OBJECTIVE: Circadian rhythm disruption (CRD) is a risk factor that correlates with poor prognosis across multiple tumor types, including hepatocellular carcinoma (HCC). However, its mechanism remains unclear. This study aimed to define HCC subtypes based on CRD and explore their individual heterogeneity. METHODS: To quantify CRD, the HCC CRD score (HCCcrds) was developed. Using machine learning algorithms, we identified CRD module genes and defined CRD-related HCC subtypes in The Cancer Genome Atlas liver HCC cohort (n = 369), and the robustness of this method was validated. Furthermore, we used bioinformatics tools to investigate the cellular heterogeneity across these CRD subtypes. RESULTS: We defined three distinct HCC subtypes that exhibit significant heterogeneity in prognosis. The CRD-related subtype with high HCCcrds was significantly correlated with worse prognosis, higher pathological grade, and advanced clinical stages, while the CRD-related subtype with low HCCcrds had better clinical outcomes. We also identified novel biomarkers for each subtype, such as nicotinamide n-methyltransferase and myristoylated alanine-rich protein kinase C substrate-like 1. CONCLUSION We classify the HCC patients into three distinct groups based on circadian rhythm and identify their specific biomarkers. Within these groups greater HCCcrds was associated with worse prognosis. This approach has the potential to improve prediction of an individual's prognosis, guide precision treatments, and assist clinical decision making for HCC patients. Please cite this article as: Li XJ, Chang L, Mi Y, Zhang G, Zhu SS, Zhang YX, et al. Integrated-omics analysis defines subtypes of hepatocellular carcinoma based on circadian rhythm. J Integr Med. 2025; 23(4): 445-456.
Humans ; Carcinoma, Hepatocellular/pathology* ; Liver Neoplasms/pathology* ; Circadian Rhythm/genetics* ; Prognosis ; Male ; Female ; Biomarkers, Tumor/genetics* ; Middle Aged ; Machine Learning ; Computational Biology

Objective To investigate the effect of astragaloside Ⅳ on high glucose-induced pyroptosis and invasive migration of human chorionic trophoblast cells(HTR-8/SVneo).Methods HTR-8/SVneo cells were divided into 4 groups:control group(untreated),high glucose group(high glucose stimulation)and astragaloside Ⅳ 50 and 100 μmol/L group(high glucose stimulation + astragaloside).Cell activity was detected by Cell Counting Kit 8(CCK-8),cell invasion and migration abilities were determined by Transwell assay and scratch assay,respectively,cell pyroptosis was assessed by Hoechst 33342/propidium iodide(PI)dual fluorescence staining.The protein expression levels of NOD-like receptor thermoprotein structural domain(NLRP3),cleaved-Caspase-1,GSDMD-NT,and IL-18 were detected by Western Blot.Results Compared with the control group,HTR-8/SVneo cell viability was significantly reduced in the high glucose group,the rate of cell migration was significantly reduced,the number of invasive cells was significantly reduced,the percentage of PI-positive cells was significantly increased,and the levels of NLRP3,cleaved-Caspase-1,GSDMD-NT and IL-18 protein expression levels were significantly increased(P<0.05 or P<0.01);compared with the high glucose group,cell viability was significantly higher in the astragaloside Ⅳ treated group,the rate of cell migration was significantly increased,the number of invasive cells was significantly increased,the percentage of PI-positive cells was significantly decreased,and the protein expressions of number of NLRP3,cleaved-Caspase-1,GSDMD-NT,IL-18 were significantly decreased(P<0.05 or P<0.01).Conclusion AstragalosideⅣcan inhibit high glucose-induced HTR-8/SVneo cell pyrolysis and improve cell invasion and migration ability.

