Cells not only contain membrane-bound organelles (MBOs), but also membraneless organelles (MLOs) formed by condensation of many biomacromolecules. Examples include RNA-protein granules such as nucleoli and PML nuclear bodies (PML-NBs) in the nucleus, as well as stress granules and P-bodies in the cytoplasm. Phase separation is the basic organizing principle of the form of the condensates or membraneless organelles (MLOs) of biomacromolecules including proteins and nucleic acids. In particular, liquid-liquid phase separation (LLPS) compartmentalises and concentrates biological macromolecules into liquid condensates. It has been found that phase separation of biomacromolecules requires some typical intrinsic characteristics, such as intrinsically disordered regions, modular domains and multivalent interactions. The phase separation of biomacromolecules plays a key role in many important cell activities. In recent years, the phase separation of biomacromolecules phase has become a focus of research in gene transcriptional regulation. Transcriptional regulatory elements such as RNA polymerases, transcription factors (TFs), and super enhancers (SEs) all play important roles through phase separation. Our group has previously reported for the first time that long-term inactivation or absence of assembly factors leads to the formation of condensates of RNA polymerase II (RNAPII) subunits in the cytoplasm, and this process is reversible, suggesting a novel regulatory model of eukaryotic transcription machinery. The phase separation of biomacromolecules provides a biophysical understanding for the rapid transmission of transcriptional signals by a large number of TFs. Moreover, phase separation during transcriptional regulation is closely related to the occurrence of cancer. For example, the activation of oncogenes is usually associated with the formation of phase separation condensates at the SEs. In this review, the intrinsic characteristics of the formation of biomacromolecules phase separation and the important role of phase separation in transcriptional regulation are reviewed, which will provide reference for understanding basic cell activities and gene regulation in cancer.

Diabetic wounds are a common complication of diabetic patients, and the incidence has been increasing in recent years. In addition, its poor clinical prognosis seriously affects the quality of life of patients, which has become the focus and difficulty of diabetes treatment. As the RNA regulating gene expression, non-coding RNA can regulate the pathophysiological process of diseases, and play an important role in the healing process of diabetic wounds. In this paper, we reviewed the regulatory role, diagnostic value, and therapeutic potential of three common non-coding RNA in diabetic wounds, in order to provide a new solution for the diagnosis and treatment of diabetic wounds at the genetic and molecular level.
Humans ; Quality of Life ; Diabetes Mellitus/genetics* ; Wound Healing ; RNA, Untranslated/genetics*

