OBJECTIVE: To evaluate the effectiveness of early internal fixation combined with free anterolateral thigh perforator flap (ALTPF) transplantation in the treatment of open ankle fracture-dislocation. METHODS: A retrospective analysis was performed on the clinical data of 13 patients with open ankle fracture-dislocation who were admitted and met the inclusion criteria between January 2021 and May 2024. Among them, there were 9 males and 4 females, with the ages ranging from 23 to 61 years (mean, 45.3 years). Fracture types included 5 cases of simple medial or lateral malleolar fracture-dislocation, 7 cases of bimalleolar (medial and lateral) fracture-dislocation, and 1 case of trimalleolar fracture-dislocation. Additionally, 3 cases were complicated with bone defects (1 medial malleolus defect and 2 lateral malleolus defects). All injuries were classified as type ⅢB according to the Gustilo-Anderson classification for open fractures. The size of wound defects ranged from 7 cm×5 cm to 18 cm×12 cm. The time from injury to surgery was 2-20 hours (mean, 4 hours). All patients underwent emergency thorough debridement upon admission. The fracture-dislocation was temporarily stabilized with an external fixator, and the wound was covered with antibiotic-impregnated bone cement sheets or vacuum sealing drainage. Definitive internal fixation of the fracture and free ALTPF transplantation were performed 5-7 days after the initial emergency procedure. Postoperatively, wound healing, flap survival, and fracture union were monitored. At last follow-up, clinical outcomes were assessed using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score. RESULTS: All 13 patients were followed up 6-24 months (mean, 8.2 months). All flaps survived completely, and all fractures achieved union, with an union time of 3-11 months (mean, 5.5 months). One patient developed a superficial infection at the wound margin, which healed after regular dressing changes and drainage. No internal fixation-related complication (e.g., deep infection, implant loosening, or secondary ankle instability) were observed. At last follow-up, the total AOFAS ankle-hindfoot score was 78.6±13.5, with 3 excellent, 7 good, 2 fair, and 1 poor cases, yielding an excellent and good rate of 76.9%. CONCLUSION Early internal fixation combined with ALTPF transplantation for open ankle fracture-dislocation can shorten the treatment course and maximize the recovery of ankle joint function.
Humans ; Fracture Fixation, Internal/methods* ; Male ; Middle Aged ; Female ; Adult ; Retrospective Studies ; Perforator Flap/transplantation* ; Ankle Fractures/surgery* ; Thigh/surgery* ; Fractures, Open/surgery* ; Treatment Outcome ; Young Adult ; Plastic Surgery Procedures/methods* ; Fracture Dislocation/surgery*

OBJECTIVE: To explore the effect of acupuncture therapy on dysphagia in patients with Parkinson's disease. METHODS: This randomized controlled study lasted 42 days and included 112 patients with Parkinson's disease and dysphagia. Participants were randomly assigned to the experimental and control groups (56 cases each group) using the completely randomized design, all under routine treatment. The experimental group was given acupuncture therapy. The primary outcome was Penetration-Aspiration Scale (PAS). The secondary outcomes were (1) Standardized Swallowing Assessment (SSA), and (2) nutritional status including body mass index (BMI), serum albumin, prealbumin, and hemoglobin. Adverse events were recorded as safety indicators. RESULTS: One participant quitted the study midway. There were no significant differences in baseline assessment (P>0.05). After treatment, both groups showed significant improvement in PAS, SSA and nutritional status except for BMI of the control group. There were significant differences between the two groups in the PAS for both paste and liquid, SSA (25.18±8.25 vs. 20.84±6.92), BMI (19.97±3.34 kg/m²vs. 21.26 ±2.38 kg/m²), serum albumin (35.16 ±5.29 g/L vs. 37.24 ±3.98 g/L), prealbumin (248.33 ±27.72 mg/L vs. 261.39 ±22.10 mg/L), hemoglobin (119.09±12.53 g/L vs. 126.67±13.97 g/L) (P<0.05). There were no severe adverse events during the study. CONCLUSION: The combination of routine treatment and acupuncture therapy can better improve dysphagia and nutritional status in patients with Parkinson's disease, than routine treatment solely. (registration No. CLINICALTRIAL gov NCT06199323).
Humans ; Parkinson Disease/therapy* ; Deglutition Disorders/physiopathology* ; Acupuncture Therapy/adverse effects* ; Male ; Female ; Aged ; Middle Aged ; Treatment Outcome ; Nutritional Status ; Body Mass Index

Objective: To investigate the independent prognostic factors affecting disease-free survival(DFS) after radical surgery in Ⅱ and Ⅲ adenocarcinoma of gastroesophageal junction(AEG) patients, and to construct a nomogram prediction model. Methods : A retrospective analysis was conducted on a cohort comprising 326 patients who were diagnosed with AEG. Chi-square test was used for categorical variable analysis. The survival analysis was drawn by Kaplan-Meier method and tested by log-rank method. Univariate and multivariate Cox regression analyses identified independent prognostic factors, and based on these factors, a nomogram was constructed to predict 3-year and 5-year DFS in AEG patients. The calibration curves evaluated the performance of nomogram. Results: Among 326 AEG patients, 281 were in the young group(<70 years old) and 45 were in the old group(≥70 years old). Kaplan-Meier curve showed that patients with advanced age, TNM stage Ⅰ-Ⅱ and no history of hepatitis B had longer DFS. Univariate and multivariate analysis showed that age, TNM stage and history of hepatitis B were independent prognostic factors for DFS. The 3-year and 5-year correction curves showed that the prediction efficiency of nomogram was good. The decision curve analysis showed that the model had a good clinical net benefit. Conclusion Age, TNM stage and history of hepatitis B are independent prognostic factors for DFS in AEG patients. The nomogram constructed and validated can be used to predict DFS in AEG patients.