OBJECTIVE: To evaluate the effectiveness and safety of Chinese medicine (CM) in the treatment of coronavirus disease 2019 (COVID-19) in China. METHODS: A multi-center retrospective cohort study was carried out, with cumulative CM treatment period of ⩾3 days during hospitalization as exposure. Data came from consecutive inpatients from December 19, 2019 to May 16, 2020 in 4 medical centers in Wuhan, China. After data extraction, verification and cleaning, confounding factors were adjusted by inverse probability of treatment weighting (IPTW), and the Cox proportional hazards regression model was used for statistical analysis. RESULTS: A total of 2,272 COVID-19 patients were included. There were 1,684 patients in the CM group and 588 patients in the control group. Compared with the control group, the hazard ratio (HR) for the deterioration rate in the CM group was 0.52 [95% confidence interval (CI): 0.41 to 0.64, P<0.001]. The results were consistent across patients of varying severity at admission, and the robustness of the results were confirmed by 3 sensitivity analyses. In addition, the HR for all-cause mortality in the CM group was 0.29 (95% CI: 0.19 to 0.44, P<0.001). Regarding of safety, the proportion of patients with abnormal liver function or renal function in the CM group was smaller. CONCLUSION This real-world study indicates that the combination of a full-course CM therapy on the basic conventional treatment, may safely reduce the deterioration rate and all-cause mortality of COVID-19 patients. This result can provide the new evidence to support the current treatment of COVID-19. Additional prospective clinical trial is needed to evaluate the efficacy and safety of specific CM interventions. (Registration No. ChiCTR2200062917).
Humans ; Retrospective Studies ; Male ; Female ; Middle Aged ; COVID-19/epidemiology* ; COVID-19 Drug Treatment ; Aged ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/adverse effects* ; SARS-CoV-2 ; Treatment Outcome ; China/epidemiology* ; Adult

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

OBJECTIVES: To investigate the clinical phenotypes, genetic characteristics, and pathological features of children with disorders of sex development (DSD). METHODS: A retrospective analysis was conducted on epidemiological, clinical phenotype, chromosomal karyotype, gonadal pathology, and genotype data of 165 hospitalized children with DSD at Children's Hospital of Hebei Province and Tangshan Maternal and Child Health Hospital from August 2008 to December 2022. RESULTS: Among the 165 children with DSD, common presenting symptoms were short stature (62/165, 37.6%), clitoromegaly (33/165, 20.0%), cryptorchidism (28/165, 17.0%), hypospadias (24/165, 14.5%), and skin pigmentation abnormalities/exteriorized pigmented labia majora (19/165, 11.5%). Chromosomal karyotype analysis was performed on 127 cases, revealing 36 cases (28.3%) of 46,XX DSD, 34 cases (26.8%) of 46,XY DSD, and 57 cases (44.9%) of sex chromosome abnormalities. Among the sex chromosome abnormal karyotypes, the 45,X karyotype (11/57, 19%) and 45,X/other karyotype mosaicism (36/57, 63%) were more common. Sixteen children underwent histopathological biopsy of gonadal tissues, resulting in retrieval of 25 gonadal tissues. The gonadal tissue biopsies revealed 3 cases of testes, 3 cases of dysplastic testes, 6 cases of ovaries, 11 cases of ovotestes, and 1 case each of streak gonad and agenesis of gonads. Genetic testing identified pathogenic/likely pathogenic variants in 23 cases (23/36, 64%), including 12 cases of 21-hydroxylase deficiency congenital adrenal hyperplasia caused by CYP21A2 pathogenic variants. CONCLUSIONS Short stature, clitoromegaly, cryptorchidism, hypospadias, and skin pigmentation abnormalities are common phenotypes in children with DSD. 45,X/other karyotype mosaicism and CYP21A2 compound heterozygous variants are major etiological factors in children with DSD. The most commonly observed gonadal histopathology in children with DSD includes ovotestes, ovaries, and testes/dysgenetic testes.
Male ; Humans ; Child ; Disorders of Sex Development/pathology* ; Hypospadias/complications* ; Cryptorchidism/complications* ; Retrospective Studies ; Adrenal Hyperplasia, Congenital ; Steroid 21-Hydroxylase

