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Cholangiocarcinoma (CCA) is widely noted for its high degree of malignancy, rapid progression, and limited therapeutic options. This study was carried out on transcriptome data of 417 CCA samples from different anatomical locations. The effects of lipid metabolism related genes and immune related genes as CCA classifiers were compared. Key genes were derived from MVI subtypes and better molecular subtypes. Pathways such as epithelial mesenchymal transition (EMT) and cell cycle were significantly activated in MVI-positive group. CCA patients were classified into three (four) subtypes based on lipid metabolism (immune) related genes, with better prognosis observed in lipid metabolism-C1, immune-C2, and immune-C4. IPTW analysis found that the prognosis of lipid metabolism-C1 was significantly better than that of lipid metabolism-C2 + C3 before and after correction. KRT16 was finally selected as the key gene. And knockdown of KRT16 inhibited proliferation, migration and invasion of CCA cells.
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With both TEMPO and O2 (in air) as the homogeneous redox mediators, BiBrO as the heterogeneous semiconductor photocatalyst, the first example of semi-heterogeneous photocatalytic decarboxylative phosphorylation of N-arylglycines with diarylphosphine oxides was established. A series of α-amino phosphinoxides were efficiently synthesized.
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PURPOSE: To compare the short-term clinical outcomes of the open versus arthroscopic modified Broström procedure in generalized joint laxity (GJL) patients. METHODS: From January 2018 to January 2020, 64 consecutive patients with chronic lateral ankle instability (CLAI) and GJL (Beighton score ≥ 4) were prospectively enrolled into two groups: those who underwent the open modified Broström procedure (open group, n = 32) and those who underwent the arthroscopic modified Broström procedure (arthroscopic group, n = 32). Patients underwent an open or arthroscopic modified Broström procedure based on the time when they attended the clinic for consultation. All patients were followed-up at 3, 6, 12, and 24 months postoperatively. The clinical outcomes were evaluated using the visual analogue scale (VAS), American Orthopaedic Foot and Ankle Society (AOFAS) score, and Karlsson score, and the radiographic outcomes were assessed using stress radiography at 24 months postoperatively. The time to return to work and the failure rate were also evaluated and compared. RESULTS: Follow-up was completed for 31 patients in the open group and 30 patients in the arthroscopic group. No significant differences were found between the two groups in terms of demographic characteristics, Beighton score (6.2 ± 1.9 vs. 5.5 ± 1.4, n.s.), or duration of symptoms. There were no significant differences in the functional scores before surgery and at 6, 12 and 24 months postoperatively or in the mean anterior translation of the talus and talar tilt angle on stress radiography at 24 months postoperatively between the open and arthroscopic groups. Compared to the open group, the arthroscopic group showed a significantly earlier return to work (6.8 ± 2.1 vs. 8.1 ± 2.4 weeks, p = 0.006). There was no significant difference in terms of the failure rate between the open and arthroscopic groups (16.1% vs. 23.3%, n.s.). CONCLUSION: Arthroscopic modified Broström procedure achieved similar short-term outcomes to the open procedure for GJL patients. Arthroscopic modified Broström procedure showed an earlier return to work than the open modified Broström procedure and was an alternative to open surgery for CLAI patients with GJL. LEVEL OF EVIDENCE: III. CLINICAL TRIAL REGISTRATION: This study is a prospective study NCT05284188.
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Instabilidade Articular , Ligamentos Laterais do Tornozelo , Ortopedia , Humanos , Tornozelo , Articulação do Tornozelo/cirurgia , Artroscopia/métodos , Instabilidade Articular/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Estudos Prospectivos , Estudos RetrospectivosRESUMO
BACKGROUND: Tibiofibular syndesmosis (TFS) widening sometimes is not evident on radiography but can be found under arthroscopy in chronic lateral ankle instability (CLAI). This study aimed to evaluate the effect of TFS widening severity on clinical outcomes and return to activities after isolated Broström operation in CLAI patients and to propose an indication for its surgical intervention. METHODS: A total of 118 CLAI patients undergoing diagnostic ankle arthroscopy and open Broström-Gould operation were included. Based on the middle width of TFS measured under arthroscopy, patients were divided into the TFS-2 group (≤2 mm, n = 44), the TFS-3 group (2-4 mm, n = 42), and the TFS-4 group (≥4 mm, n = 32). The time to return to recreational sport and work, Tegner activity score, and proportion of returning to preinjury sports at the final follow-up were evaluated and compared. Other subjective evaluations included the American Orthopaedic Foot & Ankle Society score, visual analog scale, and Karlsson-Peterson score. RESULTS: Among the 3 groups, the TFS-4 group demonstrated the longest mean time to return to work and recreational sports, with the lowest proportion returning to preinjury sports. The TFS-4 group showed a significantly higher rate of sprain recurrence (12.5%) than the other 2 groups (P =.021). All the other subjective scores significantly improved after the operation without differences among the 3 groups. CONCLUSION: Concomitant severe syndesmotic widening adversely affects the return to activities after Broström operation in CLAI cases. The CLAI patients with a middle TFS width ≥4 mm were associated with delayed return to work and sports, a lower proportion of returning to preinjury sports, and more sprain recurrence, which might require further surgical intervention for syndesmosis in addition to Broström surgery. LEVEL OF EVIDENCE: Level III, retrospective cohort study.
