Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

Liver cancer is one of the most common malignant tumors in the digestive system and ranks sixth among newly diagnosed malignant tumors worldwide. Transforming growth factor-β （TGF-β） regulates cell differentiation， proliferation， apoptosis， and other physiological and pathological mechanisms and exerts cancer-suppressive and pro-cancerous dual effects in the process of tumor development. In recent years， with the continuous exploration of the mechanism of liver cancer， it has been found that the conversion of the cancer-suppressive effect into a pro-cancerous effect of this pathway plays a key role in the development of liver cancer. Traditional Chinese medicine （TCM） provides a unique perspective for the classification， diagnosis， and treatment of liver cancer with its comprehensive regulatory effects of multi-components， multi-targets， and multi-pathways. This paper summarized that the cancer-suppressive mechanisms of the TGF-β signaling pathway included promoting cancer cell cycle arrest， apoptosis， autophagy， et al， while the pro-cancerous mechanisms included promoting cancer cell proliferation， invasion and metastasis， immunosuppression， angiogenesis， et al. The TCM compounds intervening this pathway were sorted out， including Jianpi Huayu compound， Fuyang Baoyuan compound， Yipi Yanggan compound， Fuzheng Jiedu compound， compound Astragalus and Salvia， Biejia Jianwan， Dahuang Zhechong pill， and Qingxiang powder. The single TCMs mainly included Schizocapsa plantaginea， Dendrobii Caulis， Gleditsia sinensis， and Dracaena cochinchinensis. The active ingredients of TCM are mainly concentrated on flavonoids， alkaloids， glycosides， phenolics， terpenoids， polysaccharides， and other kinds of compounds. At the same time， it summarized that the liver cancer inhibition mechanism of TCM by regulating this pathway mainly included promoting apoptosis of liver cancer cells， blocking the cell cycle， and inhibiting liver cancer cell proliferation， migration， invasion， angiogenesis， immune escape， etc. The mechanism aims to give full play to the advantages of TCM and precisely regulate the TGF-β signal， thereby exerting positive anti-tumor effects， opening up a new direction for the precise targeted treatment of liver cancer， and providing a scientific basis and a new strategy for the application of TCM in the treatment of liver cancer.

OBJECTIVE To investigate the effect of pharmaceutical services guided by root cause analysis （RCA） in a problem-oriented manner combined with knowledge-attitude-practice （KAP） theory on reducing the incidence of protocol violations of investigational medicinal products in pediatric clinical trials. METHODS A total of 617 participants from 69 drug clinical trial projects conducted in our hospital from January 2016 to December 2020 were selected as the control group， and 868 participants from 72 drug clinical trial projects from January 2022 to December 2025 as the observation group. RCA was performed on the protocol violations of investigational medicinal product in the control group to identify the types and underlying causes. The control group received routine pharmaceutical services for drug clinical trials， while the observation group was provided with precision pharmaceutical services from the three dimensions of knowledge， attitude and practice on the basis of routine pharmaceutical services， according to the root causes identified by RCA. The occurrence of investigational medicinal products protocol violations was compared between the two groups. RESULTS The total incidence of protocol violations of investigational medicinal products， as well as the incidences of minor and major protocol violations， were all significantly lower in the observation group than in the control group （ P ＜0.001）. The main types of protocol violations in both groups included missed/under-/over-dosing of medications， non-adherence to administration time， failure to adjust dosage as required， and combined medication/vaccination in violation of the protocol. Regarding the responsible subjects of protocol violations， the incidences of protocol violations attributed to participants and their guardians as well as investigators and accidental factors were significantly lower in the observation group than in the control group （ P ＜0.001， P ＜0.001， P ＝0.025）. However， there were no statistically significant differences in the incidences of protocol violations caused by sponsor-related reasons between the two groups （ P ＞0.05）. CONCLUSIONS Pharmaceutical services led by pharmacists， based on problem-oriented RCA and combined with KAP theory， can effectively reduce the protocol violations of investigational medicinal products rate in pediatric clinical trials， thereby safeguarding the safety and rights of study participants.

