Objective: The effects and molecular mechanisms of micheliolide on cytokine expression in myeloproliferative neoplasm cell lines were explored based on the signal transducer and activator of transcription 3 (STAT3)/nuclear factor-kappa B (NF-κB) signaling pathways. Methods: The UKE-1 and SET-2 cell lines were investigated, and micheliolide concentrations were screened using the CCK-8 assay. The UKE-1 and SET-2 cells were divided into the control and micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Each group received 1 mL of micheliolide solution at final concentrations of 2.5, 5.0, and 10.0 μmol/L, respectively, whereas the control group only received an equal volume of culture medium. The inhibition rates of interleukin-1β(IL-1β), tumor necrosis factor-α (TNF-α), and chemokine ligand 2 (CCL2) mRNA expression in cells from each group were detected using real-time fluorescent PCR (RT-PCR). Western blotting was used to measure STAT3 and phosphorylated STAT3 (p-STAT3) protein expression levels in cells from each group. Reversal experiments with reduced glutathione and dithiothreitol were performed using UKE-1 cells, which were divided into the control group, micheliolide, micheliolide + glutathione, micheliolide + dithiothreitol, and glutathione + dithiothreitol groups. Western blotting was used to detect the STAT3 and p-STAT3 protein expression levels in the cells of each group. UKE-1 cells were stimulated with TNF-α (5 μg/L) to replicate a pathological model of excessive cytokine secretion. Subsequently, UKE-1 cells were divided into the control, model, and three micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. RT-PCR was used to measure the indicators above. An enzyme-linked immunosorbent assay (ELISA) was used to detect the CCL2 content in the cell culture media of each group. Western blotting was performed to assess the protein expression levels of STAT3, p-STAT3, and proteins related to the NF-κB signaling pathway. Results: Compared with the control group, the proliferation inhibition rates of UKE-1 cells at 24, 48, and 72 h increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, 10.0, and 20.0 μmol/L. Similarly, the proliferation inhibition rates of SET-2 at 48 and 72 h increased in the micheliolide-treated groups at concentrations of 5.0, 10.0, and 20.0 μmol/L (P<0.05). Concentrations of 2.5, 5.0, and 10.0 μmol/L were selected for further studies to exclude the potential influence of high micheliolide concentrations on subsequent result owing to reduced cell numbers. Compared with the control group, the inhibition rates of TNF-α mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L. Similarly, the inhibition rates of IL-1β mRNA expression in UKE-1 and SET-2 cells also increased in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L. Additionally, the inhibition rate of CCL2 mRNA expression in UKE-1 and SET-2 cells increased in the micheliolide-treated group at a concentration of 10 μmol/L (P<0.05). Compared with the model group, the inhibition rates of TNF-α, IL-1β, and CCL2 mRNA expression in UKE-1 cells increased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L after stimulation with TNF-α (P<0.05). ELISA showed that compared with the control group, the CCL2 content in UKE-1 cells increased in the model group. Compared with the model group, the CCL2 content in UKE-1 cells decreased in the micheliolide-treated groups at concentrations of 2.5, 5.0, and 10.0 μmol/L (P<0.05). Western blotting showed that compared with the control group, the p-STAT3 protein expression levels in UKE-1 and SET-2 cells were downregulated in the micheliolide-treated groups at concentrations of 5.0 and 10.0 μmol/L, and the protein expression level of STAT3 in SET-2 was also downregulated (P<0.05). Compared with the control group, the p-STAT3 expression level in UKE-1 cells decreased in the micheliolide group in the reductive glutathione and dithiothreitol reversal experiments. Compared with the micheliolide group, the p-STAT3 protein expression levels in UKE-1 cells increased in the micheliolide + dithiothreitol and micheliolide + glutathione groups (P<0.05). Compared with the control group, the model group showed increased p-STAT3, p-IκKα/β, p-IκBα, and p-NF-κB p65 protein expression and decreased IκBα protein expression after stimulation with TNF-α. Compared with the model group, the micheliolide-treated groups showed decreased p-IκKα/β, p-IκBα, p-STAT3, and p-NF-κB p65 protein expression at concentrations of 2.5, 5.0, and 10.0 μmol/L, whereas the micheliolide-treated groups showed increased IκBα protein expression at concentrations of 5.0 and 10.0 μmol/L (P<0.05). Conclusion Micheliolide potently suppresses IL-1β, TNF-α, and CCL2 mRNA expression in UKE-1 and SET-2 cells, as well as CCL2 secretion by UKE-1 cells, which may be associated with STAT3 phosphorylation suppression and NF-κB signaling pathway activation.

