Ischemic stroke (IS) is a globally life-threatening disease. Presently, few therapeutic medicines are available for treating IS, and rt-PA is the only drug approved by the US Food and Drug Administration (FDA) in the US. In fact, many agents showing excellent neuroprotection but no blood flow-improving activity in animals have not achieved ideal clinical efficacy, while thrombolytic drugs only improving blood flow without neuroprotection have limited their wider application. To address these challenges and meet the huge unmet clinical need, we have designed and identified a novel compound AAPB with dual effects of neuroprotection and cerebral blood flow improvement. AAPB significantly reduced cerebral infarction and neural function deficit in tMCAO rats, pMCAO rats, and IS rhesus monkeys, as well as displayed exceptional safety profiles and excellent pharmacokinetic properties in rats and dogs. AAPB has now entered phase I of clinical trials fighting IS in China.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To systematically evaluate the application of patient-reported outcome measures (PROMs) in adult lung transplant recipients, and to explore their clinical value in assessing quality of life following transplantation.Methods:This study was a systematic review. Relevant studies published between January 2014 and July 2024 were searched in the PubMed and OVID Medline databases using keywords such as "lung transplantation" "quality of life" "HRQoL" "health indice" "patient-reported outcome measure" "questionnaire" "profile" "scale" "score" and "survey". Only English-language articles were included. Eligible studies were those that applied PROMs to assess quality of life in adult lung transplant recipients and were approved by ethics committees. Reviews, case reports, abstracts, and studies involving transplant candidates or recipients of lung-liver or lung-kidney combined transplantation were excluded. Data extracted included basic study information, study design, participant characteristics, and PROM usage. Frequently used PROMs and lung transplant-specific PROMs were summarized, and results with clearly reported time points were analyzed.Results:A total of 63 studies were included, comprising 54 (85.7%) observational studies and 9 (14.3%) interventional studies. The majority of studies originated from the United States (18 studies, 28.6%). A total of 55 different PROMs were identified, including 30 generic and 25 disease-specific instruments. The five most frequently used PROMs were the Short Form 36 (SF-36; 30 studies, 47.6%), the EuroQol 5 Dimension (EQ-5D; 12 studies, 19.0%), the St. George's Respiratory Questionnaire (SGRQ; 11 studies, 17.5%), the Hospital Anxiety and Depression Scale (HADS; 7 studies, 11.1%), and the modified Medical Research Council dyspnea scale (mMRC; 5 studies, 7.9%). Lung transplant-specific PROMs included the Lung Transplant Quality of Life questionnaire (LT-QOL), the Lung Transplant Valued Life Activities (LT-VLA) scale, and the Pulmonary-Specific Quality of Life Scale (PQLS), which were applied in only 6 studies (9.5%). Across studies, lung transplantation was associated with significant improvements in recipients' quality of life, sustained over a follow-up period of 3 to 60 months.Conclusions:A wide range of PROMs have been employed to assess health-related quality of life in lung transplant recipients; however, transplant-specific PROMs remain relatively scarce. PROMs provide valuable insights for reflecting and dynamically monitoring long-term quality of life, supplementing evidence for clinical decision-making, and optimizing post-transplant care strategies.

