TOX2 nuclear-cytosol translocation is linked to leukemogenesis of acute T-cell leukemia by repressing TIM3 transcription.

Nuclear factors TOX and TOX2 upregulate TIM3 expression and lead to T-cell exhaustion in malignancies. Here, we demonstrate two distinct TIM3 expression patterns (high & low) with high TOX and TOX2 levels in T-cell acute lymphoblastic leukemia (T-ALL) specimens and cell lines. However, the mechanisms regulated by TOX and TIM3 signaling in leukemogenesis are unclear. We found that TOX and TOX2 proteins each directly upregulated HAVCR2 transcription, while the cellular localization of TOX2 was different in Jurkat and MOLT3 cells (nucleus) and lymphoblastic cell T2 and normal T cells (cytoplasm). Nuclear TOX and TOX2 formed a protein complex and repressed HAVCR2 promoter activity by recruiting transcriptional corepressor LCOR and deacetylase HDAC3. The nuclear-cytosol translocation of TOX2 was deacetylation-dependent and cooperatively mediated by deacetylase Sirt1 and kinase TBK1. Radiation damage induced TOX2 nuclear translocation and decreased Sirt1, TIM3, and caspase 1 expression in normal T cells. Accordingly, knockdown of TOX, TOX2 or LCOR; HDAC3 inhibition; or TIM3 overexpression induced Jurkat cell apoptosis in vitro and slow growth in vivo. Thus, our findings demonstrate a novel regulatory mechanism involving TOX-TOX2 and the TIM3 pathway in the leukemogenesis of T-ALL.

Depression in Polycystic Ovary Syndrome: Focusing on Pathogenesis and Treatment.

Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies. Appeared originally in Front Psychiatry 2022; 13:1001484.

Best acupuncture method for mammary gland hyperplasia: Evaluation of randomized controlled trials and Bayesian network meta-analysis.

Objective: To evaluate the effectiveness of different acupuncture treatments for mammary gland hyperplasia (MGH) using a network meta-analysis. Methods: Several databases were searched without language restrictions from 2000 to February 2023, including PubMed, Embase, Web of Science, Cochrane Library, China Science and Technology Journal Database, China Biology Medicine Database, Wanfang Database, China National Knowledge Infrastructure Database, and other professional websites and gray literature. Inclusion criteria were adult women diagnosed with MGH; intervention measures included acupuncture and related therapies; the control group was treated with simple drugs; and the research type was a randomized controlled trial (RCT). The primary outcomes were treatment effectiveness and estradiol and progesterone levels. Secondary outcomes were breast lump size and visual analog scale (VAS) score of breast pain. Exclusion criteria were studies unrelated to MGH, incorrect study populations, control measures or interventions, incomplete data, non-RCTs, case reports, and animal experiments. Cochrane tools were used to assess the risk of bias. The R software (x64 version 4.2.1), Review Manager 5.3 software and STATA 16.0 software were used for data analysis. Results: Following a rigorous screening process, data extraction, and quality assessment, 48 eligible RCTs encompassing 4,500 patients with MGH and 16 interventions were included. The results indicated that acupuncture, alone or in combination with traditional Chinese or Western medicine, had better therapeutic effects than conventional therapy. In terms of effectiveness, warm needle acupuncture was the best choice (94.6%). Bloodletting pricking was the most effective method (85.7%) for lowering progesterone levels. Bloodletting pricking was the most effective method (98.3%) for lowering estradiol levels. Manual acupuncture combined with traditional Chinese medicine was the most effective (74.5%) treatment to improve the size of the breast lump. Warm needle acupuncture was the most effective (69.8%) in improving the VAS score. Conclusion: Acupuncture therapy was more effective in treating MGH than drug therapy alone, and warm needle acupuncture and bloodletting pricking were the two best options. However, larger sample sizes and high-quality RCTs are required.

Toripalimab plus lenalidomide for central nervous system recurrence in refractory CD5+ diffuse large B-cell lymphoma with MYD88 and CD79B comutation: a case report.

