ObjectiveTo compare the contents and relative molecular weight distributions of proteins and polypeptides in Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules of Hirudo single medicinal preparations， to evaluate the in vitro anticoagulant， antiplatelet and fibrinolytic activities of the three preparations， and to investigate the effects of temperature， pH and digestive enzymes on the anticoagulant activities of the three preparations. MethodsThe contents of soluble proteins and polypeptides in the three preparations were determined by bicinchoninic acid assay（BCA） and Bradford method， and the relative molecular weight distributions of the three preparations were determined by electrophoresis combined with gel chromatography. The antithrombin activity of the three preparations was evaluated by fibrinogen-thrombin time（Fibg-TT） method， and their anticoagulant activities were further assessed by the elongations of activated partial thromboplastin time（APTT）， prothrombin time（PT） and thrombin time（TT）. The antiplatelet aggregation activities of the three preparations were measured by turbidimetry and the fibrinolytic activities were measured by fibrin plate method. Relative TT was used as index to investigate the effects of temperature， pH and digestive enzyme buffer on anticoagulant activities of the three preparations. ResultsAt the lowest single dosage， the contents of proteins and polypeptides were in the order of Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. Both Huoxue Tongmai capsules and Maixuekang capsules had 11 electrophoretic bands between 4.0 kDa and 90 kDa， the bands of Maixuekang capsules were more clear in the range of >25 kDa， and there was 1 obvious band at 14 kDa for the two capsules. Huoxue Tongmai capsules had one specific band at 9.0 kDa and Maixuekang capsules had one specific band at 48.0 kDa. Naoxuekang dropping pills only had 2 electrophoretic bands at 6.5 kDa and 8.5 kDa， primarily containing peptides below 2 kDa， most of which were oligopeptides. The anticoagulant activity concentrations of the three preparations exhibited a certain dose-dependent effect. At the lowest single dosage， The anticoagulant activity concentrations were ranked as Naoxuekang dropping pills>Huoxue Tongmai capsules>Maixuekang capsules. The prolongation effect of the three preparations on coagulation time was dose-dependent. At the same concentration， the prolongation effect of Naoxuekang dropping pills and Huoxue Tongmai capsules was APTT prolongation rate>TT prolongation rate>PT prolongation rate， whereas for Maixuekang capsules， the sequence was TT prolongation rate>APTT prolongation rate>PT lengthening rate. At the single minimum dosage， the order of APTT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules≈Naoxuekang dropping pills， the order of PT prolongation rate was Naoxuekang dropping pills≈Maixuekang capsules>Huoxue Tongmai capsules， and the order of TT prolongation rate was Maixuekang capsules>Huoxue Tongmai capsules>Naoxuekang dropping pills. The three preparations showed dose-dependent effects on platelet aggregation induced by adenosine diphosphate（ADP） and arachidonic acid（AA）， and the effect induced by ADP was stronger than that induced by AA. The anti-platelet aggregation effect of Naoxuekang dropping pills was significantly stronger than that of Maixuekang capsules（P<0.01）， whereas Huoxue Tongmai capsules had the effect of promoting platelet aggregation. None of the three preparations had the ability to dissolve fibrin. The anticoagulant activity of Naoxuekang dropping pills was least affected by heating， while the activities of the two capsules decreased significantly within 5 min above 80 ℃， and continued to decrease within 2 h. Compared with pure water， the anticoagulant activities of the three preparations could be increased by 1-3 times under strong acidity（pH 1-3）. In the pepsin buffer， the anticoagulant activity of Naoxuekang dropping pills could be increased by 1-3 times， while the anticoagulant activities of Huoxue Tongmai capsules and Maxuekang capsules were significantly decreased， the lowest levels were about 60% and 20%， respectively. In trypsin buffer， the anticoagulant activities of Naoxuekang dropping pills， Huoxue Tongmai capsules and Maixuekang capsules decreased significantly， and the lowest levels decreased to about 41%， 41% and 35%， respectively. ConclusionThe contents of proteins and polypeptides and relative molecular weights of the preparations derived from lyophilized fresh Hirudo powder， dried Hirudo powder and reflux extract of Hirudo decrease sequentially， and the anticoagulant activity decrease gradually， but the anticoagulant pathway is different. And the anti-platelet aggregation activity of the reflux extract is significantly enhanced. The heat resistance and gastrointestinal stability of the three preparations increase successively， and the first two are suitable for enteric-soluble preparations， while the latter is suitable for routine oral administration. The above results can provide data reference for the rationality of different preparation methods， active substances， pharmacodynamics and mechanism of Hirudo preparations.

