Objective:To analyze the safety and short-term efficacy of thoracic radiotherapy combined with anlotinib in the treatment of inoperable non-small cell lung cancer (NSCLC).Methods:A prospective study was conducted on patients with unresectable locally advanced NSCLC who were intolerant to concurrent chemoradiotherapy and treated at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, from October 2020 to September 2023. Anlotinib was administered orally concurrently with radiotherapy (days 1-14, 21 days per cycle, for 3 cycles). Adverse effects and short-term tumor recurrence were observed from the beginning of radiotherapy to the 3-month post-radiotherapy. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) rates from the date of initial treatment (induction therapy), and intergroup comparisons were performed using the log-rank test.Results:The median age was 62 years (range:42-76 years), with a male predominance ( n=36, 88%) of the included 41 patients. The incidence of grade 3-4 acute hematologic adverse events was 20% (8 cases); the incidence of grade 3 hemoptysis was 2% (1 case), with no grade 4 hemoptysis; the incidence of grade 3-4 radiation pneumonitis was 10% (4 cases). No grade 5 adverse events were observed in the entire cohort. With a median follow-up of 19.7 months (range: 7.1-50.1 months), 19 patients (46%) experienced recurrence, including 4 patients (10%) with local recurrence, 6 patients (15%) with regional lymph node recurrence, and 11 patients (27%) with distant metastases. The 1-year PFS rate was 78.3%. 8 patients (20%) died, including 3 patients died from COVID-19 infection during the follow-up period, 1 patient who died from hypostatic pneumonia due to prolonged bed rest after cerebral infarction, and 4 patients died from tumor-related causes. The 1-year OS rate was 78.0%. Conclusions:Thoracic radiotherapy combined with anlotinib demonstrates good safety, manageable adverse events, and favorable short-term efficacy in NSCNC patients intolerant to concurrent chemoradiotherapy.

Objective:To evaluate the role of a single PET-CT scan in predicting survival and prognosis in patients with non-small cell lung cancer (NSCLC) who did not undergo surgery but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy.Methods:A retrospective analysis was conducted on the data of 23 NSCLC patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from May 2022 to June 2024. All patients were pathologically confirmed, received neoadjuvant chemotherapy combined with immunotherapy, did not undergo surgery for various reasons, and instead received radiotherapy. Each patient underwent only one PET-CT scan after neoadjuvant chemotherapy combined with immunotherapy and before radiotherapy. According to the maximum standardized uptake value (SUV max) on PET-CT, patients were divided into the low-uptake group (SUV max < 8, n=12) and high-uptake group (SUV max ≥ 8, n=11). Survival analysis was performed using the Kaplan-Meier method with survival curves plotted. Univariate analysis of influencing factors of survival was conducted using the Cox proportional hazards regression model. Clinical characteristics and survival outcomes of the two groups were compared, including progression-free survival (PFS) and overall survival (OS). Results:The 1-year PFS rates were 100% in the low-uptake group, 54.5% in the high-uptake group. This difference was statistically significant ( P=0.007). The 1-year and 2-year OS rates were both 100% in the low-uptake group, the 1-year and 2-year OS rates were both 90.9% in the high-uptake group, with no statistically significant difference ( P=0.394). Univariate Cox analysis identified age as an independent factor affecting PFS. Conclusions:For NSCLC patients who did not undergo surgical resection but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy, a single PET-CT scan before radiotherapy has potential value in predicting PFS. However, clinical studies with larger sample size and longer follow-up are required to evaluate its predictive value for OS.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.

Purpose The results of EBER in situ hybridization on the external quality assessment(EQA)organ-ized by the pathology Equipment Branch of the China Association of Medical Equipment were analyzed,for providing technical support for the standardization and normalization of the technology.Methods Paraffin-embedded sections of confirmed EBV-positive diffuse large B-cell lymphoma were selected as the evaluation specimens.Additionally,EBER in situ hybridization liquid cell controls were applied to the slides as evaluation references.A questionnaire was distrib-uted to collect staining information and methodologies from participating laboratories.Finally,the stained slides were collected and independently evaluated by pathology experts from the association according to predefined scoring criteria.Results A total of 38 pathology laboratories from 7 provinces and municipalities directly under the central government participated in the EQA,including 32 hospital pathology departments and 6 independent clinical laboratories.21 par-ticipants used manual staining,and others(17)used automated staining method by immunohistochemistry(IHC)stainers.The overall qualification rate of EBER in situ hybridization staining was 94.74％(36/38),and the excellent& good rate was 26.32％(10/38).The excellent & good rate of automated staining(41.12％,7/17)was significant-ly higher than that of manual staining(14.29％,3/21)(x2=4.852,P=0.028).The positive cell line control showed good consistency with the tissue control(Kappa=0.909,r=0.944).Conclusion The EBER in situ hybrid-ization technique in most of the pathology laboratories in the external quality assessment is qualified.There is a statisti-cally significant difference in the excellent & good rate between different staining methods.EBER in situ hybridization using automated IHC stainers is recommended as the preferred method.There is no difference in the performance of positive cell line control and tissue control.Some laboratories' staining techniques need to be improved.