OBJECTIVE: To observe the clinical significance of translocator proteins (TSPO) gene in the treatment of FLT3-ITD/DNMT3A R882 double-mutated acute myeloid leukemia (AML). METHODS: Seventy-six patients with AML hospitalized in the Department of Hematology of the Affiliated People's Hospital of Ningbo University from June 2018 to June 2020 were selected, including 34 patients with FLT3-ITD mutation, 27 patients with DNMT3A R882 mutation, 15 patients with FLT3-ITD/DNMT3A R882 double mutation, as well as 19 patients with immune thrombocytopenia (ITP) hospitalized during the same period as control group. RNA was routinely extracted from 3 ml bone marrow retained during bone puncture, and TSPO gene expression was detected by transcriptome sequencing (using 2-deltadeltaCt calculation). RESULTS: The expression of TSPO gene in FLT3-ITD group and DNMT3A R882 group at first diagnosis was 2.02±1.04 and 1.85±0.76, respectively, which were both higher than 1.00±0.06 in control group, but the differences were not statistically significant (P=0.671, P=0.821). The expression of TSPO gene in the FLT3-ITD/DNMT3A R882 group was 3.98±1.07, wich was significantly higher than that in the FLT3-ITD group and DNMT3A R882 group, the differences were statistically significant (P=0.032, P=0.021). The expression of TSPO gene in patients who achieved complete response after chemotherapy in the FLT3-ITD/DNMT3A R882 group was 1.19±0.87, which was significantly lower than that at first diagnosis, and the difference was statistically significant (P=0.011). CONCLUSION TSPO gene may be used as an indicator of efficacy in FLT3-ITD /DNMT3A R882 double-mutated AML.
Humans ; DNA (Cytosine-5-)-Methyltransferases/genetics* ; DNA Methyltransferase 3A ; Mutation ; Leukemia, Myeloid, Acute/drug therapy* ; Nucleophosmin ; Prognosis ; fms-Like Tyrosine Kinase 3/genetics* ; Receptors, GABA/therapeutic use*

Objective: To evaluate the influence of duodenal stump reinforcing on the short-term complications after laparoscopic radical gastrectomy. Methods: A retrospective cohort study with propensity score matching (PSM) was conducted. Clinical data of 1204 patients with gastric cancer who underwent laparoscopic radical gastrectomy at the First Affiliated Hospital of Army Medical University from April 2009 to December 2018 were collected. The digestive tract reconstruction methods included Billroth II anastomosis, Roux-en-Y anastomosis and un-cut-Roux- en-Y anastomosis. A linear stapler was used to transected the stomach and the duodenum. Among 1204 patients, 838 were males and 366 were females with mean age of (57.0±16.0) years. Duodenal stump was reinforced in 792 cases (reinforcement group) and unreinforced in 412 cases (non-reinforcement group). There were significant differences in resection range and anastomotic methods between the two groups (both P<0.001). The two groups were matched by propensity score according to the ratio of 1∶1, and the reinforcement group was further divided into purse string group and non-purse string group. The primary outcome was short-term postoperative complications (within one month after operation). Complications with Clavien-Dindo grade ≥ III a were defined as severe complications, and the morbidity of complication between the reinforcement group and the non-reinforcement group, as well as between the purse string group and the non-purse string group was compared. Results: After PSM, 411 pairs were included in the reinforcement group and the non-reinforcement group, and there were no significant differences in baseline data between the two groups (all P>0.05). No perioperative death occurred in any patient.The short-term morbidity of postoperative complication was 7.4% (61/822), including 14 cases of anastomotic leakage (23.0%), 11 cases of abdominal hemorrhage (18.0%), 8 cases of duodenal stump leakage (13.1%), 2 cases of incision dehiscence (3.3%), 6 cases of incision infection (9.8%) and 20 cases of abdominal infection (32.8%). Short-term postoperative complications were found in 25 patients (6.1%) and 36 patients (8.8%) in the reinforcement group and the non-reinforcement group, respectively, without significant difference (χ²=2.142, P=0.143). Nineteen patients (2.3%) developed short-term severe complications (Clavien-Dindo grade ≥IIIa), while no significant difference in severe complications was found between the two groups (1.7% vs. 2.9%, χ²=1.347, P=0.246). Sub-group analysis showed that the morbidity of short-term postoperative complication of the purse string group was 2.6% (9/345), which was lower than 24.2% (16/66) of the non-purse string group (χ²=45.388, P<0.001). Conclusion: Conventional reinforcement of duodenal stump does not significantly reduce the incidence of duodenal stump leakage, so it is necessary to choose whether to reinforce the duodenal stump individually, and purse string suture should be the first choice when decided to reinforce.
Adult ; Aged ; Anastomosis, Roux-en-Y/adverse effects* ; Anastomosis, Surgical/adverse effects* ; Duodenum/surgery* ; Female ; Gastrectomy/methods* ; Humans ; Laparoscopy/adverse effects* ; Male ; Middle Aged ; Postoperative Complications/etiology* ; Retrospective Studies ; Stomach Neoplasms/surgery*

