Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Mitochondrial dysfunction is a critical factor in the pathogenesis of Alzheimer's disease (AD). The mitochondrial contact site and cristae organizing system (MICOS) plays a pivotal role in shaping the inner mitochondrial membrane, forming cristae junctions and establishing interaction sites between the inner and outer mitochondrial membranes and thereby serving as a cornerstone of mitochondrial structure and function. In the past decade, MICOS abnormalities have been extensively linked to AD pathogenesis. In particular, dysregulated expression of MICOS subunits and mutations in MICOS-related genes have been identified in AD, often in association with hallmark pathological features such as amyloid-β plaque accumulation, neurofibrillary tangle formation, and neuronal apoptosis. Furthermore, MICOS subunits interact with several etiologically relevant proteins, significantly influencing AD progression. The intricate crosstalk between these proteins and MICOS subunits underscores the relevance of MICOS dysfunction in AD. Therapeutic strategies targeting MICOS subunits or their interacting proteins may offer novel approaches for AD treatment. In the present review, we introduce current understanding of MICOS structures and functions, highlight MICOS pathogenesis in AD, and summarize the available MICOS-targeting drugs potentially useful for AD.

Acute liver failure (ALF) is a life-threatening condition associated with macrophage-mediated inflammatory responses. Effective therapies and drugs are still lacking to date. Here, we reveal that a derivative of xanthohumol, CAM12203, alleviates lipopolysaccharide (LPS) + d-galactosamine (D-GalN)-induced ALF through limiting macrophage-mediated inflammation, with the most significant impact on interleukin-1β (IL-1β) transcription. Through biotin labeling-mediated pull-down and LC-MS/MS analysis, diacylglycerol kinase ζ (DGKζ), a lipid-metabolizing kinase, is identified as the direct target of CAM12203. Mechanistically, DGKζ is induced in macrophages upon inflammatory stimuli and is upregulated observed on clinical liver failure samples. Its product phosphatidic acid (PA) boosts phospholipase C (PLC)-inositol 1,4,5-trisphosphate (IP₃)-Ca²⁺ signaling and subsequent janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) cascade, ultimately promoting IL-1β production and liver failure. DGKζ knockdown/ablation or inhibition significantly impairs the DGKζ-STAT3-IL-1β pathway along with ALF progression. Finally, CAM12203 is confirmed to be a new DGKζ inhibitor and acts against inflammation in a DGKζ-reliant manner. Taken together, CAM12203 inhibits IL-1β transcription in macrophages by binding to DGKζ and blocking the DGKζ-STAT3 axis, thereby exerting an ameliorative effect on ALF. These results not only highlight CAM12203 as a promising lead compound for ALF treatment, but also define DGKζ as a novel therapeutic target.

As another major measure to accelerate the pace of medical and health system reform and benefit people's health,"one hospital with multiple campuses"has important practical significance for building a high-quality and efficient medical and health service system.How to achieve standardized,high-quality and sustainable multi hospital development,collaborative governance is the key.Based on the perspective of collaborative governance,through the analysis of the difficulties in the construction of"one hospital with multiple campuses",it is found that the positioning of"one hospital with multiple campuses"remains to be clarified,the cost-benefit balance is under pressure,and the collaborative management efficiency is insufficient.It is proposed that the party's leadership should be strengthened,the government's leading responsibility should be implemented,the institutional setting should be strictly standardized,the development scale should be reasonably controlled,the functional positioning objectives should be clear,the dislocation collaborative development should be promoted,the unified operation system should be improved,the management efficiency level should be improved,the talent recruitment mechanism should be optimized,the training and development system and the quality control system should be improved,the medical homogeneous development should be promoted,and the"three relationships"should be comprehensively grasped.