Purpose The results of EBER in situ hybridization on the external quality assessment(EQA)organ-ized by the pathology Equipment Branch of the China Association of Medical Equipment were analyzed,for providing technical support for the standardization and normalization of the technology.Methods Paraffin-embedded sections of confirmed EBV-positive diffuse large B-cell lymphoma were selected as the evaluation specimens.Additionally,EBER in situ hybridization liquid cell controls were applied to the slides as evaluation references.A questionnaire was distrib-uted to collect staining information and methodologies from participating laboratories.Finally,the stained slides were collected and independently evaluated by pathology experts from the association according to predefined scoring criteria.Results A total of 38 pathology laboratories from 7 provinces and municipalities directly under the central government participated in the EQA,including 32 hospital pathology departments and 6 independent clinical laboratories.21 par-ticipants used manual staining,and others(17)used automated staining method by immunohistochemistry(IHC)stainers.The overall qualification rate of EBER in situ hybridization staining was 94.74％(36/38),and the excellent& good rate was 26.32％(10/38).The excellent & good rate of automated staining(41.12％,7/17)was significant-ly higher than that of manual staining(14.29％,3/21)(x2=4.852,P=0.028).The positive cell line control showed good consistency with the tissue control(Kappa=0.909,r=0.944).Conclusion The EBER in situ hybrid-ization technique in most of the pathology laboratories in the external quality assessment is qualified.There is a statisti-cally significant difference in the excellent & good rate between different staining methods.EBER in situ hybridization using automated IHC stainers is recommended as the preferred method.There is no difference in the performance of positive cell line control and tissue control.Some laboratories' staining techniques need to be improved.

BACKGROUND:NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is closely related to neuroinflammation after spinal cord injury,in which microglial polarization and pyroptosis play a key role.Targeted regulation of NLRP3 can induce microglial polarization from M1 proinflammatory phenotype to M2 anti-inflammatory phenotype and regulate microglial pyroptosis,which is a promising therapeutic strategy.OBJECTIVE:To summarize the molecular mechanism and therapeutic strategies of NLRP3 inflammasome in microglia after spinal cord injury.METHODS:Databases of PubMed,Web of Science,and CNKI were searched for the articles with search terms "spinal cord injury,NLRP3,microglia,polarization,pyroptosis" in English and "spinal cord injury,NLRP3,microglia,polarization,pyroptosis,inflammation" in Chinese.Finally,a total of 79 articles were included according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1) Currently,there is no consensus on the complex pathogenesis of spinal cord injury.A large number of studies have shown that spinal cord injury is closely related to inflammatory factors and signaling pathways.The NLRP3 inflammasome is a hot topic in current research as a mechanism of disease and a breakthrough in treatment.(2) The NLRP3 inflammasome plays a key role in the inflammatory response,oxidative stress,and neuronal recovery after spinal cord injury.(3) Microglia are immune cells in the brain and spinal cord and are the most important regulatory factors in secondary spinal cord injury.After spinal cord injury,microglia adjust the internal environment,mainly manifested as polarization and necrosis,produce a large number of inflammatory factors,hinder the nerve regeneration and functional recovery of spinal cord injury,and regulating the phenotype change of microglia is another key factor in the treatment of spinal cord injury.(4) The NLRP3 inflammasome is closely related to microglia.After spinal cord injury,NLRP3 is mainly expressed in microglia,which promotes the polarization of microglia to M1 and accelerates the production of cleavage proteins,further disrupting the microenvironment and aggravating the progression of spinal cord injury.(5) Many molecules participate in the regulation of NLRP3 inflammasomes in microglia,involving signaling pathways.Among them,nuclear factor-κB and MAPK signaling pathways promote NLRP3 inflammasome,while the rest inhibit this inflammasome.(6) At present,a large number of exogenous molecules and drugs regulate NLRP3 inflammasomes,with a wide range of clinical application prospects.Relevant drugs are in the clinical trial stage and obtain good effects,such as the NLRP3-specific inhibitor MCC950.However,key issues such as how to precisely control targeted delivery and the impact on other tissues and organs urgently need to be resolved.With the deepening of research,it is expected to make new breakthroughs in delaying the treatment of spinal cord injury in the future.