Background: CD5-positive (CD5+) non-germinal center B-cell-like diffuse large B-cell lymphoma (non-GCB DLBCL) is heterogeneous with a poor prognosis. For refractory DLBCL, the median overall survival was only 6.3 months. Therefore, there is a need for approaches to elongate the survival in this subgroup of relapsed DLBCL patients. Case Description: Here, we present a rare case of a 72-year-old patient with stage IV CD5+ non-GCB DLBCL with myeloid differentiation primary response 88 (MYD88) and cluster of differentiation 79B (CD79B) comutations. Zanubrutinib and rituximab therapy was initially administered until disease progression. Subsequently, zanubrutinib plus rituximab together with attenuated standard chemotherapy (miniCHOP) was applied and a notable response was observed. The patient tolerated the treatment well and exhibited a complete response in lung for about 5 months. Afterwards, the patients experienced relapse in the brain and started programmed death protein 1 (PD-1) regimens of toripalimab plus lenalidomide, which also exhibited a good response with decreased lesions in brain after half-year treatment. However, the patient experienced relapse again in the brain 3 months later and started chemotherapy with methotrexate plus rituximab. The patient had survived for over 2 years since the initial diagnosis of stage IV DLBCL and has continued to survive after experiencing a relapse in the brain for approximately 11 months till now. Conclusions: These findings suggest that toripalimab may be a new therapeutic option for central nervous system recurrence in refractory CD5+ DLBCL with MYD88 and CD79B comutation. Further clinical trials are warranted to confirm these results.

Effect of remimazolam vs propofol on emergence from general anesthesia in patients undergoing cerebral endovascular procedures: A randomized controlled, non-inferiority trial.

STUDY OBJECTIVE: This study aimed to compare the time to emergence from general anesthesia with remimazolam versus propofol in patients undergoing cerebral endovascular procedures. DESIGN: A prospective, double-blind, randomized controlled, non-inferiority trial. SETTING: An academic hospital. PATIENTS: Adult patients scheduled for cerebral endovascular procedures. INTERVENTIONS: Patients were randomized at a 1:1 ratio to undergo surgery under general anesthesia with remimazolam (0.1 mg kg-1 for induction and 0.3-0.7 mg kg-1 h-1 for maintenance) or propofol (1-1.5 mg kg-1 for induction and 4-10 mg kg-1 h-1 for maintenance). MEASUREMENTS: The primary outcome was the time to emergence from anesthesia. The non-inferiority margin was -2.55 min in group difference. Major secondary outcomes included hypotension during induction, incidence of postoperative delirium and Modified Rankin Scale (mRs) at 30 days and 90 days after surgery. MAIN RESULTS: Of the 142 randomized patients, 129 completed the trial. In the modified intention-to-treat analysis, the mean time to emergence from anesthesia was 16.1 [10.4] min in the remimazolam group vs. 19.0 [11.2] min in the propofol group. The group difference was -2.9 min [95% CI -6.5, 0.7] (P = 0.003 for non-inferiority). The remimazolam group had lower rate of hypotension during induction (11.3% vs 25.4%, P = 0.03) and use of vasopressors during surgery (29.6% vs 62.0%, P < 0.001). The two groups did not differ in postoperative delirium and mRs at 30 and 90 days after surgery. CONCLUSIONS: In patients undergoing cerebral endovascular procedures, remimazolam did not increase the time from anesthesia vs propofol.

Development and Validation of a Predictive Model Based on LASSO Regression: Predicting the Risk of Early Recurrence of Atrial Fibrillation after Radiofrequency Catheter Ablation.