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Instabilidade Articular , Ligamentos Laterais do Tornozelo , Entorses e Distensões , Humanos , Estudos Retrospectivos , Seguimentos , Tornozelo , Articulação do Tornozelo/cirurgia , Instabilidade Articular/cirurgia , Artroscopia , Ligamentos Laterais do Tornozelo/cirurgiaRESUMO
BACKGROUND: Balance training is the first choice of treatment for chronic ankle instability (CAI). However, there is a lack of research on the effects of balance training in CAI with generalized joint hypermobility (GJH). This study is to compare the outcomes of balance training in CAI patients with and without GJH. METHODS: Forty CAI patients were assigned into the GJH group (Beighton ≥ 4, 20) and non-GJH group (Beighton < 4, 20) and they received same 3-month supervised balance training. Repeated measure ANOVA and independent t test were used to analyze self-reported questionnaires (Foot and ankle ability measure, FAAM), the number of patients experiencing ankle sprain, isokinetic muscle strength and postural control tests (Star excursion balance test, SEBT and Balance errors system, BES) before training, post-training immediately, and post-training 3 months, respectively. RESULTS: At baseline, no differences were found between groups with except for GJH group having poorer SEBT in the posteromedial direction (83.6 ± 10.1 vs 92.8 ± 12.3, %) and in the posterolateral direction (84.7 ± 11.7 vs 95.7 ± 8.7, %). Following the balance training, GJH group demonstrated lower re-sprain ratio (immediately after training, 11.1% vs 23.5%, 3 month after training, 16.7% vs 29.4%) than non-GJH group, as well as greater FAAM-S score, plantarflexion strength and dorsiflexion strength at post-training immediately and 3 months, and both groups improved similarly in the FAAM-A score, muscle strength and balance control (SEBT in the posterior-lateral and posterior-medial directions, and BES scores) compared with baseline. CONCLUSIONS: CAI patients with GJH gained equally even better postural stability and muscle strength after the balance training than the non-GJH patients. Balance training could still be an effective treatment for CAI patients with GJH before considering surgery. TRIAL REGISTRATION: ChiCTR1900023999, June 21st, 2019.
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Tornozelo , Instabilidade Articular , Humanos , Instabilidade Articular/diagnóstico , Instabilidade Articular/terapia , Estudos Prospectivos , Amplitude de Movimento Articular/fisiologia , Doença Crônica , Articulação do Tornozelo , Equilíbrio Postural/fisiologiaRESUMO
PURPOSE: To compare the return to sports and short-term clinical outcomes between the arthroscopic all-inside and the open anatomic reconstruction with gracilis tendon autograft for chronic lateral ankle instability (CLAI) patients. METHODS: From March 2018 to January 2020, 57 CLAI patients were prospectively included with arthroscopic all-inside anatomic reconstruction (n = 31) or open anatomic reconstruction (n = 26) with gracilis tendon autograft. The patients were evaluated before operation and at 3 months, 6 months, 12 months, and 24 months after surgery. The American Orthopaedic Foot and Ankle Society score (AOFAS), visual analog scale (VAS), and Karlsson-Peterson score were evaluated at each time point, and stress radiography with a Telos device was performed before surgery and at final follow-up. The time to return to full weightbearing walking, jogging, sports, and work, Tegner activity score, and complications were recorded and compared. RESULTS: All the subjective scores significantly improved after surgery from the preoperative level. Compared with the open group, the arthroscopic group demonstrated significantly earlier return to full weightbearing walking (8.9 vs 11.7 weeks, P < .001), jogging (17.9 vs 20.9 weeks, P = .012), and recreational sports (22.4 vs 26.5 weeks, P = .001) with significantly better AOFAS score and Karlsson score at 3 to 6 months, and better VAS score at 6 months after surgery. The 2 groups demonstrated no significant difference in the surgical duration or surgical complications. No significant difference was found in the clinical scores or stress radiographic measurements at 24 months after surgery (P > .05). CONCLUSION: Compared with the open procedure, the arthroscopic all-inside anatomic lateral ankle ligament reconstruction with autologous gracilis tendon could achieve earlier return to full weightbearing, jogging, and recreational sports with less pain and better ankle functional scores at 3 to 6 months after surgery. Similar favorable short-term clinical outcomes were achieved for both techniques at 2 years after surgery. STUDY DESIGN: Level I, randomized controlled trial.
