ObjectiveTo explore the target of Erzhiwan in reducing myocardial injury in ovariectomized mice through non-targeted myocardial metabolomics combined with experimental verification. MethodsOvariectomized mouse model was selected， 40 female C57BL/6 mice were randomly divided into sham operation group， model group， estrogen group（estradiol valerate， 1.3×10^-4 g·kg^-1）， Erzhiwan low and high dose groups（3.12， 9.36 g·kg^-1）， with 8 mice in each group. Each administration group was given the corresponding dose of Erzhiwan by gavage， and the sham operation group and model group were given equal volume of distilled water by gavage for 12 weeks. Echocardiography was used to detect cardiac function， hematoxylin-eosin（HE） staining was used to observe myocardial morphological changes， and enzyme-linked immunosorbent assay（ELISA） was used to detect the levels of estrogen， N-terminal pro-brain natriuretic peptide（NT-proBNP）， hypersensitive troponin T（hs-TnT）， total cholesterol（TC）， triglyceride（TG）， low density lipoprotein cholesterol（LDL-C）， high density lipoprotein cholesterol（HDL-C）， interleukin（IL）-1β， IL-18 and tumor necrosis factor-α（TNF-α）. The non-targeted metabolomics of mouse myocardium were analyzed by ultra performance liquid chromatography-quadrupole-electrostatic field orbital trap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites and corresponding metabolic pathways were obtained. The mRNA expression levels of phosphatidylinositol 3-kinase（PI3K） and protein kinase B（Akt） in mouse myocardial tissues were detected by real-time fluorescence quantitative polymerase chain reaction（Real-time PCR）， and the protein expression levels of PI3K， Akt， phosphorylated（p）-Akt were detected by Western blot. ResultsCompared with the sham operation group， the model group showed abnormal cardiac function， increased myocardial fiber space， cardiomyocyte atrophy， sarcoplasmic aggregation， and occasional dissolution or rupture of muscle fiber， the level of estrogen in the serum was decreased， the levels of NT-proBNP， hs-TnT， IL-1β， IL-18， TNF-α， TG， TC and LDL-C were increased， and the level of HDL-C was decreased（P<0.01）. Compared with the model group， Erzhiwan could increase the level of estrogen， improve the abnormal cardiac function， reduce the pathological injury of myocardial tissue， decrease the levels of myocardial injury markers（NT-proBNP， hs-TnT） and inflammatory factors（IL-1β， IL-18， TNF-α）， decrease the levels of TG， TC， LDL-C， and increased the level of HDL-C（P<0.01）. The results of non-targeted myocardial metabolomics showed that 31 of the 162 differential metabolites between the model group and sham operation group were significantly adjusted after administration of Erzhiwan， which were mainly glycerol phospholipid metabolites. Pathway enrichment results showed that Erzhiwan mainly affected glycerophospholipid metabolic pathway， PI3K-Akt pathway， cyclic guanosine monophosphate（cGMP）-protein kinase G（PKG） pathway and other metabolic pathways. Compared with the sham operation group， the levels of phosphatidylcholine（PC， 11 types） and phosphatidylethanolamine（PE， 5 types） in mouse myocardial tissue of the model group were increased（P<0.05， P<0.01）， and the mRNA and protein expressions of PI3K and p-Akt were decreased（P<0.05， P<0.01）. Compared with the model group， the levels of PC（11 types） and PE（5 types） were decreased（P<0.05， P<0.01） in myocardial tissue of Erzhiwan group， the mRNA and protein expressions of PI3K and p-Akt were elevated（P<0.01）. ConclusionErzhiwan can alleviate the pathological injury of myocardium in ovariectomized mice， improve the abnormal cardiac function， improve lipid metabolism disorder， and reduce the levels of myocardial injury markers and inflammatory factors， which involves a number of signaling and metabolic pathways in the heart， among which glycerophospholipid metabolism pathway and PI3K/Akt pathway may have key roles.

