OBJECTIVE To evaluate the clinical value of anlotinib in third-line treatment for patients with advanced non-small cell lung cancer （NSCLC） through real-world data. METHODS Clinical data of patients with advanced NSCLC who received treatment at the First Affiliated Hospital of Anhui University of Chinese Medicine from February 2021 to December 2024 were retrospectively collected. They were divided into anlotinib group （27 cases， receiving anlotinib therapy） and immunotherapy group （22 cases， receiving immunotherapy agents alone or in combination with chemotherapy drugs） according to treatment regimens. The progression-free survival （PFS） and overall survival （OS） of patients were compared between the two groups， and the occurrence of adverse drug reactions during the treatment period was recorded. Using a partitioned survival model， an economic evaluation of the two treatment regimens was conducted with a cost-utility analysis approach from the perspective of the healthcare system. RESULTS The median PFS and OS of patients in the anlotinib group were 5.93 months and 11.27 months， respectively； the median PFS and OS of patients in the immunotherapy group were 5.33 months and 9.77 months， respectively； the difference was not statistically significant （P＞0.05）. There was no statistical difference in the total incidence of adverse drug reactions and grade 3-4 serious adverse drug reactions between the two groups （P＞0.05）. Compared with the immunotherapy group， the incremental cost-effectiveness ratio of the anlotinib group was 1 806 724.60 yuan/quality-adjusted life year （QALY）， which was significantly higher than three times China’s per capita gross domestic product in 2024 （287 247 yuan/QALY）. CONCLUSIONS For third-line treatment of advanced NSCLC patients， the efficacy of anlotinib is no worse than that of immunotherapy alone or in combination with chemotherapy drugs， and the safety of the two groups is comparable. However， anlotinib is not cost-effective.

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.

Objective To study the shielding effect of the protective door of a maze-free debugging room for an 18 MV medical linear accelerator and its influencing factors, and to provide guidance for protection of debugging personal against radioactive occupational disease hazards. Methods The investigation focused on the protective door of a newly constructed maze-free debugging room for an 18 MV medical linear accelerator. The protective door was made of the following shielding materials from inside to outside: 2.5 cm steel plate + 20 cm lead + 41 cm polyethylene containing 5% boron + 6 cm lead + 2.5 cm steel plate. The right side of the protective door was provided with a groove (commonly known as “door pocket”) lap. With different lap widths, irradiation directions, and installation positions of the accelerator base, FLUKE451P and WENDI II neutron detectors were used to measure the ambient dose equivalent rate of the points of interest outside the protective door. The shielding effect and influencing factors were analyzed. Results When the lap width at both sides of the protective door was 300 mm, the ambient dose equivalent rates outside the protective door were (1.37 ± 0.05) μSv/h on the side with “door pocket” and (4.71 ± 0.11) and (4.19 ± 0.11) μSv/h on the side without “door pocket”. When the primary beam of the accelerator was directed towards the east, the ambient dose equivalent rates at the points of interest outside the protective door were higher than those of the corresponding points of interest when the primary beam was directed towards other directions. When the accelerator base was located on the south side of the machine room, the ambient dose equivalent rates of the points of interest outside the protective door under the same irradiation conditions were lower than those when the accelerator base was located on the north side of the machine room. Conclusion The study of an 18 MV accelerator and its maze-free debugging room showed that the radiation of photons and neutrons should be taken into consideration when designing the protective door at the entrance. The protective door with shiplaps on both sides of the wall has improved shielding effect outside the door.

Objective To track and evaluate the implementation of the Radiation Shielding Requirements in Room of Radiotherapy Installations—Part 1: General Principle (GBZ/T 201.1–2007) among relevant personnel in medical radiation institutions, and to provide a scientific basis for revising the standard. Methods According to the Guidelines for Health Standards Tracking Evaluation (WS/T 536–2017) and the implementation protocol of standard evaluation, an online survey was conducted among 212 relevant workers from 146 medical radiation institutions across 18 provinces in China. The data were aggregated and analyzed with the use of Microsoft Excel 2010. Results A total of 215 questionnaires were returned, of which 212 were valid. Among the valid respondents, 77.8% believe that this standard is universally applied; 96.2% believe that this standard can meet work needs; 63.7% have participated in relevant training on this standard; 74.1% use this standard once or more per year; and 10.8% believe that this standard needs to be revised. Conclusion Medial radiation workers have a high rate of awareness of the basic information and content of the standard, but the understanding and application of the standard content need to be improved. We recommend that relevant departments further strengthen the promotion of and training on the standard, revise some content based on actual situation, and improve workers’ ability to use the standard.