BACKGROUND: Although recurrence rates after radiofrequency catheter ablation (RFCA) in patients with atrial fibrillation (AF) remain high, there are a limited number of novel, high-quality mathematical predictive models that can be used to assess early recurrence after RFCA in patients with AF. PURPOSE: To identify the preoperative serum biomarkers and clinical characteristics associated with post-RFCA early recurrence of AF and develop a novel risk model based on least absolute shrinkage and selection operator (LASSO) regression to select important variables for predicting the risk of early recurrence of AF after RFCA. METHODS: This study collected a dataset of 136 atrial fibrillation patients who underwent RFCA for the first time at Peking University Shenzhen Hospital from May 2016 to July 2022. The dataset included clinical characteristics, laboratory results, medication treatments, and other relevant parameters. LASSO regression was performed on 100 cycles of data. Variables present in at least one of the 100 cycles were selected to determine factors associated with the early recurrence of AF. Then, multivariable logistic regression analysis was applied to build a prediction model introducing the predictors selected from the LASSO regression analysis. A nomogram model for early post-RFCA recurrence in AF patients was developed based on visual analysis of the selected variables. Internal validation was conducted using the bootstrap method with 100 resamples. The model's discriminatory ability was determined by calculating the area under the curve (AUC), and calibration analysis and decision curve analysis (DCA) were performed on the model. RESULTS: In a 3-month follow-up of AF patients (n = 136) who underwent RFCA, there were 47 recurrences of and 89 non-recurrences of AF after RFCA. P, PLR, RDW, LDL, and CRI-II were associated with early recurrence of AF after RFCA in patients with AF (p < 0.05). We developed a predictive model using LASSO regression, incorporating four robust factors (PLR, RDW, LDL, CRI-II). The AUC of this prediction model was 0.7248 (95% CI 0.6342-0.8155), and the AUC of the internal validation using the bootstrap method was 0.8403 (95% CI 0.7684-0.9122). The model demonstrated a strong predictive capability, along with favorable calibration and clinical applicability. The Hosmer-Lemeshow test indicated that there was good consistency between the predicted and observed values. Additionally, DCA highlighted the model's advantages in terms of its clinical application. CONCLUSIONS: We have developed and validated a risk prediction model for the early recurrence of AF after RFCA, demonstrating strong clinical applicability and diagnostic performance. This model plays a crucial role in guiding physicians in preoperative assessment and clinical decision-making. This novel approach also provides physicians with personalized management recommendations.

A Preliminary Study on the Effectiveness of K-Nearest Neighbor Algorithm Based on Local Mean for Classification of Bioinformatics Data.

The preliminary classification of biological class data is of great importance for bioinformatics. One can quickly classify object data by comparing their existing features with known traits. k-nearest neighbor algorithm is easy to apply in this field, but its drawbacks make it less meaningful to improve the efficiency of the algorithm by simply changing the distance model, so this study uses a local mean-based k-nearest neighbor classifier and compares the accuracy of the predicted classification of six different distance models used. The prediction accuracies in the experimental results were all greater than 70%, and the highest accuracy was achieved in different data sets for all distance models with K=2; the prediction accuracy of Minkowski distance with different parameters had the highest volatility in the test.and the experimental results can be used as a reference for related practitioners.

Acupuncture-related techniques for postoperative cognitive complications: a systemic review and meta-analysis.

BACKGROUND: Postoperative cognitive complications are major challenges for postoperative recovery. Acupuncture-related techniques have been used for treating neurocognitive dysfunctions. However, whether they help to prevent postoperative cognitive complicationss remains unclear. We intend to evaluate the effect of acupuncture-related techniques on the incidence of postoperative cognitive complications (PCC) in patients undergoing surgery under general anesthesia. METHODS: Based on PRISMA guidelines, a search of PubMed, EMBASE, Web of Science, and the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov was performed to identify eligible trials published from inception to June 6, 2021. The search was performed in June 2021. The inclusion criteria were prospective, randomized, controlled clinical trials that compared acupuncture-related techniques with other techniques or non-acupuncture treatment in patients undergoing surgery under general anesthesia. Pooled odds ratios (ORs), 95% CIs, and P values were estimated for end points using fixed and random effects statistical models. RESULTS: The analysis included 12 studies with 1058 patients. Compared with patients not receiving acupuncture, patients treated with acupuncture-related techniques had a lower incidence of PCCs (OR, 0.44; 95% CI, 0.33 to 0.59; P < 0.001; n = 968) and lower levels of biomarkers, including IL-6, TNF-α, and S100ß. Acupuncture with needles and without needles showed similar effects on the prevention of PCCs. The effects of acupuncture-related techniques on PCCs were observed in both English and non-English articles. Subgroup analyses showed that both agitation and/or delirium (OR, 0.51; 95% CI, 0.34 to 0.76; P < 0.001; n = 490) and delayed cognitive recovery (OR, 0.33; 95% CI, 0.21 to 0.51; P < 0.001; n = 478) were reduced after treatment with acupuncture-related techniques. In adult studies evaluating MMSE scores, the scores were not different between groups (SMD, - 0.71; 95% CI, - 1.72 to 0.3; P = 0.17; n = 441). CONCLUSIONS: Acupuncture-related techniques, including needle techniques and electrical techniques, are associated with fewer postoperative cognitive complications, suggesting that acupuncture could be considered a potential option in the perioperative setting. Additional research is needed to develop higher-quality evidence and optimal regimens. TRIAL REGISTRATION: PROSPERO (CRD42021258378).