BACKGROUND:NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is closely related to neuroinflammation after spinal cord injury,in which microglial polarization and pyroptosis play a key role.Targeted regulation of NLRP3 can induce microglial polarization from M1 proinflammatory phenotype to M2 anti-inflammatory phenotype and regulate microglial pyroptosis,which is a promising therapeutic strategy.OBJECTIVE:To summarize the molecular mechanism and therapeutic strategies of NLRP3 inflammasome in microglia after spinal cord injury.METHODS:Databases of PubMed,Web of Science,and CNKI were searched for the articles with search terms "spinal cord injury,NLRP3,microglia,polarization,pyroptosis" in English and "spinal cord injury,NLRP3,microglia,polarization,pyroptosis,inflammation" in Chinese.Finally,a total of 79 articles were included according to the inclusion and exclusion criteria.RESULTS AND CONCLUSION:(1) Currently,there is no consensus on the complex pathogenesis of spinal cord injury.A large number of studies have shown that spinal cord injury is closely related to inflammatory factors and signaling pathways.The NLRP3 inflammasome is a hot topic in current research as a mechanism of disease and a breakthrough in treatment.(2) The NLRP3 inflammasome plays a key role in the inflammatory response,oxidative stress,and neuronal recovery after spinal cord injury.(3) Microglia are immune cells in the brain and spinal cord and are the most important regulatory factors in secondary spinal cord injury.After spinal cord injury,microglia adjust the internal environment,mainly manifested as polarization and necrosis,produce a large number of inflammatory factors,hinder the nerve regeneration and functional recovery of spinal cord injury,and regulating the phenotype change of microglia is another key factor in the treatment of spinal cord injury.(4) The NLRP3 inflammasome is closely related to microglia.After spinal cord injury,NLRP3 is mainly expressed in microglia,which promotes the polarization of microglia to M1 and accelerates the production of cleavage proteins,further disrupting the microenvironment and aggravating the progression of spinal cord injury.(5) Many molecules participate in the regulation of NLRP3 inflammasomes in microglia,involving signaling pathways.Among them,nuclear factor-κB and MAPK signaling pathways promote NLRP3 inflammasome,while the rest inhibit this inflammasome.(6) At present,a large number of exogenous molecules and drugs regulate NLRP3 inflammasomes,with a wide range of clinical application prospects.Relevant drugs are in the clinical trial stage and obtain good effects,such as the NLRP3-specific inhibitor MCC950.However,key issues such as how to precisely control targeted delivery and the impact on other tissues and organs urgently need to be resolved.With the deepening of research,it is expected to make new breakthroughs in delaying the treatment of spinal cord injury in the future.

Objective:To analyze the safety and short-term efficacy of thoracic radiotherapy combined with anlotinib in the treatment of inoperable non-small cell lung cancer (NSCLC).Methods:A prospective study was conducted on patients with unresectable locally advanced NSCLC who were intolerant to concurrent chemoradiotherapy and treated at the Department of Radiation Oncology, Cancer Hospital, Chinese Academy of Medical Sciences, from October 2020 to September 2023. Anlotinib was administered orally concurrently with radiotherapy (days 1-14, 21 days per cycle, for 3 cycles). Adverse effects and short-term tumor recurrence were observed from the beginning of radiotherapy to the 3-month post-radiotherapy. Kaplan-Meier method was used to calculate progression-free survival (PFS) and overall survival (OS) rates from the date of initial treatment (induction therapy), and intergroup comparisons were performed using the log-rank test.Results:The median age was 62 years (range:42-76 years), with a male predominance ( n=36, 88%) of the included 41 patients. The incidence of grade 3-4 acute hematologic adverse events was 20% (8 cases); the incidence of grade 3 hemoptysis was 2% (1 case), with no grade 4 hemoptysis; the incidence of grade 3-4 radiation pneumonitis was 10% (4 cases). No grade 5 adverse events were observed in the entire cohort. With a median follow-up of 19.7 months (range: 7.1-50.1 months), 19 patients (46%) experienced recurrence, including 4 patients (10%) with local recurrence, 6 patients (15%) with regional lymph node recurrence, and 11 patients (27%) with distant metastases. The 1-year PFS rate was 78.3%. 8 patients (20%) died, including 3 patients died from COVID-19 infection during the follow-up period, 1 patient who died from hypostatic pneumonia due to prolonged bed rest after cerebral infarction, and 4 patients died from tumor-related causes. The 1-year OS rate was 78.0%. Conclusions:Thoracic radiotherapy combined with anlotinib demonstrates good safety, manageable adverse events, and favorable short-term efficacy in NSCNC patients intolerant to concurrent chemoradiotherapy.