Objective To analyze the value of heparin-binding protein(HBP)and interleukin-17A(IL-17A)levels in bronchoalveolar lavage fluid in predicting prognosis of elderly patients with se-vere pneumonia.Methods A total of 105 elderly patients with severe pneumonia in the hospital from May 2022 to May 2024 were selected and divided into death group(n=32)and survival group(n=73)based on their survival outcomes within 28 days after admission.The levels of HBP and IL-17A in bronchoalveolar lavage fluid were compared between the two groups;the Logistic regression analysis was conducted to explore the influencing factors for prognosis in elderly patients with severe pneumoni-a;the receiver operating characteristic(ROC)curve was plotted to analyze the predictive efficiencies of HBP and IL-17A in bronchoalveolar lavage fluid for the prognosis of elderly patients with severe pneumonia.Results The levels of HBP and IL-17A in bronchoalveolar lavage fluid in the death group were significantly higher than those in the survival group(P＜0.01).There were significant differ-ences in the Acute Physiology and Chronic Health Evaluation Ⅱ(APACHE Ⅱ)score and blood lac-tate(Lac)level between the two groups(P＜0.01).Logistic regression analysis showed that HBP(OR=3.084,95％CI,1.326 to 4.694),IL-17A(OR=4.521,95％CI,2.164 to 7.841),APACHE Ⅱscore(OR=2.039,95％CI,1.069 to 2.859),and Lac(OR=2.627,95％CI,1.168 to 3.058)were influencing factors for the prognosis of elderly patients with severe pneumonia(P＜0.05).When the optimal cut-off values were set at 15.92 ng/mL for HBP and 109.34 pg/mL for IL-17A,the area under the curve(AUC)for the combined prediction of prognosis by HBP and IL-17A in bronchoalveolar lavage fluid was 0.852,with a 95％CI of 0.801 to 0.948.The AUC for the com-bined prediction of prognosis by HBP and IL-17A in bronchoalveolar lavage fluid was significantly higher than that for single tests(Z=2.906,2.416,P=0.007,0.014).Conclusion Increased levels of HBP and IL-17A in bronchoalveolar lavage fluid,decreased APACHE Ⅱ score,and in-creased Lac are influencing factors for the prognosis of elderly patients with severe pneumonia.Com-bined detection of HBP and IL-17A in bronchoalveolar lavage fluid has high sensitivity in predicting the prognosis of elderly patients with severe pneumonia.

Objective:To investigate the therapeutic efficacy and safety of tislelizumab combined with platinum-based drugs in patients with advanced non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Eighty-six patients with clinical stage Ⅳ NSCLC in Huaibei People's Hospital from June 2020 to June 2023 were selected as the study subjects, and the patients were divided into the control group and the observation group based on the randomized numerical table method, with 43 cases in each group. The control group was treated with platinum-based drugs, the observation group was treated with platinum-based drugs combined with tislelizumab, and all patients were treated for 4-6 cycles. The two groups were compared in terms of therapeutic efficacy, serum tumor markers [carcinoembryonic antigen (CEA), cytokeratin 19 soluble fragment (CYFRA21-1) and carbohydrate antigen 125 (CA125)] detected by chemiluminescence method, serum immune function indicators [CD3 +, CD4 +, CD8 + cell ratios and CD4 + cell number-to-CD8 + cell number ratio (CD4 +/CD8 +)] detected by flow cytometry, and quality of life [European Organization for Research and Treatment of Cancer (EORTC) quality of life measurement scale (QLQ-C30) scores in functional domain and symptom domain], and incidence of adverse reactions. Results:The differences in baseline data of age, gender, degree of tumor differentiation, pathological type, lesion location, programmed