[Correlation analysis of polyclonal plasma cell proportion in the bone marrow with clinical characteristics of patients with newly diagnosed multiple myeloma].

Objective: To explore the correlation of bone marrow polychonal plasma cell proportion (pPC% ) and clinical features in newly diagnosed multiple myeloma (NDMM) patients. Methods: A retrospective analysis of 317 patients with NDMM admitted to Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology from January 2018 to January 2023 was performed. The results of the pPC% in all patients were clear. The relationship between the pPC% and clinical characteristics was analyzed. Results: A total of 317 patients were included, comprising 180 males and 137 females. The median age at diagnosis was 61 (26-91) years, and 55.8% were 60 years or older. The pPC% in the bone marrow of patients with NDMM was different in the DS, International Staging System (ISS), and revised ISS (R-ISS) stages (P=0.002, 0.010, and 0.049, respectively), whereas no statistical difference in pPC% was observed among patients with different FISH risk stratigrams (P=0.971). The correlation coefficient between pPC% and hemoglobin (HGB) at the first diagnosis in patients was 0.211 (P<0.01). The correlation coefficients with serum calcium, serum creatinine, M protein level, and ß(2)-microglobulin were -0.141, -0.120, -0.181, and -0.207, respectively, and the results of the significance test were P=0.012, 0.033, 0.004, and 0.002, respectively, indicating a negative correlation. Compared with the patients with a pPC% of ≥2.5%, the group of patients with a pPC% of <2.5% had significantly higher levels of light chain, serum calcium, serum creatinine, M protein, and ß(2)-microglobulin at the initial diagnosis (P<0.05) ; lower HGB level (P<0.001) ; and a higher proportion of patients in ISS stage Ⅲ (P=0.034) . Conclusion: In this study, the pPC% in patients with NDMM was associated with clinical features of good prognosis, including higher HGB, lower serum calcium, serum creatinine, M protein quantity, ß(2)-microglobulin, light chain involvement, lower proportion of advanced disease (DS stage and ISS stage Ⅲ), and clinical features showing lower tumor burden.

[Multicenter evaluation of minimal residual disease monitoring in early induction therapy for treatment of childhood acute lymphoblastic leukemia].

Objective: To evaluate the role of minimal residual disease (MRD) monitoring during early induction therapy for the treatment of childhood acute lymphoblastic leukemia (ALL). Methods: This was a multicenter retrospective cohort study. Clinical data of 1 164 ALL patients first diagnosed between October 2016 and June 2019 was collected from 16 hospitals in South China Children's Leukemia Group. According to MRD assay on day 15 of early induction therapy, they were divided into MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group. According to MRD assay on day 33, they were divided into MRD<0.01% group, MRD 0.01%-<1.00% group and MRD≥1.00% group. Age, onset white blood cell count, central nervous system leukemia (CNSL), molecular genetic characteristics and other data were compared between groups. Kaplan-Meier method was used for survival analysis. Cox regression model was used to analyze prognostic factors. Results: Of the 1 164 enrolled patients, there were 692 males and 472 females. The age of diagnosis was 4.7 (0.5, 17.4) years. The white blood cell count at initial diagnosis was 10.7 (0.4, 1 409.0) ×109/L. Among all patients, 53 cases (4.6%) had CNSL. The follow-up time was 47.6 (0.5, 68.8) months. The 5-year overall survival (OS) and 5-year relapse-free survival (RFS) rates were (93.1±0.8) % and (90.3±1.1) %. On day 15 of early induction therapy, there were 466 cases in the MRD<0.10% group, 523 cases in the MRD 0.10%-<10.00% group and 175 cases in the MRD≥10.00% group. The 5-year OS rates of the MRD<0.10% group, MRD 0.10%-<10.00% group and MRD≥10.00% group were (95.4±1.0) %, (93.3±1.1) %, (85.4±2.9) %, respectively, while the RFS rates were (93.2±1.6) %, (90.8±1.4) %, (78.9±4.3) %, respectively (χ2=16.47, 21.06, both P<0.05). On day 33 of early induction therapy, there were 925 cases in the MRD <0.01% group, 164 cases in the MRD 0.01%-<1.00% group and 59 cases in the MRD≥1.00% group. The 5-year RFS rates in the MRD 0.01%-<1.00% group was lowest among three groups ((91.4±1.2) % vs. (84.5±3.2) % vs. (87.9±5.1) %). The difference between three groups is statistically significant (χ2=9.11, P=0.010). Among ALL patients with MRD≥10.00% on day 15 of induction therapy, there were 80 cases in the MRD <0.01% group on day 33, 45 cases in the MRD 0.01%-<1.00% group on day 33 and 45 cases in the MRD≥1.00% group on day 33. The 5-year RFS rates of three groups were (83.9±6.0)%, (67.1±8.2)%, (83.3±6.9)% respectively (χ2=6.90, P=0.032). Univariate analysis was performed in the MRD≥10.00% group on day 15 and the MRD 0.01%-<1.00% group on day 33.The 5-year RFS rate of children with CNSL was significantly lower than that without CNSL in the MRD≥10.00% group on day 15 ((50.0±20.4)% vs. (80.3±4.4)%,χ2=4.13,P=0.042). Patients with CNSL or MLL gene rearrangement in the MRD 0.01%-<1.00% group on day 33 had significant lower 5-year RFS rate compared to those without CNSL or MLL gene rearrangement ((50.0±25.0)% vs. (85.5±3.1)%,χ2=4.06,P=0.044;(58.3±18.6)% vs. (85.7±3.2)%,χ2=9.44,P=0.002). Multivariate analysis showed that age (OR=0.58, 95%CI 0.35-0.97) and white blood cell count at first diagnosis (OR=0.43, 95%CI 0.27-0.70) were independent risk factors for OS. The MRD level on day 15 (OR=0.55,95%CI 0.31-0.97), ETV6-RUNX1 fusion gene (OR=0.13,95%CI 0.03-0.54), MLL gene rearrangement (OR=2.55,95%CI 1.18-5.53) and white blood cell count at initial diagnosis (OR=0.52,95%CI 0.33-0.81) were independent prognostic factors for RFS. Conclusions: The higher the level of MRD in early induction therapy, the worse the OS. The MRD levels on day 15 is an independent prognostic factor for RFS.The MRD in early induction therapy guided accurate risk stratification and individualized treatment can improve the survival rate of pediatric ALL.