Transcriptome analysis of brassinolide under low temperature stress in winter wheat.

Low temperatures are the main abiotic factor affecting wheat growth. Brassinolide is a novel plant hormone that can improve the cold resistance of plants; however, the molecular mechanism of brassinolide in winter wheat at low temperatures remains unclear. In this study, winter wheat Dongnong dongmai 1 was sprayed with 0.01, 0.1, or 1.0 mg·L-1 brassinolide (BR) at the three-leaf stage, and tillering nodes were sampled at different temperatures (5, -10 and -25 °C), and then physiological indexes were determined and the transcriptome was sequenced. The results showed that the optimum concentration of brassinolide for cold resistance is 0.1 mg·L-1. A total of 15 302 (8198 upregulated and 7104 downregulated) differentially expressed genes (DEGs) were identified in the B1 vs D1 comparison (B1 represents 5 °C 0.1 mg·L-1 BR treatment, D1 represents 5 °C control); 3386 (1930 upregulated and 1456 downregulated) differentially expressed genes (DEGs) were identified in the B2 vs D2 comparison (B2 represents -10 °C 0.1 mg·L-1 BR treatment, D2 represents -10 °C control); and 2684 (2102 upregulated and 582 downregulated) differentially expressed genes (DEGs) were identified in the B3 vs D3 comparison (B3 represents -25 °C 0.1 mg·L-1 BR treatment, D3 represents -25 °C control). Further studies showed that these DEGs were mainly involved in carbon fixation in photosynthetic organs, photosynthesis and plant-pathogen interactions, all of which were related to stress and energy metabolism. This indicates that brassinolide can produce substances that improve cold resistance in wheat seedlings. This study provides a theoretical basis for further research on the improvement of cold resistance in winter wheat by brassinolide.

Electroacupuncture pretreatment induces ischemic tolerance by neuronal TREM2-mediated enhancement of autophagic flux.

The mechanism of electroacupuncture (EA) pretreatment-induced neuroprotection remains unclear. In this study, we found that neuronal Triggering receptor expressed on myeloid cells 2 (TREM2) expression was increased and peaked at 48 h and 72 h after ischemia/reperfusion. After specific knockdown of TREM2 in excitatory neurons, neurological function was damaged, and the infarct volume was enlarged. Furthermore, the expression of LC3II/LC3I and Beclin1 was decreased, while the expression of p62 was increased. EA pretreatment enhanced TREM2, LC3II/LC3I and Beclin1 expression while reducing p62 in the ischemic penumbra area. The EA-induced neuroprotective effects and improvements in autophagic flux were abolished by specific knockdown of TREM2 in excitatory neurons. Taken together, our findings provide novel mechanistic insight into EA-induced ischemic tolerance and suggest a promising therapeutic strategy of targeting neuronal TREM2 to treat brain ischemia.

Remimazolam versus propofol for procedural sedation and anesthesia: a systemic review and meta-analysis.