OBJECTIVE: To explore the efficacy and survival of venetoclax based (VEN-based) regimen in the treatment of acute myeloid leukemia（AML）. METHODS: A retrospective study was conducted in patients who received VEN-based regimen and completed at least 1 course of efficacy evaluation at the The First Affiliated Hospital of Nanchang University from July 2019 to July 2022. The incidence of complete remission （CR）/CR with incomplete hematologic recovery （CRi） rate, objective remission rate（ORR） and survival of patients with different risk strati- fication and gene subtypes were analyzed. RESULTS: A total of 79 patients were enrolled, including 43 patients with newly diagnosed unfit AML （unfit AML） and 36 relapsed/refractory AML (R/R AML). The median age of the patients was 62(14-83) years old. 36 out of 79 patients achieved CR/CRi and the ORR of the whole cohort was 64.6%. The CR/CRi rate of unfit AML patients was significantly higher than that of R/R AML patients (60.5% vs 27.8%, P=0.004). In unfit AML cohort, the patients with NPM1 and IDH1/2 mutations were benefited, 8 out of 9 patients ahcieved CR/CRi, 7/8 and 5/8 patients achieved minimal residual disease (MRD) negativity, respectively. Six out of 9 patients with TET2 mutation achieved CR/CRi, 3/6 patients achieved MRD negativity. In R/R AML cohort, 2 out of 3 patients with RUNX1 mutation achieved CR/CRi, without MRD negative, while the CR/CRi rate of patients with other gene mutations was lower than 40%. The median follow-up time was 10.1(95%CI: 8.6-11.6) months. In whole cohort, the median overall survival (mOS) time was 9.1 months and the relapse free survival (RFS) time was not reached. The mOS and RFS of unfit AML patients were significantly longer than those of R/R AML patients (14.1 vs 6.8 months, P=0.013; not reached vs 3.3 months, P=0.000). In unfit AML cohort, the mOS of patients with NPM1 or IDH1/2 mutations was not reached, while that of patients without NPM1 or IDH1/2 mutations was 8.0 months (P=0.009; P=0.022). Furthermore, the mOS of patients with TP53 mutaion was significantly shorter than that of patients without TP53 mutation (5.2 vs 14.1 months， P=0.049). In R/R AML cohort, there was no significant difference in mOS between patients with mutation in each gene subtype and those without gene mutation (P>0.05). All patients had hematology adverse reactions, 91.1% patients had AE grade≥3. The most common non-hematology adverse reactions was infection, with an incidence of 91.1%. VEN-based regimen was tolerable for AML patients. CONCLUSION VEN-based regimen can achieve a high response rate, especially in unfit AML with acceptable safety, and some patients can achieve MRD negative. It is also effective in NPM1-, IDH1/2-positive patients with long survival time.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Retrospective Studies ; Nucleophosmin ; Bridged Bicyclo Compounds, Heterocyclic/adverse effects* ; Leukemia, Myeloid, Acute/genetics* ; Recurrence ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Objective: To understand the current situation and influencing factors of cervical and lumbar spine diseases of the express delivery employees, and provide scientific basis for carrying out their occupational health protection in a targeted manner. Methods: From February 2020 to January 2021, the current situation research method was used to obtain 527 express delivery employees by cluster sampling. Online questionnaires were used to investigate sociodemographic characteristics and emotional characteristics, and clinical data were obtained by digital X-ray (DR) examination of the neck and waist. Pearson χ(2) test and multivariate logistic regression were used to analyze the influencing factors of cervical and lumbar spine diseases in express delivery employees. Results: The prevalence rates of cervical spine and lumbar spine diseases among express delivery employees were 49.15% (259/527) and 67.74% (357/527) , respectively. Univariate analysis showed that there were statistically significant differences in the distribution of cervical and lumbar spine disease among express delivery employees with different ages, length of service, working hours per week, and different degrees of distress due to emotional factors (P<0.05) . Multivariate analysis showed that express delivery employees aged ≥25 years old had a higher risk of cervical spine disease (P<0.05) , the express delivery employees who worked 49-55 hours per week had a lower risk of cervical spine disease (P<0.05) . Express delivery employees aged≥35 years old had a lower risk of lumbar spine disease (P<0.05) , and the risk of lumbar spine disease was higher among express delivery workers who suffered moderate or more distress due to emotional factors (such as anxiety, depression, or irritability) in the past 4 weeks (P<0.05) . Conclusion: The prevalence of cervical and lumbar spine diseases is relatively high among express delivery employees. It is recommended to adjust the weekly working hours of express delivery employees, organize psychological counseling training, and effectively protect the occupational health rights of express delivery employees.
Adult ; Health Services Accessibility ; Human Rights ; Humans ; Occupational Health ; Prevalence ; Surveys and Questionnaires