Objective:To evaluate the clinical equivalence between a domestic calcipotriol/betamethasone dipropionate ointment and the originator product in the treatment of stable plaque psoriasis.Methods:A multicenter, randomized, double-blind, three-arm, parallel-group, active- and placebo-controlled study was conducted, and 449 patients aged 18 - 65 years with stable plaque psoriasis were enrolled from 25 hospitals (such as the First Affiliated Hospital of China Medical University). Eligible patients had a baseline physician's global assessment (PGA) score of ≥ 3 points, baseline body surface area (BSA) involvement of 5% - 30%, and a target lesion psoriasis area and severity index (TL-PASI) for plaque elevation of ≥ 3 points. Participants were randomly assigned in a 2:2:1 ratio to the test group ( n = 179), reference group ( n = 180), and placebo group ( n = 90), and applied the domestic calcipotriol/betamethasone dipropionate ointment, originator product, and ointment base respectively, once daily in the evening for 4 weeks. Efficacy and safety were assessed at weeks 1, 2, and 4. The primary efficacy endpoints were the treatment success rates and clinical success rates in each group at week 4. The per-protocol set (PPS) was used for the primary efficacy analysis, and the intention-to-treat (ITT) set for supplementary efficacy analysis. Equivalence between the test and reference preparations was tested using the Cochran-Mantel-Haenszel method adjusted for randomization strata. Superiority of the test and reference preparations over the placebo was also tested. Measurement data were compared among the 3 groups using analysis of variance or non-parametric tests, while treatment success rates, clinical success rates, and incidence rates of adverse reactions were compared using the chi-square test. Results:The ITT, PPS, and safety sets included 447, 420, and 448 patients, respectively. In the ITT set, patients were aged 43.6 ± 12.8 years, including 320 (71.6%) males and 127 (28.4%) females, and the disease duration was 11.21 ± 9.05 years; 316 (70.7%) had a PGA score of 3 points and 131 (29.3%) had a PGA score of 4 - 5 points. No significant differences in the baseline characteristics (including age, sex, disease duration and disease severity) were observed among the 3 groups (all P > 0.05). Based on the PPS analysis, the treatment success rates were 57.9% (99/171) in the test group, 50.3% (86/171) in the reference group, and 7.7% (6/78) in the placebo group, and the clinical success rates were 57.9% (99/171), 50.3% (86/171), and 10.3% (8/78), respectively; both the test and reference groups were superior to the placebo group in both treatment and clinical success rates (all P < 0.001) ; the rate differences for treatment success (90% confidence interval [ CI]: -1.3% - 16.4%) and clinical success (90% CI: -1.3% - 16.3%) between the test and reference groups were entirely within the pre-defined equivalence margin (-20% - 20%). Subgroup analyses by baseline PGA scores: for patients with a baseline PGA score of 3 points, the treatment success rates in the test, reference, and placebo groups were 60.8% (73/120), 52.1% (62/119), and 11.1% (6/54), respectively, and the corresponding clinical success rates were 61.7% (74/120), 53.8% (64/119), and 13% (7/54), respectively; the test and reference groups did not differ significantly in treatment or clinical success rates (both P > 0.05), but both showed higher success rates than the placebo group (all P < 0.001) ; the results of statistical comparisons among the 3 groups in patients with a baseline PGA score of 4 - 5 points were consistent with those observed in patients with a baseline PGA score of 3 points. The percentage reductions in PGA and TL-PASI scores from baseline to weeks 1, 2, and 4 showed significant differences among the 3 groups, which were significantly higher in the test and reference groups than in the placebo group (all P < 0.001), but did not differ between the test and reference groups (all P > 0.05). The primary adverse reactions were local skin reactions, such as pruritus, pain, and erythema. The incidence rates of adverse reactions were 8.9% (16/179) in the test group, 7.3% (13/179) in the reference group, and 7.8% (7/90) in the placebo group, with no significant difference among the 3 groups ( P > 0.05) . Conclusions:The domestic calcipotriol/betamethasone dipropionate ointment demonstrated clinical equivalence to the originator product in the treatment of stable plaque psoriasis, and the two agents exhibited comparable efficacy for patients with varying degrees of disease severity, and were comparable in the speed and degree of clinical improvement, with similar favorable safety profiles.