Objective: To investigate the current situation of cell phone use and sleep quality among college students, establish a sleep quality trajectory model and explore the influence of cell phone use on the sleep quality trajectory. Methods: Based on data from the College Student Behavior and Health Cohort Study 2019-2020, a latent class growth modeling was used to establish a sleep quality trajectory model among college students. The baseline influencing factors of sleep quality trajectories among college students were analyzed by χ² test, and the effects of cell phone use on sleep quality trajectories were analyzed by binary logistic regression. Results: A total of 1 092 college students were included in the analysis. The detection rates of cell phone use and poor sleep quality were 24.5% and 13.3%. Latent class growth model identified two groups of sleep quality trend trajactories: an improved sleep quality group (86.0%) and a decreased sleep quality group (14.0%). The result of binary logistic regression showed that the cell phone use was a risk factor of sleep quality trajectories. Conclusion: The cell phone use during college period could increase the risk of poor sleep quality. Targeted intervention measures about cell phone use should be adopted to improve the sleep quality among college students.
Humans ; Sleep Quality ; Cohort Studies ; Cell Phone Use ; Surveys and Questionnaires ; Students ; Sleep Initiation and Maintenance Disorders ; Cell Phone ; Sleep

Objective: To compare the clinical efficacy and quality of life between uncut Roux-en-Y and Billroth II with Braun anastomosis in laparoscopic distal gastrectomy for gastric cancer patients. Methods: A retrospective cohort study was performed. Inclusion criteria: (1) 18 to 75 years old; (2) gastric cancer proved by preoperative gastroscopy, CT and pathological results and tumor was suitable for D2 radical distal gastrectomy; (3) postoperative pathological diagnosis stage was T1-4aN0-3M0 (according to the AJCC-7th TNM tumor stage), and the margin was negative; (4) Eastern Cooperative Oncology Group (ECOG) physical status score <2 points, and American Association of Anesthesiologists (ASA) grade 1 to 3; (5) no mental illness; (6) able to answer questionnaires independently; (7) patients agreed to undergo laparoscopic distal gastrectomy and signed an informed consent. Exclusion criteria: (1) patients with severe chronic diseases and American Association of Anesthesiologists (ASA) grade >3; (2) patients with other malignant tumors; (3) patients suffered from serious mental diseases; (4) patients received neoadjuvant chemotherapy or immunotherapy. According to the above criteria, clinical data of 200 patients who underwent laparoscopic distal gastrectomy at the Department of General Surgery of the First Affiliated Hospital of Army Medical University from January 2016 to December 2019 were collected. Of the 200 patients, 108 underwent uncut Roux-en-Y anastomosis and 92 underwent Billroth II with Braun anastomosis. The general data, intraoperative and postoperative conditions, complications, and endoscopic evaluation 1 year after the surgery were compared. Besides, the quality of life of two groups was also compared using the Chinese version of