death receptor ligand 1 expression between the observation group and the control group were not statistically significant (all P > 0.05). After treatment, the objective remission rates in the observation and control groups were 34.9% (15/43) and 18.6% (8/43), respectively, and the difference was not statistically significant ( χ2 = 2.91, P = 0.088); the disease control rate in the observation group was 74.4% (32/43), which was higher than that in the control group [51.2% (22/43)], and the difference was statistically significant ( χ2 = 4.98, P = 0.026). The differences in the serum levels of CEA, CYFRA21-1 and CA125 between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the serum levels of CEA, CYFRA21-1 and CA125 in the observation group were lower than those in the control group after treatment, and the differences were all statistically significant (all P < 0.01). The differences in the CD3 +, CD4 +, CD8 + cell ratios and CD4 +/CD8 + between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the CD3 +, CD4 + cell ratios and CD4 +/CD8 + in the observation group were higher than those in the control group, the CD8 + cell ratio was lower than that in the control group after treatment, and the differences were all statistically significant (all P < 0.01). Before treatment, there were no statistically significant differences in the scores of EORTC QLQ-C30 functional domain and symptom domain between the observation group and the control group (both P > 0.05); after treatment, the functional domain score of the observation group was higher than that of the control group, the symptom domain score was lower than that of the control group, and the differences were statistically significant (both P < 0.01). The incidence rates of skin itching, rash and diarrhea in the observation group were 23.3% (10/43), 20.9% (9/43) and 48.8% (21/43), respectively, which were higher than those in the control group [4.7% (2/43), 2.3% (1/43) and 27.9% (12/43)], and the differences were statistically significant (all P < 0.05). Conclusions:Tislelizumab combined with platinum-based drugs in advanced NSCLC patients can enhance the short-term efficacy, reduce serum tumor marker levels, and improve the immune function and quality of life of the patients, but it will increase the occurrence of skin and digestive tract adverse reactions.

Real-time, noninvasive programmed death-ligand 1 (PD-L1) testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy. However, the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography (PET/CT) remains limited. This investigation involved the synthesis of [¹⁸F]AlF-NOTA-PCP2, which is a novel peptide-based radiolabeled tracer that targets PD-L1, and evaluated its imaging capabilities in orthotopic glioblastoma (GBM) models. Using this tracer, we could noninvasively monitor radiation-induced PD-L1 changes in GBM. [¹⁸F]AlF-NOTA-PCP2 exhibited high radiochemical purity (>95%) and stability up to 4 h after synthesis. It demonstrated specific, high-affinity binding to PD-L1 in vitro and in vivo, with a dissociation constant of 0.24 nM. PET/CT imaging, integrated with contrast-enhanced magnetic resonance imaging, revealed significant accumulation of [¹⁸F]AlF-NOTA-PCP2 in orthotopic tumors, correlating with blood-brain barrier disruption. After radiotherapy (15 Gy), [¹⁸F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51% ± 0.73% to 12.04% ± 1.43%, indicating enhanced PD-L1 expression consistent with immunohistochemistry findings. Fractionated radiation (5 Gy × 3) further amplified PD-L1 upregulation (13.9% ± 1.54% ID/cc) compared with a single dose (11.48% ± 1.05% ID/cc). Taken together, [¹⁸F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.

