PURPOSE: To assess the relationship between dislocation and functional outcomes in supination-external rotation (SER) ankle fractures. METHODS: A retrospective case series study was performed on patients with ankle fractures treated surgically at a large trauma center from January 2015 to December 2021. The inclusion criteria were young and middle-aged patients of 18 - 65 years with SER ankle fractures that can be classified by Lauge-Hansen classification and underwent surgery at our trauma center. Exclusion criteria were serious life-threatening diseases, open fractures, fractures delayed for more than 3 weeks, fracture sites ≥ 2, etc. Then patients were divided into dislocation and no-dislocation groups. Patient demographics, injury characteristics, surgery-related outcomes, and postoperative functional outcomes were collected and analyzed. The functional outcomes of SER ankle fractures were assessed postoperatively at 1-year face-to-face follow-up using the foot and ankle outcome score (FAOS) and American Orthopedic Foot and Ankle Society ankle hindfoot score and by 2 experienced orthopedic physicians. Relevant data were analyzed using SPSS version 22.0 by Chi-square or t-test. RESULTS: During the study period, there were 371 ankle fractures. Among them, 190 (51.2%) were SER patterns with 69 (36.3%) combined with dislocations. Compared with the no-dislocation group, the dislocation group showed no statistically significant differences in gender, age composition, fracture type, diabetes, or smoking history, preoperative waiting time, operation time, and length of hospital stay (all p > 0.05), but a significantly higher Lauge-Hansen injury grade (p < 0.001) and syndesmotic screw fixation rate (p = 0.033). Moreover, the functional recovery was poorer, revealing a significantly lower FAOS in the sport/rec scale (p < 0.001). Subgroup analysis showed that among SER IV ankle fracture patients, FAOS was much lower in pain (p = 0.042) and sport/rec scales (p < 0.001) for those with dislocations. American Orthopedic Foot and Ankle Society ankle hindfoot score revealed no significant difference between dislocation and no-dislocation patients. CONCLUSION Dislocation in SER ankle fractures suggests more severe injury and negatively affects functional recovery, mainly manifested as more pain and poorer motor function, especially in SER IV ankle cases.
Humans ; Ankle Fractures/physiopathology* ; Male ; Female ; Retrospective Studies ; Adult ; Middle Aged ; Supination ; Aged ; Young Adult ; Rotation ; Joint Dislocations/surgery* ; Fracture Fixation, Internal/methods* ; Adolescent ; Recovery of Function ; Treatment Outcome

This study evaluated the scientific nature and effectiveness of iterative optimization of prevention and control measures for local outbreaks caused by the BA.2 and BA.5.2 COVID-19 strains in Fujian Province in 2022,to provide a scientif-ic basis for responding to future new or recurrent respiratory infectious diseases.According to the theory of infectious disease dynamics,relevant information regarding the local epidemic situation caused by the BA.2 sub-type Omicron virus strain in March 2022 and BA.5.2 sub-type Omicron virus strain in October 2022 in Fujian Province was collected.The susceptible exposed infectious removed(SEIAR)model of COVID-19 infection with a latent period and asymptomatic infected persons was used to analyze the transmission dynam-ics of two local epidemic situations,and evaluate the preven-tion and control effects.The incubation period of the BA.2 epidemic was 3 days(1～9 days),the intergenerational inter-val was 3 days(1～5 days),and the initial Rt was 3.0(95％CI:2.7～3.3).The incubation period of the BA.5.2 epidemic was 2 days(1～6 days),the intergenerational interval was 1 day(0～2 days),and the initial R,was 1.9(95％CI:1.7～2.1).The fittingresults for the BA.2 and BA.5.2 epidemics were good,and no statistical difference was observed between the predic-ted and actual numbers of cases(x2BA.2=31.53,x2BA.5.2=27.88,P＞0.05).If an emergency response had not been initiated,the BA.2 epidemic would have continued to spread andpeak on April 7th,with an estimated 638 035 cases.The BA.5.2 epidemic would have rapidly spread,reaching a peak on November 14th,with an estimated 685 940 cases.If one incubation period were detected early,the scale of the BA.2 epidemic would have decreased by 25.73％;if two incubation periods were detected early,the scale would have decreased by 79.56％,and if one incubation period had been delayed,the scale would have expanded by 13.72％.If one incubation period had been detected early in the BA.5.2 epidemic,the scale would have decreased by 35.04％;if two incubation periods had been detected early,the scale would have decreased by 92.47％;and if one incubation period had been delayed,the scale would have increased by 19.75％.The guiding ideology,and the prevention and control measures for handling two local epidemics were optimized and iterated.Our study indicated that implementing the"four early"measures ef-fectively decreased the scale of the epidemic,and earlier detection was associated with more significant control effects.This study provides valuable information for the prevention and control of new or recurrent respiratory infectious diseases.