Objective:To systematically evaluate the application of patient-reported outcome measures (PROMs) in adult lung transplant recipients, and to explore their clinical value in assessing quality of life following transplantation.Methods:This study was a systematic review. Relevant studies published between January 2014 and July 2024 were searched in the PubMed and OVID Medline databases using keywords such as "lung transplantation" "quality of life" "HRQoL" "health indice" "patient-reported outcome measure" "questionnaire" "profile" "scale" "score" and "survey". Only English-language articles were included. Eligible studies were those that applied PROMs to assess quality of life in adult lung transplant recipients and were approved by ethics committees. Reviews, case reports, abstracts, and studies involving transplant candidates or recipients of lung-liver or lung-kidney combined transplantation were excluded. Data extracted included basic study information, study design, participant characteristics, and PROM usage. Frequently used PROMs and lung transplant-specific PROMs were summarized, and results with clearly reported time points were analyzed.Results:A total of 63 studies were included, comprising 54 (85.7%) observational studies and 9 (14.3%) interventional studies. The majority of studies originated from the United States (18 studies, 28.6%). A total of 55 different PROMs were identified, including 30 generic and 25 disease-specific instruments. The five most frequently used PROMs were the Short Form 36 (SF-36; 30 studies, 47.6%), the EuroQol 5 Dimension (EQ-5D; 12 studies, 19.0%), the St. George's Respiratory Questionnaire (SGRQ; 11 studies, 17.5%), the Hospital Anxiety and Depression Scale (HADS; 7 studies, 11.1%), and the modified Medical Research Council dyspnea scale (mMRC; 5 studies, 7.9%). Lung transplant-specific PROMs included the Lung Transplant Quality of Life questionnaire (LT-QOL), the Lung Transplant Valued Life Activities (LT-VLA) scale, and the Pulmonary-Specific Quality of Life Scale (PQLS), which were applied in only 6 studies (9.5%). Across studies, lung transplantation was associated with significant improvements in recipients' quality of life, sustained over a follow-up period of 3 to 60 months.Conclusions:A wide range of PROMs have been employed to assess health-related quality of life in lung transplant recipients; however, transplant-specific PROMs remain relatively scarce. PROMs provide valuable insights for reflecting and dynamically monitoring long-term quality of life, supplementing evidence for clinical decision-making, and optimizing post-transplant care strategies.

Experimental animal models are an essential part of basic research on colorectal cancer.It is important for basic research on colorectal tumor treatment in TCM to construct animal models with the characteristics of TCM based on the theory of TCM diagnosis and treatment,so that the animal models can meet the characteristics of both western medicine and TCM symptoms.In this paper,we summarize the methods and characteristics of animal models of colorectal tumors and the combination of disease and evidence for scientific research on colorectal tumors through literature review,in order to provide reference for researchers engaged in scientific research on colorectal tumors.

Background Self-perceived burden,anxiety and depression are among the most important factors affecting quality of life.At present,there is a lack of understanding on the research status and influencing factors of self-perceived burden in liver transplant recipients.Previous studies have shown that self-perceived burden,anxiety,depression and quality of life are correlated in pairs,but the effecting path among the three are not yet clear.Objective To explore the correlation of self-perceived burden and anxiety/depression with quality of life in liver transplant recipients,so as to provide guidance for psychological nursing intervention in clinical patients.Methods A total of 200 patients liver transplant recipients were enrolled from the liver transplantation inpatient and outpatient clinics of Jiangsu Province Hospital and Qinhuai Medical Area,General Hosptial of Eastern Theater Command of People's Liberation Army of China from March 2022 to February 2023.Patients were evaluated using Self-perceived Burden Scale(SPBS),Hospital Anxiety and Depression Scale(HADS)and the Chinese version of Post Liver Transplant Quality of Life Questionnaire(pLTQ).Spearman correlation analysis was used to examine the correlation among the scales.A structural equation model using Mplus 8.3 was utilized to testify the relationship among self-perceived burden,anxiety/depression and quality of life in liver transplant recipients.Bootstrap method was used to test the effecting pathway.Results There were statistically significant differences in SPBS scores of liver transplant recipients with different levels of education and fannual family income(H=9.656,18.796,P<0.05).There were statistically significant differences in HADS scores of liver transplant recipients with different numbers of somatic symptoms(H=9.859,P<0.05).There were statistically significant differences in the Chinese version of pLTQ scores of liver transplant recipients with different levels of education,postoperative survival time and numbers of somatic symptoms(H=6.892,8.023,16.099,P<0.05).The total and each dimension scores in SPBS of liver transplant recipients were positively correlated with the total score and anxiety/depression dimension scores in HADS(r=0.464～0.586,0.460～0.593,0.286～0.408,0.464～0.583,P<0.01)and negatively correlated with the total score and each dimension scores in the Chinese version of pLTQ(r=-0.572～-0.416,-0.599～-0.441,-0.365～-0.213,-0.559～-0.428,P<0.01).Structural equation model denoted that self-perceived burden negatively affected quality of life(β=-0.186,P<0.01).Anxiety/depression also negatively affected quality of life(β=-0.679,P<0.01).The self-perceived burden indirectly affected the quality of life of liver transplant recipients through anxiety and depression,with an effect value of-0.429,accounting for 69.76％of the total effect.Conclusion The quality of life in liver transplant recipients may be related to their self-perceived burden and anxiety/depression.Self-perceived burden may affect the quality of life of liver transplant patients through anxiety and depression.