Background::Pulmonary arterial hypertension (PAH) is characterized by excessive proliferation of small pulmonary arterial vascular smooth muscle cells (PASMCs), endothelial dysfunction, and extracellular matrix remodeling. G protein-coupled receptor kinase 2 (GRK2) plays an important role in the maintenance of vascular tone and blood flow. However, the role of GRK2 in the pathogenesis of PAH is unknown.Methods::GRK2 levels were detected in lung tissues from healthy people and PAH patients. C57BL/6 mice, vascular smooth muscle cell-specific Grk2-knockout mice ( Grk2?SM22), and littermate controls ( Grk2flox/flox) were grouped into control and hypoxia mice ( n = 8). Pulmonary hypertension (PH) was induced by exposure to chronic hypoxia (10%) combined with injection of the SU5416 (cHx/SU). The expression levels of GRK2 and Yes-associated protein (YAP) in pulmonary arteries and PASMCs were detected by Western blotting and immunofluorescence staining. The mRNA expression levels of Grk2 and Yes-associated protein ( YAP) in PASMCs were quantified with real-time polymerase chain reaction (RT-PCR). Wound-healing assay, 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-di-phenytetrazoliumromide (MTT) assay, and 5-Ethynyl-2′-deoxyuridine (EdU) staining were performed to evaluate the proliferation and migration of PASMCs. Meanwhile, the interaction among proteins was detected by immunoprecipitation assays. Results::The expression levels of GRK2 were upregulated in the pulmonary arteries of patients with PAH and the lungs of PH mice. Moreover, cHx/SU-induced PH was attenuated in Grk2?SM22 mice compared with littermate controls. The amelioration of PH in Grk2?SM22 mice was accompanied by reduced pulmonary vascular remodeling. In vitro study further confirmed that GRK2 knock-down significantly altered hypoxia-induced PASMCs proliferation and migration, whereas this effect was severely intensified by overexpression of GRK2. We also identified that GRK2 promoted YAP expression and nuclear translocation in PASMCs, resulting in excessive PASMCs proliferation and migration. Furthermore, GRK2 is stabilized by inhibiting phosphorylating GRK2 on Tyr86 and subsequently activating ubiquitylation under hypoxic conditions. Conclusion::Our findings suggest that GRK2 plays a critical role in the pathogenesis of PAH, via regulating YAP expression and nuclear translocation. Therefore, GRK2 serves as a novel therapeutic target for PAH treatment.

Objective:To assess the effectiveness of a 6-month Ba Duan Jin exercise program in improving the balance of community-dwelling older adults.Methods:A two arms, parallel-group, cluster randomized controlled trial was conducted in 1 028 community residents aged 60-80 years in 40 communities in 5 provinces of China. Participants in the intervention group (20 communities, 523 people) received Ba Duan Jin exercise 5 days/week, 1 hour/day for 6 months, and three times of falls prevention health education, and the control group (20 communities, 505 people) received falls prevention health education same as the intervention group. The Berg balance scale (BBS) score was the leading outcome indicator, and the secondary outcome indicators included the length of time of standing on one foot (with eyes open and closed), standing in a tandem stance (with eyes open and closed), the closed circle test, and the timed up to test.Results:A total of 1 028 participants were included in the final analysis, including 731 women (71.11%) and 297 men (28.89%), and the age was (69.87±5.67) years. After the 3-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 3.05 (95% CI: 2.23-3.88) points ( P<0.001). After the 6-month intervention, compared with the baseline data, the BBS score of the intervention group was significantly higher than the control group by 4.70 (95% CI: 4.03-5.37) points ( P<0.001). Ba Duan Jin showed significant improvement ( P<0.05) in all secondary outcomes after 6 months of exercise in the intervention group compared with the control group. Conclusions:This study showed that Ba Duan Jin exercise can improve balance in community-dwelling older adults aged 60-80. The longer the exercise time, the better the improvement.