Although immunotherapy has made a breakthrough in the treatment of cancer,the emergence of drug resistance has limited be-nefits in most patients,and reversing immunotherapy resistance remains a hotly debated and unresolved issue.The tumor microenviron-ment(TME)comprises a large number of T lymphocytes.During the biological processes of proliferation,activation,and the effect of tumor-infiltrating lymphocytes(TILs),TILs face severe local metabolic stress,resulting in metabolic reprogramming to meet the markedly increased energy demand and biosynthesis requirements.This process of adaptive changes in the metabolic pattern is closely related to the pheno-type and function of TILs,affecting immunotherapy efficacy and mediating immunotherapy resistance.In recent years,with the study of TIL metabolism and the search for specific metabolic regulatory points,targeting the TIL metabolic pathway could restore the tumor-killing func-tion and reverse immunotherapy resistance.This review explores the relationship between the metabolic reprogramming of TILs and im-mune resistance,and provides a new strategy for reversing immune resistance.

Objective:To investigate the efficacy of fixation through dual minimally invasive incisions and dual osseous channels with a loop titanium plate combined with a Dog-Bone titanium plate for acute Rockwood Ⅲ acromioclavicular dislocation in comparison with open reduction and fixation with a clavicular hook plate.Methods:A retrospective study was conducted to analyze the data of the 60 patients with acute type Ⅲ acromioclavicular dislocation who had been treated at Department of Orthopedics, Liaocheng People's Hospital from February 2019 to May 2022. There were 35 males and 25 females with an age of (43.2±8.0) years, and 34 left sides and 26 right sides affected. According to different surgical methods, they were divided into a double titanium plates group of 32 cases who had been treated by fixation through dual minimally invasive incisions and dual osseous channels with a loop titanium plate combined with a Dog Bone titanium plate and a hook plate group of 28 cases who had been treated by open reduction and internal fixation with a clavicle hook plate. The time from injury to operation was (2.1±1.3) d. The 2 groups were compared in terms of incision length, operation time, intraoperative bleeding, and visual analogue scale (VAS) pain score, Constant-Murley shoulder function score and the coracoclavicular distance on the affected side which were recorded preoperatively and at the last follow-up. Complications such as infection, loosening of internal fixation or secondary fracture were observed.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P > 0.05). All patients were followed up for (11.2±2.1) months. The incision length in the double titanium plates group [(3.5±0.3) cm] was significantly shorter than that in the hook plate group [(6.2±0.7) cm], and the intraoperative bleeding [(45.3±7.5) mL] in the former was significantly less than that in the latter [(64.1±6.2) mL] ( P < 0.05). However, there was no statistically significant difference in the operation time between the 2 groups ( P > 0.05). The VAS score [0.5 (0, 1.0) points] and Constant-Murley shoulder function score [(95.1±2.1) points] in the double titanium plates group were significantly better than those in the hook plate group [0.8 (0, 1.0) points, (86.0±4.4) points] at the last follow-up ( P < 0.05). However, there was no statistically significant difference between the 2 groups in the coracoclavicular distance on the affected side ( P > 0.05). Good acromioclavicular joint repositioning and fixation were achieved in all patients. There were no surgery-related complications except for sinus tract formation in one patient in the double titanium plates group. Conclusion:In the treatment of acute Rockwood Ⅲ acromioclavicular dislocation, fixation through dual minimally invasive incisions and dual osseous channels with a loop titanium plate combined with a Dog-Bone titanium plate is superior to open reduction and internal fixation with a clavicular hook plate, showing advantages of minimal invasion, better safety, less intraoperative bleeding, and faster joint function recovery.