Objective:To evaluate the role of a single PET-CT scan in predicting survival and prognosis in patients with non-small cell lung cancer (NSCLC) who did not undergo surgery but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy.Methods:A retrospective analysis was conducted on the data of 23 NSCLC patients treated at the Cancer Hospital of the Chinese Academy of Medical Sciences from May 2022 to June 2024. All patients were pathologically confirmed, received neoadjuvant chemotherapy combined with immunotherapy, did not undergo surgery for various reasons, and instead received radiotherapy. Each patient underwent only one PET-CT scan after neoadjuvant chemotherapy combined with immunotherapy and before radiotherapy. According to the maximum standardized uptake value (SUV max) on PET-CT, patients were divided into the low-uptake group (SUV max < 8, n=12) and high-uptake group (SUV max ≥ 8, n=11). Survival analysis was performed using the Kaplan-Meier method with survival curves plotted. Univariate analysis of influencing factors of survival was conducted using the Cox proportional hazards regression model. Clinical characteristics and survival outcomes of the two groups were compared, including progression-free survival (PFS) and overall survival (OS). Results:The 1-year PFS rates were 100% in the low-uptake group, 54.5% in the high-uptake group. This difference was statistically significant ( P=0.007). The 1-year and 2-year OS rates were both 100% in the low-uptake group, the 1-year and 2-year OS rates were both 90.9% in the high-uptake group, with no statistically significant difference ( P=0.394). Univariate Cox analysis identified age as an independent factor affecting PFS. Conclusions:For NSCLC patients who did not undergo surgical resection but received radiotherapy after neoadjuvant chemotherapy combined with immunotherapy, a single PET-CT scan before radiotherapy has potential value in predicting PFS. However, clinical studies with larger sample size and longer follow-up are required to evaluate its predictive value for OS.

Objective:To analyze the prognostic value of systemic inflammatory score (SIS) in patients with unresectable stage Ⅲ non-small cell lung cancer (NSCLC) treated by definitive chemoradiotherapy (dCRT) combined with or without consolidation immunotherapy with immune checkpoint inhibitor (ICI).Methods:The medical record data of 229 patients who received dCRT from January 2014 to December 2017 and 183 patients who received dCRT combined with any form of ICI (induction, concurrent, consolidation or combination) from August 2018 to August 2022 in the Cancer Hospital, Chinese Academy of Medical Sciences were retrospectively analyzed. Upon admission, 1 and 3 months after treatment (efficacy evaluation) and upon tumor recurrence, peripheral blood count was collected, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and SIS were calculated, respectively. The SIS before, 1 and 3 months after treatment was defined as SIS 0, SIS 1 and SIS 3, respectively. Overall survival (OS) was considered as the primary endpoint. All patients were divided into dCRT group and dCRT+ICI group according to whether received immunotherapy, and then divided into different subgroups based on the cutoff value of SIS determined by X-Tile software. The prognostic value of SIS was evaluated by Kaplan-Meier survival analysis. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the predictive efficiency. The predictive value of SIS was compared with inflammatory indexes (NLR, PLR) and independent prognostic factors. Results:In the dCRT group, the optimal cutoff value of SIS 0 was 590×10 9 and 530×10 9 in the dCRT+ICIs group. Univariate and multivariate analyses indicated that SIS 0 was an independent predictive factor of OS, progression - free survival (PFS), local - recurrence free survival (LRFS) and distant metastasis free survival (DMFS) in the dCRT group, but not associated with DMFS in the dCRT+ICI group. In the dCRT group, SIS 1>970×10 9 (optimal cutoff value) predicted poor OS ( HR=2.512, 95% CI=1.622-3.198, P<0.001), PFS ( HR=1.726, 95% CI=1.187-2.509, P=0.004), and DMFS ( HR=1.625, 95% CI=1.029-2.564, P=0.037). In the dCRT+ICI group, SIS 3>1570×10 9 (optimal cutoff value) indicated poor OS ( HR=5.107, 95% CI=1.731-15.069, P=0.003). In both groups, the AUC of SIS was higher than NLR, PLR and other traditional clinicopathological predictive indexes except T stage. Conclusions:SIS before treatment can be considered as an independent, dependable and easily acquired prognostic marker in patients with unresectable stage Ⅲ NSCLC treated by dCRT or dCRT+ICI. In the dCRT+ICI group, the optimal time point of post-radiotherapy SIS (3 months after treatment) is postponed than that (1 month after treatment) in the dCRT group.