ObjectiveTo observe and analyze the plasma metabolite differences among colorectal cancer patients with spleen-qi deficiency， damp-heat stasis-toxin syndrome（SRYD）， non-spleen-qi deficiency， damp-heat stasis-toxin syndrome（non-SRYD）， and normal human beings（Normal）， aiming to identify unique metabolites specific to SRYD colorectal cancer patients and their potential biomarkers. MethodsBased on the diagnostic criteria of SRYD and non-SRYD colorectal cancer， 30 patients were included， including 10 patients with SRYD colorectal cancer and 20 patients with non-SRYD colorectal cancer， while 10 individuals were recruited for the Normal group. Metabolome sequencing of plasma from the three groups was performed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS）. Multivariate statistical analysis were performed by principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）， and the intergroup differential metabolites were identified based on variable importance in the projection（VIP） value>1 and t-test P<0.05. And pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes（KEGG） was performed to explore the metabolites and metabolic pathways specific to SRYD colorectal cancer patients. ResultsMetabolome sequencing results showed some differences in metabolic profiles between the groups. A total of 111 plasma differential metabolites were found in the SRYD group and the Normal group， of which 31 were up-regulated and 80 were down-regulated， mainly including stearoyl lysophosphatidylcholine， indole-3-acrylic acid， and dehydroepiandrosterone sulfate（P<0.05）. The non-SRYD group exhibited 97 differentially expressed metabolites compared to the Normal group， with 36 up-regulated and 61 down-regulated， mainly including stearoyl lysophosphatidylcholine， sphingosine， and palmitoyl lysophosphatidylcholine（P<0.05）. And the SRYD group exhibited 19 differentially expressed metabolites compared to the non-SRYD group， of which 5 were up-regulated and 14 were down-regulated， mainly including dihydrosphingosine， palmitic acid， and linoleoylethanolamide（P<0.05）. The significant differential metabolites were subjected to KEGG analysis to obtain significantly enriched metabolic pathways in each group， and the results showed that 11 metabolic pathways such as primary bile acid synthesis， cholesterol metabolism and bile secretion were differential signaling pathways specific to SRYD colorectal cancer. Further retrieval of the above key signaling pathways showed that bile acids were up-regulated in both bile secretion and primary bile acid synthesis pathways， and there was a trend of up-regulation of glycochenodeoxycholic acid， taurochenodeoxycholic acid， and chenodeoxycholic acid. ConclusionPrimary bile acid synthesis， cholesterol metabolism， and bile secretion-related pathways may be differential signaling pathways specific to SRYD colorectal cancer， and bile acid is a core molecule in the metabolic pathway， which can serve as potential biomarkers closely related to the development and progression of SRYD colorectal cancer.