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Instabilidade Articular , Ligamentos Laterais do Tornozelo , Ortopedia , Humanos , Tornozelo , Articulação do Tornozelo/cirurgia , Artroscopia/métodos , Instabilidade Articular/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Estudos Retrospectivos , Tendões/transplanteRESUMO
High tumor mutation load (TMB-H, or TMB ≥ 10) has been approved by the U.S. FDA as a biomarker for pembrolizumab treatment of solid tumors, including nonsmall cell lung cancer (NSCLC). Patients with cancer who have immunotherapy-resistant gene mutations cannot achieve clinical benefits even in TMB-H. In this study, we aimed to identify gene mutations associated with immunotherapy resistance and further informed mechanisms in NSCLC. A combined cohort of 350 immune checkpoint blockade-treated patients from Memorial Sloan Kettering Cancer Center (MSKCC) was used to identify genes whose mutations could negatively influence immunotherapy efficacy. An external NSCLC cohort for which profession-free survival (PFS) data were available was used for independent validation. CIBERSORT algorithms were used to characterize tumor immune infiltrating patterns. Immunogenomic features were analysed in the TCGA NSCLC cohort. We observed that PBRM1 mutations independently and negatively influence immunotherapy efficacy. Survival analysis showed that the overall survival (OS) and PFS of patients with PBRM1 mutations (MT) were significantly shorter than the wild type (WT). Moreover, compared with PBRM1-WT/TMB-H group, OS was worse in the PBRM1-MT/TMB-H group. Notably, in patients with TMB-H/PBRM1-MT, it was equal to that in the low-TMB group. The CIBERSORT algorithm further confirmed that the immune infiltration abundance of CD8+ T cells and activated CD4+ memory T was significantly lower in the MT group. Immunogenomic differences were observed in terms of immune signatures, T-cell receptor repertoire, and immune-related genes between WT and MT groups. Nevertheless, we noticed an inverse relationship, given that MT tumors had a higher TMB than the WT group in MSKCC and TCGA cohort. In conclusion, our study revealed that NSCLC with PBRM1 mutation might be an immunologically cold phenotype and exhibited immunotherapy resistance. NSCLC with PBRM1 mutation might be misclassified as immunoresponsive based on TMB.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/terapia , Fenótipo , Imunoterapia , Mutação , Fatores Imunológicos , Proteínas de Ligação a DNA , Fatores de Transcrição/genéticaRESUMO
PURPOSE: To compare the return-to-activity and long-term clinical outcomes between anatomic lateral ligament reconstruction using the autologous gracilis tendon and modified Broström-Gould (MBG) procedure in chronic lateral ankle instability (CLAI). It was hypothesised that there was no difference between the two techniques. METHODS: From 2013 to 2018, 30 CLAI patients with grade III joint instability confirmed by anterior drawer test underwent anatomic reconstruction of lateral ankle ligament with the autologous gracilis tendon (reconstruction group) in our institute. Another 30 patients undergoing MBG procedure (MBG group) were matched in a 1:1 ratio based on demographic parameters. The post-operative American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) pain score, Tegner activity score, Karlsson-Peterson score, surgical complications, return-to-activities and work were retrospectively evaluated and compared between the two groups. RESULTS: All subjective scores significantly improved after the operation (all with p < 0.001) without difference between the two groups (all n.s.). The MBG group showed a significantly higher proportion of postoperative sprain recurrence than the reconstruction group (26.7% vs. 0, p = 0.002). The reconstruction group showed a significantly longer period to start walking with full weight-bearing (10.5 ± 6.9 vs. 7.0 ± 3.1 weeks, p = 0.015), jogging (17.1 ± 8.9 vs. 12.7 ± 6.9 weeks, p = 0.043) and return-to-work (13.5 ± 12.6 vs. 8.0 ± 4.7 weeks, p = 0.039) than the MBG group. CONCLUSIONS: Both anatomic reconstruction using the autologous gracilis tendon and MBG procedure could equally achieved reliable long-term clinical outcomes and the tendon reconstruction showed a relatively lower incidence of postoperative sprain recurrence but delayed recovery to walking, jogging and return-to-work. The MBG procedure was still the first choice with rapid recovery but the tendon reconstruction was recommended for patients with higher strength demand. LEVEL OF EVIDENCE: III.
