Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To investigate the predictive value of systemic immune inflammation index for the efficacyof neoadjuvant chemotherapy in triple negative breast cancer patients, and analyzed the relationship between pathological complete response (pCR) and prognosis.Methods:The clinical data of 146 patients with triple-negative breast cancer admitted to the 926th Hospital of the Joint Service Support Force of the PLA from January 2018 to December 2020 were retrospectively collected. All patients received neoadjuvant chemotherapy. After chemotherapy, the patients were divided into pCR group (62 cases) and non-pCR group (84 cases) according to whether the patients achieved pCR. Pathological characteristics and systemic immunoinflammatory index levels of the two groups were compared. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of systemic immunoinflammatory index for pCR after neoadjuvant chemotherapy in patients with triple-negative breast cancer, and survival curves were drawn to compare the disease-free survival of the two groups.Results:The rate of axillary lymph node metastasis in pCR group was lower than that in non-pCR group: 37.10% (23/62) vs. 64.29% (54/84), there was statistical difference ( χ2 = 10.58, P<0.01). There were no significant differences in TNM stage, Ki-67 level and histological grade between the two groups ( P>0.05). Compared with the non -pCR group, the systemic immune inflammation index in the pCR group was significantly reduced: 617.42 ± 166.40 vs. 853.67 ± 202.41, P<0.01. Systemic immune inflammation index was valuable in predicting non-pCR of triple negative breast cancer patients after neoadjuvant chemotherapy, and the area under the curve was 0.807 (95% CI: 0.738 - 0.875, P<0.01). Compared with the non-pCR group, the disease-free survival of patients in the pCR group was significantly prolonged ( P = 0.033). Conclusions:Systemic immune inflammation index was related to the efficacy of neoadjuvant chemotherapy in triple negative breast cancer patients, and can be used as a biological indicator to predict the efficacy of neoadjuvant chemotherapy in triple negative breast cancer.

Purpose To investigate the clinicopathological features and differential diagnosis of anaplastic large-cell lymphoma(ALCL)with the small cell variant.Methods The clinical data of 15 cases of small cell variant of ALCL were retrospectively analyzed.Hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization,TCR and IgG rearrangement were performed.The clinicopathological features,prognosis and differential diagnosis were summarized with review of the literature.Results Among the 15 cases of small cell ALCL,5 were females and 10 were males,with a male-to-female ratio of 2:1.Among the 15 cases of small cell ALCL,14 were systemic ALCL[(12 cases of ALK+),and the age range was 5-63 years old(median age 20 years);There were 2 cases of ALK(-),aged more than 60 years],and 1 case of ALCL of primary cutaneous ALK(-).Microscopic features were dominated by small to medium-sized tumor cells,with irregular nuclear membranes,inconspicuous nucleoli,and a lack of or few iconic large cells.Immunohistochemically:3 cases were ALK-negative and 12 cases were ALK-positive.Tumor cells were CD30 positive in 14/15 cases,CD3 positive in 7/15 cases,CD2 positive in 2/6 cases,CD4 positive in 5/11 cases,CD5 positive in 2/8 cases,CD7 positive in 4/6 cases,CD8 positive in 1/8 cases,TIA-1 positive in 7/7 cases,Granzyme B positive in 4/6 cases and EMA positive in 6/7 cases.CD20 was negative in all cases.Immuno-globulin IgG and TCR gene rearrangement were negative in case 4 and case 11.Case 13 was positive for TCR rear-rangement and negative for immunoglobulin IgG.Twelve of the 15 patients were followed up for 0.7-165 months(me-dian,7 months),3 patients were lost to follow-up and 7 patients died.Conclusion Small cell variant ALCL is easily misdiagnosed as an inflammatory or infectious disease.A group of antibodies,including CD30 and ALK,should be routinely used in routine work,especially in young patients with systemic symptoms and leukemia manifestations or in small biopsies,to reduce misdiagnosis and missed diagnosis.