Abstract The prevention and control of myopia in Chinese children and adolescents has become a major public health issue. While maintaining increased outdoor activity as a cornerstone intervention, there is an urgent need to explore new complementary approaches that can be effectively implemented in both indoor and outdoor settings. In recent years, environmental spatial frequency has gained increasing attention as one of the key environmental factors influencing the development and progression of myopia. Both animal studies and human research have confirmed that indoor environments lacking mid to high spatial frequency components, often characterized as "visually impoverished", can promote axial elongation and myopia through mechanisms such as disruption of retinal neural signaling, impaired accommodative function, and altered expression of related molecules. Based on the scientific consensus, it is recommended that "enriching of environmental spatial frequency" should be integrated into the myopia prevention and control framework. Following the principles of schoolled organization, family cooperation, community involvement, and student participation, specific measures are put forward in three areas：optimizing school visual settings, improving home spatial environments, and promoting healthy visual behavior. The aim is to create "visually friendly" indoor environments as an important supplement to outdoor activity, thereby providing a novel perspective and strategy for comprehensively advancing myopia prevention and control among children and adolescents.

This paper systematically elaborates on the key points of diagnosis and differential diagnosis of salivary gland tumors characterized by a substantial amount of extracellular mucus as a main or prominent feature, and clarifies the core differential features. The term "mucus-rich" specifically denotes that mucus is a major component of the tumor, rather than a focal or minor one. This phenomenon is associated with distinct histogenetic mechanisms: it may result from specific genetic mutations (e.g., AKT1 E17K in mucinous adenocarcinoma) that drive ductal epithelial differentiation into mucus-secreting cells, or from myoepithelial cells secreting glycosaminoglycans that form a myxoid stroma. Salivary gland tumors with abundant extracellular mucus include mucinous cystadenoma, sialadenoma papilliferum-like intraductal papillary tumors, mucinous myoepithelioma, pleomorphic adenoma with mucin-rich stroma, mucinous adenocarcinoma, low-grade mucoepidermoid carcinoma, mucin-rich salivary duct carcinoma and intestinal-type adenocarcinoma. The diagnosis of these tumors is complicated by the dual nature of extracellular mucus: while it is a defining feature of some entities, it can also obscure key diagnostic architectural features in others, leading to histological overlap and inconspicuous diagnostic areas. Given the frequent histological morphological overlap among these tumors, immunohistochemical findings and molecular characteristics have emerged as crucial differential diagnostic criteria. Core differential diagnostic points include the following: histologically, there must be meticulous identification of typical structures obscured by mucin (such as squamoid cells in mucoepidermoid carcinoma and apocrine features in salivary duct carcinoma); in immunohistochemical staining, CK20 is useful for distinguishing intestinal-type adenocarcinoma (positive) from mucinous adenocarcinoma (negative), while androgen receptor aids in differentiating salivary duct carcinoma (positive) from mucoepidermoid carcinoma (negative); and molecular testing plays a critical role in definitive diagnosis (e.g., the AKT1 E17K mutation for mucinous adenocarcinoma, MAML2 rearrangement for mucoepidermoid carcinoma, and MEF2C::SS18 fusion for microsecretory adenocarcinoma). This paper systematically summarizes the core pathological features and differential diagnostic points of mucin-rich salivary gland tumors, aiming to provide a practical reference for clinical pathological diagnosis.