INTRODUCTION: The aim of this systemic review and meta-analysis was to evaluate the efficacy and safety of remimazolam compared with propofol when used for procedural sedation and general anesthesia. EVIDENCE ACQUISITION: Data sources were PubMed, EMBASE, Web of Science, the Cochrane Central Register of Controlled Trials, and ClinicaTrials.gov, searched up to March 21, 2022. RCTs comparing remimazolam and propofol in patients undergoing procedural sedation or general anesthesia were searched. Pooled risk ratios (RRs) or standardized mean difference, 95% CIs, and P values were estimated for end points using the fixed- and random-effects statistical model. The trial sequential analysis was used for sensitivity analysis. EVIDENCE SYNTHESIS: Ten studies with 1813 patients were included. Compared with propofol, remimazolam had lower success rate of sedation/general anesthesia (RR, 1.02; 95% CI: 1.01 to 1.03; P=0.004; N.=1402). However, remimazolam had lower incidence of hypoxia, hypotension, and injection pain than propofol. No difference in incidence of nausea and vomiting, time to awake and to discharge was found. Subgroup studies showed that remimazolam had lower success rate than propofol when used for procedural sedation, not general anesthesia. The trial sequential analysis adjusted confidence interval was 1.01 to 1.04 for success rate. CONCLUSIONS: Remimazolam could be alternatively used in procedural sedation and general anesthesia. Additional research is needed to develop higher quality evidence on the use of remimazolam, especially in general anesthesia.

Depression in polycystic ovary syndrome: Focusing on pathogenesis and treatment.

Polycystic ovary syndrome (PCOS) is one of the most prevalent gynecological endocrine conditions affecting reproductive women. It can feature a variety of symptoms, such as obesity, insulin resistance, skin conditions, and infertility. Women with PCOS are susceptible to illnesses including mood disorders, diabetes, hypertension, and dyslipidemia. Among them, depression is the most common in PCOS and has a detrimental effect on quality of life. Depression may occasionally develop due to the pathological traits of PCOS, but its exact pathogenesis in PCOS have eluded researchers to date. Therefore, there is an urgent need to explore the pathogenesis and treatments of depression in PCOS. The present review discusses the epidemiology of depression in PCOS, potential pathogenic mechanisms underlying PCOS and depression, as well as some potential factors causing depression in PCOS, including obesity, insulin resistance, hyperandrogenism, inflammation, and infertility. Meanwhile, some common treatment strategies for depression in PCOS, such as lifestyle intervention, acupuncture, oral contraceptive pills, psychological intervention, and insulin-sensitizer, are also reviewed. To fully understand the pathogenesis and treatment of depression in PCOS, a need remains for future large-scale multi-center randomized controlled trials and in-depth mechanism studies.

Effect of Etomidate vs Propofol for Total Intravenous Anesthesia on Major Postoperative Complications in Older Patients: A Randomized Clinical Trial.

Importance: Older patients may benefit from the hemodynamic stability of etomidate for general anesthesia. However, it remains uncertain whether the potential for adrenocortical suppression with etomidate may increase morbidity. Objective: To test the primary hypothesis that etomidate vs propofol for anesthesia does not increase in-hospital morbidity after abdominal surgery in older patients. Design, Setting, and Participants: This multicenter, parallel-group, noninferiority randomized clinical trial (Etomidate vs Propofol for In-hospital Complications [EPIC]) was conducted between August 15, 2017, and November 20, 2020, at 22 tertiary hospitals in China. Participants were aged 65 to 80 years and were scheduled for elective abdominal surgery. Patients and outcome assessors were blinded to group allocation. Data analysis followed a modified intention-to-treat principle. Interventions: Patients were randomized 1:1 to receive either etomidate or propofol for general anesthesia by target-controlled infusion. Main Outcomes and Measures: Primary outcome was a composite of major in-hospital postoperative complications (with a noninferiority margin of 3%). Secondary outcomes included intraoperative hemodynamic measurements; postoperative adrenocortical hormone levels; self-reported postoperative pain, nausea, and vomiting; and mortality at postoperative months 6 and 12. Results: A total of 1944 participants were randomized, of whom 1917 (98.6%) completed the trial. Patients were randomized to the etomidate group (n = 967; mean [SD] age, 70.3 [4.0] years; 578 men [59.8%]) or propofol group (n = 950; mean [SD] age, 70.6 [4.2] years; 533 men [56.1%]). The primary end point occurred in 90 of 967 patients (9.3%) in the etomidate group and 83 of 950 patients (8.7%) in the propofol group, which met the noninferiority criterion (risk difference [RD], 0.6%; 95% CI, -1.6% to 2.7%; P = .66). In the etomidate group, mean (SD) cortisol levels were lower at the end of surgery (4.8 [2.7] µg/dL vs 6.1 [3.4] µg/dL; P < .001), and mean (SD) aldosterone levels were lower at the end of surgery (0.13 [0.05] ng/dL vs 0.15 [0.07] ng/dL; P = .02) and on postoperative day 1 (0.14 [0.04] ng/dL vs 0.16 [0.06] ng/dL; P = .001) compared with the propofol group. No difference in mortality was observed between the etomidate and propofol groups at postoperative month 6 (2.2% vs 3.0%; RD, -0.8%; 95% CI, -2.2% to 0.7%) and 12 (3.3% vs 3.9%; RD, -0.6%; 95% CI, -2.3% to 1.0%). More patients had pneumonia in the etomidate group than in the propofol group (2.0% vs 0.3%; RD, 1.7%; 95% CI, 0.7% to 2.8%; P = .001). Results were consistent in the per-protocol population. Conclusions and Relevance: Results of this trial showed that, compared with propofol, etomidate anesthesia did not increase overall major in-hospital morbidity after abdominal surgery in older patients, although it induced transient adrenocortical suppression. Trial Registration: ClinicalTrials.gov Identifier: NCT02910206.