Objective:To investigate the efficacy and safety of combining venetoclax (VEN) with hypomethylated drugs (HMA) in the treatment of higher-risk (IPSS-R score >3.5) myelodysplastic syndromes (MDS) .Methods:From March 2021 to December 2022, forty-five MDS patients with intermediate and high risk were treated with VEN in combination with HMAs. Clinical data were collected and analyzed retrospectively, including gender, age, MDS subtype, IPSS-R score, treatment regimen, and efficacy, etc. Kaplan-Meier method and Cox regression model were used to analyze univariate and multivariate of survival prognosis.Results:①Forty-five patients with MDS, including ninety-one percent were classified as high or very high risk. According to the 2023 consensus proposal for revised International Working Group response criteria for higher-risk MDS, the overall response rate (ORR) was 62.2% (28/45), with the complete response rate (CR) was 33.3% (15/45). For twenty-five na?ve MDS, the ORR was 68% (17/25) and the CR rate was 32% (8/25). In nonfirst-line patients, the ORR and CR were 55% (11/20) and 35% (7/20) respectively. The median cycle to best response was 1 (1-4). ②With a median followup of 189 days, the median overall survival (OS) time was 499 (95% confidence interval, 287-711) days, and most patients died from disease progression. Responders had a significantly better median OS time than nonresponders (499 days vs 228 days, P<0.001). Multifactor analysis revealed that IPSS-R score and response to treatment were independent prognostic factors for OS; the presence of SETBP1 gene mutations was associated with a longer hospital stay (51.5 days vs 27 days, P=0.017) . Conclusions:There is clinical benefit of venetoclax in combination with hypomethylated agents in patients with higher-risk MDS, but adverse events such as severe hypocytopenia during treatment should be avoided.

Objective:To analyze the clinical characteristics and prognosis of patients with myelodysplastic syndrome (MDS) with a bone marrow nucleated erythroid cell proportion of greater than or equal to 50% (MDS-E) .Methods:The clinical characteristics and prognostic factors of patients with MDS-E were retrospectively analyzed by collecting the case data of 1 436 newly treated patients with MDS diagnosed in the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from May 2014 to June 2023.Results:A total of 1 436 newly diagnosed patients with complete data were included in the study, of which 337 (23.5%) patients with MDS-E had a younger age of onset and lower neutrophil and platelet counts compared with those in patients with an erythroid cell proportion of less than 50% (MDS-NE) (all P<0.05). The proportion of MDS cases with ring sideroblasts (MDS-RS) was higher in the MDS-E group than in the MDS-NE group, and multi-hit TP53 mutations were more enriched in the MDS-E group than in the MDS-NE group (all P<0.05). Among patients with MDS-RS, the frequency of complex karyotypes and the TP53 mutation rate were significantly lower in the MDS-E group than in the MDS-NE group (0 vs 11.9%, P=0.048 and 2.4% vs 15.1%, P=0.053, respectively). Among patients with TP53 mutations, the frequencies of complex karyotypes and multi-hit TP53 mutations were significantly higher in the MDS-E group than in the MDS-NE group (87.5% vs 64.6%, P=0.003 and 84.0% vs 54.2%, P<0.001, respectively). Survival analysis of patients with MDS-RS found that the overall survival (OS) in the MDS-E group was better than that in the MDS-NE group [not reached vs 63 (95% CI 53.3-72.7) months, P=0.029]. Among patients with TP53 mutations and excess blasts, the OS in the MDS-E group was worse than that in the MDS-NE group [6 (95% CI 2.2-9.8) months vs 12 (95% CI 8.9-15.1) months, P=0.022]. Multivariate analysis showed that age of ≥65 years ( HR=2.47, 95% CI 1.43-4.26, P=0.001), mean corpuscular volume (MCV) of ≤100 fl ( HR=2.62, 95% CI 1.54-4.47, P<0.001), and TP53 mutation ( HR=2.31, 95% CI 1.29-4.12, P=0.005) were poor prognostic factors independent of the Revised International Prognostic Scoring System (IPSS-R) prognosis stratification in patients with MDS-E. Conclusion:Among patients with MDS-RS, MDS-E was strongly associated with a lower proportion of complex karyotypes and TP53 mutations, and the OS in the MDS-E group was longer than that in the MDS-NE group. Among patients with TP53 mutations, MDS-E was strongly associated with complex karyotypes and multi-hit TP53 mutations, and among TP53-mutated patients with excess blasts, the OS in the MDS-E group was shorter than that in the MDS-NE group. Age of ≥65 years, MCV of ≤100 fl, and TP53 mutation were independent adverse prognostic factors affecting OS in patients with MDS-E.