Objective: To explore the value of cerebral hypoxic-ischemic injury markers in the early diagnosis of sepsis associated encephalopathy (SAE) in burn patients with sepsis. Methods: A retrospective case series study was conducted. From October 2018 to May 2021, 41 burn patients with sepsis who were admitted to Zhengzhou First People's Hospital met the inclusion criteria, including 23 males and 18 females, aged 18-65 (35±3) years. According to whether SAE occurred during hospitalization, the patients were divided into SAE group (21 cases) and non-SAE group (20 cases). The gender, age, deep partial-thickness burn area, full-thickness burn area, and acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) scores of patients were compared between the two groups. The serum levels of central nervous system specific protein S100β and neuron specific enolase (NSE) at 12, 24, and 48 h after sepsis diagnosis (hereinafter referred to as after diagnosis), the serum levels of interleukin-6 (IL-6), IL-10, tumor necrosis factor α (TNF-α), Tau protein, adrenocorticotropic hormone (ACTH), and cortisol at 12, 24, 48, 72, 120, and 168 h after diagnosis, and the mean blood flow velocity of middle cerebral artery (VmMCA), pulsatility index, and cerebral blood flow index (CBFi) on 1, 3, and 7 d after diagnosis of patients in the two groups were counted. Data were statistically analyzed with chi-square test, analysis of variance for repeated measurement, independent sample t test, and Bonferroni correction. The independent variables to predict the occurrence of SAE was screened by multi-factor logistic regression analysis. The receiver operating characteristic (ROC) curve was drawn for predicting the occurrence of SAE in burn patients with sepsis, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. Results: The gender, age, deep partial-thickness burn area, full-thickness burn area, and APACHE Ⅱ score of patients in the two groups were all similar (χ²=0.02, with t values of 0.71, 1.59, 0.91, and 1.07, respectively, P>0.05). At 12, 24, and 48 h after diagnosis, the serum levels of S100β and NSE of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 37.74, 77.84, 44.16, 22.51, 38.76, and 29.31, respectively, P<0.01). At 12, 24, 48, 72, 120, and 168 h after diagnosis, the serum levels of IL-10, Tau protein, and ACTH of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 10.68, 13.50, 10.59, 8.09, 7.17, 4.71, 5.51, 3.20, 3.61, 3.58, 3.28, 4.21, 5.91, 5.66, 4.98, 4.69, 4.78, and 2.97, respectively, P<0.01). At 12, 24, 48, 72, and 120 h after diagnosis, the serum levels of IL-6 and TNF-α of patients in SAE group were all significantly higher than those in non-SAE group (with t values of 8.56, 7.32, 2.08, 2.53, 3.37, 4.44, 5.36, 5.35, 6.85, and 5.15, respectively, P<0.05 or P<0.01). At 12, 24, and 48 h after diagnosis, the serum level of cortisol of patients in SAE group was significantly higher than that in non-SAE group (with t values of 5.44, 5.46, and 3.55, respectively, P<0.01). On 1 d after diagnosis, the VmMCA and CBFi of patients in SAE group were significantly lower than those in non-SAE group (with t values of 2.94 and 2.67, respectively, P<0.05). On 1, 3, and 7 d after diagnosis, the pulsatile index of patients in SAE group was significantly higher than that in non-SAE group (with t values of 2.56, 3.20, and 3.12, respectively, P<0.05 or P<0.01). Serum IL-6 at 12 h after diagnosis, serum Tau protein at 24 h after diagnosis, serum ACTH at 24 h after diagnosis, and serum cortisol at 24 h after diagnosis were the independent risk factors for SAE complicated in burn patients with sepsis (with odds ratios of 2.42, 1.38, 4.29, and 4.19, 95% confidence interval of 1.76-3.82, 1.06-2.45, 1.37-6.68, and 3.32-8.79, respectively, P<0.01). For 41 burn patients with sepsis, the AUC of ROC of serum IL-6 at 12 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.84-1.00), the best threshold was 157 pg/mL, the sensitivity was 81%, and the specificity was 89%. The AUC of ROC of serum Tau protein at 24 h after diagnosis for predicting SAE was 0.92 (95% confidence interval was 0.82-1.00), the best threshold was 6.4 pg/mL, the sensitivity was 97%, and the specificity was 99%. The AUC of ROC of serum ACTH at 24 h after diagnosis for predicting SAE was 0.96 (95% confidence interval was 0.89-1.00), the best threshold was 14.7 pg/mL, the sensitivity was 90%, and the specificity was 94%. The AUC of ROC of serum cortisol at 24 h after diagnosis for predicting SAE was 0.93 (95% confidence interval was 0.86-1.00), the best threshold was 89 nmol/L, the sensitivity was 94%, and the specificity was 97%. Conclusions: Serum Tau protein, ACTH, and cortisol have high clinical diagnostic value for SAE complicated in burn patients with sepsis.
Adolescent ; Adult ; Aged ; Burns/complications* ; Early Diagnosis ; Female ; Humans ; Male ; Middle Aged ; Prognosis ; ROC Curve ; Retrospective Studies ; Sepsis/diagnosis* ; Sepsis-Associated Encephalopathy ; Young Adult

INTRODUCTION: Bystander cardiopulmonary resuscitation (B-CPR) is associated with improved out-of hospital cardiac arrest survival. Community-level interventions including dispatcher-assisted CPR (DA-CPR) and myResponder were implemented to increase B-CPR. We sought to assess whether these interventions increased B-CPR. METHODS: The Singapore out-of-hospital cardiac arrest registry captured cases that occurred between 2010 and 2017. Outcomes occurring in 3 time periods (Baseline, DA-CPR, and DA-CPR plus myResponder) were compared. Segmented regression of time-series data was conducted to investigate our intervention impact on the temporal changes in B-CPR. RESULTS: A total of 13,829 out-of-hospital cardiac arrest cases were included from April 2010 to December 2017. Higher B-CPR rates (24.8% versus 50.8% vs 64.4%) were observed across the 3 time periods. B-CPR rates showed an increasing but plateauing trend. DA-CPR implementation was significantly associated with an increased B-CPR (level odds ratio [OR] 2.26, 95% confidence interval [CI] 1.79-2.88; trend OR 1.03, 95% CI 1.01-1.04), while no positive change was detected with myResponder (level OR 0.95, 95% CI 0.82-1.11; trend OR 0.99, 95% CI 0.98-1.00). CONCLUSION B-CPR rates in Singapore have been increasing alongside the implementation of community-level interventions such as DA-CPR and myResponder. DA-CPR was associated with improved odds of receiving B-CPR over time while the impact of myResponder was less clear.

