Objective To investigate the effects of Buyang Huanwu Decoction on nerve regeneration after cerebral ischemia in mice based on Cav-1/Notch1/Hes1 signaling pathway.Methods Wild(WT)and Cav-1-/-(KO)male mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group,with 10 mice in each group.The middle cerebral artery occlusion method was used to construct the mouse cerebral ischemia model.After modeling,5-ethynyl-2'-deoxyuridine(EdU)was injected intraperitoneally every 7 days for 3 times(with an interval of 8 hours).Buyang Huanwu Decoction group was given 18.5 g/kg Buyang Huanwu Decoction by gavage daily,while the sham-operation group and model group were given distilled water of equal volume by gavage for 21 consecutive days.The neurological function of mice was evaluated using modified neurological severity score,brain tissue morphology was observed through HE staining,nerve regeneration in the ischemic side injury area was detected using dual immunofluorescence staining,Western blot was used to detect the expressions of Notch1 and Hes1 protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurological function score of the mice in the WT and KO model groups significantly increased(P<0.01),the arrangement of neurons in the ischemic cortical area was disordered,with nucleoli shrinking,marginalization,and even rupture,widened intercellular spaces,intracellular edema and vacuolar changes,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area significantly increased(P<0.01).Compared with the same genotype model group,the neurological function score of the WT and KO Buyang Huanwu Decoction group significantly decreased(P<0.01),the neurons in the ischemic cortical area were arranged neatly and structurally intact,with reduced intercellular space and clear nucleoli,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area was significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area were significantly decreased(P<0.01).Compared with the corresponding WT group,the neurological function scores of mice in the KO model group and KO Buyang Huanwu Decoction group significantly increased(P<0.01),the neurons in the ischemic cortical area had more severe nucleolar condensation,marginalization and rupture,with more vacuolar changes and ischemic injury,the co-localization of EdU/Nestin and EdU/NeuN in the ischemic side injury area was significantly decreased(P<0.01),and the expression of Notch1 and Hes1 proteins in ischemic cortical area significantly increased(P<0.01).Conclusion Buyang Huanwu Decoction can promote nerve regeneration after cerebral ischemia,which may be related to the regulation of Cav-1 thereby inhibition Notch1//Hes1 signaling pathway activity.

Objective:To design a set of simulation system for surgical operation based on virtual reality(VR)technique and intelligent scoring functions,so as to assess its clinical application effect.Methods:The Digital Imaging and Communications in Medicine(DICOM)images of typical patients were collected.Materialise Interactive Medical Image Control System(MIMICS)software was adopted to reconstruct the three-dimensional(3D)model of diseased organs.Surgical instrument models were constructed by using 3D Max software.Unity 3D software was adopted to construct simulation system for surgical operation with VR+intelligent scoring.A total of 40 surgical resident physicians,who were employed with 3 years since 2019 in The Second Affiliated Hospital of Kunming Medical University,were selected.They were divided into observation group and control group,with 20 cases in each group.The observation group used simulation system for surgical operation to conduct intelligent scoring for cholecystectomy under laparoscope,and the control group used conventional scoring for surgical operation.The scores of surgical operation and test between the two groups were compared.Results:The mean value of surgical operation time of the observation group was(1.72±0.41)h,and the average incidence of complication was(0.03±0.02)%,both of them of the observation group were significantly lower than those of the control group[(2.25±0.42)h and(0.05±0.03)%].The differences of them between two groups were statistically significant(t=9.00,4.08,P<0.05).The test scores of surgical operation of the observation group was also significantly higher than that of the control group(t=5.26,P<0.001).Conclusion:The developed simulation system for surgical operation with VR+intelligent scoring can significantly enhance users'surgical operation skills and improve learning outcomes,which has favorable prospects in future applications.