Zinc finger protein 280C contributes to colorectal tumorigenesis by maintaining epigenetic repression at H3K27me3-marked loci.

Dysregulated epigenetic and transcriptional programming due to abnormalities of transcription factors (TFs) contributes to and sustains the oncogenicity of cancer cells. Here, we unveiled the role of zinc finger protein 280C (ZNF280C), a known DNA damage response protein, as a tumorigenic TF in colorectal cancer (CRC), required for colitis-associated carcinogenesis and Apc deficiency­driven intestinal tumorigenesis in mice. Consistently, ZNF280C silencing in human CRC cells inhibited proliferation, clonogenicity, migration, xenograft growth, and liver metastasis. As a C2H2 (Cys2-His2) zinc finger-containing TF, ZNF280C occupied genomic intervals with both transcriptionally active and repressive states and coincided with CCCTC-binding factor (CTCF) and cohesin binding. Notably, ZNF280C was crucial for the repression program of trimethylation of histone H3 at lysine 27 (H3K27me3)-marked genes and the maintenance of both focal and broad H3K27me3 levels. Mechanistically, ZNF280C counteracted CTCF/cohesin activities and condensed the chromatin environment at the cis elements of certain tumor suppressor genes marked by H3K27me3, at least partially through recruiting the epigenetic repressor structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1). In clinical relevance, ZNF280C was highly expressed in primary CRCs and distant metastases, and a higher ZNF280C level independently predicted worse prognosis of CRC patients. Thus, our study uncovered a contributor with good prognostic value to CRC pathogenesis and also elucidated the essence of DNA-binding TFs in orchestrating the epigenetic programming of gene regulation.

Application effects of remimazolam and propofol on elderly patients undergoing hip replacement.