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Instabilidade Articular , Ligamentos Laterais do Tornozelo , Entorses e Distensões , Humanos , Instabilidade Articular/cirurgia , Articulação do Tornozelo/cirurgia , Tornozelo , Estudos Retrospectivos , Ligamentos Laterais do Tornozelo/cirurgia , Ligamentos Laterais do Tornozelo/lesões , Tendões/cirurgiaRESUMO
Purpose: This study aims to evaluate the mid- to long-term outcome of concurrent arthroscopic treatment of osteochondral lesion (OCL) and open anatomical repair of lateral ankle ligaments for severe acute ankle sprain patients and compare them to the outcome of those without OCL. Methods: A total of 166 patients with grade III acute lateral ankle ligament injuries underwent concurrent ankle arthroscopy and open anatomic ligament repair. Forty-three patients (group A) with OCL underwent arthroscopic treatment followed by open ligament repair. A total of 105 patients (group B) without OCL were followed up as the control. The evaluation parameters included sports recovery, postoperative visual analog scale (VAS) pain score, American Orthopaedic Foot and Ankle Society (AOFAS) score, Tegner score, sprain recurrence, satisfaction, and range of motion. Patients in group A were then subgroup-analyzed according to age, sex, body mass index, injury side, OCL location, and stage (Ferkel and Cheng's staging system). Results: The postoperative exercise level of the two groups recovered to more than 90% of the normal level (91.2% ± 11.2% in group A and 90.9% ± 13.3% in group B, n.s.). The average time of group A and group B to return to preinjury sports activity was respectively 4.4 ± 1.0 months and 4.4 ± 1.2 months with no significant difference (p = 0.716). No significant differences were found in the preoperation VAS pain score, AOFAS score, and Tegner score between the two groups. The postoperative VAS pain score in group A was significantly higher than that in group B (0.8 ± 1.7 vs. 0.3 ± 0.8, p = 0.027), but the difference was not clinically important. The postoperative VAS pain score of patients with stage D-F lesions was significantly higher than that of patients with stage B-C lesions (1.3 ± 2.1 vs. 0.3 ± 0.9, p = 0.038). Conclusions: For the severe acute ankle sprain combined with OCL, the simultaneous arthroscopic treatment and open lateral ankle ligament repair achieved good mid- to long-term outcomes. Except that the pain was more pronounced than in the control group, there were no differences in other outcomes. Postoperative pain was positively correlated with the grade of OCL.
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PURPOSE: To compare the mid- to long-term clinical and radiological outcomes of the confluent L-shaped tunnel technique with the Y-graft technique for anatomic lateral ankle ligament reconstruction. METHODS: This retrospective study involved 41 patients who underwent lateral ankle ligament reconstruction between 2013 and 2018. Based on the tunnel direction and tendon fixation method at the fibula side, patients were divided into two groups, with 17 patients in the L-shaped tunnel group and 24 patients in the Y-graft group. The American Orthopaedic Foot and Ankle Society (AOFAS) score, visual analogue scale (VAS) pain score, Tegner score, and Karlsson score were evaluated and compared preoperatively and at follow-up. Anterior talar translation and talar tilt at stress radiographs, postoperative sprain recurrence, range of motion (ROM) restriction, sensory disturbance, etc., were also collected and compared. RESULTS: The mean follow-up times were 72 and 42 months for the L-shaped group and Y-graft group, respectively. The median VAS pain score, Tegner score, AOFAS score, Karlsson score significantly improved from a preoperative level in both groups (all with p < 0.01). No significant difference was found between the two groups regarding the changes from preoperatively to postoperatively except for the VAS pain score reduction (1.58 ± 1.58 in the L-shaped group vs. 2.53 ± 1.29 in the Y-graft group, p = 0.035). The incidence of flexion-extension ROM restriction (≥ 5°) was significantly higher in the Y-graft group (41.2%) than in the L-shaped group (12.5%) (p = 0.035). CONCLUSIONS: Both the confluent L-shaped tunnel technique and the Y-graft technique significantly improved symptoms, ankle function, and radiographic outcomes in patients with chronic lateral ankle instability (CLAI) at mid- to long-term follow-up. The confluent L-shaped tunnel technique resulted in lower rates of flexion-extension ROM restriction, while the Y-graft technique showed better VAS pain reduction. This result could provide further evidence for the surgical treatment of CLAI. LEVEL OF EVIDENCE: III.