OBJECTIVE: To retrospectively analyze clinical effect of 3D mirror printing combining with minimally invasive percutaneous plate osteosynthesis(MIPPO) technology in the treatment of adult clavicle fracture. METHODS: The clinical data of 32 adult patients with collarbone AllmanⅠdisplacement of fracture who had undergone the combination of 3D mirror printing with MIPPO technology treatment were collected from October 2019 to October 2020. There were 19 males and 13 females, aged from 19 to 55 years old with an average of(34.12±16.42) years old. According to Allman classification, there were 14 cases of AllmanⅠb and 18 cases of AllmanⅠc. Fracture occurred on the left in 17 cases and on the right in 15 cases. Postoperative complications, operation time, incision length, intraoperative blood loss, the number of fluoroscopies, fracture healing time of all patients were retrospectively analyzed, and the curative effect was evaluated by Constant-Murley shoulder joint score before operation, 1 and 6 months after operation. RESULTS: All the 32 patients were followed up for 6 to 8 months, with an average of (6.67±2.13) months. All the patients did not have postoperative complications such as incision infection and skin numbness in the operating area. The operation time was (35.37±4.28) min. The incision length was (3.78±0.45) cm. Intraoperative blood loss was(37.23±4.76) ml. The number of fluoroscopies was(3.12±0.47) times. Fracture healing time was (8.18±2.58) weeks. Constant-Murley shoulder joint score of the affected side at 1 and 6 months after operation was 81.08±3.92 and 98.03±1.05 respectively, which had a significant difference compared with 54.62±5.25 before operation(P<0.05). According to Constant-Murley shoulder function score at 6 months after operation, 30 cases were excellent and 2 cases were good. CONCLUSION 3D mirror printing can effectively assist MIPPO technique in the treatment of adult clavicle AllmanⅠdisplaced fracture. It not only has the advantages of less trauma and fewer complications of the MIPPO technique, but also can further shorten the operation time and improve the operation maneuverability. It is a better method in the treatment of adult clavicle AllmanⅠdisplaced fracture.
Adolescent ; Adult ; Blood Loss, Surgical ; Bone Plates ; Clavicle/surgery* ; Female ; Fracture Fixation, Internal/methods* ; Fractures, Bone/surgery* ; Humans ; Male ; Middle Aged ; Minimally Invasive Surgical Procedures/methods* ; Printing, Three-Dimensional ; Retrospective Studies ; Treatment Outcome ; Young Adult