Objective:To investigate the major considerations of domestic orthopaedic trauma surgeons in China when they diagnose and treat Mason type Ⅱ radial head fractures.Methods:A questionnaire survey was conducted from January 15, 2022 to January 16, 2022 using the convenience sampling method among domestic orthopedic trauma surgeons in China. The survey covered the surgeons' basic information, evaluation of Mason type Ⅱ radial head fractures, treatment preferences, and surgical indications recognized.Results:The present survey retrieved 474 eligible questionnaires. 358 surgeons (75.5%, 358/474) believed that the Morrey modified classification for Mason type Ⅱ radial head fracture could properly guide their diagnosis and treatment. 460 surgeons (97.0%, 460/474) believed that diagnosis of the fracture should be based on a combination of elbow X-ray and elbow CT examinations. Young age (80.2%, 380/474), dominant side involvement (66.2%, 314/474), concomitant ipsilateral upper limb injury (78.7%, 373/474), large fracture displacement (67.7%, 321/474), separation of fracture fragments from the main bone (91.6%, 434/474), and fracture involvement area >30% (81.6%, 387/474) were the main factors considered by the orthopedic trauma surgeons when they chose surgical treatment. Large fracture displacement (71.7%, 340/474), especially large articular steps (83.5%, 443/474), separation of fracture fragments from the main bone (75.9%, 360/474), and limited forearm rotation or joint clicking (82.7%, 392/474) found during physical examination were recognized as surgical indications for Mason type Ⅱ fracture by orthopedic trauma surgeons.Conclusion:Domestic orthopedic trauma surgeons in China prefer surgical treatment for Mason type Ⅱ radial head fractures with loss of cortical contact and large displacement, especially large articular steps.

Objective:To investigate the current status and developing trends of study of adult radial head fracture and its treatment.Methods:The literature related to radial head fracture from January 2010 to September 2022 was reviewed through Web of science database. A bibliometric method and visualization software were used to study all the data collected and the 100 most-cited studies related to the treatment of radial head fracture to understand the research status, related cooperation, research trends and research hotspots in the field of adult radial head fracture.Results:A total of 387 studies were included, with a citation frequency of 4,982 times, an average citation frequency of 12.9 times for each study, and an H index of 36. The most studies were published in 2020 (38 studies). The citation frequency increased year by year, reaching the highest (783 times) in 2019. For the 100 most-cited studies, the citation frequency was 2,235 times, and the average citation frequency was 22.4 times for each study. The United States (100 studies), Harvard University (30 studies), Journal of Shoulder and Elbow Surgery (69 studies), and Ring D (19 studies) were, respectively, the most contributing country/region, institution, journal, and author. The country/region, institution, and author that participated the most in the collaboration were, respectively, the United States, Amphia Hospital, and Eygendaal D. Radial head fractures of Mason types Ⅱ and Ⅲ and combined with other elbow fractures and dislocations have attracted the intense attention since 2010. The current research hotspots are combined injuries and radial head prosthesis. Conclusion:Analysis of the bibliometric characteristics of the literature related to adult radial head fracture since 2010 displays the current research status and research hotspots to help following researchers to fully understand the historical development and recent hotspots in the field of adult radial head fracture.