Design and analysis of radio frequency window for the China Fusion Engineering Test Reactor ion cyclotron range of frequency heating system.

The Ion Cyclotron Range of Frequency (ICRF) heating system of the China Fusion Engineering Test Reactor (CFETR) is intended to provide plasma heating with a minimum power output of 20 MW, which demands the Radio Frequency (RF) window to possess a higher performance requirement. This paper presents the design of an RF window for the CFETR ICRF heating system and focuses primarily on the design and confirmation of its electromagnetic performance. The RF window can be effectively matched in the operating frequency range and has an S11 of under -59 dB. The geometry of the cone type ceramics was optimized to reduce the surface tangential electric field distribution. An analysis of the electric field distribution of the RF window at 50 kV indicates that the pressure side was below 2.3 kV/mm and the vacuum side was below 1.3 kV/mm. Furthermore, a transmission line test bench with an open-terminated setup was constructed to conduct withstand voltage tests on the mockup, and the results showed that the mockup could withstand 62 kV for 2 s and 47 kV for 120 s.

Imaging features of temporomandibular joint synovial chondromatosis with associated osseous degenerative changes.

Synovial chondromatosis (SC) of the temporomandibular joint (TMJ) is a rare benign disease associated with the formation of multiple cartilaginous nodules in the synovial tissue of the TMJ. This can result in pain, swelling, clicking, limited mouth opening, and osseous degenerative joint changes. A retrospective cross-sectional study was performed to summarize the clinical features, radiographic findings, and surgical and histopathological findings of TMJ SC patients who underwent open surgery over a 24-year period. A radiographic scoring system was used to evaluate osseous changes and correlate condyle and joint fossa degeneration. The study included 38 patients and focused on 38 joints. All 38 of these joints showed degenerative changes in the condyle, while 37 showed osseous degenerative changes in the articular fossa. The degree of condylar degenerative changes was related to the duration of the chief complaints (r = 0.342, P = 0.036) and the histopathological stage of the TMJ SC (r = 0.440, P = 0.006), while the degree of joint fossa degenerative changes was associated with the radiographic extent of the SC (r = 0.504, P = 0.001), type of calcification (r = 0.365, P = 0.024), and the histopathological stage (r = 0.458, P = 0.004).

MicroRNA-206 Contributes to the Progression of Preeclampsia by Suppressing the Viability and Mobility of Trophocytes via the Inhibition of AGTR1.

The development of preeclampsia (PE) is associated with the impaired trophoblast motility. MicroRNAs (miRs) contribute to the modulation of trophoblast invasion. In the current study, the role of miR-206/AGTR1 in the TNF-alpha-induced invasion defect of trophoblasts was explored. The levels of miR-206 and ATGR1 in clinical placenta tissues were investigated. Trophoblasts were treated with TNF-alpha, and the levels of miR-206 and ATGR1 were modulated. Changes in cell viability, invasion, and inflammation in trophoblasts were detected. The level of miR-206 was induced, while the level of AGTR1 was suppressed in placenta tissues. In in vitro assays, TNF-alpha suppressed viability, induced inflammatory response, inhibited invasion, upregulated miR-206, and down-regulated AGTR1. The inhibited expression of miR-206 or the overexpression of AGTR1 counteracted the effects of TNF-alpha, indicating the key role of the miR-206/AGTR1 in progression of PE. Collectively, miR-206 suppressed viability, induced inflammatory response, and decreased invasion of trophoblasts by inhibiting AGTR1.

Opioid-free anesthesia with lidocaine for improved postoperative recovery in hysteroscopy: a randomized controlled trial.