Objective To analyze the correlation of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammatory index(SII)with short-term outcome and long-term prognosis in patients with advanced non-small cell lung cancer(NSCLC).Methods A retrospective study was conducted.A total of 215NSCLC patients who received a complete 4-cycle chemotherapy combined with immunotherapy or chemotherapy alone in the Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Xuzhou Medical University from January 2021 to January 2023 were selected as the research subjects.The patients were divided into remission group(n=97)and non-remission group(n=118)based on the efficacy of the treatments,and the differences in NLR,PLR,SII,and decline rate of each index were compared between the two groups.NLR,PLR,SII and decline rate before and after treatment were grouped by the best cut-off value or median,and the differences in progression-free survival and overall survival were analyzed by each index group.Results NLR and PLR in the remission group before each cycle of treatment were signifi-cantly lower than those in the non-remission group,and SII in the remission group before cycles 2nd,3rd,and 4th of treatment were sig-nificantly lower than those in the non-remission group(P＜0.05);From initial treatment to before the fourth treatment cycle,NLR and SII decline rates in the remission group were significantly higher than those in the non-remission group(P＜0.05);the tumor stage,NLR before cycle 4th of treatment were independent influencing factors of short-term efficacy in patients with advanced NSCLC(P＜0.05);patients with low NLR,PLR,SII and higher rates of decline in NLR and SII before cycle 4th treatment had longer progression-free survival and overall survival(P＜0.05).Conclusion Tumor stage and post-treatment NLR are significantly correlated with the short-term outcomes of patients with advanced NSCLC,and high post-treatment NLR often suggests a poorer response to treatment.The prognosis of advanced NSCLC patients with higher NLR decline rate and higher SII decline rate after treatment is better.

Objective To analyze the correlation of neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammatory index(SII)with short-term outcome and long-term prognosis in patients with advanced non-small cell lung cancer(NSCLC).Methods A retrospective study was conducted.A total of 215NSCLC patients who received a complete 4-cycle chemotherapy combined with immunotherapy or chemotherapy alone in the Department of Respiratory and Critical Care Medicine,Affiliated Hospital of Xuzhou Medical University from January 2021 to January 2023 were selected as the research subjects.The patients were divided into remission group(n=97)and non-remission group(n=118)based on the efficacy of the treatments,and the differences in NLR,PLR,SII,and decline rate of each index were compared between the two groups.NLR,PLR,SII and decline rate before and after treatment were grouped by the best cut-off value or median,and the differences in progression-free survival and overall survival were analyzed by each index group.Results NLR and PLR in the remission group before each cycle of treatment were signifi-cantly lower than those in the non-remission group,and SII in the remission group before cycles 2nd,3rd,and 4th of treatment were sig-nificantly lower than those in the non-remission group(P＜0.05);From initial treatment to before the fourth treatment cycle,NLR and SII decline rates in the remission group were significantly higher than those in the non-remission group(P＜0.05);the tumor stage,NLR before cycle 4th of treatment were independent influencing factors of short-term efficacy in patients with advanced NSCLC(P＜0.05);patients with low NLR,PLR,SII and higher rates of decline in NLR and SII before cycle 4th treatment had longer progression-free survival and overall survival(P＜0.05).Conclusion Tumor stage and post-treatment NLR are significantly correlated with the short-term outcomes of patients with advanced NSCLC,and high post-treatment NLR often suggests a poorer response to treatment.The prognosis of advanced NSCLC patients with higher NLR decline rate and higher SII decline rate after treatment is better.