Objective: To analyze the results of national external quality assessment (EQA) for transfusion compatibility test from 2018 to 2023, with the aim of providing references for improving laboratory testing quality and ensuring the safety of clinical blood transfusion. Methods: Three EQA programs were conducted annually, each distributing 22 quality assessment samples. Participating transfusion laboratories were required to complete testing within specified deadlines and to submit results along with documentation of testing methodologies, reagents, and equipment used. National Center for Clinical Laboratories (NCCL) conducted statistical analysis of laboratory results, evaluated testing outcomes and related circumstances, and provided feedback to participating laboratories. EQA data from transfusion laboratories across China from 2018 to 2023 were collected and systematically analyzed. Results: From 2018 to 2023, the qualification rates for all five items (ABO forward typing, ABO reverse typing, Rh blood group typing, antibody screening, and cross-matching) were 67.59%, 77.11%, 77.38%, 72.78%, 79.96%, and 85.16%, respectively. The mean qualification rates for ABO forward typing, ABO reverse typing, RhD blood group typing, antibody screening, and cross-matching over the past six years were 96.25%±0.59%, 90.45%±4.52%, 96.05%±0.71%, 90.88%±2.86%, and 88.34%±3.48%, respectively. The qualification rates in 2019, 2020, 2022, and 2023 all showed a stable trend of "blood stations>tertiary hospitals>secondary hospitals". The mean qualification rate of laboratories in secondary hospitals from 2018 to 2023 was significantly lower than those of laboratories in tertiary hospitals and blood stations (P<0.05), while no significant difference was observed between laboratories in tertiary hospitals and blood stations (P>0.05). The micro column agglutination method was the most widely used in all five tests. In the four test items, namely ABO forward typing, ABO reverse typing, antibody screening, and cross-matching, there was a statistically significant difference in the qualification rate of micro column agglutination method compared to other methods (P<0.05). There was a statistical difference in the qualification rate between manual and automated detection using micro column agglutination method in the cross-matching tests (P<0.05), whereas no significant difference was noted for the other test items (P>0.05). Conclusion: From 2018 to 2023, the number of laboratories participating in EQA activities has been increasing year by year, and the qualification rate has shown an overall upward trend. The type of laboratory is a key factor affecting the qualification rate, and the testing capabilities of some laboratories still need to be improved. The micro column agglutination method is widely used in transfusion compatibility tests. The established EQA program effectively monitors quality issues in laboratories, drives continuous improvement, and ensures sustained enhancement of testing standards to safeguard clinical blood safety.

Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography(PET/CT)remains limited.This investigation involved the synthesis of[18F]AlF-NOTA-PCP2,which is a novel peptide-based radiolabeled tracer that targets PD-L1,and evaluated its imaging capabilities in orthotopic glioblastoma(GBM)models.Using this tracer,we could noninvasively monitor radiation-induced PD-L1 changes in GBM.[18F]AlF-NOTA-PCP2 exhibited high radiochemical purity(＞95％)and stability up to 4 h after synthesis.It demonstrated specific,high-affinity binding to PD-L1 in vitro and in vivo,with a dissociation constant of 0.24 nM.PET/CT imaging,integrated with contrast-enhanced magnetic resonance imaging,revealed significant accumulation of[18F]AlF-NOTA-PCP2 in orthotopic tumors,correlating with blood-brain barrier disruption.After radiotherapy(15 Gy),[18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51％±0.73％to 12.04％±1.43％,indicating enhanced PD-L1 expression consistent with immunohisto-chemistry findings.Fractionated radiation(5 Gy × 3)further amplified PD-L1 upregulation(13.9％±1.54％ID/cc)compared with a single dose(11.48％±1.05％ID/cc).Taken together,[18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.

Objective:To investigate the therapeutic efficacy and safety of tislelizumab combined with platinum-based drugs in patients with advanced non-small cell lung cancer (NSCLC).Methods:A prospective randomized controlled study was conducted. Eighty-six patients with clinical stage Ⅳ NSCLC in Huaibei People's Hospital from June 2020 to June 2023 were selected as the study subjects, and the patients were divided into the control group and the observation group based on the randomized numerical table method, with 43 cases in each group. The control group was treated with platinum-based drugs, the observation group was treated with platinum-based drugs combined with tislelizumab, and all patients were treated for 4-6 cycles. The two groups were compared in terms of therapeutic efficacy, serum tumor markers [carcinoembryonic antigen (CEA), cytokeratin 19 soluble fragment (CYFRA21-1) and carbohydrate antigen 125 (CA125)] detected by chemiluminescence method, serum immune function indicators [CD3 +, CD4 +, CD8 + cell ratios and CD4 + cell number-to-CD8 + cell number ratio (CD4 +/CD8 +)] detected by flow cytometry, and