Objective To develop an exercise rehabilitation program for the patients with upper limb lymphedema in order to provide standardised guidance for specialised management and nursing practice,and to promote the recovery of patients.Methods With the evidence-based methods,domestic and international literaturs were retrieved and the quality of the papers was evaluated.A research team was established to discuss and draft an initial version of the rehabilitation program for the patients with upper limb lymphedema.Delphi method was used to conduct two rounds of consultation with 15 experts in lymphedema between June and September 2023.According to the expert opinions,the exercise rehabilitation program for patients with upper limb lymphedema was finalised after screening and modification of the indicators.Results The final version of the exercise rehabilitation program for patients with upper limb lymphedema includes four tier-1 indicators(routine upper limb rehabilitation exercises,aerobic exercise,anti-resistance exercise and respiratory training),15 tier-2 indicators,and 33 tier-3 indicators.The positive response rate in both rounds of expert consultation was 100.00%,with the authority coefficient at 0.95.In the second round of expert consultation,it was founds that the importance of tier-3 indicators was from 3.93 to 5.00,with the rationality from 4.13 to 5.00 and the feasibility from 3.53 to 4.93.The coefficient of variation in tier-1 and tier-2 indicators was 0.00-0.17 and 0.07-0.23,respectively.The coefficients of variation of per tier-3 indicator in importance,rationality and feasibility were from 0.00 to 0.22,0.00 to 0.22 and 0.05 to 0.22,respectively.The Kendall's coefficient of concordance(W)for tier-1 and tier-2 indicators was 0.490 and 0.387,respectively.The Kendall's W of per tier-3 indicator in importance,rationality and feasibility was 0.427,0.311 and 0.530,respectively,with statistically significant differences(P<0.001).Conclusion The exercise rehabilitation program developed in this study is scientific,comprehensive and highly targeted.It provides a theoretical basis and practical guidance for exercise rehabilitation and nursing care of the patients with upper limb lymphedema.

Objective:To evaluate the efficacy and safety of rivaroxaban and investigate the clinical features of Mycoplasma pneumoniae pneumonia (MPP) associated with pulmonary thromboembolism (PTE) in children. Methods:A case series study was conducted on 36 children, diagnosed with MPP associated with PTE and hospitalized in our institution from January 2020 to June 2024 of Department of Pediatric Respiratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University. Clinical data and follow-up information were collected to analyze their clinical characteristics, outcomes, and adverse events to rivaroxaban. Comparison of coagulation indices before and after treatment with rivaroxaban using the Mann-Whitney rank sum test.Results:Among the 36 children, there were 27 males and 9 females, and the age of onset was (7.8±2.8) years. PTE was diagnosed (17±6) days after the onset of MPP. Thirty-four cases (94%) were classified as low-risk PTE, and 13 cases (36%) had thromboembolism of multiple anatomic sites. All patients presented with cough and fever, manifesting as shortness of breath in 33 cases (92%), chest pain in 12 case (33%), hemoptysis in 6 case (17%) and dyspnea in 5 cases (14%). Pulmonary artery involvement was demonstrated by CT pulmonary angiography in all 36 children. The D-dimer level was 5.1 (4.2, 12.2) mg/L. D-dimer levels were 5.1 (4.2, 12.2) mg/L, of which 29 cases (81%) were ≥4.0 mg/L. The total duration of anticoagulation 3.1 (2.5, 4.2) months. All children received rivaroxaban for 2.7 (2.2, 3.8) months. Of the 36 children, 35 cases were followed up after 3 months of anticoagulant therapy, and 30 cases (83%) showed pulmonary artery thrombus absorption. Finally, follow-up outcome data were available for 34 cases, of which 33 showed complete resolution of thrombus in the affected areas, and 1 showed partial resolution. There were no cases of death, thrombus recurrence or progression, major bleeding events occurred or chronic thromboembolic pulmonary hypertension. Adverse events included hemoptysis in 2 cases and elevated liver enzymes in 4 cases. After the treatment of rivaroxaban, the levels of D-dimer were decreased compared with those before the treatment of PTE (0.3 (0.2, 0.5) vs. 5.1 (4.2, 12.2) mg/L, Z=-7.12, P<0.05), and the levels of prothrombin time levels were significantly longer compared with those before the treatment of PTE (3.6 (12.4, 14.9) vs. 13.0 (11.8, 13.6) s, Z=2.34, P<0.05). Conclusions:During the course of MPP, the emergence of clinical symptoms such as short of breath, chest pain, hemoptysis, dyspnea or along with elevated D-dimer levels, should raise suspicion for the occurrence of PTE. Rivaroxaban has shown good efficacy and a favorable safety profile.

