The circadian clock plays a critical role in regulating various physiological processes, including gene expression, metabolic regulation, immune response, and the sleep-wake cycle in living organisms. Post-translational modifications (PTMs) are crucial regulatory mechanisms to maintain the precise oscillation of the circadian clock. By modulating the stability, activity, cell localization and protein-protein interactions of core clock proteins, PTMs enable these proteins to respond dynamically to environmental and intracellular changes, thereby sustaining the periodic oscillations of the circadian clock. Different types of PTMs exert their effects through distincting molecular mechanisms, collectively ensuring the proper function of the circadian system. This review systematically summarized several major types of PTMs, including phosphorylation, acetylation, ubiquitination, SUMOylation and oxidative modification, and overviewed their roles in regulating the core clock proteins and the associated pathways, with the goals of providing a theoretical foundation for the deeper understanding of clock mechanisms and the treatment of diseases associated with circadian disruption.
Protein Processing, Post-Translational/physiology* ; Circadian Rhythm/physiology* ; Humans ; Animals ; CLOCK Proteins/physiology* ; Circadian Clocks/physiology* ; Phosphorylation ; Acetylation ; Ubiquitination ; Sumoylation

68Ga-DOTATOC injection is a radiopharmaceutical agent for positron emission tomography localization of somatostatin receptor positive neuroendocrine tumors(NETs)in adult and pediatric patients.68 Ga-DOTATOC binds to cells that express somatostatin receptors(SSTRs),including malignant neuroendocrine cells that overexpress SSTR2 receptor.Gallium-68 is a radionuclide used in positron emission tomography for tumor diagnosis.This paper introduces its the mechanism of action,pharmacokinetics,usage and dosage,clinical evaluation,safety and use in specific populations.

Objective:To analyze the proportion of patients with acute primary angle-closure glaucoma (PACG) after the outbreak of coronavirus disease 2019 (COVID-19) in patients undergoing glaucoma surgery and the factors influencing morbidity.Methods:A cross-sectional study was performed.The cluster sampling method was used to collect 141 glaucoma patients hospitalized for glaucoma surgery after the outbreak of COVID-19 in Xuzhou First People's Hospital from December 16, 2022, to January 16, 2023, and 231 glaucoma patients hospitalized for surgery in the same 1-month period from 2019 to 2020, 2020 to 2021, 2021 to 2022 through the hospital information system.Ninety-two eyes of 92 patients with acute PACG after the outbreak were selected as a study group, and 21 eyes of 21 patients with acute PACG hospitalized during the same 1-month period from 2021 to 2022 were selected as a control group.The proportion of patients with different types of glaucoma during the observation period was analyzed.The proportion of patients with acute PACG and the clinical characteristics of acute PACG were analyzed, including age, sex, visual acuity, intraocular pressure (IOP), and anterior chamber angle status.Epidemiological data such as the use of anti-cold medications, and changes in living habits and moods (including daily water intake and anxiety) of patients after COVID-19 infection were obtained by telephone follow-up.Anxiety levels of patients in the study group were assessed using the Hospital Depression and Anxiety Scale (HADS).The triggering factors of acute PACG attack after the COVID-19 outbreak were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Xuzhou First People's Hospital (No.xyyll[2023]114).Written informed consent was obtained from each subject.Results:The proportion of acute PACG patients in Xuzhou First People's Hospital within one month after the outbreak in 2022 to 2023 increased significantly compared with the same period in 2021 to 2022, 2020 to 2021 and 2019 to 2020, and the differences were statistically significant ( χ2=31.066, 33.331, 20.804; all at P<0.001).There was no statistical significance in the distribution of the number of eyes with different grades of visual acuity, IOP, the number of eyes with IOP ≥30 mmHg (1 mmHg=0.133 kPa), and the distribution of the number of eyes with different anterior chamber angles between the two groups (all at P>0.05).Patients in the control group had no history of COVID-19 infection or use of cold medicines at disease onset.During disease onset, all 92 (100%) patients in the study group had positive COVID-19 nucleic acid test results, of which 57 (61.96%) patients had a history of oral anti-cold medication use.During the same period, 49 (100%) hospitalized patients with other types of glaucoma had positive COVID-19 nucleic acid test results, of which 20 (40.82%) patients had a history of oral cold medication.There was a statistically significant difference in the proportion of patients taking oral cold drugs between acute PACG and other types of glaucoma in the study group ( χ2=5.764, P=0.016).During the outbreak of COVID-19, the study group reported that the daily water intake had increased to varying degrees than before.In the study group, 76 patients had anxiety, accounting for 82.6%.Multiple linear regression analysis showed that IOP=19.052+ 0.009×daily water intake+ 0.858×HADS score ( R2=0.780), and the standardized coefficients of daily water intake and HADS score were 0.542 and 0.452, respectively.Daily water intake had a greater effect on IOP than HADS score. Conclusions:The proportion of acute PACG patients among hospitalized surgical glaucoma patients increased significantly after the COVID-19 outbreak, which is related to risk factors such as oral anti-cold medications containing vasoconstrictors or antihistamines, increased daily water intake, anxiety and other lifestyle, and mood changes.