Objective To investigate the correlation between peripheral blood total bilirubin(TBIL)levels and the efficacy and prognosis of immunotherapy in advanced non-small cell lung cancer(NSCLC),as well as its relationship with immune inflammation.Methods A retrospective analysis was conducted on 246 patients with advanced NSCLC who received immunotherapy from June 2019 to June 2022.Pre-treatment TBIL levels were collected,and the optimal cutoff value for TBIL was determined using the"X-tile"software and the ROC curve.The impact of pre-treatment TBIL on the short-term efficacy and long-term prognosis of advanced NSCLC was an-alyzed.Results The optimal cutoff value for TBIL was identified as 10.5μmol/L using the"X-tile"software and the ROC curve.A-nalysis of short-term efficacy indicated that patients with higher TBIL levels had a significantly better objective response rate(ORR)compared to those with lower levels(51.3％vs 33.8％,P=0.006).The disease control rate(DCR)was also higher in the higher TBIL level group compared to the low level group(92.9％vs 81.2％,P=0.007).Kaplan-Meier survival analysis revealed that patients with elevated TBIL levels had a longer median progression-free survival(PFS)compared to those with lower TBIL levels,with 13.0 vs 7.0 months,respectively(P＜0.001).Similarly,the median overall survival(OS)was greater in the higher TBIL level group than in the lower TBIL level group,with 16.0 vs 12.0months,respectively(P＜0.001).Additionally,there were significant differences in neutro-phil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammation index(SII)between two groups of different TBIL levels(P＜0.05).Conclusion In immunotherapy for advanced non-small cell lung cancer,patients with higher baseline levels of TBIL exhibit a positive correlation with the efficacy and prognosis of immunotherapy.TBIL might be served as an important predictive marker for immunotherapy in patients with advanced NSCLC.

Objective To investigate the correlation between peripheral blood total bilirubin(TBIL)levels and the efficacy and prognosis of immunotherapy in advanced non-small cell lung cancer(NSCLC),as well as its relationship with immune inflammation.Methods A retrospective analysis was conducted on 246 patients with advanced NSCLC who received immunotherapy from June 2019 to June 2022.Pre-treatment TBIL levels were collected,and the optimal cutoff value for TBIL was determined using the"X-tile"software and the ROC curve.The impact of pre-treatment TBIL on the short-term efficacy and long-term prognosis of advanced NSCLC was an-alyzed.Results The optimal cutoff value for TBIL was identified as 10.5μmol/L using the"X-tile"software and the ROC curve.A-nalysis of short-term efficacy indicated that patients with higher TBIL levels had a significantly better objective response rate(ORR)compared to those with lower levels(51.3％vs 33.8％,P=0.006).The disease control rate(DCR)was also higher in the higher TBIL level group compared to the low level group(92.9％vs 81.2％,P=0.007).Kaplan-Meier survival analysis revealed that patients with elevated TBIL levels had a longer median progression-free survival(PFS)compared to those with lower TBIL levels,with 13.0 vs 7.0 months,respectively(P＜0.001).Similarly,the median overall survival(OS)was greater in the higher TBIL level group than in the lower TBIL level group,with 16.0 vs 12.0months,respectively(P＜0.001).Additionally,there were significant differences in neutro-phil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),and systemic immune-inflammation index(SII)between two groups of different TBIL levels(P＜0.05).Conclusion In immunotherapy for advanced non-small cell lung cancer,patients with higher baseline levels of TBIL exhibit a positive correlation with the efficacy and prognosis of immunotherapy.TBIL might be served as an important predictive marker for immunotherapy in patients with advanced NSCLC.