BACKGROUND: Anesthesia with opioids negatively affects patients' quality of recovery. Opioid-free anesthesia attempts to avoid these effects. This study aimed to evaluate the effect of opioid-free anesthesia on the quality of recovery, using lidocaine on patients undergoing hysteroscopy. METHODS: A parallel-group, randomized, double-blind, controlled trial was conducted in Yichang Central Peoples' Hospital, Hubei Province, China, from January to April, 2022. We included 90 female patients (age: 18-65 years, American Society of Anesthesiologists Physical Status Class I-II) scheduled for elective hysteroscopy, 45 of whom received lidocaine (Group L), and 45 received sufentanil (Group S). Patients were randomly allocated to receive either lidocaine or sufentanil perioperatively. The primary outcome was the quality of postoperative recovery, which was assessed using the QoR-40 questionnaire (a patient-reported outcome questionnaire measuring the quality of recovery after surgery). RESULTS: The two groups were similar in age, American Society of Anesthesiology physical status, height, weight, body mass index, and surgical duration. The QoR scores were significantly higher in Group L than Group S. The incidence of postoperative nausea and vomiting, as well as the time to extubation were significantly lower in Group L than Group S. CONCLUSION: Opioid-free anesthesia with lidocaine achieves a better quality of recovery, faster recovery, and a shorter time to extubation than general anesthesia with sufentanil. TRIAL REGISTRATION: The trial was registered on January 15, 2022 in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showprojen.aspx?proj=149386 ), registration number ChiCTR2200055623.(15/01/2022).

[Landscape and metastases of the lymph nodes in prostatic anterior fat pad at radical prostatectomy].

Objectives: To examine the landscape and metastases of the lymph nodes in prostatic anterior fat pad (PAFP) at radical prostatectomy (RP), and to describe the clinical characteristic of the patients with lymph node metastases in PAFP. Methods: The clinical and pathological data of 287 prostate cancer patients underwent RP from December 2019 to August 2021 in Department of Urology, Sun Yat-sen University Cancer Center were collected and analyzed retrospectively. All patients were male, aging (66±7) years (range: 42 to 83 years). The preoperative prostate-specific antigen (PSA) (M(IQR)) were 16.00(29.64) µg/L (range: 0.01 to 99.90 µg/L). There were 244 patients with localized or locally advanced prostate cancer and 43 patients with metastatic prostate cancer. All PAFP were dissected at RP routinely and were sent for pathologic analysis respectively. The PAFP was dissected from the prostate apex caudally toward the bladder neck and dissection extended to the joint of the prostate and the endopelvic fascia bilaterally. All the specimen of PAFP were examined and reported by subspecialty pathologists of genitourinary tumors. Statistical analysis was performed by Student t test, Wilcoxon rank-sum test, χ2 test or Fisher exact test. Results: There were 8.0% (23/287) patients with lymph nodes in PAFP, 3.8% (11/287) patients with PAFP lymph node metastases. Pathologically upstaged occurred in 1 patient due to the PAFP lymph node as the solitary metastatic lesion. Patients with lymph node metastases in PAFP presented higher preoperative PSA (M(IQR): 48.2(73.0) µg/L vs. 15.4(26.5) µg/L, Z=3.158, P=0.002), clinical T stage and N stage (Z=2.977, P=0.003; Z=2.780, P=0.005) and preoperative Gleason score (Z=2.205, P=0.027). Conclusions: Routine dissection of PAFP at RP and separately pathological analysis may allow more lymph nodes and lymph node metastases detection. More accurate pathological N stage may be acquired and consequently may improve the survival of patients by offering more appropriate adjuvant or salvage therapy.

[Impact of Streptococcus pneumoniae colonization in upper airway on the clinical manifestations of children with respiratory syncytial virus infection].

Objective: To investigate the effects of Streptococcus pneumoniae (Spn) colonization and the change of upper airway microbiome on the clinical manifestations in children with respiratory syncytial virus (RSV) infection. Methods: A retrospective cohort included 508 RSV-infected children with pneumonia and hospitalized in Respiratory Department of Children's Hospital of Chongqing Medical University from July 2009 to July 2018. A total of 508 cases of RSV-infected children (RSV non-sequencing group) were divided into 2 groups: children with Spn airway colonization (RSV+Spn group) and children without with Spn airway colonization (RSV group) according to the detection for virus and bacteria in nasopharyngeal aspirate, and these 2 groups were compared in terms of clinical manifestations by chi-square test in different age groups. In addition, in RSV pandemic season from November 2018 to February 2020, nasopharyngeal aspirates were collected from 20 children hospitalized in Respiratory Department of Children's Hospital of Chongqing Medical University and infected with RSV but without any positive detection of bacteria (RSV 16 S-sequencing group) and from children undergoing surgery without any sign of respiratory infection (control group). The difference of microbiome detected by 16 S RNA sequencing was compared using rank sum test between RSV 16 S-sequencing group and control group, and also between children with severe and mild pneumonia in RSV 16 S-sequencing group. Results: A total of 508 RSV non-sequencing group included 346 males and 162 females, and the visiting age was 6 (2, 12)  months. RSV group included 443 cases and RSV+Spn group included 65 cases. In the study 244 cases were aged <6 months and 264 cases were aged ≥6 months. In children aged ≥6 months of RSV non-sequencing group, the proportion of cases presenting fever over 38 ℃ and cases with severe pneumonia in RSV+Spn group were higher than those in RSV group (53.2% (25/47) vs. 34.6% (72/217), 38.3% (18/47) vs. 21.2% (46/217), χ²=5.70,6.15, both P<0.05). RSV 16 S-sequencing group included 16 males and 4 females and the visiting age was 3.0 (1.9, 8.0) months. Airway microbiome diversity in RSV 16 S-sequencing group was lower than that in control group (alpha index: 0.93 (0.42, 2.51) vs. 3.05 (2.88, 3.61), U=60.00, P=0.001). Conclusions: RSV infection is associated with the changes of the upper airway microbiome. When the balance of airway microbiome is broken and the presence of the dominant colonization of Spn follows, it may aggravate the severity of RSV infection in children aged ≥6 months.