Objective: To describe the current status and trends in the treatment of patent ductus arteriosus (PDA) among very preterm infants (VPI) admitted to the neonatal intensive care units (NICU) of the Chinese Neonatal Network (CHNN) from 2019 to 2021, and to compare the differences in PDA treatment among these units. Methods: This was a cross-sectional study based on the CHNN VPI cohort, all of 22 525 VPI (gestational age<32 weeks) admitted to 79 tertiary NICU within 3 days of age from 2019 to 2021 were included. The overall PDA treatment rates were calculated, as well as the rates of infants with different gestational ages (≤26, 27-28, 29-31 weeks), and pharmacological and surgical treatments were described. PDA was defined as those diagnosed by echocardiography during hospitalization. The PDA treatment rate was defined as the number of VPI who had received medication treatment and (or) surgical ligation of PDA divided by the number of all VPI. Logistic regression was used to investigate the changes in PDA treatment rates over the 3 years and the differences between gestational age groups. A multivariate Logistic regression model was constructed to compute the standardized ratio (SR) of PDA treatment across different units, to compare the rates after adjusting for population characteristics. Results: A total of 22 525 VPI were included in the study, with a gestational age of 30.0 (28.6, 31.0) weeks and birth weight of 1 310 (1 100, 1 540) g; 56.0% (12 615) of them were male. PDA was diagnosed by echocardiography in 49.7% (11 186/22 525) of all VPI, and the overall PDA treatment rate was 16.8% (3 795/22 525). Of 3 762 VPI who received medication treatment, the main first-line medication used was ibuprofen (93.4% (3 515/3 762)) and the postnatal day of first medication treatment was 6 (4, 10) days of age; 59.3% (2 231/3 762) of the VPI had been weaned from invasive respiratory support during the first medication treatment, and 82.2% (3 092/3 762) of the infants received only one course of medication treatment. A total of 143 VPI underwent surgery, which was conducted on 32 (22, 46) days of age. Over the 3 years from 2019 to 2021, there was no significant change in the PDA treatment rate in these VPI (P=0.650). The PDA treatment rate decreased with increasing gestational age (P<0.001). The PDA treatment rates for VPI with gestational age ≤26, 27-28, and 29-31 weeks were 39.6% (688/1 737), 25.9% (1 319/5 098), and 11.4% (1 788/15 690), respectively. There were 61 units having a total number of VPI≥100 cases, and their rates of PDA treatment were 0 (0/116)-47.4% (376/793). After adjusting for population characteristics, the range of standardized ratios for PDA treatment in the 61 units was 0 (95%CI 0-0.3) to 3.4 (95%CI 3.1-3.8). Conclusions: From 2019 to 2021, compared to the peers in developed countries, VPI in CHNN NICU had a different PDA treatment rate; specifically, the VPI with small birth gestational age had a lower treatment rate, while the VPI with large birth gestational age had a higher rate. There are significant differences in PDA treatment rates among different units.
Infant ; Infant, Newborn ; Male ; Humans ; Female ; Ductus Arteriosus, Patent/drug therapy* ; Infant, Premature ; Cross-Sectional Studies ; Ibuprofen/therapeutic use* ; Infant, Very Low Birth Weight ; Persistent Fetal Circulation Syndrome ; Infant, Premature, Diseases/therapy*

To identify the active constituents in vitro and blood-absorbed ingredients in vivo from Yin Chen Hao decoction provides scientific evidence for probing its prevention and treatment mechanism on acute liver injury. An ultrahigh performance liquid chromatography quadrupole-time of flight-mass spectrometry (UPLC-QTOF/MS) method was applied for analysis of Yin Chen Hao decoction and the serum samples of mice with con-A induced acute liver injury after preventive oral administration for 14 days (the use of all laboratory animals in this study was approved by the Ethics Committee of the Naval Medical University, 19YF1459400). A total of 90 chemical constituents were identified from Yin Chen Hao decoction, mainly were flavonoids, terpenoids, tannins, quinones. 5 prototype compounds were identified in the serum, including chrysophanol, deoxyrhapontin-8-O-gallate, mussaenosidic acid, herniarin, emodin. The established UPLC-QTOF/MS method could efficiently and sensitively identify the constituents in vitro and blood-absorbed ingredients of Yin Chen Hao decoction, primarily clarify the material basis of its hepatoprotective effect, and provided a scientific basis for the quality marker selection and the pharmacodynamic material basis research on the decoction.