Objective: Previous research has explored a variety of mental disorders associated with Internet Gaming Disoder (IGD) and Social Media Addiction (SMA). To date, few studies focused on the network characteristics and investigated mood and sleep symptoms across SMA and IGD of adolescence at a group-specific level. This study aims to identify different characteristics of IGD and SMA and further determine the group-specific psychopathology process among adolescents. Methods: We conducted a cross-sectional study to recruit a cohort of 7,246 adolescents who were scored passing the cutoff point of Internet Gaming Disorder Scale-Short Form and Bergen Social Media Addiction Scale, as grouped in IGD and SMA, or otherwise into the control group. Patient Health Questionnaire-9, Generalized Anxiety Disorder 7-item, and Pittsburgh Sleep Quality Index were assessed for the current study, and all assessed items were investigated using network analysis. Results: Based on the analytical procedure, the participants were divided into three groups, the IGD group (n=789), SMA group (n=713) and control group (n=5,744). The edge weight bootstrapping analysis shows that different groups of networks reach certain accuracy, and the network structures of the three groups are statistically different (pcontrol-IGD=0.004, pcontrol-SMA<0.001, pIGD-SMA<0.001). The core symptom of SMA is “feeling down, depressed, or hopeless”, while IGD is “feeling tired or having little energy”. Conclusion Although IGD and SMA are both subtypes of internet addiction, the psychopathology processes of IGD and SMA are different. When dealing with IGD and SMA, different symptoms should be addressed.

Objective To investigate the clonal rearrangement characteristics and clinical application value of IGH gene in B-cell non-Hodgkin's lymphoma(B-NHL).Methods Demographic and clinical data as well as IGH sequencing results of 55 patients with B-NHL who underwent next-generation sequencing(NGS)testing were collected,and IGH gene clonal rearrangement was detected.The characteristics of IGH gene clonal rearrangement,IGHV gene usage,and the clinical application value of NGS for IGH clonal rearrangement were analyzed.Results Among 55 patients with B-NHL and IGH clonal rearrangement,single dominant clones were mainly detected(85.45%,47/55);a few patients had two(12.73%,7/55)and three dominant clones(1.82%,1/55).In terms of preference for IGHV gene usage,IGHV3 gene had the highest frequency of access in B-NHL,followed by IGHV4.Among the IGHV subtypes,IGHV3-23 had the highest frequency in chronic lymphocytic leukemia/small lymphocytic lymphoma,and IGHV4-34 had the highest frequency in primary central nervous system diffuse large B-cell lymphoma and not otherwise specified diffuse large B-cell lymphoma.Conclusion A preference for IGHV gene usage in clonal rearr-angement of IGH genes is noted in B-NHL patients with different pathological types.Using NGS to detect IGHclonal rearrangement can identify subclones and clonal correlations,and assist in disease diagnosis.

Purpose To explore the application of intra voxel incoherent motion diffusionweighted imaging (IVIM-DWI) quantitative parameters in evaluating the pathological stage of pancreatic cancer by comparing the manifestations of IVIM-DWI in patients with pancreatic cancer in different differentiaed degrees as there lacked effective screening instrument for the early diagnosis of pancreatic cancer.Materials and Methods Sixteen patients with pathologically proved pancreatic cancer (10 with high-moderation differentiation while 6 with low differentiation) were enrolled,and 3.0T MRI was used to conduct pancreatic DWI with multiple b values.IVIM double-exponential model was used to analyze the measurement parameters of DWI with multiple b values,so as to measure the slow apparent diffusion coefficient (ADCslow),fast apparent diffusion coefficient (ADCfast) and filling fraction (f).Results The ADCslow value was evidently lower in patients with high-moderate differentiated pancreatic cancer than those with low differentiated pancreatic cancer [(0.546± 0.041)× 10-3 mm2/s vs.(0.677± 0.120)× 10-3 mm2/s,P＜0.05],and f value was notably higher in patients with high-moderate differentiated pancreatic cancer than those with low differentiated pancreatic cancer [(59.3 ± 8.8)％ vs.(41.7±22.4)％,P＜0.05].The area under the curve of ADCslow was higher than that of f when distinguishing high-moderate differentiated and low differentiated pancreatic cancer (0.850＞0.750).The sensitivity and specificity were 100.00％ and 83.33％ when ADCslow ≤ 0.599×10-3 mm2/s,and were 100.00％ and 66.67％ when f＞44.7％ in distinguishing high-moderate differentiated and low differentiated pancreatic cancer,respectively.Conclusion ADCslow and f,as the quantitative parameters for IVIM-DWI,can distinguish high-moderate differentiated and low differentiated pancreatic cancer,and predict the pathological stage of pancreatic cancer before operation.Moreover,they also have high diagnostic efficacy in distinguishing high-moderate differentiated and low differentiated pancreatic cancer.