This is the first reported case of a female with monkeypox infection in Kunming City,Yunnan Province.An epi-demiological investigation was conducted to provide a scientific basis for the prevention and control of monkeypox epidemics in China,especially for early detection in females in accordance with the"Monkeypox prevention and control program(2023 ver-sion)".Diagnosis was performed as described in the"Monkeypox Diagnosis and Treatment Guidelines(2022 version)".Speci-mens were collected for laboratory testing.The epidemiological investigation determined that the female patient had sexual in-tercourse with her newly married husband once before disease onset and the husband hid his history of male homosexual sex.The laboratory test results of the woman and her husband were positive for the nucleic acid of the monkeypox virus.Both had typical clinical symptoms,including rash.The epidemiological investigation,clinical symptoms,laboratory test results,and previous epidemic data of monkeypox in Yunnan province confirmed the woman as the first female infected with monkeypox in Yunnan Province and her husband was the presumed source of infection.

Objective:To explore the changes in acoustic features of 9-10-year-old primary school students with depressive symptoms, and based on these features and the random forest (RF) algorithm, construct a model for identifying depressive symptoms in primary school students, so as to provide an intelligent psychological health screening tool for schools and education departments.Methods:This was a case-control study.A total of 1 186 primary school students aged 9-10 from three primary schools in three regions of Jiangsu Province were selected as research subjects for psychological health screening from October 26, 2022 to February 13, 2023.Their demographic data, Depression-Anxiety-Stress Scale (DASS-21) scores, Insomnia Severity Index scores, and voice recordings were collected.Based on the DASS-21 scores, the participants were divided into a control group ( n=1 086) and a depression group ( n=100).Voice recordings were made using the neutral text " The North Wind and the Sun". openSMILE was used to extract 523 acoustic features from the pre-processed voice recordings.Group differences were assessed using independent-samples t-tests or chi-square tests.Pearson correlation analysis was conducted to examine the relationship between acoustic features and depression scores.Depressive symptoms were set as the dependent variable, and the correlated acoustic features were set as the independent variable to construct a classification model using the RF algorithm.The model performance was assessed using the receiver operating characteristic (ROC) curve, the area under the curve (AUC), precision, accuracy, recall, and F1 score. Results:Compared with the control group, the depression group showed significant differences in 105 acoustic features (44 spectral features, 49 source features, and 12 prosodic features) (all P<0.05).Correlation analysis showed that 12 acoustic features (7 spectral features, 4 source features, and 1 prosodic feature) were significantly correlated with the depression score (all P<0.05).Among the RF algorithm-based classification models, the spectral features demonstrated superior performance compared to source features and prosodic features (AUC=0.793), and the performance of the model based on the combination of these features was the best (AUC=0.818). Conclusions:Acoustic features may be an objective indicator to identify the depression of 9-10-year-old primary school students, and the classification model established based on acoustic features can identify the depressed primary school students.

Inducing the degradation of KRAS represents a novel strategy to combat cancers with KRAS mutation. In this study, we identify ubiquitin-specific protease 2 (USP2) as a novel deubiquitinating enzyme of KRAS in multiple myeloma (MM). Specifically, we demonstrate that gambogic acid (GA) forms a covalent bond with the cysteine 284 residue of USP2 through an allosteric pocket, inhibiting its deubiquitinating activity. Inactivation or knockdown of USP2 leads to the degradation of KRAS, resulting in the suppression of MM cell proliferation in vitro and in vivo. Conversely, overexpressing USP2 stabilizes KRAS and partially abrogates GA-induced apoptosis in MM cells. Furthermore, elevated USP2 levels may be associated with poorer prognoses in MM patients. These findings highlight the potential of the USP2/KRAS axis as a therapeutic target in MM, suggesting that strategically inducing KRAS degradation via USP2 inhibition could be a promising approach for treating cancers with KRAS mutations.

italic>Tussilago farfara L. is a perennial herb of Tussilago genus in the Compositae family. Its dried buds and leaves have good biological activities and have a long history of medicinal use in China and Europe. In this paper, we investigated the whole chloroplast genome characteristics, sequence duplication, structural variation and phylogeny of the Tussilago farfara L. After sequencing the Tussilago farfara L. chloroplast genome using Illumination technology, the complete Tussilago farfara L. chloroplast genome was further obtained by assembly and annotation, followed by a series of inverted repeat-large single copy/small single copy region contraction and expansion analysis, genome sequence variation, etc. The sequences of 13 homologous plants downloaded from NCBI were used to construct a neighbor-joining phylogenetic tree. The results showed that the total GC content of the chloroplast genome was 37.4% and the length was 150 300 bp; 125 genes were annotated, including 82 protein-coding genes, 35 tRNAs and 8 rRNAs; 148 (simple sequence repeats, SSR) loci were detected, and the relative synonymous codon usage showed that 31 codons out of 64 codons had a usage of >1. In the phylogenetic analysis, the chloroplast genomes of the seven species of Asteraceae, including the Yulin Tussilago farfara L., were highly conserved, and the sequence variation of the (large single-copy, LSC) and (small single-copy, SSC) regions was higher than that of the (inverted repeat, IR) region. This is in general agreement with the reported phylogeny of Yulin Tussilago farfara L. In this study, we obtained a high quality chloroplast genome and analyzed its genome characteristics, codon preference, SSR characteristics, SC/IR boundary, sequence variation and phylogeny, which can provide a basis for species identification, genetic diversity analysis and resource development of this medicinal plant.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*