Chemoimmunotherapy has attracted much attention as an emerging therapy pattern for the treatment of cancers. Exploring effective drug combination schemes and reasonable delivery methods remained the key issue in current research. Herein, we designed sorafenib (SF) and anti-Tim-3 monoclonal antibody (Tim-3 mAb) co-loaded MMP2-responsive mesoporous silica nanoparticles (ST-MSNs) for combined chemoimmunotherapy of hepatocellular carcinoma (HCC). The shell of ST-MSNs was fabricated by Tim-3 mAb through matrix metalloproteinase 2 (MMP2) sensitive peptides as "gatekeepers" to prevent drug release during the blood circulation. In tumor microenvironment, the high levels of MMP2 caused the responsive shedding of Tim-3 mAb, leading to the triggerred release of SF and Tim-3 mAb. Then, SF could be delivered to tumor cells and Tim-3 mAb could be delivered to T cells, respectively. In vivo tumor inhibition study results demonstrated that ST-MSNs can significantly enhance synergistic antitumor activity compared with sequential administration of free SF solution and Tim-3 mAb solution. Meanwhile, the expression of antitumor cytokines IFN-γ, IL-12 and the percentage of CD3⁺CD4⁺ cells, CD3⁺CD8⁺ cells in tumors were upregulated after the administration of ST-MSNs, demonstrating good immunomodulatory ability. In addition, within the dosage range, the ST-MSNs had low cytotoxicity and hemolysis, and no obvious tissue toxicity was observed. All animal experiments were performed in line with national regulations and approved by the Animal Experiments Ethical Committee of Shandong University. In conclusion, this study provided a promising drug combination of chemoimmunotherapy with good application prospects for clinical HCC treatment, and exhibited a potential drug carrier for clinical chemoimmunotherapy.

The antidepressant effect of Xiaoyaosan has been demonstrated. It is of value to explore the biological mechanism of Xiaoyaosan in the treatment of depression from the perspective of functional modules by using the method of functional module division of the metabolic network. The differential metabolites and related enzymes and proteins regulated by Xiaoyaosan were identified in the database. Pathway enrichment analysis and crosstalk pathway analysis of Xiaoyaosan regulated metabolites was carried out. A network of differentially regulated metabolites and their enzymes and proteins was constructed by using the STRING tool. The CNM decomposition algorithm was used to extract the functional modules of the network and enrichment analysis of functional modules was carried out. The results show that Xiaoyaosan regulates 97 differential metabolites, 234 related enzymes and 258 depression-related proteins. The pathways crosstalk analysis was divided into two sub-networks, one of which is related to the neural system and cell signal transduction, the other is related to the endocrine system and metabolic pathways. KEGG pathway enrichment analysis of the network and 9 functional modules extracted by the CNM algorithm shows that module 1 and module 3 belong to the pathways that can be enriched into more pathways with fewer proteins. The corresponding functions of these pathways include the endocrine system, amino acid metabolism, the nervous system and signal transduction. In this study, pathway crosstalk analysis and metabolic network module division strategies were used to explain the biological mechanism of Xiaoyaosan in the treatment of depression, providing ideas and methods for in-depth study of the pharmacological mechanism of this traditional Chinese medicine from the perspective of metabolic regulation.

Objective: The relationship between serum uric acid (SUA) levels and glycemic indices, including plasma glucose (FPG), 2-hour postload glucose (2h-PG), and glycated hemoglobin (HbA1c), remains inconclusive. We aimed to explore the associations between glycemic indices and SUA levels in the general Chinese population. Methods: The current study was a cross-sectional analysis using the first follow-up survey data from The China Cardiometabolic Disease and Cancer Cohort Study. A total of 105,922 community-dwelling adults aged ≥ 40 years underwent the oral glucose tolerance test and uric acid assessment. The nonlinear relationships between glycemic indices and SUA levels were explored using generalized additive models. Results: A total of 30,941 men and 62,361 women were eligible for the current analysis. Generalized additive models verified the inverted U-shaped association between glycemic indices and SUA levels, but with different inflection points in men and women. The thresholds for FPG, 2h-PG, and HbA1c for men and women were 6.5/8.0 mmol/L, 11.0/14.0 mmol/L, and 6.1/6.5, respectively (SUA levels increased with increasing glycemic indices before the inflection points and then eventually decreased with further increases in the glycemic indices). Conclusion An inverted U-shaped association was observed between major glycemic indices and uric acid levels in both sexes, while the inflection points were reached earlier in men than in women.
Aged ; Asian Continental Ancestry Group ; Blood Glucose/analysis* ; China/epidemiology* ; Cohort Studies ; Diabetes Mellitus/blood* ; Female ; Glucose Tolerance Test ; Glycated Hemoglobin A/analysis* ; Glycemic Index ; Humans ; Male ; Middle Aged ; Uric Acid/blood*