ObjectiveTo observe and analyze the plasma metabolite differences among colorectal cancer patients with spleen-qi deficiency， damp-heat stasis-toxin syndrome（SRYD）， non-spleen-qi deficiency， damp-heat stasis-toxin syndrome（non-SRYD）， and normal human beings（Normal）， aiming to identify unique metabolites specific to SRYD colorectal cancer patients and their potential biomarkers. MethodsBased on the diagnostic criteria of SRYD and non-SRYD colorectal cancer， 30 patients were included， including 10 patients with SRYD colorectal cancer and 20 patients with non-SRYD colorectal cancer， while 10 individuals were recruited for the Normal group. Metabolome sequencing of plasma from the three groups was performed by ultra-performance liquid chromatography-quadrupole-electrostatic field orbitrap mass spectrometry（UPLC-Q-Exactive-Orbitrap-MS）. Multivariate statistical analysis were performed by principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA）， and the intergroup differential metabolites were identified based on variable importance in the projection（VIP） value>1 and t-test P<0.05. And pathway enrichment analysis based on Kyoto Encyclopedia of Genes and Genomes（KEGG） was performed to explore the metabolites and metabolic pathways specific to SRYD colorectal cancer patients. ResultsMetabolome sequencing results showed some differences in metabolic profiles between the groups. A total of 111 plasma differential metabolites were found in the SRYD group and the Normal group， of which 31 were up-regulated and 80 were down-regulated， mainly including stearoyl lysophosphatidylcholine， indole-3-acrylic acid， and dehydroepiandrosterone sulfate（P<0.05）. The non-SRYD group exhibited 97 differentially expressed metabolites compared to the Normal group， with 36 up-regulated and 61 down-regulated， mainly including stearoyl lysophosphatidylcholine， sphingosine， and palmitoyl lysophosphatidylcholine（P<0.05）. And the SRYD group exhibited 19 differentially expressed metabolites compared to the non-SRYD group， of which 5 were up-regulated and 14 were down-regulated， mainly including dihydrosphingosine， palmitic acid， and linoleoylethanolamide（P<0.05）. The significant differential metabolites were subjected to KEGG analysis to obtain significantly enriched metabolic pathways in each group， and the results showed that 11 metabolic pathways such as primary bile acid synthesis， cholesterol metabolism and bile secretion were differential signaling pathways specific to SRYD colorectal cancer. Further retrieval of the above key signaling pathways showed that bile acids were up-regulated in both bile secretion and primary bile acid synthesis pathways， and there was a trend of up-regulation of glycochenodeoxycholic acid， taurochenodeoxycholic acid， and chenodeoxycholic acid. ConclusionPrimary bile acid synthesis， cholesterol metabolism， and bile secretion-related pathways may be differential signaling pathways specific to SRYD colorectal cancer， and bile acid is a core molecule in the metabolic pathway， which can serve as potential biomarkers closely related to the development and progression of SRYD colorectal cancer.

OBJECTIVES: To investigate the role of PTEN-induced putative kinase 1 (PINK1) in regulating the viability, migration, and apoptosis of colorectal cancer (CRC) cells, and to explore its potential epigenetic mechanisms. METHODS: PINK1 was overex-pressed or knocked down in HCT116 and DLD1 CRC cell lines using lentiviral vectors, with efficiency verified by qRT-PCR and Western blotting. Cell proliferation, colony formation, migration, and apoptosis were assessed using CCK-8, colony formation, wound healing, Transwell, and Hoechst 33258 staining assays, respectively. Protein levels of apoptosis-related and histone modification-related markers were analyzed by Western blotting. Genome-wide chromatin accessibility was profiled using ATAC-seq. RESULTS: PINK1 expression was significantly downregulated at both mRNA and protein levels in CRC tissues compared to normal tissues. PINK1 overexpression inhibited cell prolifera-tion, colony formation, and migration in HCT116 and DLD1 cells (all P<0.05), whereas PINK1 knockdown promoted these malignant phenotypes (all P<0.05). PINK1 overex-pression induced apoptosis, associated with decreased levels of anti-apoptotic proteins (Mcl-1, Bcl-2, Bcl-xl) and increased pro-apoptotic Bax (all P<0.05), without altering p53 expression. Mechanistically, PINK1 overexpression reduced the expression of histone H3 lysine 9 trimethylation (H3K9me3) and histone H3 lysine 27 trimethylation (H3K27me3), and increased the expression of histone H3 lysine 9 acetylation (H3K9ac) and histone H3 lysine 27 acetylation (H3K27ac). It also downregulated key histone-modifying enzymes, including EZH2, EZH1, SUZ12, and histone deacetylase 3 (HDAC3) (all P<0.01). ATAC-seq revealed that PINK1 overexpression increased chromatin accessibility, particularly around transcription start sites. CONCLUSIONS PINK1 acts as a tumor suppressor in colorectal cancer by inhibiting proliferation and migration, promoting apoptosis, and remodeling the epigenetic landscape through altering histone modifications and enhancing chromatin accessibility.