OBJECTIVE: To explore the anesthetic and analgesic effects of remimazolam and propofol in elderly patients undergoing hip replacement and their effects on respiratory and circulatory systems, stress and cognitive function. METHODS: Sixty elderly patients undergoing elective hip replacement in the hospital were selected as the research subjects, and they were divided into the remimazolam group and the propofol group according to the admission sequence of patients. The remimazolam group was anesthetized with remimazolam, and the propofol group was anesthetized with propofol. The anesthesia-related indicators, perioperative pain degree [Visual Analogue Scale (VAS)], circulatory indicators [heart rate, mean arterial pressure (MAP)] before anesthesia (T0), immediately before laryngeal mask insertion (T1), at 5 min after laryngeal mask insertion (T2), at 30 min after laryngeal mask insertion (T3) and at 5 min after laryngeal mask removal (T4), stress response indicators (plasma epinephrine, norepinephrine, cortisol) before anesthesia induction and at 24 h and 72 h after surgery, cognitive function [Mini-Mental State Examination (MMSE)] and adverse reactions were compared between the two groups. RESULTS: Among the 60 enrolled patients, only 1 case was excluded due to withdrawal, thus 30 cases in the remimazolam group and 29 cases in the propofol group were included. There were statistically significant differences in the heart rate, MAP, plasma epinephrine, norepinephrine, cortisol and VAS score in the two groups from the aspects of interaction effect and time-point effect (P < 0.05). The heart rate and MAP at T1, T2 and T3 in the two groups were significantly decreased compared with those at T0, but the heart rate and MAP in the remimazolam group at T1, T2 and T3 were significantly higher than those in the propofol group (P < 0.05). There were no statistical differences in the anesthesia time, awakening time and extubation time between the remimazolam group and the propofol group (P > 0.05). The levels of plasma epinephrine, norepinephrine and cortisol in the two groups were significantly higher at 24 h and 72 h after surgery than those before anesthesia induction, and the above levels were significantly lower in the remimazolam group than those in the propofol group (P < 0.05). The VAS scores at each time point in the two groups were significantly reduced compared to before surgery, but there was no statistically significant difference between the two groups after surgery (P > 0.05). The MMSE scores of the two groups were significantly lower at 1 d and 3 d after surgery compared with those before anesthesia induction, but the score in the remimazolam group was significantly higher than that in the propofol group (P < 0.05). In addition, the incidence rates of adverse reactions were significantly lower in the remimazolam group compared to the propofol group (P < 0.05). CONCLUSION: Compared with propofol, remimazolam can achieve equivalent anesthetic and analgesic effects in elderly patients undergoing hip replacement. However, the latter one can significantly relieve respiratory and circulatory suppression, stress response and cognitive dysfunction, with good safety. TRIAL REGISTRATION: This single-center, prospective, RCT has completed the registration of the Chinese Clinical Trial Center at 31/12/2021 with the registration number ChiCTR2100055039 .

Transcutaneous electrical acupoint stimulation before surgery reduces chronic pain after mastectomy: A randomized clinical trial.

STUDY OBJECTIVE: Despite multiple interventions, the incidence of chronic pain after mastectomy could be as high as 50% after surgery. This study aimed to determine the efficacy of transcutaneous electrical acupoint stimulation (TEAS) before anesthesia induction in reducing chronic pain and to compare the effect of combined acupoint TEAS with that of single acupoint TEAS. DESIGN: A multicenter randomized clinical trial. SETTING: The study was conducted at six medical centers in China from May 2016 to April 2018. Final follow-up was on October 26, 2018. PARTICIPANTS: Eligible patients were women scheduled for radical mastectomy under general anesthesia. INTERVENTIONS: Patients were randomly and equally grouped into sham control (n = 188), single acupoint (PC6, n = 198), or combined acupoints (PC6 and CV17, n = 190) TEAS groups using a centralized computer-generated randomization system. TEAS was applied for 30 min before anesthesia induction. The sham-operated control group received electrode attachment but without stimulation. Anesthesiologists, surgeons, and outcome assessors were blinded to the interventions. MEASURES: The primary endpoint was the incidence of chronic pain 6 months after surgery. Incidences were compared among the groups using the unadjusted χ2 test. RESULTS: Of the 576 randomized patients, 568 completed the trial. In the intention-to-treat analysis, post-mastectomy pain at 6 months was reported in 42 of 190 patients (22.1%) in the combined acupoints group, 65 of 188 patients (34.6%) in the sham-operated group (P = 0.007; relative risk [RR], 95% confidence interval [CI]: 0.68, 0.52-0.89), and 72 of 198 patients (36.4%) in the single acupoint group (P = 0.002; RR, 95% CI: 0.72, 0.55-0.93). Remifentanil consumption during surgery and postoperative nausea and vomiting at 24 h after surgery were lower in the combined acupoint group than that in the sham-operated group. CONCLUSION: TEAS at combined acupoints before surgery was associated with reduced chronic pain 6 months after surgery. TRIAL REGISTRATION: Clinicaltrials.gov identifier: NCT02741726. Registered on April 13, 2016.

Transient aphasia following general anesthesia in patient undergoing laparoscopic gynecologic surgery: A case report and literature review.