Objective:To investigate the clinical manifestations, therapeutic strategies and prognostic outcomes in pediatric patients with severe Mycoplasma pneumoniae pneumonia (SMPP) complicated by cardiac thrombosis. Methods:This case series study retrospectively analyzed 15 pediatric patients with SMPP complicated by cardiac thrombosis. The patients was recruited from the Department of Pediatric Respiratory Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University between July 2018 and January 2025. Comprehensive clinical data and follow-up information were collected.Results:Among the 15 children, 10 were male and 5 were female, and the age of onset was 8.0 (6.3, 10.0) years. All 15 children presented with fever and cough, while additional symptoms included dyspnea in 7 cases, chest pain in 6 cases, hemoptysis in 3 cases, and chest tightness in 1 case. The white blood cell count was 11.7 (9.5, 15.9)×10 9/L, C-reactive protein was 31.6 (17.5, 64.8) mg/L and lactate dehydrogenase was 548.2 (410.4, 768.3) U/L. A total of 14 children underwent testing for the Mycoplasma pneumoniae drug resistance genes 2063A>G and 2064A>G, of which 13 tested positive. The plasma D-dimer levels of 15 children were 8.77 (7.23, 12.50) mg/L, all of which were higher than normal. Among the 15 children, 5 had decreased activity of anticoagulant proteins (protein C, protein S, antithrombin Ⅲ), and 8 tested positive for antiphospholipid antibodies. Chest CT scans of all 15 children showed pulmonary consolidation and (or) atelectasis, with pleural effusion present in 12 cases. In the 15 children, thrombosis was detected at 14.0 (11.0, 18.0) days after the onset of illness. The locations of cardiac thrombosis included the right ventricle in 9 cases, the right atrium in 5 cases, and the left atrium in 1 case. Additionally, 10 cases had pulmonary vascular embolism, comprising 9 cases of pulmonary artery thrombosis and 1 case of pulmonary vein thrombosis. After anticoagulant treatment, cardiac thrombi disappeared in 10 children. Five children who did not show improvement with anticoagulation underwent surgical thrombectomy. In the follow-up of 15 children, lung imaging basically returned to normal, with no major hemorrhagic events or other adverse events. Conclusions:In children with Mycoplasma pneumoniae pneumonia, the presence of clinical symptoms such as shortness of breath, chest pain and hemoptysis, along with elevated plasma D-dimer levels, should raise suspicion for the possibility of cardiac thrombosis. SMPP complicated by cardiac thrombosis, prognosis is good following anticoagulation or surgical treatment.

Objective:This study starts from the main problems existing in the current stage of the development of pediatric clinical research in China and focuses on the construction of a clinical research management system. By innovating the platform management model and enhancing personnel skills, we can provide support and assurance for improving the clinical research platform and its sustainable development in the future.Methods:This study established an integrated management platform for Industry-Sponsored Initiated Clinical Research Trial (IST) and Investigator Initiated Clinical Research (IIT) and implement integrated management of IST and IIT projects. At the same time, in response to the weak links in quality management, synchronous training of management and research talents should be implemented to achieve dual improvement in project management quality and platform service efficiency throughout the process.Results:We had optimized the clinical research organization structure, improved the management system, and strengthened the quality supervision of IIT projects by establishing rules and systems to improve the quality and efficiency of project management.Conclusions:Based on analyzing the current situation in China and referring to international experience, we have built a clinical research management platform in line with the development of the hospital, and implemented centralized management of the entire process of IST and IIT projects, strengthened project process quality control, which is expected to provide a reference for peers.

Objective To construct a health management information service platform for glaucoma patients to achieve continuous care.Methods The architecture of the health management information service platform for glaucoma patients was designed,and the platform was developed and implemented.Results A WeChat mini program-based health management information service platform was developed,consisting of a medical staff interface,a patient interface,and a backend management center.The platform integrates functions such as whole-process disease tracking,surgical management,medication and follow-up record-keeping with reminders,communication for follow-ups,and health education.From March 2021 to March 2024,the platform registered 2764 patients and 45 medical staff,with a total of 10 947 platform interactions.An overall assessment with the post-study system usability questionnaire yielded a mean score of 28.2,indicating good user experience.Conclusion This platform realizes closed-loop management for continuous care of glaucoma patients and provides a practical reference for the development and exploration of health management information service platforms.