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Instabilidade Articular , Ligamentos Laterais do Tornozelo , Tornozelo , Articulação do Tornozelo/diagnóstico por imagem , Articulação do Tornozelo/cirurgia , Humanos , Instabilidade Articular/cirurgia , Ligamentos Laterais do Tornozelo/cirurgia , Dor , Estudos RetrospectivosRESUMO
BACKGROUND: To determine the effectiveness and sustainability of supervised balance training in people with chronic ankle instability (CAI) with grade III ligament injury. METHODS: Twenty young adults (12 males and 8 females) diagnosed with CAI with grade III ligament injury underwent 3 months of supervised balance training. The self-reported functional questionnaire, plantar pressure (walking and single leg standing), and isokinetic ankle strength were consecutively evaluated at pre-training, 3 months, 6 months and one year. Paired T tests were used to explore changes in muscle strength and plantar pressures following the supervised balance training. According to whether the patient had sprain recurrence, the patients were divided into sprain recurrence group and control group. The risk factors of sprain recurrence were explored with univariate analysis and multivariable logistic regression. RESULTS: The self-reported functional scores, the plantar pressure distribution and the muscle strength showed significant immediate improvements after 3 months of supervised balance training. At 6 months post-training, peak force under 2nd metatarsal, time to peak force under the medial hindfoot, time to boundary measurements and dorsiflexion, and eversion strength were partly declined to the pre-training level. 16 patients (80%) resumed the daily life and sports without sprain recurrence during the follow-up. Four patients (20%) reported ankle sprain during the follow-up, and the sprain recurrence group showed significantly higher Beighton scores (p = 0.012) and weaker initial inversion strength (p = 0.022) than the control group. CONCLUSIONS: Three months' of supervised balance training could effectively improve postural control and muscle strength of CAI cases with grade III ligament injury, although these improvements would partially deceased over time. Additional strength exercises for dorsiflexion and eversion should be supplemented from 6 months. Higher Beighton score and initial inversion muscle strength weakness might increase the risk of sprain recurrence. TRIAL REGISTRATION: ChiCTR, ChiCTR1900023999, Registered 21 June 2019, https://www.chictr.org.cn/edit.aspx?pid=39984&htm=4.
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Traumatismos do Tornozelo , Instabilidade Articular , Tornozelo , Feminino , Humanos , Ligamentos , Masculino , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Few studies have measured the dimensions of intercondylar notch under direct arthroscopic visualization. The purpose of our study was to analyse the association between time from anterior cruciate ligament (ACL) injury to reconstruction and the morphological changes of intercondylar notch using magnetic resonance imaging (MRI) and arthroscopy. METHODS: Data was collected for patients who received knee arthroscopic surgery during 2014-2015. According to the time from ACL injury to reconstruction, these patients were divided into five groupsACL non-injured group (NI), acute rupture group (AR, <3 months), chronic rupture group 1 (CR1, 3-12 months), 2 (CR2, 1-5 years) and 3 (CR3, >5 years). MRI measurements of femoral condylar width (FCW) and intercondylar width (ICW) were undertaken before surgery. The widths at the base, middle and top of the intercondylar notch (ICWb, ICWm, ICWt, respectively) and the intercondylar notch height (ICH) were measured during arthroscopy. Intercondylar notch width index (NWI) and notch shape index (NSI) were then calculated and analysed among groups. RESULTS: A total of 272 patients were allocated to groups NI (n = 89), AR (n = 84), CR1 (n = 51), CR2 (n = 30) or CR3 (n = 18). Statistical analysis showed significant differences in ICW, ICWb, ICH, NWI and NSI between groups NI and AR. Among the groups with ACL-injury, ICWb and ICWt and NWI in group CR3 were statistically smaller than the other three groups (P = 0.004, 0.016, and 0.005, respectively). CONCLUSIONS: The width of intercondylar notch had a negative correlation with time from ACL injury to reconstruction. Significant secondary notch stenosis was observed over 5 years after ACL rupture.
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Lesões do Ligamento Cruzado Anterior , Artroscopia , Imageamento por Ressonância Magnética , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/cirurgia , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Humanos , Articulação do Joelho , Fatores de RiscoRESUMO
We analytically and numerically discuss the dynamics of two pseudospin components Bose-Einstein condensates (BECs) with spin-orbit coupling (SOC) in deep optical lattices. Rich localized phenomena, such as breathers, solitons, self-trapping, and diffusion, are revealed and strongly depend on the strength of the atomic interaction, SOC, Raman detuning, and the spin polarization (i.e., the initial population difference of atoms between the two pseudospin components of BECs). The critical conditions for the transition of localized states are derived analytically. Based on the critical conditions, the detailed dynamical phase diagram describing the different dynamical regimes is derived. When the Raman detuning satisfies a critical condition, localized states with a fixed initial spin polarization can be observed. When the critical condition is not satisfied, we use two quenching methods, i.e., suddenly and linearly quenching Raman detuning from the soliton or breather state, to discuss the spin dynamics, phase transition, and wave packet dynamics by numerical simulation. The sudden quenching results in a damped oscillation of spin polarization and transforms the system to a new polarized state. Interestingly, the linear quenching of Raman detuning induces a controllable phase transition from an unpolarized phase to an expected polarized phase, while the soliton or breather dynamics is maintained.