[Clinical significance of No.11p posterior lymph nodes dissection in gastric cancer surgery].

Objective: To analyze the association of No.11p posterior lymph node metastasis with clinicopathological features and its prognostic significance in gastric cancer. Methods: A single-center retrospective cohort study was conducted. Clinicopathological data of patients with primary gastric cancers undergoing No.11p posterior lymph node dissection from January 2016 to December 2020 were retrieved from the Database of Gastric Cancer, West China Hospital, Sichuan University. Case inclusion criteria: (1) gastric cancer proved by pathology; (2) radical resection with intraoperative No.11p posterior lymph node dissection; (3) operations performed by the same surgical team; (4) no previous history of other malignant tumors and no concurrent malignant tumors. Those with stump gastric cancer, history of gastrectomy, neoadjuvant chemotherapy, incomplete clinicopathological data and lost to follow-up were excluded. During the operation, the upper edge of the pancreas was retracted forward to expose the area between the upper edge of the pancreas and the splenic vessels. The proximal segment of the splenic artery was skeletonized to remove lymphatic tissue anterior and superior to the splenic artery for No.11p lymph node dissection. For patients with lymphadenopathy in the area between the splenic artery and the splenic vein, dissection was performed. The enlarged lymph nodes were labeled with titanium clips and named as No.11p posterior lymph node. Pathological examination was performed separately after the specimen was isolated. Statistical analysis was performed using R software. Results: A total of 127 gastric cancer patients, who underwent No.11p posterior lymph nodes dissection were included in this study, of which 120 patients without No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes negative) and 7 patients with No.11p posterior lymph nodes metastasis (No.11p posterior lymph nodes positive). A total of 8 metastatic No.11p posterior lymph nodes were detected in 7 patients, metastasis rate and with a ratio of 5.5% (7/127) and 6.8% (8/127), respectively. In the subgroup analysis of T3-4 stage patients, the metastasis rate and ratio of No.11p posterior lymph nodes were 9.0% (7/78) and 10.7% (8/75), respectively. Compared to negative cases, patients with No.11p posterior lymph nodes metastasis had larger tumor (P=0.002), higher proportion of Borrmann type Ⅲ and Ⅳ tumors (P=0.005), more metastatic lymph nodes (P<0.001), more advanced T stage (P=0.043), N stage (P=0.004) and TNM stage (P=0.015). In survival analysis, patients with No.11p posterior lymph node metastasis had a significantly worse prognosis than those without metastasis after adjusting for TNM stage (hazard ratio=3.009, 95% confidence interval: 1.824-4.964, P<0.001). Conclusions: The No.11p posterior lymph node metastasis in gastric cancer is associated with worse prognosis. For patients of T3-4 stage gastric cancer, No.11p posterior lymph node dissection should be emphasized during radical operation.

Effect of concentrated growth factor on lower lip hypoesthesia after osseous genioplasty: a prospective, split-mouth, double-blind randomized controlled trial.

Lower lip hypoesthesia is the most common complication following osseous genioplasty. Concentrated growth factor (CGF) has recently been shown to improve neural regeneration. The aim of this study was to evaluate the effect of concentrated growth factor on neurosensory recovery after osseous genioplasty. Patients who underwent osseous genioplasty between June 2017 and February 2020 were enrolled. CGF was applied to the mental nerve on one side. The treatment side was randomized, and the other side was considered as the control. Lower lip hypoesthesia was assessed preoperatively and postoperatively (1 week, 1, 3, 6, and 9 months) using the two-point discrimination test and a 10-point visual analogue scale (self-reported paresthesia). The assessor was blinded. Twenty-six female patients completed the study. At 1 and 3 months, both the mean two-point discrimination value and mean visual analogue scale score were significantly lower in the CGF group than in the control group (P < 0.001). At 3 months, the percentage of patients with lower lip hypoesthesia in the CGF group was significantly lower than that in the control group (P < 0.001). Both groups showed resolution of lower lip hypoesthesia at 6 months. Concentrated growth factor may accelerate the recovery of long-standing sensory nerve impairment following mental osteotomy.

[Clinical investigation and research on Axis â ¡ evaluation of patients with temporomandibular disorders].