Purpose To investigate the clinicopathological features and differential diagnosis of anaplastic large-cell lymphoma(ALCL)with the small cell variant.Methods The clinical data of 15 cases of small cell variant of ALCL were retrospectively analyzed.Hematoxylin-eosin staining,immunohistochemistry,EBER in situ hybridization,TCR and IgG rearrangement were performed.The clinicopathological features,prognosis and differential diagnosis were summarized with review of the literature.Results Among the 15 cases of small cell ALCL,5 were females and 10 were males,with a male-to-female ratio of 2:1.Among the 15 cases of small cell ALCL,14 were systemic ALCL[(12 cases of ALK+),and the age range was 5-63 years old(median age 20 years);There were 2 cases of ALK(-),aged more than 60 years],and 1 case of ALCL of primary cutaneous ALK(-).Microscopic features were dominated by small to medium-sized tumor cells,with irregular nuclear membranes,inconspicuous nucleoli,and a lack of or few iconic large cells.Immunohistochemically:3 cases were ALK-negative and 12 cases were ALK-positive.Tumor cells were CD30 positive in 14/15 cases,CD3 positive in 7/15 cases,CD2 positive in 2/6 cases,CD4 positive in 5/11 cases,CD5 positive in 2/8 cases,CD7 positive in 4/6 cases,CD8 positive in 1/8 cases,TIA-1 positive in 7/7 cases,Granzyme B positive in 4/6 cases and EMA positive in 6/7 cases.CD20 was negative in all cases.Immuno-globulin IgG and TCR gene rearrangement were negative in case 4 and case 11.Case 13 was positive for TCR rear-rangement and negative for immunoglobulin IgG.Twelve of the 15 patients were followed up for 0.7-165 months(me-dian,7 months),3 patients were lost to follow-up and 7 patients died.Conclusion Small cell variant ALCL is easily misdiagnosed as an inflammatory or infectious disease.A group of antibodies,including CD30 and ALK,should be routinely used in routine work,especially in young patients with systemic symptoms and leukemia manifestations or in small biopsies,to reduce misdiagnosis and missed diagnosis.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective To analyze the pharmacological mechanism of Shenling Baizhu powder in the treatment of cancer cachexia based on the network pharmacological method and provide a reference for the clinical application of classical traditional Chinese medicine(TCM) prescriptions. Methods Through TCMSP and BATMAN-TCM databases, the main chemical components and their targets of the TCM prescription of Shenling Baizhu powder were obtained, and the active components of the TCM were screened according to ADME. The main targets of cancer cachexia were obtained through OMIM, Genecards, Disgenet and DRUGBANK databases, and protein interaction analysis was conducted using String platform to build a PPI network. The “drug-active ingredient-target” network of Shenling Baizhu powder was constructed by Cytoscape 3.7.2 software, and then the biological processes and pathways involved were analyzed by using Metascape platform. Finally, molecular docking verification was conducted by Discovery Studio. Results The core active ingredients of Shenling Baizhu powder in the treatment of cancer cachexia were quercetin, kaempferol, pyrolignous acid, stigmasterol, luteolin, β-sitosterol, etc. The core targets were AKT1, TP53, TNF, IL-6, MAPK3, CASP3, JUN, CTNNB1, HIF1A, EGFR, etc. The molecular docking test also showed that the top 10 active ingredients, such as pyrolignous acid, stigmasterol and β-sitosterol, had good binding activities with most of the target sites. The biological pathway of Shenling Baizhu powder in treating cancer cachexia wss mainly to regulate tumor related pathway, metabolism related pathway, inflammatory factors and appetite related pathway. Conclusion This study preliminarily revealed the mechanism of action of Shenling Baizhu powder in treating cancer cachexia with multi components, multi targets and multi pathways, which provided a basis for the clinical development and utilization of Shenling Baizhu powder.