Aphasia could be a manifestation of postoperative psychoemotional disorder. Early differential diagnosis is important.

Targeted inhibition of KDM6 histone demethylases eradicates tumor-initiating cells via enhancer reprogramming in colorectal cancer.

Tumor-initiating cells (TICs) maintain heterogeneity within tumors and seed metastases at distant sites, contributing to therapeutic resistance and disease recurrence. In colorectal cancer (CRC), strategy that effectively eradicates TICs and is of potential value for clinical use still remains in need. Methods: The anti-tumorigenic activity of a small-molecule inhibitor of KDM6 histone demethylases named GSK-J4 in CRC was evaluated by in vitro assays and in vivo imaging of xenografted tumors. Sphere formation, flow cytometry analysis of cell surface markers and intestinal organoid formation were performed to examine the impact of GSK-J4 on TIC properties. Transcriptome analysis and global profiling of H3K27ac, H3K27me3, and KDM6A levels by ChIP-seq were conducted to elucidate how KDM6 inhibition reshapes epigenetic landscape and thereby eliminating TICs. Results: GSK-J4 alleviated the malignant phenotypes of CRC cells in vitro and in vivo, sensitized them to chemotherapeutic treatment, and strongly repressed TIC properties and stemness-associated gene signatures in these cells. Mechanistically, KDM6 inhibition induced global enhancer reprogramming with a preferential impact on super-enhancer-associated genes, including some key genes that control stemness in CRC such as ID1. Besides, expression of both Kdm6a and Kdm6b was more abundant in mouse intestinal crypt when compared with upper villus and inhibition of their activities blocked intestinal organoid formation. Finally, we unveiled the power of KDM6B in predicting both the overall survival outcome and recurrence of CRC patients. Conclusions: Our study provides a novel rational strategy to eradicate TICs through reshaping epigenetic landscape in CRC, which might also be beneficial for optimizing current therapeutics.

Oncogenic HOXB8 is driven by MYC-regulated super-enhancer and potentiates colorectal cancer invasiveness via BACH1.

Aberrant activation of Homeobox genes in human cancers has long been documented, whereas the mechanisms underlying remain largely obscure. Super-enhancers (SEs) act as key regulatory elements for both cell identity genes and cancer genes. Herein, we reported that SE-associated HOXB gene cluster represented a common feature of colorectal cancer (CRC) cell lines and multiple HOXB genes within this cluster were overexpressed in CRC. Among them, we found that HOXB8 was oncogenic and its activation in CRC was driven by SE instead of genetic alteration. We further demonstrated that the master transcription factor MYC preferentially occupied SEs over TEs (typical enhancers) and regulated HOXB8 transcription by binding to the active elements of its SE. HOXB8 silencing induced reversal of transcriptional signatures associated with malignant phenotypes of CRC. Mechanistically, HOXB8 interacted with a key metastasis regulator BACH1 and instigated BACH1-mediated transcriptional cascade by directly occupying and activating BACH1 gene transcription together with BACH1 itself. Lastly, the relevance of HOXB8 activation in clinical settings was strengthened by its close association with prognostic outcomes of CRC patients.

Effectively Measuring Respiratory Flow With Portable Pressure Data Using Back Propagation Neural Network.

Continuous respiratory monitoring is an important tool for clinical monitoring. The most widely used flow measure device is nasal cannulae connected to a pressure transducer. However, most of these devices are not easy to carry and continue working in uncontrolled environments which is also a problem. For portable breathing equipment, due to the volume limit, the pressure signals acquired by using the airway tube may be too weak and contain some noise, leading to huge errors in respiratory flow measures. In this paper, a cost-effective portable pressure sensor-based respiratory measure device is designed. This device has a new airway tube design, which enables the pressure drop efficiently after the air flowing through the airway tube. Also, a new back propagation (BP) neural network-based algorithm is proposed to stabilize the device calibration and remove pressure signal noise. For improving the reliability and accuracy of proposed respiratory device, a through experimental evaluation and a case study of the proposed BP neural network algorithm have been carried out. The results show that giving proper parameters setting, the proposed BP neural network algorithm is capable of efficiently improving the reliability of newly designed respiratory device.