Background: We found microRNA (miR)-1246 to be significantly differentially expressed between severe active alopecia areata (AA) patients and healthy individuals. Objective: To explore the role and mechanism of miR-1246 in severe AA. Methods: Expression of miR-1246, dual-specific tyrosine phosphorylation-regulated kinase 1A (DYRK1A), and nuclear factor of activated T cells 1c (NFATc1) in peripheral CD4+ T cells and in scalp tissues of patients were detected using RT-qPCR, Western blot, and immunohistochemistry assays. Peripheral CD4+ T cells from the AA patients were transfected with lentiviral vectors overexpressing miR-1246. RT-qPCR and Western blot analysis were used to measure mRNA or protein expression of retinoic-acid-receptor-related orphan nuclear receptor gamma (ROR-γt), interleukin (IL)-17, DYRK1A, NFATc1, and phosphorylated NFATc1. Flow cytometry was used to assay the CD4+ IL-17+ cells proportion. ELISA was used to measure cytokine levels. Results: miR-1246 levels decreased and DYRK1A and NFATc1 mRNA levels significantly increased in the peripheral CD4+ T cells and scalp tissues of severe active AA samples.NFATc1 protein expression was also significantly increased in the peripheral CD4+ T cells but not in the scalp tissues. NFATc1 positive cells were mainly distributed among infiltrating inflammatory cells around hair follicles. In peripheral CD4+ T cells of severe active AA, overexpression of miR-1246 resulted in significant downregulation of DYRK1A, NFATc1, ROR-γt, and IL-17 mRNA and phosphorylated NFATc1 protein, as well as a decrease in the CD4+ IL-17+ cells proportion and the IL-17F level. Conclusion miR-1246 can inhibit NFAT signaling and Th17 cell activation, which may be beneficial in the severe AA treatment.

Targeted therapeutic drugs for acute myeloid leukemia (AML) are showing immense development, thereby laying a solid foundation for the precise treatment of AML patients. The paper reviews four types of targeted drugs that have progressed rapidly for AML treatment (by targeting genes or signaling-pathway alterations, targeting apoptosis-related pathways, targeting cell-surface antigens, and targeting immune-related substances). We look forward to the future development directions of targeted drugs, providing references for hematologists and developers of new drugs for AML.

Traditional Chinese medicine （TCM） health technology assessment （HTA） provides scientific information and decision-making basis for decision-makers at all levels to choose TCM health technology reasonably. However， it is still in its infancy. In the future， it is necessary to strengthen top-level design， improve cognition and attention， enhance talent training and cooperation， and speed up the development of evaluation criteria in line with the characteristics of TCM， so as to promote the development of HTA in TCM. Therefore， it is imperative to create a method system and tools suitable for TCM HTA. Evidence and value impact on decisionmaking （EVIDEM） framework is developed by EVIDEM collaboration. It combines evidence and value to form a relatively complete decision-making framework system， which can provide methodological support for medical insurance reimbursement， clinical practice decision-making， drug selection and so on. The introduction of EVIDEM framework into the field of TCM has methodological feasibility and practical operability， but it is still necessary to further integrate and optimize the TCM characteristics. On the basis of theoretical research， pilot studies are carried out with Chinese patent medicine as the breakthrough point， forming a preliminary framework and implementation path for the research of TCM HTA， in order to promote healthcare decision-making and achievement transformation.

SARS-CoV-2 can cause multiple organ injuries in some susceptible people in a short time, which seriously threatens the health and safety of people, and intensive care and multiple extracorporeal organ support are important means of treatment. Although many experts’ consensus and clinical guidelines have been published, a series of clinical problemsstill exist during the treatment procedure, and no consensushas not been reached until now. Therefore,in this paper wemake some reflections and explorations to provide experience and help for clinicians.

OBJECTIVE: To evaluate the incidence and clinical characteristics of metabolic syndrome (MS) within one year after hematopoietic stem cell transplantation (HSCT) in order to screen the risk factors for HSCT-MS, provide early intervention and improve the long-term quality of survival of patients. METHODS: The clinical follow-up data of 64 HSCT patients (survival time > 1 year) who received HSCT in our center from January 2007 to August 2018 were collected. Among them, 50 cases were allogeneic hematopoietic stem cell transplantation (allo-HSCT) and 14 cases were autologous hematopoietic stem cell transplantation (auto-HSCT). The changes of MS-related indexes and clinical characteristics before and 1, 3, 6 and 12 months after HSCT were analyzed retrospectively. RESULTS: In allo-HSCT group, 14 cases were diagnosed as MS before operation, including high-density lipoprotein cholesterol (hypo-HDL-C)> hyper triglycerides（hyper-TG）> hyper fasting glucose（hyper-FBG）> abdominal obesity (AO) > hypertension. The preoperative diagnosis of MS in the auto-HSCT group was 5 cases, in the order of hyper-FBG> hyper-TG> AO> hypo-HDL-C> hypertension. Incidence of MS at 1, 3, 6 and 12 months after transplantation: 19, 26, 24 and 20 cases in the allo-HSCT group, respectively; auto-HSCT group were 7, 7, 6 and 6 cases, respectively. Hyper-TG and hypo-HDL-C were prominent in both groups. CONCLUSION The incidence of HSCT-MS is significantly higher within 1 year after HSCT. Regardless of allo-HSCT and auto-HSCT, the prevention and control of HSCT-MS is emphasized as an important guarantee to improve the long-term survival quality of HSCT patients.
Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells ; Humans ; Metabolic Syndrome ; Retrospective Studies ; Transplantation, Homologous