Objective: To screen the physical, psychological and behavioral factors related to patients with temporomandibular disorders (TMD) by using Axis Ⅱ assessment instruments of diagnostic criteria for TMD(DC/TMD). And to provide a reference to establish personalized diagnosis and treatment plans for TMD patients so as to prevent TMD and reduce predisposing factors. Methods: A total of 141 TMD patients, who were admitted in the Department of Oral and Maxillofacial Surgery in School and Hospital of Stomatology, Wuhan University from October 2018 to February 2021 were selected. There were 121 females and 20 males, with an average age of 30 years. A total of 90 healthy people were included as controls. A full-time psychologist conducted relevant questionnaire surveys. The questionnaires include general clinical survey forms and TMD symptom questionnaire. In addition, Axis Ⅱ assessment instruments include graded chronic pain scale, jaw functional limitation scale, oral behaviors checklist, patient health questionnaire-9 (depression), generalized anxiety disorder scale, patient health questionnaire-15 (physical symptoms), etc. The main observational indicators include: pain level, pain impact rates, overall classification of chronic pain, limited chewing function score, limited motor function score, limited communication function score, total jaw function restricted score, depression score, anxiety score, somatic symptom score and oral behavior score.The survey data were imported into SPSS 22.0 software for statistical analysis. Results: In the TMD group 60.3% (85/141) patients had various degrees of pain, 24.1% (34/141) of those with pain effect grades from 1 to 3 and 61.0% (86/141) showed chronic pain overall grades from Ⅰ to Ⅳ. The chewing function restricted score was 2.67(1.17, 4.25), motor function restricted score was 4.25(1.75, 6.12), communication function restricted score was 1.13(1.00, 2.25) and total jaw function restricted score was 2.56(1.47, 4.15) respectively. Patients with mild depression or above accounted for 59.6%(84/141), patients with mild anxiety or above accounted for 56.7%(80/141), 46.1%(65/141) patients had somatization symptoms. Statistical differences (P<0.05) were determined between TMD group and control group in various scores of jaw function, oral behavior grading, depression, anxiety, and physical symptoms. Physical symptoms had significantly statistical difference between different diagnostic classification(P<0.05). Meanwhile, among the different chronic pain levels in the TMD group, there were statistical differences in the various scales of mandibular dysfunction, depression, anxiety, and somatization. In the TMD group, other significant differences were noticed between males and females in terms of the average score of mouth opening, verbal and facial communication, the total score of mandibular dysfunction as well as physical symptoms (P<0.05). Conclusions: Compared with the healthy people, patients with TMD had more abnormal oral behaviors, different restriction of the mandibular functional activities. At the same time, depression, anxiety, and somatization were more serious. Patients with osteoarthritis and subluxation of temporomandibular joint were more likely to suffer physical symptoms. TMD patients suffering from pain had more severe mandibular dysfunction and symptoms of depression, anxiety, and somatization.

Melatonin Abates TMJOA Chronic Pain by MT2R in Trigeminal Ganglion Neurons.

Temporomandibular joint osteoarthritis (TMJOA) is one of the most common diseases causing chronic pain in the oral and maxillofacial region. So far, there are few ways to relieve the pain of TMJOA. Melatonin (MT) has a good analgesic effect in many diseases, including fibromyalgia, neuropathic pain, chronic headache, and burn pain, with very low acute toxicity and side effects. This study was to investigate the role and mechanism of MT in TMJOA chronic pain. In rats TMJOA chronic pain occurred at day 14 after an intra-temporomandibular joint injection of monosodium iodoacetate, which we previously reported. The enzyme-linked immunosorbent assay results showed that MT levels were higher in the synovial fluid from patients and rats with TMJOA as compared with those from control. Fluorescent retrograde tracing (Dil) identified that upregulation of MT type 2 receptor (MT2R) in trigeminal ganglion (TG) neurons innervating rat temporomandibular joints was accompanied by TMJOA chronic pain. Nociceptive behavior as assessed by von Frey and the Rat Grimace Scale demonstrated that exogenous administration of MT relieved chronic pain in TMJOA rats, whereas blocking MT2R with 4P-PDOT reversed the analgesic effect of MT. Immunofluorescence analysis also confirmed that MT inhibited CGRP and IB4 expression of TG neurons, and this inhibition was reversed by administering the MT2R antagonist in TMJOA rats. By using Fluo-3 AM-based calcium imaging in vitro, MT elicited calcium transients in Dil+ TG neurons, which were significantly abolished by 4P-PDOT. Collectively, this study suggested that MT relieves the TMJOA chronic pain of rats through downregulation of sensitized CGRP+ and IB4+ neurons in TG via MT2R. This will be helpful for health care professionals utilizing MT as an option against TMJOA chronic pain.

Aberrantly low STAT3 and STAT5 responses are associated with poor outcome and an inflammatory gene expression signature in pediatric acute myeloid leukemia.

The relapse rate for children with acute myeloid leukemia is nearly 40% despite aggressive chemotherapy and often stem cell transplant. We sought to understand how environment-induced signaling responses are associated with clinical response to treatment. We previously reported that patients whose AML cells showed low G-CSF-induced STAT3 activation had inferior event-free survival compared to patients with stronger STAT3 responses. Here, we expanded the paradigm to evaluate multiple signaling parameters induced by a more physiological stimulus. We measured STAT3, STAT5 and ERK1/2 responses to G-CSF and to stromal cell-conditioned medium for 113 patients enrolled on COG trials AAML03P1 and AAML0531. Low inducible STAT3 activity was independently associated with inferior event-free survival in multivariate analyses. For inducible STAT5 activity, those with the lowest and highest responses had inferior event-free survival, compared to patients with intermediate STAT5 responses. Using existing RNA-sequencing data, we compared gene expression profiles for patients with low inducible STAT3/5 activation with those for patients with higher inducible STAT3/5 signaling. Genes encoding hematopoietic factors and mitochondrial respiratory chain subunits were overexpressed in the low STAT3/5 response groups, implicating inflammatory and metabolic pathways as potential mechanisms of chemotherapy resistance. We validated the prognostic relevance of individual genes from the low STAT3/5 response signature in a large independent cohort of pediatric AML patients. These findings provide novel insights into interactions between AML cells and the microenvironment that are associated with treatment failure and could be targeted for therapeutic interventions.

