30， 2023， a total of 340 subjects in the cohort experienced secondary infections， with a median interval of 170 days between the first and second infections. ConclusionThis study applies cohort study method to acute infectious disease surveillance， providing crucial data support for estimating infection rates and forecasting alerts for acute infectious diseases in the community. This method can be promoted and applied as a new approach for acute infectious disease surveillance.

Objective:To investigate the effect of combination of infrared thermography (IRT) and high frequency colour Doppler ultrasound (HFCDU) in location of superficial fascia perforating vessels and to guide the design and harvest of super-thin anterolateral thigh flap (ALTF) .Methods:A total of 15 patients who received medical treatment in the Department of Orthopaedics, Zhoushan Hospital and Department of Foot and Ankle Surgery, Wuxi No.9 People’s Hospital from January 2022 to July 2023 were selected to participate the study. The patients were 11 males and 4 females, aged 26 to 64 years with an average age of 48.3 years. A total of 14 wounds of foot, 1 of hand, 1 of forearm and 1 of ankle were reconstructed with 17 free super-thin ALTFs. The sizes of soft tissue defect were 5 cm×3 cm-23 cm×7 cm. The flaps were 6 cm×4 cm to 25 cm×8 cm in size. The donor sites were directly pulled together and sutured. Before surgery, HFCDU was applied to locate the perforator vessels across deep fascia into superficial fascia of the ALTF. IRT was further employed to locate the superficial perforator vessels on the superficial fascia in operating room. The running course of a perforating branch in the superficial fascia was determined by the running courses of the perforating branch located by the two location methods. Super-thin ALTFs were harvested and the precise locations of the perforating vessels were verified in surgery. SPSS 23.0 software was used for data analysis. Rank sum test was performed on the location data of superficial fascial perforating branches found by IRT and the data in surgery. P<0.05 was considered a statistically significant difference. All patients were included in the postoperative follow-up by means of visit of outpatient clinic and via WeChat reviews, where the survival and functional recovery of the flaps were observed. Results:A total of 30 perforating vessels had been located by HFCDU and 30 by IRT, and a total of 31 perforating vessels were found in superficial fascia in surgery. The true positive rate was 93.3%, with a false positive rate at 6.7% and a false negative rate at 9.7%. The rank sum test calculated P=0.853 for the number of perforating vessels located by the IRT and those found from surgery. There was no significant difference between the 2 detecting methods. No postoperative complication occurred in all 14 flaps. Partial necrosis occurred in 1 flap but healed after dressing changes. Venous occlusion had occurred in 1 flap, it was rectified after surgical exploration. Superficial infection happened in 1 flap and it was improved after anti-infection treatment. Postoperative follow-up was conducted for 3-12 months. The flaps were in good texture with satisfactory appearance and function of limbs. All donor sites healed well without scar hyperplasia. Conclusion:IRT combined with HFCDU is a reliable method in location of perforator vessels of ALTF, and it is an ideal technique in the exploration of perforator vessels and in the harvest of a super-thin flap.

According to the differences in function and structure, the nasal cavity can be roughly divided into three regions:the vestibule, respiratory zone, and olfactory zone. The current mainstream of research believes that the process of drugs entering the brain through the nasal cavity mainly occurs in the latter two regions, with the olfactory zone being the primary area. To allow more effective ingredients to enter the brain or reach the above-mentioned delivery pathway targets quickly, when developing related drug products, it should be possible to deliver the drug to the upper nasal cavity, like the upper respiratory zone and olfactory zone. Therefore, special drug delivery devices that can target the upper nasal cavity play a key and core role in Nose-to-Brain delivery. It is nasal spray device Nose-to-Brain delivery products approved by FDA mainly use. The following are three main research directions of the Nose-to-Brain delivery devices. 1) In-depth assessment and research of critical quality attributes and their influencing factors. Many research institutions and enterprises have conducted extensive research on liquid or powder sprays aided by nasal spray devices, and it is currently agreed that spray pattern, plume geometry, and particle size are the critical quality attributes, which can be mainly affected by spray devices and content properties. A spray with a smaller angle can penetrate the nasal valve easier and deliver to the upper nasal cavity. 2) The study of delivery platforms for such complex drug-device combinations is also a key direction, such as Exhalation Delivery Systems (EDS), Precision Olfactory Delivery Systems (POD®), and Controlled Particle Dispersion Technology (CPD) platforms, etc., which are general technology platforms established by drug delivery device manufacturers to better achieve Nose-to-Brain delivery. They have indeed achieved more accurate drug delivery, more significant therapeutic effects, and more convenient use for patients. 3) Combining drug delivery devices with new technologies. For example, adding mucosal adsorbents and permeation enhancers to the prescription, and preparing medicinal products using nanoparticle formulation technology. It is new directions for future research and development which can further meet the needs of Nose-to-Brain delivery. Nose-to-Brain delivery bring new hope to a wide range of clinical needs for brain diseases due to its special advantages. In order to play the truly important role of Nose-to-Brain delivery, it is not only the industry make efforts in research and industrialization, but also regulatory aspects need scientific evaluation and reasonable regulation of emerging technologies. Here are our thoughts. First, we need to pay attention to the important role of regulatory science in the technical research and evaluation of Nose-to-Brain delivery products. Next, we need to pay attention to the interaction and collaboration between scientific researchers, industry, regulators, and users. Then, regulatory authorities needs to broaden its thinking flexibility and attach importance to the role of individual drug guidelines, summary key technical points and solutions from multiple cases. Finally, we need to pay attention to the design, research and development support, and industrialization security of domestic drug delivery devices.