Objective:To analyze the compliance with enhanced recovery after surgery (ERAS) protocol in geriatric patients with fresh fracture.Methods:A retrospective study was conducted on the data of the patients with fresh extremity fracture which had been included in the ERAS perioperative protocol database during May 2019 and January 2022 at Department of Orthopaedic Trauma, Beijing Jishuitan Hospital. The patients ≥65 years were selected as a study group which was matched by a control group of the patients < 65 years in sex, fracture type and date frame of hospitalization at a ratio of 1∶1. The 2 groups were compared in the compliance with the 14 ERAS core perioperative elements.Results:The study group and the control group each included 66 patients who were matched in sex and fracture type. 62.1% (41/66) of the patients in the study group had combined diseases, significantly more than that [16.7% (11/66)] in the control group( P<0.001). Altogether, the compliance with the 14 ERAS core perioperative elements was 78.6 (71.4, 85.7) % in both groups, showing no significant difference between them ( P>0.05). Respectively, the compliance with the postoperative oral intake in the study group (80.3%, 53/66) was significantly lower than that in the control group (92.4%, 61/66) ( P<0.05); the compliance with the other 13 elements showed no statistically significant difference between the 2 groups ( P>0.05). Conclusion:The ERAS perioperative protocol can be carried out smoothly in geriatric patients with fresh fracture whose compliance may be comparable to that of the none-elderly patients.

Objective:To compare the outcomes of isolated Mason type Ⅱ radial head fracture between operative and non-operative treatments.Methods:A retrospective study was conducted to analyze the data of patients who had been treated for isolated Mason type Ⅱ radial head fracture either operatively or nonoperatively at Department of Trauma and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University from January 2017 to October 2020. The patients were divided into a non-operative group and an operative group according to their treatment method. After 1:1 propensity score matching method was used to match the patients in the 2 groups, a total of 58 pairs of patients were successfully matched. In the operative group, there were 24 males and 34 females with a mean age of (40±14) years and a body mass index of (23.7±3.4) kg/m 2; in the non-operative group, there were 22 males and 36 females with a mean age of (42±13) years and a body mass index of (23.5±3.9) kg/m 2. Elbow flexion-extension, forearm rotation, Mayo elbow performance score (MEPS), Quick-disabilities of the arm, shoulder and hand (q-DASH) score and complications were compared between the 2 groups. Results:There was no significant difference in the baseline data between the 2 groups, indicating comparability ( P>0.05). All the patients were followed up for (24±9) months. At the last follow up in the operative and the non-operative groups, respectively, the elbow flexion-extension was 134° (132°, 136°) and 134°(131°, 136°), the forearm rotation 176° (174°, 179°) and 178° (175°, 179°), the MEPS 100 (100, 100) and 100 (100, 100), the q-DASH score 0 (0, 0) and 0 (0, 0), showing no significant differences between the 2 groups in the above items ( P>0.05). Elbow pain was reported respectively in 4 (6.9%) and 6 (10.3%) patients in the operative and non-operative groups, showing no significant difference between the 2 groups ( P>0.05). Conclusion:The outcomes of operative and non-operative treatments of isolated Mason type Ⅱ radial head fracture are comparable.