The correlation between tissue Doppler imaging and N-terminal pro-brain natriuretic peptide concentration during left ventricular diastolic function recovery after coronary artery bypass grafting.

OBJECTIVE: This study aims to evaluate the changes in left ventricular diastolic function after coronary artery bypass grafting through tissue Doppler imaging (TDI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) concentration and the correlation between the two. PATIENTS AND METHODS: A total of 133 patients who underwent coronary artery bypass grafting between January 2016 and December 2018 were included in this study. Echocardiography and NT-proBNP concentration were reviewed pre-operation, 1 month post-operation, and 3-6 months post-operation. The transmitral peak flow velocity (E) of the mitral valve was measured at each of the three-time points using spectral Doppler imaging. The mitral annulus displacement (Ea peak and Aa peak) was then measured at each of the time points using TDI, and the E/Ea ratio was calculated. Subsequently, the correlation of the E value, Ea value, and E/Ea ratio with NT-proBNP concentration was statistically analyzed. RESULTS: The data obtained at the three-time points were compared with the respective concentrations of NT-proBNP. Multiple linear regression analysis revealed a correlation between NT-proBNP concentration and E value, Ea value, and E/Ea ratio. CONCLUSIONS: Left ventricular diastolic function gradually recovered at 1 month and 3-6 months after coronary artery bypass grafting. There was a correlation between TDI-related values and NT-proBNP concentration.

Synovial fluid levels of VEGF and FGF-2 before and after intra-articular injection of hyaluronic acid in patients with temporomandibular disorders: a short-term study.

Our purpose was to measure the temporomandibular joint (TMJ) synovial fluid (SF) levels of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF-2) before and after intra-articular injection of hyaluronic acid (HA) and to investigate the possible mechanism involved in the therapeutic value of HA. We analysed the synovial fluid of 30 patients with unilateral internal derangement (ID) or osteoarthritis (OA) of the TMJ (confirmed by magnetic resonance imaging and cone-beam computed tomography) and recorded clinical signs and symptoms including maximal mouth opening, subjective joint pain, and joint noise at the patient's each visit. All clinical signs significantly improved after injection of HA, and there was no significant difference between ID and OA groups. In synovial fluid parameters, the concentration of VEGF was significantly higher before treatment with HA than after treatment, but there was no significant difference in the concentration of FGF-2 between before and after treatment. The study findings suggest intra-articular injection of HA may reduce the synovitis and improve the internal state of the TMJ in a short period.

Tobacco smoking confers risk for severe COVID-19 unexplainable by pulmonary imaging.

BACKGROUND: COVID-19 is a new pneumonia. It has been hypothesized that tobacco smoking history may increase severity of this disease in the patients once infected by the underlying coronavirus SARS-CoV-2 because smoking and COVID-19 both cause lung damage. However, this hypothesis has not been tested. OBJECTIVE: Current study was designed to focus on smoking history in patients with COVID-19 and test this hypothesis that tobacco smoking history increases risk for severe COVID-19 by damaging the lungs. METHODS AND RESULTS: This was a single-site, retrospective case series study of clinical associations, between epidemiological findings and clinical manifestations, radiographical or laboratory results. In our well-characterized cohort of 954 patients including 56 with tobacco smoking history, smoking history increased the risk for severe COVID-19 with an odds ratio (OR) of 5.5 (95% CI: 3.1-9.9; P = 7.3 × 10-8 ). Meta-analysis of ten cohorts for 2891 patients together obtained an OR of 2.5 (95% CI: 1.9-3.3; P < 0.00001). Semi-quantitative analysis of lung images for each of five lobes revealed a significant difference in neither lung damage at first examination nor dynamics of the lung damage at different time-points of examinations between the smoking and nonsmoking groups. No significant differences were found either in laboratory results including D-dimer and C-reactive protein levels except different covariances for density of the immune cells lymphocyte (P = 3.8 × 10-64 ) and neutrophil (P = 3.9 × 10-46 ). CONCLUSION: Tobacco smoking history increases the risk for great severity of COVID-19 but this risk is achieved unlikely by affecting the lungs.

[A preliminary study on the registration of MRI and cone beam CT images of temporomandibular joint disc].