Objective:To explore the differences on contraindication information for children in domestic and foreign drug instructions, and provide reference for improving the relevant information in Chinese drug insert sheets.Methods:Chinese drug insert sheets of chemicals and biological products contained in the China Pharmacopoeia 2020 and those of the western medicines in the 2023 China′s Basic Medical Insurance, Work-related Injury Insurance and Childbirth Insurance Drug Catalog were collected; drugs that were marked as contraindication for children were selected and relevant contraindication information in the Chinese drug insert sheets was collected. Instructions of the above-mentioned drugs approved by the U.S. Food and Drug Administration (English labels) were also collected, and the information on pediatric medication was reviewed and compared with the Chinese drug insert sheets. Results:A total of 222 drugs were labeled as contraindication for children in the Chinese drug insert sheets, of which 149 were available for their English labels; 123 drugs (17.5%) were not labeled as contraindication for children in English labels, and 26 (82.5%) were labeled. The 123 drugs that were not labeled as contraindication for children in the English labels included the following conditions: 58 were labeled as contraindication for children of some age in the Chinese drug insert sheets but not in the English labels, and relevant medication information was provided; 40 were labeled as contraindication for children of some age group in the Chinese drug insert sheets but was described as the effectiveness and safety of the use for children have not yet been determined for this age group in the English labels; 13 were labeled as contraindication for children in the Chinese drug insert sheets, but the medication information on children in the English labels was not clear or missing; 12 were labeled as contraindicated for children in Chinese drug insert sheets but not in the English labels, only expressed as not yet determined or not recommended for use, etc., with inconsistent age group. Among the 26 drugs labeled as contraindication for children in both Chinese and English instructions, the contraindication age group were the same in above 2 instructions for 20 drugs, and were inconsistent for the other 6 drugs; reasons for contraindication were described in both the 2 instructions for 17 drugs (13 were consistent, 4 were inconsistent), only in English labels for 8 drugs, and only in Chinese drug insert sheets for 1 drug.Conclusions:Many drugs are labeled as contraindication for children in Chinese drug insert sheets, but reasons for contraindication are rarely explained. Differences in children′s age in contraindications exist for some drugs between the Chinese drug insert sheets and English labels. The information on contraindications for children in Chinese drug insert sheets still needs to be further improved.

As another major measure to accelerate the pace of medical and health system reform and benefit people's health,"one hospital with multiple campuses"has important practical significance for building a high-quality and efficient medical and health service system.How to achieve standardized,high-quality and sustainable multi hospital development,collaborative governance is the key.Based on the perspective of collaborative governance,through the analysis of the difficulties in the construction of"one hospital with multiple campuses",it is found that the positioning of"one hospital with multiple campuses"remains to be clarified,the cost-benefit balance is under pressure,and the collaborative management efficiency is insufficient.It is proposed that the party's leadership should be strengthened,the government's leading responsibility should be implemented,the institutional setting should be strictly standardized,the development scale should be reasonably controlled,the functional positioning objectives should be clear,the dislocation collaborative development should be promoted,the unified operation system should be improved,the management efficiency level should be improved,the talent recruitment mechanism should be optimized,the training and development system and the quality control system should be improved,the medical homogeneous development should be promoted,and the"three relationships"should be comprehensively grasped.

Objective:To explore the differences on contraindication information for children in domestic and foreign drug instructions, and provide reference for improving the relevant information in Chinese drug insert sheets.Methods:Chinese drug insert sheets of chemicals and biological products contained in the China Pharmacopoeia 2020 and those of the western medicines in the 2023 China′s Basic Medical Insurance, Work-related Injury Insurance and Childbirth Insurance Drug Catalog were collected; drugs that were marked as contraindication for children were selected and relevant contraindication information in the Chinese drug insert sheets was collected. Instructions of the above-mentioned drugs approved by the U.S. Food and Drug Administration (English labels) were also collected, and the information on pediatric medication was reviewed and compared with the Chinese drug insert sheets. Results:A total of 222 drugs were labeled as contraindication for children in the Chinese drug insert sheets, of which 149 were available for their English labels; 123 drugs (17.5%) were not labeled as contraindication for children in English labels, and 26 (82.5%) were labeled. The 123 drugs that were not labeled as contraindication for children in the English labels included the following conditions: 58 were labeled as contraindication for children of some age in the Chinese drug insert sheets but not in the English labels, and relevant medication information was provided; 40 were labeled as contraindication for children of some age group in the Chinese drug insert sheets but was described as the effectiveness and safety of the use for children have not yet been determined for this age group in the English labels; 13 were labeled as contraindication for children in the Chinese drug insert sheets, but the medication information on children in the English labels was not clear or missing; 12 were labeled as contraindicated for children in Chinese drug insert sheets but not in the English labels, only expressed as not yet determined or not recommended for use, etc., with inconsistent age group. Among the 26 drugs labeled as contraindication for children in both Chinese and English instructions, the contraindication age group were the same in above 2 instructions for 20 drugs, and were inconsistent for the other 6 drugs; reasons for contraindication were described in both the 2 instructions for 17 drugs (13 were consistent, 4 were inconsistent), only in English labels for 8 drugs, and only in Chinese drug insert sheets for 1 drug.Conclusions:Many drugs are labeled as contraindication for children in Chinese drug insert sheets, but reasons for contraindication are rarely explained. Differences in children′s age in contraindications exist for some drugs between the Chinese drug insert sheets and English labels. The information on contraindications for children in Chinese drug insert sheets still needs to be further improved.