Objective:We study the prognostic value of TNM stage and L3-skeletal muscle mass index in overall survival(OS)in elderly patients with colorectal cancer after surgery.Furthermore, investigate the prognostic value of combined scoring system(TNM-SMI score)in patients with colorectal cancer.Methods:From January 1, 2018 to January 31, 2019, the clinical data of elderly patients who were diagnosed with colorectal cancer for the first time in Longyan First Hospital, Fujian Medical University were retrospectively analyzed.The baseline data were compared in patients with different TNM stage and L3SMI.The relevant factors that might affect the prognosis of the patients were analyzed to determine the independent risk factors in cox regression analyses.Survival curves were plotted by using the Kaplan-Meier method, and Log-rank test was used to compare Overall Survival.Predictive efficacy was compared by plotting (ROC)curve and calculating the area under the curve(AUC).Results:A total of 128 eligible patients aged 65-88(73.96±6.20)years were enrolled.Among them, 82 were male.Univariate and multifactorial cox regression analyses showed that TNM stage( HR=3.944, 95% CI: 1.519-10.237, P<0.05)and L3SMI( HR=3.194, 95% CI: 1.222-8.349, P<0.05)were the independent risk factors for OS in elderly colorectal cancer patients; Survival curves plotted by Kaplan-Meier method showed that the 5-year survival rate(OS rate)of patients in TNM(Ⅲ and Ⅳ)group was lower than in TNM(Ⅰ and Ⅱ)group(58.8% vs.88.9%, P<0.001), and the 5-year survival rate(OS rate)of patients in low L3SMI group was lower than in high L3SMI group(51.0% vs.88.3%, P<0.001); Elderly colorectal patients were risk stratified by TNM-SMI score, the patients with higher score had worse 5-year OS rate; The AUC of L3SMI, TNM stage, and TNM-SMI score are 0.729, 0.695, and 0.800. Conclusions:The TNM stage and L3SMI are independent risk factors of OS after colorectal cancer surgery; TNM-SMI score, which combines TNM stage and L3SMI, can predict prognosis more efficiency compare to single-factor.The higher TNM-SMI score had the worse prognosis; TNM stage in combination with L3SMI improves the efficiency prediction of OS after colorectal cancer surgery.

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 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.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

To analyze the standard establishment approach and compilation rationale for metallic pharmaceutical packaging standard development in the 2025 edition of the Pharmacopeia of the People's Republic of China.This article systematically explained the background and process of establishing the guiding principles for metallic materials and containers used in pharmaceutical packaging in the Chinese Pharmacopoeia through basic information,relevant domestic and international standards,the establishment of key quality attributes of metallic pharmaceutical packaging materials,and the construction of metallic pharmaceutical packaging material standards.The newly established guidelines,the Pharmacopeia of the People's Republic of China 9625,prioritized product critical quality attributes(CQAs)and real-world applicability.This dual emphasis on rigidity and adaptability enhances drug safety,meets the regulatory requirements,and promotes the globalization and scientific advancement of China's pharmaceutical packaging industry.

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 effects of Buyang Huanwu Decoction on nerve regeneration after cerebral ischemia in mice based on Cav-1/Notch1/Hes1 signaling pathway.Methods Wild(WT)and Cav-1-/-(KO)male mice were randomly divided into sham-operation group,model group and Buyang Huanwu Decoction group,with 10 mice in each group.The middle cerebral artery occlusion method was used to construct the mouse cerebral ischemia model.After modeling,5-ethynyl-2'-deoxyuridine(EdU)was injected intraperitoneally every 7 days for 3 times(with an interval of 8 hours).Buyang Huanwu Decoction group was given 18.5 g/kg Buyang Huanwu Decoction by gavage daily,while the sham-operation group and model group were given distilled water of equal volume by gavage for 21 consecutive days.The neurological function of mice was evaluated using modified neurological severity score,brain tissue morphology was observed through HE staining,nerve regeneration in the ischemic side injury area was detected using dual immunofluorescence staining,Western blot was used to detect the expressions of Notch1 and Hes1 protein in ischemic cortical area.Results Compared with the same genotype sham-operation group,the neurological function score of the mice in the WT and KO model groups significantly increased(P<0.01),the arrangement of neurons in the ischemic cortical area was disordered,with nucleoli shrinking,marginalization,and even rupture,widened intercellular spaces,intracellular edema and vacuolar changes,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area significantly increased(P<0.01).Compared with the same genotype model group,the neurological function score of the WT and KO Buyang Huanwu Decoction group significantly decreased(P<0.01),the neurons in the ischemic cortical area were arranged neatly and structurally intact,with reduced intercellular space and clear nucleoli,the co-localization of EdU/Nestin,EdU/DCX and EdU/NeuN in the ischemic side injury area was significantly increased(P<0.01),and the expression of Notch1 and Hes1 protein in ischemic cortical area were significantly decreased(P<0.01).Compared with the corresponding WT group,the neurological function scores of mice in the KO model group and KO Buyang Huanwu Decoction group significantly increased(P<0.01),the neurons in the ischemic cortical area had more severe nucleolar condensation,marginalization and rupture,with more vacuolar changes and ischemic injury,the co-localization of EdU/Nestin and EdU/NeuN in the ischemic side injury area was significantly decreased(P<0.01),and the expression of Notch1 and Hes1 proteins in ischemic cortical area significantly increased(P<0.01).Conclusion Buyang Huanwu Decoction can promote nerve regeneration after cerebral ischemia,which may be related to the regulation of Cav-1 thereby inhibition Notch1//Hes1 signaling pathway activity.