Nasal preparation are preparations that directly delivery drugs on the nasal cavity and exert local or systemic effects. It has the clinical advantages of rapid absorption, high bioavailability, avoid the first-pass effect of liver, and better patient compliance, et al. For nasal-brain administration, nasal preparation can be administered directly to the central nervous system(CNS) via olfactory nerve or trigeminal nerve bypassing the blood-brain barrier, which providing a sager, more effective and convenient route for brain or CNS diseases. In this paper, the label information of Food and Drug Administration(FDA) approved nasal-brain delivery related nasal spray preparations was reviewed, the similarities and differences between these nasal preparations were analyzed in order to provide reference for the development of domestic nasal preparations.

ObjectiveTo investigate the regulatory effect and molecular mechanism of berberine （BBR） on lipophagy in the prevention and treatment of atherosclerotic （AS） lesions in mice. MethodFifty apolipoprotein E-knockout （ApoE^-/-） mice were randomly divided into an AS model group， an atorvastatin group （5 mg·kg^-1）， and low-， medium-， and high-dose BBR groups （2.5， 5， 10 mg·kg^-1）. Ten C57BL/6J mice were assigned to the control group. After 12 weeks， hematoxylin-eosin （HE） and oil red O staining were performed to assess the histopathological changes of AS plaques in the aorta. Biochemical analysis was used to measure serum lipid levels， and enzyme-linked immunosorbent assay （ELISA） was employed to measure the levels of inflammatory cytokines interleukin-6 （IL-6） and tumor necrosis factor-α （TNF-α）， oxidative stress marker reactive oxygen species （ROS）， and serum lipophagy marker Beclin1 and microtubule-associated protein 1 light chain 3 Ⅱ （LC3Ⅱ）. The xanthine oxidase method was used to measure serum superoxide dismutase （SOD） activity. Immunohistochemistry （IHC） was used to detect the distribution of wingless-type MMTV integration site family member 5a （Wnt5a） and Nieman Pick type C1 （NPC1） in the aorta， and Western blot was used to determine the protein expression of Wnt5a and NPC1 in the aorta. ResultCompared with the control group， the AS model group showed significant AS plaque formation， significantly elevated levels of serum total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein cholesterol （LDL-C）， IL-6， TNF-α， and ROS， aortic Wnt5a distribution and protein expression （P<0.01）， and significantly reduced levels of serum high-density lipoprotein cholesterol （HDL-C）， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.01）. Compared with the AS model group， the atorvastatin group， and high- and medium-dose BBR groups showed a significant reduction in AS plaque area （P<0.05， P<0.01）， significantly decreased levels of serum TC， TG， LDL-C， IL-6， TNF-α， ROS， and aortic Wnt5a distribution and protein expression （P<0.05， P<0.01）， and significantly increased levels of serum HDL-C， SOD， Beclin1， LC3Ⅱ， and aortic NPC1 distribution and protein expression （P<0.05， P<0.01）. There was no statistically significant difference in the above indicators between the atorvastatin group and the medium-dose BBR group. ConclusionBBR can competitively bind to Wnt5a to activate NPC1 expression， upregulate lipophagy levels， reduce blood lipids， and inhibit the release of inflammatory mediators and oxidative stress damage， thereby exerting a preventive and therapeutic effect on AS.