Ethical review represents the core of the scientific and technological ethical governance， and its quality depends on the participation of ethics. The absence of ethics and ethical experts will compromise the quality of the review. According to the spirit of the Guidelines on Strengthening the Governance over Ethics in Science and Technology， this paper analyzed the process of separating scientific and technological ethics from the field of scientific research morality， clarified the ethical attributes of ethical review， and argued that scientific research and technological innovation activities originated from ethics. On this basis， the fundamental principle of “ethics first” was proposed， aiming to proactively embed ethical considerations throughout the entire process of scientific and technological activities. This principle was the primary requirement for ensuring governance effectiveness and can also eliminate the risk of ethics being obscured in ethical governance. In practice， “ethics first” manifested specifically in dimensions such as prioritizing academic systems， prioritizing publicity， education， and training， as well as further advancing ethical considerations.

OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

Objective: To investigate the mechanism of shed syndecan-4 (sSDC4) in temporomandibular joint osteoarthritis (TMJOA) in rats, aiming to provide experimental evidence for its prevention and treatment. Methods: This study was approved by the Institutional Animal Ethics Committee. Twelve 6-week-old female Sprague Dawley (SD) rats were randomly divided into two groups. They received a single intra-articular injection into the bilateral superior cavity of temporomandibular joint, which consisted of either 50 μL of 4 mg/mL monosodium iodoacetate (TMJOA model group) or 50 μL of phosphate-buffered saline (PBS, control group). After 4 weeks, the mandibular condylar cartilage was harvested for hematoxylin & eosin (H&E) staining, Safranin O-fast green (SO) staining, and type II collagen (Col-Ⅱ) immunohistochemical staining to assess the degree of cartilage degeneration. The synovium of the temporomandibular joint was collected for immunohistochemical staining to detect the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) to evaluate the degree of synovial inflammation. Synovial fluid from the temporomandibular joint cavity was collected to measure sSDC4 levels by enzyme-linked immunosorbent assay (ELISA). In addition, 12 6-week-old female SD rats were randomly divided into a His-SDC4 group and a control group, receiving injections into the bilateral superior cavity of temporomandibular joint of either 100 ng/mL (50 μL) of His-SDC4 protein or 50 μL of PBS once every 3 days for a total of 28 days. The same experimental procedures were performed for H&E staining, SO staining, and immunohistochemical staining (Col-Ⅱ IL-6, TNF-α) to observe condylar cartilage degeneration and detect synovial inflammation. Rat synovial fibroblasts and condylar chondrocytes were cultured in vitro and randomly divided into a His-SDC4-stimulated (10 ng/mL) group and control group. Perform CCK-8 cytotoxicity assays and observe cellular morphology under optical microscopy, the mRNA expression levels of IL-6 and TNF-α were detected by real-time quantitative polymerase chain reaction (RT-qPCR), and the levels of IL-6 and TNF-α in cell culture supernatants were measured by ELISA. Results: Compared with the control group, the TMJOA group showed decreased condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area (all P<0.001); an increased synovitis score (P<0.001) and increased percentages of IL-6- and TNF-α-positive cells in the synovium (all P<0.001); and a significant increase in sSDC4 levels in the synovial fluid (P=0.011). Following intra-articular injection of His-SDC4, condylar cartilage thickness, percentage of SO-positive area, and percentage of Col-Ⅱ-positive area all decreased (all P<0.001); the synovitis score increased (P=0.006), and the percentages of IL-6- and TNF-α-positive cells in the synovium increased (all P<0.001). In vitro experiments showed that His-SDC4 stimulation significantly upregulated the expression levels of IL-6 and TNF-α in both synovial fibroblasts and condylar chondrocytes (all P<0.01), and the levels of these two cytokines in the culture supernatants also significantly increased (all P<0.01). Conclusion During TMJOA progression, the level of sSDC4 in the synovial fluid is significantly elevated, which can directly stimulate synovial fibroblasts and condylar chondrocytes to secrete more pro-inflammatory cytokines, forming a vicious cycle that accelerates TMJOA progression.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

Objective: To define the mechanism by which swine TRIM25 restricts vesicular stomatitis virus replication. Methods: Porcine 3D4/21 cells with TRIM25 overexpression or knockdown were infected with vesicular stomatitis virus. Viral replication was quantified by immunoblotting, quantitative reverse transcription polymerase chain reaction, and 50% tissue culture infectious dose assays. Type I interferon signaling was assessed by transcript quantification, interferon-beta and interferon-stimulated response element reporter assays, and co-immunoprecipitation.Viral RNA binding was tested by RNA immunoprecipitation. Results: TRIM25 overexpression reduced viral RNA and infectious titers, whereas TRIM25 knockdown increased replication (p < 0.01). TRIM25 increased interferon-beta and interferon-stimulated gene expression and enhanced interferon-beta and interferonstimulated response element promoter activity (p < 0.01). Mechanistically, TRIM25 promoted Lys63-linked ubiquitination of RIG-I and increased phosphorylation of TANK-binding kinase 1 and interferon regulatory factor 3. TRIM25 also bound vesicular stomatitis virus genomic RNA, and binding required the C-terminal region. Conclusions and Relevance: Porcine TRIM25 restricts vesicular stomatitis virus replication by amplifying type I interferon signaling and directly binding viral RNA.