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BACKGROUND: Achilles tendon rupture (ATR) can lead to significant disability of patients. However, whether serum lipid levels are associated with ATR is still unclear. This study aimed to examine the difference in lipid levels between patients with and those without ATR. METHODS: Patients who received ATR surgery during January 2017 to December 2017 were categorized into the case group, and those who had physical examinations during the same period without ATR were in the control group. Different matching methods [case-control matching (CCM) and propensity score matching (PSM)] were used to match the cases and controls at a 1:1 ratio. RESULTS: Among a total of 216 pairs of subjects with CCM, cholesterol, triglyceride, and low-density lipoprotein (LDL) levels were significantly higher (all P<0.05) in the case group than in the control group. Among 241 pairs of subjects with PSM, the same results as those with CCM were obtained. Abnormal rates of cholesterol, triglyceride, and LDL levels in the case group were also significantly higher than those in the control group in CCM and PSM (all P<0.05). After adjusting for the factors of height and weight, there were still significant differences in cholesterol, triglyceride, and LDL levels, as well as high-density lipoprotein levels, between the case and control groups (all P<0.05). CONCLUSIONS: Cholesterol, triglyceride, and LDL levels in patients with ATR are higher than those in healthy people. Further studies are required to verify the effect of some components of lipids on Achilles tendon structure.
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OBJECTIVE: To investigate the effects of quercetin on the apoptosis of platelets and to analyze the intrinsic mechanism. METHODS: Firstly, the effects of quecetin on the apoptosis of platelets was detected by flow cytometry. Secondly, Western blot was used to detect the expression of apoptosis-related proteins in the platelets treated with quercetin for 2 and 4 day. RESULTS: By flow cytometry, it was found that the apoptosis of platelets in the quercetin-treated group (2, 4 and 8 µmol/L) was inhibited, the apoptosis rate of platelets in 2, 4 and 8 µmol/L quercetin group was 3.12%±0.32%, 2.89%±0.15% and 2.31%±0.28%, respectively, which were signigicantly lover than that in control group (Pï¼0.01). With the increase of quecetin concentration, the proportion ratio of platelets significantly decreased in a concentration-dependent mannerï¼r=-0.9985ï¼. Similar results were observed on the 4th day. Western blot showed that the treatment with quercetin (2, 4 and 8 µmol/L) promoted the expression of anti-apoptotic protein BCL-2, inhibited the expression of pro-apoptotic protein BAX, resulting in a significant increase in the ratio of BCL-2/BAX (Pï¼0.01), thereby inhibiting the apoptosis of platelets. Similar results were observed on the 4th day. CONCLUSION: Quercetin can inhibit platelet apoptosis by increasing the ratio of apoptosis-related protein BCL-2/BAX in a concentration-dependent manner.
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Plaquetas , Apoptose , Proteínas Reguladoras de Apoptose , QuercetinaRESUMO
Normal adult mammary stem cells (AMSCs) are promising sources for breast reconstruction, particularly following the resection of breast tumors. However, carcinogenic events can potentially convert normal AMSCs to cancer stem cells, posing a safety concern for the use of AMSCs for clinical tissue regeneration. In the present study, AMSCs and autologous primary breast cancer cells were isolated and compared for their ability to differentiate, their gene expression profile, and their potential to form tumors in vivo. AMSCs were isolated from normal tissue surrounding primary breast tumors by immunomagnetic sorting. The pluripotency of these cells was investigated by differentiation analysis, and gene expression profiles were compared with microarrays. Differentially expressed candidate genes were confirmed by reverse transcription-polymerase chain reaction and western blot analyses. The in vivo tumorigenicity of these cells, compared with low-malignancy MCF-7 cells, was also investigated by xenograft tumor formation analysis. The results revealed that AMSCs isolated from normal tissues surrounding primary breast tumors were positive for the stem cell markers epithelial-specific antigen and keratin-19. When stimulated with basic fibroblast growth factor, a differentiation agent, these AMSCs formed lobuloalveolar structures with myoepithelia that were positive for common acute lymphoblastic leukemia antigen. The gene expression profiles revealed that, compared with cancer cells, AMSCs expressed low levels of oncogenes, including MYC, RAS and ErbB receptor tyrosine kinase 2, and high levels of tumor suppressor genes, including RB transcriptional corepressor 1, phosphatase and tensin homolog, and cyclin-dependent kinase inhibitor 2A. When injected into nude non-obese diabetic/severe combined immunodeficiency-type mice, the AMSCs did not form tumors, and regular mammary ductal structures were generated. The AMSCs isolated from normal tissue adjacent to primary breast tumors had the normal phenotype of mammary stem cells, and therefore may be promising candidates for mammary reconstruction subsequent to breast tumor resection.