BACKGROUND: Vascular endothelial dysfunction is considered a key pathophysiologic process for the development of acute lung injury. In this study, we aimed at investigating the effects of unfractionated heparin (UFH) on the lipopolysaccharide (LPS)-induced changes of vascular endothelial-cadherin (VE-cadherin) and the potential underlying mechanisms. METHODS: Male C57BL/6 J mice were randomized into three groups: vehicle, LPS, and LPS + UFH groups. Intraperitoneal injection of 30 mg/kg LPS was used to induce sepsis. Mice in the LPS + UFH group received subcutaneous injection of 8 U UFH 0.5 h before LPS injection. The lung tissue of the mice was collected for assessing lung injury by measuring the lung wet/dry (W/D) weight ratio and observing histological changes. Human pulmonary microvascular endothelial cells (HPMECs) were cultured and used to analyze the effects of UFH on LPS- or tumor necrosis factor-alpha (TNF-α)-induced vascular hyperpermeability, membrane expression of VE-cadherin, p120-catenin, and phosphorylated myosin light chain (p-MLC), and F-actin remodeling, and on the LPS-induced activation of the phosphatidylinositol-3 kinase (PI3K)/serine/threonine kinase (Akt)/nuclear factor kappa-B (NF-κB) signaling pathway. RESULTS: In vivo, UFH pretreatment significantly attenuated LPS-induced pulmonary histopathological changes (neutrophil infiltration and erythrocyte effusion, alveolus pulmonis collapse, and thicker septum), decreased the lung W/D, and increased protein concentration (LPS vs. LPS + UFH: 0.57 ± 0.04 vs. 0.32 ± 0.04 mg/mL, P = 0.0092), total cell count (LPS vs. LPS + UFH: 9.57 ± 1.23 vs. 3.65 ± 0.78 × 10/mL, P = 0.0155), polymorphonuclear neutrophil percentage (LPS vs. LPS + UFH: 88.05% ± 2.88% vs. 22.20% ± 3.92%, P = 0.0002), and TNF-α (460.33 ± 23.48 vs. 189.33 ± 14.19 pg/mL, P = 0.0006) in the bronchoalveolar lavage fluid. In vitro, UFH pre-treatment prevented the LPS-induced decrease in the membrane expression of VE-cadherin (LPS vs. LPS + UFH: 0.368 ± 0.044 vs. 0.716 ± 0.064, P = 0.0114) and p120-catenin (LPS vs. LPS + UFH: 0.208 ± 0.018 vs. 0.924 ± 0.092, P = 0.0016), and the LPS-induced increase in the expression of p-MLC (LPS vs. LPS + UFH: 0.972 ± 0.092 vs. 0.293 ± 0.025, P = 0.0021). Furthermore, UFH attenuated LPS- and TNF-α-induced hyperpermeability of HPMECs (LPS vs. LPS + UFH: 8.90 ± 0.66 vs. 15.84 ± 1.09 Ω·cm, P = 0.0056; TNF-α vs. TNF-α + UFH: 11.28 ± 0.64 vs. 18.15 ± 0.98 Ω·cm, P = 0.0042) and F-actin remodeling (LPS vs. LPS + UFH: 56.25 ± 1.51 vs. 39.70 ± 1.98, P = 0.0027; TNF-α vs. TNF-α + UFH: 55.42 ± 1.42 vs. 36.51 ± 1.20, P = 0.0005) in vitro. Additionally, UFH decreased the phosphorylation of Akt (LPS vs. LPS + UFH: 0.977 ± 0.081 vs. 0.466 ± 0.035, P = 0.0045) and I kappa B Kinase (IKK) (LPS vs. LPS + UFH: 1.023 ± 0.070 vs. 0.578 ± 0.044, P = 0.0060), and the nuclear translocation of NF-κB (LPS vs. LPS + UFH: 1.003 ± 0.077 vs. 0.503 ± 0.065, P = 0.0078) in HPMECs, which was similar to the effect of the PI3K inhibitor, wortmannin. CONCLUSIONS The protective effect of UFH against LPS-induced pulmonary endothelial barrier dysfunction involves VE-cadherin stabilization and PI3K/Akt/NF-κB signaling.