Objective This study conducted molecular biological identification of the viruses carried by Culex pipiens pallens specimens collected in Shunyi District, Beijing in 2023, and observed the changes in the infection rate of the viruses carried by Cx. pipiens pallens at different collection times. Methods Cx. pipiens pallens were collected using carbon dioxide mosquito traps. The mosquito samples were ground in batches and analyzed by molecular biology technologies. The virus infection rate at different collection times was analyzed statistically. Results 17 strains of Culex pipiens pallens densovirus(CppDNV)were identified from Cx. pipiens pallens samples collected in Shunyi District, Beijing, in 2023. The nucleotide sequence analysis of the virus genome coding region showed that CppDNV was a single-stranded DNA virus with a total length of 3 335 nt, encoding 2 non-structural proteins(NS1, NS2)and 1 capsid protein(VP). The nucleotide(amino acid)sequence lengths of the three proteins were 2 376 nt(791 aa),1 092 nt(363 aa)and 1 071 nt(356 aa), respectively. Phylogenetic analysis showed that CppDNV was located in genus Brevihamaparvovirus. Statistical analysis showed no significant difference in infection rates across collection times(χ2=4.429, P=0.194). Conclusions CppDNV was identified in Cx. pipiens pallens in Beijing, and it was stably maintained in this natural population.

Skeletal muscle atrophy refers to a pathological condition characterized by muscle fiber atrophy as well as decreased muscle mass and muscle strength induced by various predisposing factors. It falls under the category of “flaccidity syndrome” in traditional Chinese medicine， and its pathogenesis is mainly associated with disturbed protein homeostasis， mitochondrial dysfunction and oxidative stress injury. Active ingredients of traditional Chinese medicine exerts synergistic regulatory effects via multiple pathways， thus possessing unique advantages in the clinical prevention and treatment of skeletal muscle atrophy. This paper reviews the mechanisms by which active ingredients of traditional Chinese medicine alleviate skeletal muscle atrophy. Existing studies have demonstrated that such active ingredients can ameliorate skeletal muscle atrophy through multiple approaches： regulating protein metabolic balance （geniposide， matrine， schisandrin A， etc.） and oxidative stress （astragaloside Ⅳ， Gastrodia elata polysaccharide， Angelica sinensis polysaccharide， etc.）， improving mitochondrial function （parthenolide， berberine， curcumin， etc.）， facilitating myogenesis and myogenic differentiation （cucurbitacin Ⅱb， saikosaponin A， saikosaponin D， etc.）， suppressing inflammatory response （ursolic acid， triptolide， emodin， etc.）， ameliorating insulin resistance （akebiasaponin D， etc.）. In the future， active ingredients of traditional Chinese medicine are expected to achieve breakthroughs in clinical treatment for skeletal muscle atrophy， providing novel ideas and strategies for the prevention and treatment of degenerative disorders.

Objective To systematically evaluate the efficacy and safety of pyrotinib-based therapy in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer based on real-world data, and to explore factors associated with prognosis. Methods A total of 102 patients with HER2-positive advanced breast cancer who received pyrotinib at Zhongshan Hospital, Fudan University, were included retrospectively from January 1, 2019, to January 31, 2024, and prospectively from February 1, 2024, to November 30, 2025. Follow-up was conducted until March 31, 2026. Clinical and follow-up data of the patients were collected, and survival analysis was performed by Kaplan-Meier method. Prognostic factors were analyzed through multivariable Cox regression and logistic regression. Results Among the 102 patients, the median follow-up duration was 31.3 months, the median progression-free survival (PFS) was 12.9 months, the median overall survival (OS) has not been reached (estimated to be 64.8 months), and the objective response rate (ORR) was 35.29%. Multivariate Cox regression analysis revealed that lung metastasis (HR＝2.562，P＝0.006), third-line and subsequent treatment (HR＝3.857，P＝0.010), and pyrotinib monotherapy (HR＝3.682，P＝0.015) were associated with shorter PFS. Eastern Cooperative Oncology Group performance status (ECOG PS)≥2 (HR＝16.948，P＜0.001) and third-line and subsequent treatment (HR＝3.958，P＝0.034) were associated with shorter OS. No associated factors related to ORR were found. Regarding safety, diarrhea was the most common adverse event, occurring in 74.51% of patients. Conclusions In real-world clinical practice, pyrotinib-based therapy demonstrated clinical efficacy and manageable safety in patients with HER2-positive advanced breast cancer. Lung metastasis, pyrotinib monotherapy, ECOG PS≥2, and pyrotinib administration in multiple lines of therapy may affect patient prognosis.