The theory of yin and yang is the modest differentiation thought of the traditional Chinese medicine under the guidance of overall dialectics,and the dynamic changes of yin and yang profit and loss can reflect the life activities of the human body.In the early literature research and clinical practice,the author's team found that the"yang deficiency and yin stagnation"is the key pathogen of colorectal cancer,the yang qi is insufficient,and the metabolites of the yin such as phlegm,wetness and stasis are lost in gasification and accumulate to form a"yin tumor",which is stagnant in the intestine and forms colorectal cancer.Yang Qi is the process of normal cell metabolism to produce energy,Yang Qi is insufficient,the"yin knot"of the thing in the body polymerizes into tumors,The imbalance of yin and yang can cause changes in energy or substance metabolism in the body,and glutamine is one of the amino acid which is the largest consumption of tumor cells,and its metabolic process not only provides a material basis for tumor cell growth,but also creates an acidic microenvironment of hypoxia to promote the proliferation and growth of tumor cells.This paper discusses the characteristics of glutamine metabolism of colorectal cancer cells in detail,aiming to explain the occurrence of colorectal cancer from the pathogenesis of"yang deficiency yin knot",and to explain the scientific theory of traditional Chinese medicine in the treatment of coloral cancer with the principle of Wenyang Tongxia,aiming to provide new ideas and methods for the comprehensive treatment of CRC.

Objective:To investigate the clinical features and prognosis of testicular relapse in pediatric acute lymphoblastic leukemia (ALL).Methods:Clinical data including the age, time from initial diagnosis to recurrence, relapse site, and therapeutic effect of 37 pediatric ALL with testicular relapse and treated in Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences between November 2011 and December 2022 were analyzed retrospectively. Patients were grouped according to different clinical data. Kaplan-Meier analysis was used to evaluate the overall survival (OS) rate and event free survival (EFS) rate for univariate analysis, and Cox proportional-hazards regression model was used to evaluate the influencing factors of OS rate and EFS rate for multivariate analysis.Results:The age at initial diagnosis of 37 pediatric testicular relapse patients was (5±3) years and the time from initial diagnosis to testicular recurrence was (37±15) months. The follow-up time was 43 (22, 56) months. Twenty-three patients (62%) were isolated testis relapse. The 5-year OS rate and EFS rate of the 37 relapsed children were (60±9) % and (50±9) % respectively. Univariate analysis showed that the 2-year EFS rate in the group of patients with time from initial diagnosis to testicular recurrence >28 months was significantly higher than those ≤28 months ((69±10)% vs. (11±11)%, P<0.05), 2-year EFS rate of the isolated testicular relapse group was significantly higher than combined relapse group ((66±11)% vs. (20±13) %, P<0.05), 2-year EFS rate of chimeric antigen receptor T (CAR-T) cell treatment after relapse group was significantly higher than without CAR-T cell treatment after relapse group ((78±10)% vs. (15±10)%, P<0.05). ETV6-RUNX1 was the most common genetic aberration in testicular relapsed ALL (38%, 14/37). The 4-year OS and EFS rate of patients with ETV6-RUNX1 positive were (80±13) % and (64±15) %, respectively. Multivariate analysis identified relapse occurred≤28 months after first diagnosis ( HR=3.09, 95% CI 1.10-8.72), combined relapse ( HR=4.26, 95% CI 1.34-13.52) and CAR-T cell therapy after relapse ( HR=0.15,95% CI 0.05-0.51) were independent prognostic factors for 2-year EFS rate (all P<0.05). Conclusions:The outcome of testicular relapse in pediatric ALL was poor. They mainly occurred 3 years after initial diagnosis. ETV6-RUNX1 is the most common abnormal gene.Patients with ETV6-RUNX1 positive often have a favorable outcome. Early relapse and combined relapse indicate unfavorable prognosis, while CAR-T cell therapy could significantly improve the survival rate of children with testicular recurrence.