A new fungus, Ophiocordyceps alboperitheciata, parasitic on the larva of Noctuidae (Lepidoptera) was identified from a survey of entomopathogenic fungi in Kunming Wild Duck Forest Park, Yunnan Province, China. It can be primarily distinguished from relatives by its longer fertile parts, sterile tips, superficial perithecia, narrower asci, and smaller septa of ascospores. As revealed from phylogenetic analyses inferred from nrSSU, nrLSU, tef-1α, rpb1, and rpb2 sequence data, O. alboperitheciata belongs to the Hirsutella citriformis clade in the genus Ophiocordyceps of Ophiocordycipitaceae, and forms a separated clade from other related species. The uniqueness of the taxon is significantly evidenced by both molecular phylogeny and morphology. Furthermore, the interspecific relationships in the H. citriformis clade are discussed.

A new fungus, Ophiocordyceps alboperitheciata, parasitic on the larva of Noctuidae (Lepidoptera) was identified from a survey of entomopathogenic fungi in Kunming Wild Duck Forest Park, Yunnan Province, China. It can be primarily distinguished from relatives by its longer fertile parts, sterile tips, superficial perithecia, narrower asci, and smaller septa of ascospores. As revealed from phylogenetic analyses inferred from nrSSU, nrLSU, tef-1α, rpb1, and rpb2 sequence data, O. alboperitheciata belongs to the Hirsutella citriformis clade in the genus Ophiocordyceps of Ophiocordycipitaceae, and forms a separated clade from other related species. The uniqueness of the taxon is significantly evidenced by both molecular phylogeny and morphology. Furthermore, the interspecific relationships in the H. citriformis clade are discussed.

Objective:To analyze the effects of proprioceptive neuromuscular facilitation (PNF) on balance, motor and activities of daily living (ADL) for stroke patients. Methods:The randomized controlled trials about the effects of PNF on motor, balance and ADL in stroke patients were retrieved from PubMed, Embase, CNKI, Wanfang data, and VIP, since establishment to December, 2019. The primary outcome measures were Berg Balance Scale (BBS), Fugl-Meyer Assessment (FMA) and modified Bathel Index (MBI). The secondary outcome measures were Functional Reach Test (FRT), Trunk Impairment Scale (TIS), and Timed 'Up and Go' Test (TUGT). The literatures were independently screened by two investigators, and the quality of the articles was evaluated using the Cochrane Library systematic review criteria, and meta-analysis was performed using RevMan 5.3. Results:A total of 13 articles were included with 786 stroke patients. PNF increased the score of BBS for sequelae patients (MD = 3.31, 95%CI 2.58 to 4.04, P < 0.001), FMA for recovery patients (MD = 8.31, 95%CI 5.68 to 10.97, P < 0.001); as well as MBI score (MD = 6.84, 95%CI 5.20 to 8.48, P < 0.001), FRT distance (MD = 1.11, 95%CI 0.39 to 1.84, P = 0.003) and TIS score (MD = 1.75, 95%CI 1.19 to 2.31, P < 0.001) for all the patients, and decreased TUGT time for sequelae patients (MD = -1.86, 95%CI -2.62 to -1.10, P < 0.001). Conclusion:PNF can significantly improve balance, motor and ADL for stroke patients. The effectiveness is various with the course of disease. More high-quality researches are needed.

Cell-penetrating peptides (CPPs) offer a non-selective and receptor-independent mode to promote cellular uptake. Although the non-specificity of CPP-mediated internalization allows this approach applicable to a wide range of tumor types potentially, their universality is a significant obstacle to their clinical utility for targeted delivery of cancer therapeutics and imaging agents. Accordingly, many reports have focused on selective switching of systemically delivered inert CPPs into their active form in lesions (tumor). In this review, our attention is mainly confined to such an enzyme-sensitive domain incorporated delivery system with activatable CPPs (ACPPs), which have displayed the exciting strength in balancing the CPPs' pros and cons, and potential in the treatment and diagnosis of some diseases.
Cell-Penetrating Peptides ; chemistry ; Drug Delivery Systems ; Enzymes ; chemistry ; Humans ; Neoplasms ; drug therapy