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AIM: To evaluate the numbers of different subsets of monocytes and their associations with the values of clinical measures in mild acute pancreatitis (MAP) patients. METHODS: The study included one group of 13 healthy controls and another group of 24 patients with new-onset MAP. The numbers of different subsets of monocytes were examined in these two groups of subjects by flow cytometry. The concentrations of plasma interleukin (IL)-10 and IL-12 were determined by cytometric bead array. The acute physiology and chronic health evaluation (APACHE) II scores of individual patients were evaluated, and the levels of plasma C-reactive protein (CRP) as well as the activities of amylase and lipase were measured. RESULTS: In comparison with that in the controls, significantly increased numbers of CD14+CD163-, CD14+CD163-MAC387+ M1 monocytes, but significantly reduced numbers of CD14+CD163+IL-10+ M2 monocytes were detected in the MAP patients (P < 0.01 or P < 0.05). Furthermore, significantly higher levels of plasma IL-10 and IL-12 were observed in the MAP patients (P < 0.01 for all). More importantly, the levels of plasma CRP were positively correlated with the numbers of CD14+CD163- (R = 0.5009, P = 0.0127) and CD14+CD163-MAC387+ (R = 0.5079, P = 0.0113) M1 monocytes and CD14+CD163+CD115+ M2 monocytes (R = 0.4565, P = 0.0249) in the patients. The APACHE II scores correlated with the numbers of CD14+CD163+CD115+ (R = 0.4581, P = 0.0244) monocytes and the levels of plasma IL-10 (R = 0.4178, P = 0.0422) in the MAP patients. However, there was no significant association among other measures tested in this population. CONCLUSION: Increased numbers of CD14+CD163- and CD14+ CD163-MAC387+ monocytes may contribute to the pathogenesis of MAP, and increased numbers of CD14+CD163+CD115+ monocytes may be a biomarker for evaluating the severity of MAP.
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Monócitos/citologia , Pancreatite/sangue , Doença Aguda , Adulto , Amilases/sangue , Antígenos CD/sangue , Antígenos de Diferenciação Mielomonocítica/sangue , Proteína C-Reativa/metabolismo , Estudos de Casos e Controles , Citocinas/metabolismo , Feminino , Humanos , Inflamação , Interleucina-10/sangue , Interleucina-12/sangue , Lipase/sangue , Receptores de Lipopolissacarídeos/sangue , Masculino , Pessoa de Meia-Idade , Fenótipo , Prognóstico , Receptor de Fator Estimulador de Colônias de Macrófagos/sangue , Receptores de Superfície Celular/sangueRESUMO
AIM: To investigate serum interleukin (IL)-38 level and its clinical role in predicting virological response (VR) to telbivudine (LdT) in patients with chronic hepatitis B (CHB). METHODS: The study participants were divided into two groups; one group consisted of 43 healthy controls (HCs) and the other group consisted of 46 patients with hepatitis B e antigen-positive CHB. All patients were administered 600 mg of oral LdT daily for 52 wk, and they visited physicians every 12 wk for physical examination and laboratory tests. Serum IL-38 levels were determined using ELISA. The concentrations of serum Th1- and Th2-type cytokines were measured using the cytometric bead array (CBA) method. RESULTS: Serum levels of IL-38 at baseline in all patients were higher than those in HCs [306.97 (123.26-492.79) pg/mL vs 184.50 (135.56-292.16) pg/mL, P = 0.019]; the levels returned to normal after the first 12 wk of treatment with LdT [175.51 (103.90-331.91) pg/mL vs 184.50 (135.56-292.16) pg/mL, P > 0.05]. Serum IL-38 levels at baseline were positively associated with serum aspartate aminotransferase levels in patients with CHB (r = 0.311, P = 0.036). Higher levels of serum IL-38 at baseline were associated with a greater probability of VR to LdT treatment at 24 wk (48.15% vs 15.79%, P = 0.023) and 52 wk (66.67% vs 36.84%, P = 0.044). The levels of serum IL-38 in patients with primary non-response at week 12 after treatment initiation were lower than those in patients with primary response [64.44 (49.85-172.08) pg/mL vs 190.54 (121.35-355.28) pg/mL, P = 0.036]. Serum IL-38 levels were correlated with serum IL-6 and IL-12 levels in patients with CHB during treatment with LdT. CONCLUSION: Elevated serum IL-38 levels in untreated CHB patients reflect ongoing liver injury. Higher serum IL-38 levels before treatment indicate a greater probability of VR to LdT treatment.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Interleucinas/sangue , Resposta Viral Sustentada , Timidina/análogos & derivados , Administração Oral , Adulto , Antivirais/administração & dosagem , Biomarcadores/sangue , Estudos de Casos e Controles , DNA Viral/sangue , Esquema de Medicação , Ensaio de Imunoadsorção Enzimática , Feminino , Antígenos E da Hepatite B/sangue , Hepatite B Crônica/sangue , Hepatite B Crônica/diagnóstico , Humanos , Masculino , Telbivudina , Equilíbrio Th1-Th2 , Timidina/administração & dosagem , Timidina/uso terapêutico , Fatores de Tempo , Regulação para Cima , Carga Viral , Adulto JovemRESUMO