OBJECTIVE: To investigate the clinical characteristics of myelodysplastic syndrome (MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients. METHODS: The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed. RESULTS: Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5 (23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower (P=0.001, P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group (P=0.002, P＜0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and β2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group (P＜0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk. CONCLUSION MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.
Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Karyotype ; Karyotyping ; Male ; Middle Aged ; Mutation ; Myelodysplastic Syndromes ; genetics ; Prognosis ; Retrospective Studies ; Tumor Suppressor Protein p53 ; genetics ; Young Adult

OBJECTIVETo investigate the ability of UCB-derived MSCs to support the expansion of HSCs ex vivo and the possible mechanisms involved in this process.

METHODSHSCs from UCB were co-cultured with UCB-derived MSCs for 14 days, and then the total number of HSCs and colony-forming units (CFU) were detected. Cytokines levels of MSCs supernatant were analyzed using ELISA.

RESULTSThe proliferation rate of HSCs co-cultured with MSCs was significantly higher than that of cultured HSCs alone (P<0.05). Furthermore, the addition of exogenous cytokines to the culture system significantly increased the proliferation rate of HSCs (P<0.05). MSCs had secretion of many cytokines, including GM-CSF, IL-7, IL-8, IL-11, SCF and SDF-1α.

CONCLUSIONUCB-derived MSCs as a feeder layer can be an alternative approach for ex vivo expansion of HSCs, and the cytokines by secreted UCB-MSCs may mediate the supportive role of MSC to HSC proliferation.

Antigens, CD34 ; Cell Proliferation ; Coculture Techniques ; Cytokines ; Fetal Blood ; Humans ; Mesenchymal Stromal Cells

OBJECTIVETo compare the quality of life in patients with prevertebral or retrosternal reconstruction after cervical tubular gastroesophagostomy.

METHODSA total of 167 patients enrolled in this prospective study from July 2008 to June 2012 in Shantou Central Hospital, and divided into prevertebral route group(85 cases) and retrosternal route group(82 cases) according to the random number table method. Quality of life questionnaire was investigated 1, 3, 6, 9, and 12 months after operation respectively.

RESULTSThe incidence of anastomotic stenosis was lower in the prevertebral route group (P<0.05). However, the differences in perioperative general conditions between the two groups were not statistically significant(all P>0.05). One hundred and forty-nine patients completed the postoperative quality of life questionnaire. Dysphagia and swallowing retching symptom were better, while acid reflux and heartburn symptom were more serious in prevertebral route group as compared to retrosternal route group(all P<0.05). Overall quality of life score difference between the two groups was not statistically significant(P>0.05).

CONCLUSIONSFor digestive tract reconstruction after resection of esophageal cancer, tubular gastroesophagostomy by prevertebral or retrosternal route both can obtain better quality of life after surgery. Swallowing function after surgery of the former is superior to the latter, but the reflux symptoms is more serious. Therefore the two mehods have their own advantages and disadvantages, and the choice of route should be depended on clinical experience and patient condition.

Deglutition Disorders ; Digestive System Surgical Procedures ; Esophageal Neoplasms ; Esophagectomy ; Gastrectomy ; Humans ; Postoperative Period ; Prospective Studies ; Quality of Life ; Reconstructive Surgical Procedures