quality of life [European Organization for Research and Treatment of Cancer (EORTC) quality of life measurement scale (QLQ-C30) scores in functional domain and symptom domain], and incidence of adverse reactions. Results:The differences in baseline data of age, gender, degree of tumor differentiation, pathological type, lesion location, programmed death receptor ligand 1 expression between the observation group and the control group were not statistically significant (all P > 0.05). After treatment, the objective remission rates in the observation and control groups were 34.9% (15/43) and 18.6% (8/43), respectively, and the difference was not statistically significant ( χ2 = 2.91, P = 0.088); the disease control rate in the observation group was 74.4% (32/43), which was higher than that in the control group [51.2% (22/43)], and the difference was statistically significant ( χ2 = 4.98, P = 0.026). The differences in the serum levels of CEA, CYFRA21-1 and CA125 between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the serum levels of CEA, CYFRA21-1 and CA125 in the observation group were lower than those in the control group after treatment, and the differences were all statistically significant (all P < 0.01). The differences in the CD3 +, CD4 +, CD8 + cell ratios and CD4 +/CD8 + between the observation group and the control group before treatment were not statistically significant (all P > 0.05); the CD3 +, CD4 + cell ratios and CD4 +/CD8 + in the observation group were higher than those in the control group, the CD8 + cell ratio was lower than that in the control group after treatment, and the differences were all statistically significant (all P < 0.01). Before treatment, there were no statistically significant differences in the scores of EORTC QLQ-C30 functional domain and symptom domain between the observation group and the control group (both P > 0.05); after treatment, the functional domain score of the observation group was higher than that of the control group, the symptom domain score was lower than that of the control group, and the differences were statistically significant (both P < 0.01). The incidence rates of skin itching, rash and diarrhea in the observation group were 23.3% (10/43), 20.9% (9/43) and 48.8% (21/43), respectively, which were higher than those in the control group [4.7% (2/43), 2.3% (1/43) and 27.9% (12/43)], and the differences were statistically significant (all P < 0.05). Conclusions:Tislelizumab combined with platinum-based drugs in advanced NSCLC patients can enhance the short-term efficacy, reduce serum tumor marker levels, and improve the immune function and quality of life of the patients, but it will increase the occurrence of skin and digestive tract adverse reactions.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.

Cancer of unknown primary(CUP)refers to a group of histopathologically confirmed malignancies that cannot be identified in terms of their primary origin despite thorough investigations.CUP accounts for approximately 3%-5%of all newly diagnosed cancers worldwide,with an overall survival(OS)ranging from 2.7 to 16.0 months.CUP has long been a significant scientific challenge due to the elusive nature and heterogeneity of the primary sites.In the era of immunohistochemistry(IHC),IHC has been applied to identify the primary site in approximately 70%of CUP cases.However,IHC also has limitations for undifferentiated cancers of unknown primary,and results can be influenced by experimental and human factors.In recent years,with the development of molecular tumor profiling(MTP),techniques such as cytology,histology,gene expression profiling(GEP),genomics and epigenomics have been able to accurately detect the primary site in 90%of cases.Currently,the 90-gene tumor tissue origin test has been proven to have an accuracy rate of 94.4%in diagnosing the primary site of CUP,laying the foundation for precision treatment.In the past,platinum and taxane-based empirical chemotherapy was commonly used for treating CUP.However,these treatments did not yield significant improvements in patient survival and prognosis.Since 2008,there has been a global emergence of clinical studies on MTP-guided first-line therapy for CUP.However,due to study design flaws and result controversies,there is no international consensus on the superiority of organ-specific treatment over empirical chemotherapy in terms of improving progression-free survival(PFS)and OS for CUP.Based on this,our center conducted the world's first phase Ⅲ clinical trial in 2017,and demonstrated improved PFS and favorable OS by GEP-guided site-specific therapy of CUP,which established the primacy of site-specific first-line therapy for CUP.In this review,we detailed the epidemiology,pathogenesis,clinical characteristics and the progression of CUP diagnosis from the era of IHC to MTP.Furthermore,we reviewed the advancements in CUP treatment from empirical chemotherapy to MTP-guided organ-specific treatment.Additionally,this review delved into the exploration of second-line treatment options and the establishment of a clinical stratified management model,which are two topics in future research of CUP.This review aimed to summarize the progress in the diagnosis and treatment of CUP,further explore future research directions for CUP,and improve the survival and prognosis of patients with CUP.