the European Organization For Research and Treatment of Cancer (EORTC) quality of life questionnaire-Core 30 (QLQ-C30) and quality of life questionnaire-stomach 22 (QLQ-STO22). Results: There were no significant differences in baseline data between the two groups (all P>0.05). All the 200 patients successfully underwent laparoscopic distal gastrectomy without intraoperative complications, conversion to open surgery or perioperative death. There were no significant differences between two groups in operative time, intraoperative blood loss, postoperative complications, time to flatus, time to removal of gastric tube, time to liquid diet, time to removal of drainage tube or length of postoperative hospital stay (all P>0.05). Endoscopic evaluation was conducted 1 year after surgery. Compared to Billroth II with Braun group, the uncut Roux-en-Y group had a significantly lower incidences of gastric stasis [19.8% (17/86) vs. 37.0% (27/73), χ(2)=11.199, P=0.024], gastritis [11.6% (10/86) vs. 34.2% (25/73), χ(2)=20.892, P<0.001] and bile reflux [1.2% (1/86) vs. 28.8% (21/73), χ(2)=25.237, P<0.001], and the differences were statistically significant. The EORTC questionnaire was performed 1 year after surgery, there were no significant differences in the scores of QLQ-C30 scale between the two groups (all P>0.05), while the scores of QLQ-STO22 showed that, compared to the Billroth II with Braun group, the uncut Roux-en-Y group had a lower pain score (median: 8.3 vs. 16.7, Z=-2.342, P=0.019) and reflux score (median: 0 vs 5.6, Z=-2.284, P=0.022), and the differences were statistically significant (all P<0.05), indicating milder symptoms. Conclusion: The uncut Roux-en-Y anastomosis is safe and reliable in laparoscopic distal gastrectomy, which can reduce the incidences of gastric stasis, gastritis and bile reflux, and improve the quality of life of patients after surgery.
Adolescent ; Adult ; Aged ; Anastomosis, Roux-en-Y/adverse effects* ; Anastomosis, Surgical/adverse effects* ; Gastrectomy/methods* ; Gastroenterostomy/adverse effects* ; Humans ; Laparoscopy/methods* ; Middle Aged ; Postoperative Complications/epidemiology* ; Quality of Life ; Retrospective Studies ; Stomach Neoplasms/pathology* ; Treatment Outcome ; Young Adult

Fifteen compounds were isolated from the 70% EtOH extract of leaves of Chinese hawthorn(Crataegus pinnatifida var. major) by various purification steps, and their structures were determined as 2α,3α,12β,19α,-tetrahydroxyursan-13β,28-olide(1),euscaphic acid(2), tormentic acid(3), ursolic acid(4), pomolic acid(5), corosolic acid(6), maslinic acid(7), linalyl rutinoside(8),(Z)-3-hexenyl β-D-glucoside(9),(3S, 6S)-cis-linalool-3,7-oxide-β-D-glucopyranoside(10), pisumionoside(11), icariside B6(12), byzantionoside B(13),(6R,7E,9R)-9-Hydroxy-4,7-megastigmadien-3-one 9-O-β-D-glucopyranoside(14) and(6S,7E,9R)-6,9-dihydroxy-4,7-megastigmadien-3-one 9-O-β-D-glucopyranoside(15) mainly based on the mass spectrum(MS) and nuclear magnetic resonance(NMR) spectroscopic techniques, of which compound 1 was a new pentacyclic triterpene, and compounds 2, 5, 6, 8, 10, 13 and 15 were isolated form this plant for the first time.
China ; Crataegus ; Molecular Structure ; Plant Leaves ; Terpenes ; Triterpenes