OBJECTIVE To explore the effects and potential mechanism of plumbagin on the inflammatory response and oxidative stress in rats with acute exacerbation of chronic obstructive pulmonary disease （AECOPD） based on Notch1/GATA3 signaling pathway. METHODS Ten rats were randomly selected as the control group； another 65 rats were used to establish the AECOPD model by inhaling cigarette smoke， intratracheal administration of endotoxin， and nasal inoculation of bacteria. The 50 successfully modeled rats were randomly divided into the AECOPD group， plumbagin low-dose group （10 mg/kg）， plumbagin high-dose group （50 mg/kg）， positive control group （dexamethasone 0.09 mg/kg）， and high-dose plumbagin+Jagged1 （Notch1 activator） group （50 mg/kg+25 mg/kg）， with 10 rats in each group. Each group was administrated intragastrically or intraperitoneally with the corresponding drug solution or normal saline， once a day for 28 consecutive days. After the last administration， the lung function indicators （peak expiratory flow， the ratio of forced expiratory volume in 0.3 seconds to forced vital capacity）， the number of inflammatory cells （white blood cells， lymphocytes， neutrophils， macrophages） in bronchoalveolar lavage fluid， the levels of inflammatory factors [interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）] in lung tissue， and the contents of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in lung tissue were all determined in each group； the pathological changes of lung tissue and the pathological scores， as well as protein expressions of mucin 5ac （Muc5ac）， Notch1 and GATA3 in lung tissue were also detected. RESULTS Compared with the control group， the lung tissue of the AECOPD group rats showed severe damage to the alveolar wall structure， with a large number of inflammatory cells infiltration and accompanied by pathological changes such as thickening of the airway wall； their lung function indicators， IL-10 level， and SOD content were significantly decreased； while the number of various inflammatory cells， IL-6 and TNF-α levels， MDA content， pathological score， as well as protein expressions of Muc5ac， Notch1 and GATA3 were significantly increased or upregulated （P＜0.05）. Compared with the AECOPD group， the pathological changes in the lung tissue of the rats in each plumbagin dose group were significantly alleviated， and the above quantitative indicators were significantly improved， and the improvement was more obvious in the plumbagin high- dose group （P＜0.05）. Jagged1 significantly reversed the protective effect of high-dose plumbagin on lung injury and related indicators in AECOPD rats （P＜0.05）. CONCLUSIONS Plumbagin can inhibit the inflammatory response and oxidative stress in the lungs of AECOPD rats， alleviate lung damage， and improve lung function. The above effects may be related to the inhibition of the Notch1/GATA3 signaling pathway.

In recent years,with the continuous advancement of deep space exploration missions,astronauts have been increasingly exposed to complex and extreme environmental factors in space,such as microgravity,space radiation,circadian rhythm disruption,and confined isolation.These conditions can easily induce brain dysfunction in astronauts,manifesting as cognitive decline,emotional disturbances,sleep disorders,and neuroinflammatory responses.Traditional Chinese Medicine(TCM),characterized by its holistic regulation and syndrome differentiation-based treatment principles,exhibits multi-target regulation and systemic coordination,and has attracted growing attention in the field of brain function protection.This study systematically reviews the protective applications and research progress of TCM and related techniques in both actual spaceflight missions and simulated space environment models against brain functional disorders.The underlying mechanisms and future prospects are discussed,with the aim of providing insights for safeguarding astronauts'brain health and laying a theoretical foundation for the precise intervention and systematic protection strategies of TCM in future deep space missions.

In recent years,real-time fluorescence quantitative polymerase chain reaction(qPCR)technology has become an essential tool for molecular diagnosis,pathogen detection,and gene expression analysis,thanks to its high sensitivity,speed,and real-time quantification capabilities.In 2022,the global market size of nucleic acid testing-related products and services,including instruments,reagents,consumables,and after-sales service support,reached 7.3 billion US dollars,with PCR-based technologies accounting for 66.7%of the market share and exhibiting a consistent growth trend.Although qPCR technology has been widely applied across multiple fields,the preclinical development of diagnostic kits—a process that includes primer design and reaction system optimization—still faces such issues as unclear procedures,non-standardized methods,and inconsistent evaluation criteria.Herein,we reviewed the guidelines,key resources,and standardized processes of qPCR assay reagent development,aiming to provide theoretical support for improving the efficiency and quality control of assay reagent development,and to discuss future directions for the optimizing and improving qPCR technology in the context of artificial intelligence.