Objective: To evaluate the MRI and cone beam CT (CBCT) image registration methods of the temporomandibular joint (TMJ), and to explore the clinical application of the registered images and clinical diagnostic data for examining the relationship between the articular disc and condyle. Methods: Three patients with TMJ disc disposition were recruited at the Department of Oral and Maxillofacial Surgery, School of Stomatology, Wuhan University from January to March 2018. One patient was male, aged 30, and the others were females, aged 21 and 26 respectively. Three-dimensional (3D) images of CBCT and MRI of the TMJ were reconstructed and registered by using Mimics software. The images were then evaluated after the registration. The evaluation indicators selected were the area and volume of the articular disc, the position of the articular disc or the distance between the highest point of the condyle (point C) to the center point of the articular disc (point D), the distance between the last point of the joint disc (point P) to point C, as well as the angle between line CD and FH plane (∠DCF) at either opened- or closed-mouth condition. Results: The registration images of TMJ, at the closed- and opened-mouth positions of the 3 patients, showed the anatomical structures and interrelationships of the articular disc, articular nodules, joint fossa and condyle. Combined with clinical diagnosis, the difference of CD distances at the normal articular disc position was the minimum (1.94 mm), the difference of CD distances was small at the anterior disc displacement with non-reduction and larger with reduction. When the joint disc was in the opened-mouth position, ∠DCF angle was minimal (3.81°). The patients with anterior disc displacement with non-reduction showed the largest ∠DCF angle (48.03°). Conclusions: The position of the articular disc relative to the condyle and articular nodules, either at closed- or opened-mouth conditionds, could be accurately displayed after the image registration and fusion. The registration image not only could fully show the shape and position of the articular disc in different status from a 3D perspective, but also might provide basis for clinical study of TMJ disc displacement.

Impact of the radiation effect on the energy storage density and wake-up behaviors of antiferroelectric-like Al-doped HfO2 thin films.

The effect of the γ-ray total dose radiation on the energy storage density (ESD) and the phase transition of antiferroelectric-like (AFE-like) Al-doped HfO2 (HfAlO) thin films was investigated. The ESD property and wake-up behavior of the phase transition during the field cycling of the AFE-like HfAlO thin films were quantified before and after the radiation. The efficiency of the AFE-like thin films for energy storage slightly decreases as the total dose increases from 200 krad (Si) to 5 Mrad (Si), which is attributed to the radiation-induced trapped defects at the interfaces of HfAlO/TiN. Both the J-E, C-V, and εr-f characteristics of the AFE-like HfAlO thin films were also measured before and after the radiation at the same electrodes. These results further confirm that the ferroelectricity of the thin films can be reduced due to the radiation oxide trapped defects. It is worth noting that an enhanced wake-up behavior of the AFE-like HfAlO thin films can be observed after the radiation, which indicates that the transition from the antiferroelectric phase to the ferroelectric phase could be accelerated by the increased radiation-induced defects.

[Palmitoylome profiling indicates that androgens promote the palmitoylation of metabolism-related proteins in prostate cancer-derived LNCaP cells].

OBJECTIVE: To explore potential therapeutic targets other than androgen-deprivation treatment for prostate cancer by screening the proteins induced by androgen at palmitoylation modification level in LNCaP cells. METHODS: The LNCaP cells were treated with androgen (Methyltrienolone, R1881, 5 nmol/L) or dimethyl sulfoxide (DMSO) for 24 h, and then labeled with alkynyl palmitic acid Alk-C16 (100 µmol/L). After that, the cells were collected, lysed, the total protein was extracted, agarose beads labeled with azide (1 mmol/L) were added, and the click-chemistry reaction was carried out at room temperature for 1 h. The covalent bond formed by click-chemistry reaction of azide and alkynyl group was used to enrich the palmitoylated proteins on agarose beads. Label-free quantitation (LFQ) was used to compare the protein palmitoylation level of R1881 treated and untreated cells to screen the proteins induced by androgen at palmitoylation modification level. RESULTS: In this experiment, 907 potential palmitoylated proteins (mascot score>2, P<0.05) were identified, among which 430 proteins had LFQ values not zero at least twice. Among the 430 proteins, the palmitoylation levels of 92 candidates were increased by androgen treatment, and their LFQ values were significantly upregulated (>1.5-fold, P<0.05) in ≥2 samples of androgen-treated vs. untreated LNCaP cells. We also used the software of cytoscape to classify the 92 proteins, and found that the known functional proteins of them could be divided into three categories: metabolism related, protein folding related and translation initiation related. Among them, metabolism related proteins included lipid metabolism (6), glucose metabolism (7) and respiratory electron transport chain (8), and a small amount of amino acid metabolism (2) and other metabolism related proteins (2). Notably, the ratio of LFQ of cytochrome b-c1 complex subunit 2 (UQCRC2) was significantly (>3-fold, P<0.05) higher in androgen-treated cells compared with untreated cells, indicating that the palmitoylation level of UQCRC2 was enhanced by androgen most significantly than that of others. The second was long-chain acyl CoA dehydrogenase (ACADVL) related to lipid metabolism and glucose 6-phosphate dehydrogenase (PGD) related to glucose metabolism, but the LFQ ratio of them was less than 3-fold. CONCLUSION: The research on palmitoylation mechanism of metabolism, especially the proteins related to respiratory electron transport chain, will provide a new guidance for the diagnosis and treatment of prostate cancer and the development of targeted drugs.

[Impact and related mechanism on the improvement of hyperglycemia-induced pyroptosis in H9c2 cells by mircoRNA-214].