OBJECTIVE: To identify the underlying molecular mechanism of Modified Hu-Lu-Ba-Wan (MHW) in alleviating renal lesions in mice with diabetic kidney disease (DKD). METHODS: The db/db mice were divided into model group and MHW group according to a random number table, while db/m mice were settled as the control group (n=8 per group). The control and model groups were gavaged daily with distilled water [10 mL/(kg·d)], and the MHW group was treated with MHW [17.8 g/(kg·d)] for 6 weeks. After MHW administration for 6 weeks, indicators associated with glucolipid metabolism and urinary albumin were tested. Podocytes were observed by transmission electron microscopy. Kidney transcriptomics was performed after confirming therapeutic effects of MHW on DKD mice. The relevant target of MHW' effect in DKD was further determined by enzyme-linked immunosorbent assay, Western blot analysis, immunohistochemistry, and immunofluorescence staining. RESULTS: Compared with the model group, MHW improved glucose and lipid metabolism (P<0.05), and reduced lipid deposition in the kidney. Meanwhile, MHW reduced the excretion of urinary albumin (P<0.05) and ameliorated renal damage. Transcriptomic analysis revealed that the inflammation response, particularly the interleukin-17 (IL-17) signaling pathway, may be responsible for the effect of MHW on DKD. Furtherly, our results found that MHW inhibited IL-17A and alleviated early fibrosis in the diabetic kidney. CONCLUSION MHW ameliorated renal damage in DKD via inhibiting IL-17A, suggesting a potential strategy for DKD therapy.
Animals ; Diabetic Nephropathies/genetics* ; Interleukin-17/antagonists & inhibitors* ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Kidney/ultrastructure* ; Podocytes/metabolism* ; Mice ; Albuminuria ; Lipid Metabolism/drug effects* ; Mice, Inbred C57BL

OBJECTIVE: To study the clinical efficacy of Wenyang Lishui Formula (WYLSF) in preventing ovarian hyperstimulation syndrome (OHSS) and explore the suitable range of estradiol (E₂) on the human chorionic gonadotropin (HCG) day in patients with OHSS using WYLSF. METHODS: Part I: eligible patients at high risk for OHSS undergoing ovulation induction between January and December, 2023 were randomized into 2 groups based on the actual treatment. The treatment group received 200 mL WYLSF formula twice daily for 5 days after oocyte retrieval in a combination of lifestyle coaching (LC) intervention including regular diet and exercise, whereas the LC group received LC intervention alone. The incidence of OHSS, OHSS self-assessment scales, changes in E₂ levels on HCG day and 5 days after oocyte retrieval, ovarian morphology changes, and menstrual recovery were compared between the two groups. Part II: patients at high risk for OHSS treated with WYLSF were studied. The optimal E₂ threshold on the HCG day was determined using the maximum selection test, and a multivariate analysis was adopted to compare the relationship between different E₂ levels on HCG day and hospitalization rate, incidence of moderate to severe OHSS, and self-assessment scales, to explore the preventive effect of WYLSF on OHSS in patients with varying E₂ levels. RESULTS: A total of 120 patients were included in the Part I analysis. The treatment group (60 cases) showed a significant reduction in the incidence, duration, and severity of abdominal distension, as well as the incidence of vomiting compared with the LC group (P<0.05). The post-retrieval E₂ levels in the treatment group decreased significantly more (P=0.032). Among 1,652 patients treated with WYLSF in the Part II, 90 patients with ⩽ 10092 pmol/L, 159 with >31074 pmol/L, and 1,403 in the middle range group were formed based on E₂ levels on HCG day in Part two analysis. Univariate and regression analyses showed that patients with E₂ levels >31073 pmol/L had a significantly higher incidence of moderate to severe OHSS compared to those with E₂ levels ⩽ 10092 pmol/L (P<0.05). CONCLUSIONS WYLSF can effectively reduce specific symptoms in high-risk OHSS patients after ovulation induction and significantly lower E₂ levels. It may be more suitable for high-risk OHSS patients with E₂ levels <31073 pmol/L on HCG day. (Registration No. MR-11-23-032493, https://www.medicalresearch.org.cn/login ).
Humans ; Ovarian Hyperstimulation Syndrome/blood* ; Female ; Adult ; Prospective Studies ; Drugs, Chinese Herbal/pharmacology* ; Estradiol/blood* ; Ovulation Induction ; Chorionic Gonadotropin