Objective:To explore differences in the efficacy and safety of ruxolitinib in patients with myelofibrosis by age and to identify prognostic factors by analyzing clinical features and characteristics of chromosomes and gene mutations.Methods:This study retrospectively analyzed 188 patients with myelofibrosis who received ruxolitinib in the Department of Hematology, Qilu Hospital, Shandong University from January 1, 2017, to July 1, 2024. According to age at diagnosis, the patients were divided into the middle-aged group (≤55 years), young elderly group (56-65 years), and elderly group (>65 years). Clinical features, the characteristics of chromosomes and gene mutations, and the efficacy and safety of ruxolitinib treatment were compared across the three age groups. Independent factors influencing overall survival were identified through Cox proportional risk regression analysis.Results:Before treatment, the elderly group had more underlying comorbidities, a heavier symptom burden, higher leukocyte count, higher proportion and frequency of JAK2 mutations, and lower proportion of CALR mutations. The incidence of nondriver gene mutations was significantly higher in the young elderly group. After ruxolitinib treatment, the degree of reduction in spleen size did not differ significantly among the three groups. The length of the palpable spleen below the left costal margin reduced by more than 50% from baseline in 50.9% (27/53) of the patients in the middle-aged group, 43.5% (27/62) in the young elderly group, and 45.5% (20/44) in the elderly group ( P=0.720). No significant difference was observed among the three groups in the degree of reduction in Myeloproliferative Neoplasm Symptom Assessment Form (10-item version) score ( P=0.153), with a reduction in total symptom score by more than 50% achieved by 54.0% (27/50), 60.3% (41/68), and 66.7% (34/51) of the patients from the three groups, respectively ( P=0.429). The most common hematological adverse events were anemia and thrombocytopenia, while the most common nonhematological adverse events were electrolyte disturbance, elevated transaminase activity, and pulmonary infection. Multivariate analysis indicated that in ruxolitinib-treated patients with myelofibrosis, poor overall survival was independently predicted by increased age, reduced hemoglobin, percentage of bone marrow blasts ≥ 1%, absence of JAK2 mutations, chromosomal abnormalities, ≥2 high-molecular-risk mutations, and TP53 mutations. Conclusions:Patients with myelofibrosis stratified by age exhibited heterogeneous clinical features and gene mutation profiles but similar efficacy of ruxolitinib treatment and occurrence of adverse events.

Objective To establish a risk prediction model for the occurrence of venous thromboembolism(VTE)in hospitalized children and to validate the application of the model.Methods Retrospective analysis was conducted on 62 children who developed VTE during hospitalization in our hospital from January 2022 to July 2023 and were selected in a VTE group.In the ratio of 1∶4,248 children from the same department and time who did not develop VTE were selected in a non-VTE group.Logistic regression analysis was used to develop the risk prediction model.Hosmer-Lemeshow test and receiver operator characteristic(ROC)curves were used to test the goodness of fit and predictive effectiveness of the model.Bootstrap self-help method was used for the internal validation of the model by re-sampling the sample l,000 times.Results In our study,the incidence of VTE was 0.43‰.Logistic regression analysis showed that the length of central venous access device(PICC)stay ≥3 d,stay with fully implantable intravenous port,chemotherapy,ICU length of stay ≥4 d,and bracing duration＞72 h were the independent risk factors for the development of VTE in hospitalized children(P＜0.05).Hosmer-Lemeshow test showed that x2=5.291,P=0.152.Sensitivity was 0.857,specificity was 0.218,and area under the R0C curve was 0.823 by Bootstrap self-help method resampling method.Conclusion The risk predictive model of VTE risk in hospitalized children constructed in this study has good predictive performance,which can be used for clinical medical staff to identify children at high risk of VTE at an early stage and take preventive measures.

Prepubertal-type testicular neuroendocrine tumor is a rare neoplasm of low malignant potential, which is classified as germ cell tumors unrelated to germ cell neoplasia in situ, and needs to be differentiated from metastatic neuroendocrine tumor, postpubertal-type testicular neuroendocrine tumor, and testicular seminoma. The clinicopathological and molecular features of a case of prepubertal-type testicular neuroendocrine tumor were reported. The tumour cells were uniform in size and arranged in nested and insular pattern. The tumor was positive for CgA and Syn, and the Ki-67 index was less than 2% by immunostaining. Next-generation sequencing identified no variants of pathogenicity, potential pathogenicity or uncertain significance. The patient was followed without evidence of recurrence and metastasis 56 months after surgery.