AIM: Systemic lupus erythematosus (SLE) presents as the abnormal activation and over-proliferation of immune competent cells. Few studies have characterized the role of natural killer (NK) and NK T (NKT) cells in the pathogenesis of SLE, and therefore a consensus has not been reached as yet. METHOD: Thirty-two patients with new-onset SLE and 15 healthy controls were recruited. Activated and inhibitory NK and NKT cells in peripheral blood were quantified by flow cytometry. The proportions of spontaneous and stimulated interferon (IFN)-γ(+) NK and NKT cells and CD107a(+) NK cells was examined. Finally, the potential relationship between the cell subsets and clinical indexes was analyzed. RESULTS: The proportions of NK and NKT cells (P = 0.002 and 0.004, respectively) as well as the proportions of NKG2C(+) NK cells, inhibitory NK and NKT cell subsets (P = 0.016, P = 0.019, P = 0.049, and P = 0.028, respectively) in SLE patients were significantly lower than those in controls. In contrast, the proportions of activated NK cells and NKT cell subsets were significantly higher (P = 0.036, P = 0.034, P = 0.005, and P = 0.007, respectively). Moreover, the proportions of stimulated IFN-γ(+) NKT cells were significantly higher than in the controls, and the proportions of stimulated CD107a(+) NKT cells in SLE patients were significantly lower than in the controls (P = 0.032 and P = 0.02, respectively). CONCLUSION: Lower proportions of NK and NKT cells, higher proportions of activated NK cells and activated NKT cells, lower proportions of inhibitory NK and NKT cells, higher NKT cell activity, and lower NKT cell degranulation may induce the autoimmune reaction involved in the pathogenesis of SLE.
Assuntos
Células Matadoras Naturais/metabolismo , Lúpus Eritematoso Sistêmico/sangue , Células T Matadoras Naturais/metabolismo , Receptores de Células Matadoras Naturais/sangue , Adolescente , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Degranulação Celular , Células Cultivadas , Criança , Feminino , Humanos , Interferon gama/sangue , Células Matadoras Naturais/imunologia , Lúpus Eritematoso Sistêmico/diagnóstico , Lúpus Eritematoso Sistêmico/imunologia , Ativação Linfocitária , Proteína 1 de Membrana Associada ao Lisossomo/sangue , Proteína 1 de Membrana Associada ao Lisossomo/imunologia , Masculino , Pessoa de Meia-Idade , Subfamília C de Receptores Semelhantes a Lectina de Células NK/sangue , Subfamília C de Receptores Semelhantes a Lectina de Células NK/imunologia , Células T Matadoras Naturais/imunologia , Fenótipo , Receptores de Células Matadoras Naturais/imunologia , Adulto JovemRESUMO
BACKGROUND: This study is aimed at investigating the frequency of different functional IL-22(+) CD4(+) T cells in Chinese patients with type 2 diabetes mellitus (T2DM). METHODS: The frequency of circulating IFN-γ+IL-17-IL-22-CD4(+) (Th1), IFN-γ-IL-17A+IL-22-CD4(+) (Th17), and IFN-γ-IL-17A-IL-22(+) CD4(+) (Th22), and other subsets of IL-22(+) CD4(+) T cells in 31 patients with new onset T2DM and 16 healthy controls was characterized by flow cytometry. The levels of serum IL-22, IL-17, IFN-γ, insulin C-peptide, hemoglobin A1c (HbA1c), fasting plasma glucose, and insulin were examined. RESULTS: The frequency of Th1, Th17, Th22, IFN-γ(+) IL-17(-) IL-22(+) , and IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells and the concentrations of IL-22, but not IL-17 and IFNγ, in the patients were significantly higher than controls. The percentages of Th22 cells were correlated positively with the frequency of IFN-γ(-) IL-17(+) IL-22(+) CD4(+) T cells, the values of body mass index (BMI) and homeostatic model assessment insulin resistance (HOMA-IR), and the levels of serum IL-22 in those patients. CONCLUSION: Our data suggest that IL-22(+) CD4(+) T cells may contribute to the early process of T2DM.