Cardiac arrest (CA) is a critical condition in the field of cardiovascular medicine. Despite successful resuscitation, patients continue to have a high mortality rate, largely due to post CA syndrome (PCAS). However, the injury and pathophysiological mechanisms underlying PCAS remain unclear. Experimental animal models are valuable tools for exploring the etiology, pathogenesis, and potential interventions for CA and PCAS. Current CA animal models include electrical induction of ventricular fibrillation (VF), myocardial infarction, high potassium, asphyxia, and hemorrhagic shock. Although these models do not fully replicate the complexity of clinical CA, the mechanistic insights they provide remain highly relevant, including post-CA brain injury (PCABI), post-CA myocardial dysfunction (PAMD), systemic ischaemia/reperfusion injury (IRI), and the persistent precipitating pathology. Summarizing the methods of establishing CA models, the challenges encountered in the modeling process, and the mechanisms of PCAS can provide a foundation for developing standardized CA modeling protocols.
Animals ; Disease Models, Animal ; Post-Cardiac Arrest Syndrome/physiopathology* ; Heart Arrest/physiopathology* ; Humans ; Ventricular Fibrillation/complications*

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

Humans ; Urinary Bladder Neoplasms/pathology* ; Carcinoma, Transitional Cell/pathology* ; Genetic Markers ; Biomarkers, Tumor/genetics* ; Urothelium/pathology*

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.

Objective To observe the effect of omeprazole enteric-coated capsules on clinical symptoms and serum inflammatory factor levels in children with chronic gastritis and peptic ulcer.Methods Children with chronic gastritis and peptic ulcer were divided into treatment group and control group by random number table method.The control group was given triple therapy of ranitidine hydrochloride tablets,amoxicillin and clarithromycin,while the treatment group was treated with omeprazole enteric-coated capsules combined with amoxicillin and clarithromycin.Clinical efficacy,symptom relief time,and changes in serum motilin(MOT),gastrin(GAS)and inflammatory factors[interlrukin-6(IL-6)and interlrukin-8(IL-8)]were compared between the two groups.Results There were 48 cases in treatment group and 48 cases in control group.After treatment,the total effective rates in treatment group and control group were 93.74％(45 cases/48 cases)and 85.42％(41 cases/48 cases),with significant difference(P＜0.05).After treatment,the disappearance time of ulcer induced pain in treatment group and control group were(1.51±0.26)and(2.08±0.42)d;the disappearance time of acid regurgitation were(2.29±0.40)and(2.93±0.33)d;the disappearance time of burning sensation were(2.37±0.21)and(2.85±0.54)d;the length of hospital stay were(6.21±1.07)and(6.94±1.25)d;serum MOT levels were(298.48±35.15)and(273.58±31.25)pg·mL-1;serum GAS levels were(167.28±19.46)and(128.32±18.61)ng·L-1;IL-6 levels were(58.67±5.39)and(76.14±6.63)mg·mL-1;IL-8 levels were(50.08±5.16)and(58.68±5.49)mg·mL-1.The above indexes were significantly different between control group and treatment group(all P＜0.05).The total incidence of adverse drug reactions in treatment group and control group were 8.33％and 12.50％,with no statistical significance(P＞0.05).Conclusion Omeprazole enteric-coated capsules in the treatment of children with chronic gastritis and peptic ulcer can effectively alleviate various clinical symptoms and improve clinical efficacy.At the same time,it can lower serum levels of inflammatory factors and improve inflammation,with good effect.