Objective: To investigate whether microRNA(miR)-214 can improve hyperglycemia induced pyroptosis in H9c2 cells through targeting caspase-1. Methods: H9c2 cells of rats those in good growth condition were selected and incubated into the T25 culture bottle after digestion and passage. Cells were cultured in an incubator at 37 ℃ with 5%CO(2), repeat passage was made after cell density reached about 80%, The 5(th) to 8(th) generations of cells were selected for the subsequent experiments. To observe the effect of overexpression of miR-214 on pyroptosis and caspase-1 expression in H9c2 cells induced by hyperglycemia, the cells were divided into 4 groups: Control group(H9c2 cells cultured normally), Hyperglycemia group (HG group, 50 mmol/L glucose was used to intervene H9c2 cells for 24 hours), miR-214 mimics+hyperglycosis group (mimics+HG group, H9c2 cells were transfected with miR-214 mimics for 24 hours and then treated with 50 mmol/L hyperglycosis for 24 hours), miR-214 mimic-negative control+hyperglycaemic group(MNC+HG group, H9c2 cells were transfected with miR-214 mimic-negative control for 24 hours and then treated with 50 mmol/L hyperglycaemic for 24 hours). In order to further verify the anti-pyroptosis effect of miR-214 was mediated by targeted inhibition on caspase-1, cells overexpressing caspase-1 were used in the rescue experiment. The cells overexpressing caspase-1 were divided into 4 groups: Hyperglycemia group (HG group, 50 mmol/L glucose was used to intervene H9c2 cells for 24 hours), miR-214 mimics+hyperglycosis group (mimics+HG group, H9c2 cells were transfected with miR-214 mimics for 24 hours and then treated with 50 mmol/L hyperglycosis for 24 hours), miR-214 mimics+hyperglycosis+recombinant adenovirus (Ad-caspase-1-EGFP) group with caspase-1 gene and EGFP green fluorescent protein expression (mimics+HG+Ad-caspase-1-EGFP group, H9c2 cells were transfected with caspase-1-green fluorescent protein-carrying adenovirus for 48 hours, followed by transfection of miR-214 mimics for 24 hours, and then treated with 50 mmol/L hyperglycaemia for 24 hours), miR-214 mimics+HG+Ad-EGFP empty virus group (mimics+HG+Ad-EGFP group, H9c2 cells were transfected with empty adenovirus containing green fluorescent protein for 48 hours, followed by transfection with miR-214 mimics for 24 hours, and then treated with 50 mmol/L hyperglycosis for 24 hours). The mRNA expression levels of miRNA-214 and caspase-1 in cells were detected by real-time quantitative PCR. The expression and localization of caspase-1 protein were detected by immunofluorescence assay. Western blot was used to detect protein expression levels of procaspase-1, cleaved caspase-1, NLRP3 and ACS with ß-actin as internal reference. The secretion of IL-1ß and IL-18 in cell culture medium was detected by ELISA. The correlation between miR-214 and caspase-1 was detected by double luciferase reporter gene. Results: (1) The mRNA expression levels of miR-214 and caspase-1 in each group: the mRNA expressions of miR-214 in HG group and MNC+HG group were significantly lower than that in control group(P<0.05). The mRNA expression of miR-214 in mimics+HG group was significantly higher than that in control group (P<0.05). The mRNA expression levels of caspase-1 in HG group and MNC+HG group were significantly higher than that in control group(P<0.05). The mRNA expression level of caspase-1 in mimics+HG group was lower than that in control group(P<0.05). (2) The expression of caspase-1 in each group: the green fluorescence intensity in the control group was weak, which was strong in the HG group and MNC+HG group. The green fluorescence expression was weaker in mimics+HG group than in HG group. (3) ASC and NLRP3 protein expression levels in each group: ASC and NLRP3 protein expression levels in HG group and MNC+HG group were higher than those in control group(P<0.05). ASC and NLRP3 protein expression levels were significantly lower in mimics+HG group than in mimics+HG group (P<0.05). (4) The secretion of IL-1ß and IL-18 in the cell culture medium of each group: the content of IL-1ß and IL-18 in the cell culture medium of HG group and MNC+HG group was significantly higher than that of control group (P<0.05). The content of IL-1ß and IL-18 in the cell culture medium of mimics+HG group was significantly lower than that of the HG group (P<0.05). (5) Correlation between miR-214 and caspase-1: miR-214 specifically binds to caspase-1 3 'UTR. Meanwhile, Western blot results showed that cleaved caspase-1 protein expression levels were significantly higher in both HG group and MNC+HG group than in control group (P<0.05). The levels of cleaved caspase-1 were significantly lower in mimics+HG group than in HG group (P<0.05). There was no significant difference in procaspase-1 expression among groups (P>0.05). (6) The expression levels of procaspase-1, cleaved caspase-1, ASC and NLRP3 in each group in rescue experiment: there was no significant difference in the expression of procaspase-1 in each group (P>0.05). Cleaved caspase-1, ASC and NLRP3 protein expressions were significantly lower in mimics+HG group than in HG group (P<0.05). However, cleaved caspase-1, ASC and NLRP3 protein expressions were significantly higher in mimics+HG+ Ad-caspase-1-EGFP group than in mimics+HG group (P<0.05). (7) The expression of IL-1ß and IL-18 in rescue experiment: the secretions of IL-1ß and IL-18 in the cell culture medium of the mimics+HG group were significantly lower than that of HG group (P<0.05), which were significantly higher in mimics+HG+Ad-caspase-1-EGFP group than in mimics+HG group (P<0.05). Conclusion: miR-214 can improve the hyperglycemia induced pyroptosis in H9c2 cells by targeted inhibition of the caspase-1.