Background and purpose:Colorectal cancer(CRC)is one of the major malignant tumors threatening human health worldwide,with long-term high incidence and mortality rate.Potassium channel modulatory factor 1(KCMF1)is a member of the E3 ubiquitin ligase family.It binds to target proteins through the RING domain and participates in the regulation of a variety of biological processes in vivo.However,the function of KCMF1 in CRC remains unclear.This study aimed to investigate the expression level of E3 ubiquitin ligase KCMF1 in colorectal tumor,and to explore the effects of KCMF1 on the proliferation of CRC cells and its underlying molecular mechanism.Methods:The The Cancer Genome Atlas(TCGA)and Genotype-Tissue Expression(GTEx)databases were used to analyze the expression level of KCMF1 in CRC tissues and adjacent tissues and the association between the KCMF1 expression and the prognosis of CRC patients.Furthermore,immunohistochemical staining was performed to detect the protein level of KCMF1 in 90 paired human CRC tissues and adjacent non-tumor tissues.Lentiviral shRNA delivery system was employed to specifically target the KCMF1 gene(shKCMF1)in HCT116 and HCT15 CRC cell lines.The effects of KCMF1 knockdown on cell proliferation,apoptosis and cell cycle distribution were assessed by methyl thiazoyl terazolium(MTT)assay,colony formation assay,Western blot and flow cytometry.Changes in the transcriptional profile in HCT116 cells upon KCMF1 knockdown were identified by RNA sequencing(RNA-Seq),and the affected signaling pathways were evaluated by bioinformatics analysis.Real-time fluorescence quantitative polymerase chain reaction(RTFQ-PCR),Western blot,luciferase reporter assay and cell immunofluorescence assay were utilized to validate the alteration of the affected signaling pathway.Results:The TCGA and GTEx databases and IHC results showed that the mRNA and protein expression levels of KCMF1 in CRC tissues were significantly upregulated compared with adjacent tissues(P＜0.01).KCMF1 expression level was negatively correlated with the survival time of patients with CRC(P＜0.01),and was positively associated with CRC clinical stage(P＜0.05).Compared with control cells,KCMF1 knockdown significantly inhibited the proliferation of HCT116 and HCT15 cells(P＜0.001),induced cell apoptosis(P＜0.001),and led to cell cycle arrest in G1 phase(P＜0.01).RNA-Seq analysis showed that KCMF1 was involved in the regulation of several signaling pathways,including nuclear factor-κB(NF-κB)signaling pathway.KCMF1 knockdown reduced the transcription levels of the target genes of NF-κB signaling pathway,including BCL-XL,XIAP and CIAP(P＜0.05),and suppressed the expression of phosphorylated p65 and nuclear translocation of p65(P＜0.01).Meanwhile,the activity of NF-κB reporter was reduced in tumor cells upon KCMF1 knockdown(P＜0.01).Conclusion:The expression of KCMF1 is significantly upregulated in human CRC tissues and positively associated with advanced clinical stage and poor prognosis.KCMF1 may promote the proliferation of CRC cells by activating the NF-κB signaling pathway.KCMF1 may be a potential new therapeutic target for CRC.

Traditional antibody drug conjugates(ADC)combine monoclonal antibodies with cytotoxic drugs to accurately strike cancer cells,but there are still many shortcomings in stability,targeting,efficacy,and safety.Novel ADC,such as bi-specific,site-specific,dual-payload,and pro-drug type ADC,can be optimized by simultaneously binding 2 different antigens or epitopes,selecting more stable linkers,coupling with specific amino acid sites of antibodies,carrying different drug payloads,and adopting prodrug strategies,while retaining the characteristics of traditional ADC.Significantly improving the stability,targeting,efficacy and safety of drugs can better meet the needs of clinical treatment.Novel ADC will play a more important role in cancer treatment in the future.Discussing the progress of novel ADC in cancer treatment and analyzing their advantages and challenges can provide theoretical support for the development of anti-cancer strategies and provide directions for drug research and development.