Objective To explore the application value of monoexponential, biexponential models multiple b values diffusion weighted imaging(DWI) in distinguishing pancreatic cancer from non-tumorous pancreas.Methods Subjects comprised 37 pancreatic cancers confirmed by clinical or surgery.Pancreas multiple b values DWI was performed using 3.0T scanner.Standard apparent diffusion coefficient (ADCstandard) was calculated using monoexponential diffusion model.Pure diffusion coefficient (ADCslow), pseudodiffusion coefficient (ADCfast) and perfusion fraction (f) were calculated using intravoxel incoherent motion(IVIM) diffusion model.Parameters of pancreatic cancers and non-tumorous pancreas were compared using independent samples t test.Results Mean ADCslow value of pancreatic cancer was higher than that of non-tumorous pancreas (0.611×10-3 mm2/s vs 0.521×10-3 mm2/s,P=0.037).Mean ADCfast and f values of pancreatic cancer were lower than that of non-tumorous pancreas (5.066×10-3 mm2/s vs 7.188×10-3 mm2/s,P=0.035;55.8% vs 64.0%,P=0.016;respectively).ADCslow of pancreatic cancer was positively correlated to ADCstandard (r=0.824,P=0.000).ADCfast of pancreatic cancer was negatively correlated to f(r=-0.558,P=0.000).Conclusion ADCslow, ADCfast and f derived from IVIM-DWI model can distinguish pancreatic cancer from non-tumorous pancreas.IVIM-DWI may be a promising and non-invasive tool for early diagnosing and differentiating pancreatic carcinoma from non-tumorous pancreas.

Objective To analyze CT findings of insulinoma,and to summarize the causes of missed diagnosis of nontypical insuli-noma.Methods Clinical and CT manifestations of 18 patients with 18 insulinomas were analyzed retrospectively which were proved by surgery and pathology,and the causes of the missed diagnosis of nontypical insulinoma were also summarized.Results 10 patients with 10 insulinoma underwent CT plain scan with isodensity in 9 and slightly lower density in 1 with thread-like capsule.Other 18 patients underwent enhanced CT scan,10 of whom showed obvious enhancement in arterial phase with isodentisy in 6 and slightly higher density in 4 in portal phase,and isodensity in 10 in delayed phase.4 lesions showed mild-to-moderate enhancement in arterial phase with slightly higher density than normal pancreas in 2 and isodentisy in 2 in portal phase,and slightly higher density than nor-mal pancreas in 1 and similar density to pancreas in 3 in delayed phase.In portal phase,the enhanced degree in 8 was similar to the pancreas,and that in 6 was slightly higher or higher than that of pancreas.In delayed phase,13 were similar to the pancreas and other 1 was higher than that.3 of 18 lesions were easily missed,and 4 lesions with missed diagnosis showed isodensity on plain CT and en-hanced CT,and were further detected by other imaging methods.Conclusion Multiphase enhancement CT scanning can be used as the first choice for the insulinoma.