Objective To explore the correlation of bilateral knee joint strength asymmetry with balance,walking ability,and motor function in hemiplegic stroke patients,providing a reference for clinical assessment of stroke patients.Methods A total of 46 hemiplegic stroke patients admitted to the Rehabilitation Medicine Department of People's Hospital of Shijiazhuang from February to December 2023 were selected.According to the Berg Balance Scale(BBS)scores,patients were divided into Group A(BBS score≤20,n=23)and Group B(BBS score>20,n=23).The peak torque and differences of bilateral knee flexors and extensors were compared between two groups.Isokinetic technology was used to assess the differences in peak torque of bilateral knee joints at 60°/s and 120°/s.BBS,Functional Ambulation Classification(FAC),and Fugl-Meyer Assessment of Lower Extremity(FMA-LE)were used to evaluate patients'balance,walking ability,and lower limb motor function.The correlation between bilateral knee joint peak torque and its difference with the scores of three functional scales was analyzed.Results The peak torque of knee flexors and extensors at 60°/s in group A was significantly lower than that in group B(P<0.05).At both 60°/s and 120°/s the differences in peak torque between the healthy and affected sides of knee flexors and extensors were greater than those in group B(P<0.05).At 60°/s,the difference in peak torque of bilateral knee extensors in hemiplegic stroke patients was negatively correlated with the scores of BBS,FAC,and FMA-LE(r=-0.569,-0.582,-0.606,P<0.01),as did the knee flexors(r=-0.534,-0.386,-0.458,P<0.05).At 120°/s,similar negative correlations were observed for both knee extensors(r=-0.304,-0.304,-0.443,P<0.05)and flexors(r=-0.337,-0.349,-0.370,P<0.05).Conclusions Bilateral knee joint strength asymmetry in hemiplegic stroke patients is negatively correlated with balance and walking ability.The difference in strength between the two sides of knee joint may be one of the clinical indicators for evaluating the motor function of stroke patients.

Objective:To investigate the effect of insulin-like growth factor 1 (IGF-1) on acute lung injury in septic mice and its underlying molecular mechanism.Methods:Twenty SPF male C57BL/6J mice aged 6-8 weeks were randomly (random number) divided into the sham-operated group, sham-operated + IGF-1 group, sepsis group and sepsis + IGF-1 group, with 5 mice in each group. IGF-1 [60 μg/(kg·d)] was injected via the tail vein for 3 consecutive days in the sham-operated + IGF-1 group and sepsis + IGF-1 group, and mice in the sham-operated group and sepsis group were injected with an equal volume of saline. The tissue of the upper lobe of the right lung was taken to calculate the wet-to-dry ratio, and the upper lobe of the left lung was subjected to HE staining to analyze pathological changes and evaluate lung injury. The levels of interleukin (IL)-6 and IL-1β in the bronchoalveolar lavage fluid (BALF) and serum of mice were detected by ELISA. The expression of p-PI3K, PI3K, p-AKT and AKT in lung tissues was determined via Western blotting. The quantitative data with a normal distribution and homogeneity of variance were compared between the two groups by two independent sample t test. Results:Lung volume was reduced in the sepsis group than in the sham-operated group, obvious surface congestion, dark red color, large bruises and hemorrhagic foci were observed under the pericardium, and the wet-to-dry ratio was significantly elevated ( P<0.05). Compared with the sepsis group, the sepsis + IGF-1 group had slightly increased lung volume, less congestion, darker red color, fewer bruises and hemorrhagic foci, and a lower wet-to-dry ratio ( P<0.05). There was no significant change in lung tissue morphology in the sham-operated + IGF-1 group compared with the sham-operated group. HE staining and lung histopathological scores showed that lung tissue was significantly damaged in the sepsis group than the sham-operated group ( P<0.001), and the pathological score of lung tissue was less damaged in the sepsis + IGF-1 group compared with the sepsis group ( P<0.01). The ELISA results demonstrated that the serum levels of IL-6 and IL-1β were markedly decreased in the sepsis + IGF-1 group than in the sepsis group [(26.22±1.60) pg/mL vs. (45.61±7.85) pg/mL, P<0.05; (87.99±11.80) pg/mL vs. (181.26±10.11) pg/mL, P<0.001]. Moreover, the IL-6 and IL-1β contents in the BALF of the sepsis + IGF-1 group were notably lower than those in the BALF of the sepsis group [(7.67±0.42) pg/mL vs. (20.25±0.43) pg/mL, P<0.001; (17.00±6.08) pg/mL vs. (108.61±5.18), pg/mL P <0.001]. Western blot analysis revealed that the expression of p-PI3K, PI3K, p-AKT and AKT in the lung tissues of mice in the sepsis+IGF-1 group were markedly lower than that in the sepsis group [(0.71±0.05) vs. (1.21±0.09), P<0.05; (0.57±0.08) vs. (1.24±0.22), P<0.01; (0.29±0.07) vs. (1.10±0.04), P<0.001; (0.65±0.17) vs. (1.19±0.07), P<0.01]. Conclusion:IGF-1 ameliorates sepsis-induced acute lung injury in mice, and its protective effect may be achieved by inhibiting the PI3K/AKT pathway.