Objective:To evaluate the effect of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) on regional cerebral oxygen saturation (rScO 2) during induction of general anesthesia in patients undergoing traumatic brain injury (TBI) emergency surgery. Methods:A prospective randomized controlled trial was conducted. The TBI emergency general anesthesia patients who underwent intracranial hematoma removal surgery at the Northern Jiangsu People's Hospital from January to July in 2023 were enrolled. The patients were divided into a conventional mask ventilation group and a THRIVE group using a random number table method. The patients in the conventional mask ventilation group were anesthetized and induced to pre oxygenate without positive pressure ventilation in the front mask for 10 minutes, with an oxygen flow rate of 8 L/min and an fraction of inspired oxygen (FiO 2) of 1.00. After anesthesia induction for about 90 s, tracheal intubation was performed after the muscle relaxant took effect (patient's jaw muscle was relaxed). The patients in the THRIVE group were pre oxygenated with THRIVE for 10 minutes, with an oxygen flow rate of 30 L/min and a FiO 2 of 1.00. During anesthesia induction, the oxygen flow rate was increased to 50 L/min, and anesthesia induction medication was used. The lower jaw of patient was supported with both hands to maintain airway patency, and the patient's mouth was kept closed throughout the process. After the muscle relaxant took effect (the patient's jaw muscle was relaxed), tracheal intubation was performed. At the time of patient entering the operating room, 10 minutes of pre oxygenation, and immediately after successful intubation, rScO 2 was measured on the surgical and non-surgical sides. At the same time, ultrasound was used to measure the cross-sectional area (CSA) of the gastric antrum and arterial blood gas analysis was performed. The partial pressure of end-tidal carbon dioxide (P ETCO 2) during the first mechanical ventilation after successful tracheal intubation, the incidence of hypoxemia [pulse oxygen saturation (SpO 2) < 0.95] during tracheal intubation, as well as prognostic indicators such as the length of intensive care unit (ICU) stay, total length of hospital stay, and Glasgow outcome scale (GOS) score at discharge were recorded. Results:During the study period, a total of 70 TBI patients underwent emergency general anesthesia surgery, of which 2 patients died postoperatively, 2 patients were unable to cooperate with closed mouth breathing, and 3 patients had poor ultrasound image acquisition in the gastric antrum, all of whom were excluded. A total of 63 patients were ultimately enrolled, including 32 in the conventional mask ventilation group and 31 in the THRIVE group. There were no statistically significant differences in gender, age, body mass index (BMI), American Society of Anesthesiologists (ASA) classification, Glasgow coma scale (GCS) score, optic nerve sheath diameter (ONSD), baseline vital signs, fasting situation, anesthesia time, surgical time, and intraoperative blood loss between the patients in the two groups, indicating comparability. When entering the operating room, there was no statistically significant difference in rScO 2 on the surgical and non-surgical sides, and blood gas analysis indexes arterial partial pressure of oxygen (PaO 2) and arterial partial pressure of carbon dioxide (PaCO 2) between the patients in the two groups. When pre oxygenated for 10 minutes, both the surgical and non-surgical sides rScO 2 levels in the THRIVE group were significantly higher than those in the conventional mask ventilation group (surgical side: 0.709±0.036 vs. 0.636±0.028, non-surgical side: 0.791±0.016 vs. 0.712±0.027, both P < 0.01), and the PaO 2 was significantly increased [mmHg (1 mmHg≈0.133 kPa): 450.23±60.99 vs. 264.88±49.33, P < 0.01], PaCO 2 was significantly reduced (mmHg: 37.81±3.65 vs. 43.59±3.76, P < 0.01), and the advantage continues tilled immediately after successful intubation. There was no statistically significant difference in CSA at each time point of ultrasound examination between the two groups. Compared with the conventional mask ventilation group, the patients in the THRIVE group showed a significant decrease in P ETCO 2 during the first mechanical ventilation after successful tracheal intubation (mmHg: 43.10±2.66 vs. 49.22±3.31, P < 0.01), and the incidence of hypoxemia during tracheal intubation was also significantly reduced [0% (0/31) vs. 28.12% (9/32), P < 0.01]. In terms of prognostic indicators, there was no statistically significant difference in the length of ICU stay and total length of hospital stay between the patients in the conventional mask ventilation group and the THRIVE group [length of ICU stay (days): 10 (9, 10) vs. 10 (9, 11), total length of hospital stay (days): 28.00 (26.00, 28.75) vs. 28.00 (27.00, 29.00), both P > 0.05]. However, the proportion of patients in the THRIVE group with a good prognosis at discharge (GOS score > 3) was significantly higher than that in the conventional mask ventilation group [35.5% (11/31) vs. 12.5% (4/32), P < 0.05]. Conclusion:THRIVE can significantly increase rScO 2 during anesthesia induction in TBI emergency surgery patients and improve their neurological function prognosis.

Tumors pose a serious challenge to global public health. The sensitive and precise detection of tumor biomarkers is very important for early screening and diagnosis of cancers. DNAzymes with outstanding physical, chemical, and biological properties are widely applied in the design of biosensing strategies. By the use of sensing platforms such as fluorescence, electrochemistry, and surface-enhanced Raman scattering, DNAzymes facilitate the early screening and detection of tumors. This article summarizes the functional mechanism and common classifications of DNAzymes, and the updates of DNAzymes-based novel biosensing technologies within the field of liquid biopsy, expecting the technical challenges yet to be surmounted and future developmental directions.