Objective:To evaluate the relationship between sleep arousal, ambulatory blood pressure and new-onset heart failure(NOHF)in elderly patients with obstructive sleep apnea(OSA).Methods:A total of 584 elderly patients with OSA who were diagnosed and treated in our hospital between March 2015 and March 2019 were prospectively and consecutively selected, with a mean age of(70.1±7.2)years.Polysomnography(PSG)results were obtained at baseline, and the arousal index(AI)was calculated.Based on the quartiles of AI, patients were divided into 4 groups: a low-level group(AI<18.4/h, 186 cases), a low-medium level group(18.4-29.1/h, 177 cases), a medium-high level group(29.2-41.2/h, 137 cases)and a high-level group(>41.2 /h, 84 cases). Participants were followed up for 18 months, the results of ambulatory blood pressure were recorded and compared, and the relationship between AI and the risk of NOHF was analyzed.Results:Compared with the low-level group, patients in the low-medium, medium-high, and high-level groups were older(70.1, 70.3, 73.3 vs.68.7 years, F=2.726, P=0.043)and had more smokers(43.8%, 49.6%, 54.8% vs.38.2%, χ2=8.809, P=0.032), a larger body mass index(26.3, 26.7, 27.6 vs.25.4 kg/m 2, F=2.731, P=0.042), a higher Epworth sleepiness scale score(7.83, 8.50, 9.91 vs.7.64, F=5.124, P=0.018), a higher apnea hypopnea index(23.5, 34.8, 52.7 vs.17.6, F=5.632, P=0.007), lower nocturnal oxygen saturation(80.2, 75.3, 72.1 vs.83.7 mmHg, F=4.811, P=0.024), and higher N-terminal pro-B-type natriuretic peptide(NT-proBNP)levels(317.5, 337.5, 359.2 vs.267.5 pg/L, F=4.307, P=0.033). At the median follow-up(18 months, 14-24 months), the results of ambulatory blood pressure monitoring showed that 24-hour systolic blood pressure(24 h SBP)(147.3, 148.6, 156.2 vs.143.8 mmHg, F=5.4311, P=0.013), 24-hour diastolic blood pressure(24 h DBP)(80.1, 79.5, 83.7 vs.76.5 mmHg, F=5.679, P=0.011)in the low-medium, medium-high and high-level groups were higher than those in the low-level group.The results of survival analysis showed that there were 75(12.8%)cases of NOHF, mostly with preserved ejection fraction(47 cases)or mid-range ejection fraction heart failure(20 cases). The incidences of NOHF were 6.5%, 12.4%, 16.1% and 22.4%, respectively for the low level, low-medium, medium-high and high-level groups, and the risk of NOHF in the low-medium, medium-high and high-level groups was significantly higher than in the low level group(log-rank χ2=11.624, P=0.007). Variables with P<0.2 in the univariate analysis, age and sex were included in the multivariate Cox regression analysis.The results showed that age( HR=1.724, 95% CI: 1.216-3.135), diabetes( HR=1.514, 95% CI: 1.127-3.058), NT proBNP( HR=1.517, 95% CI: 1.232-2.366), nocturnal diastolic blood pressure( HR=2.004, 95% CI: 1.332-4.638), and middle-high AI level( HR=1.611, 95% CI: 1.204-2.967)and high AI level( HR=1.863, 95% CI: 1.272-3.538)were independent factors of NOHF in elderly OSA patients. Conclusions:Sleep arousal in elderly patients with OSA increases blood pressure levels and the risk of NOHF.

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.

Objective:To investigate the reliability and repeatability of 3 classification systems for coronal fractures of distal humerus.Methods:Included were the imaging data (X-ray and CT scan) of the 64 patients with distal humeral coronal fracture who had been admitted to the outpatient and emergency departments of Beijing Jishuitan Hospital from January, 2015 to December, 2021. Four orthopedic surgeons (1 chief surgeon, 1 associate chief surgeon, 1 attending surgeon, and 1 resident surgeon) served as observers who classified the fractures by their imaging data respectively according to the Bryan-Morrey, Ring and Dubberley classifications. Four weeks later when the imaging data of 64 patients were renumbered, the 4 orthopedic surgeons performed the same classifications again. Inter-observer and intra-observer Kappa values were calculated for the 3 classifications. Landis and Koch Kappa's Benchmark Scale was used to interpret the results.Results:Interobserver confidence: The average agreement of the Bryan-Morrey classification was 75.0%, and its Kappa value was 0.546, indicating moderate agreement. The average consistency of Ring classification was 74.7%, and its Kappa value was 0.702, indicating high consistency. The average consistency of Dubberley classification was 84.1%, and its Kappa value was 0.785, indicating high consistency. Intra-observer repeatability: The average consistency of Bryan-Morrey classification was 89.9% and its Kappa value was 0.824 for the same observer. The average consistency of Ring classification was 91.0%, and its Kappa value was 0.884. The average consistency of Dubberley classification was 91.8%, and its Kappa value was 0.888.Conclusions:The 3 classification systems for distal humeral coronal fractures all demonstrate high reproducibility. As the Dubberley classification system is relatively more reliable, it has a certain guiding value for the treatment of coronal fractures of the distal humerus. However, in clinical practice, an optimal surgical strategy should take into account various factors that may affect fracture typing.