Objective This study aimed to analyze the characteristics and clinical significance of peripheral lymphocytic subsets and cytokine levels, including interleukin 1β(IL-1β), IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12P70, IL-17A, tumor necrosis factor α(TNF-α), interferon γ(IFN-γ) and IFN-α, in patients with primary biliary cholangitis (PBC), to provide some novel insights into the pathogenesis of PBC. Methods We retrospectively collected clinical features and laboratory data from hospitalized patients who were primarily diagnosed with PBC and from healthy physical examinees at the Third People's Hospital of Changzhou between January 1, 2023, and June 30, 2024. Results A total of 152 PBC patients and 96 healthy controls who met the inclusion and exclusion criteria were enrolled. Significant differences were observed in baseline characteristics and laboratory data between the two groups. After the propensity score matching (PSM) analysis, 61 PBC patients and 61 healthy controls were successfully matched, ensuring that the general characteristics (age and gender) of the two groups were balanced and comparable. Compared to the control group, the proportion of peripheral lymphocytes was significantly higher in the PBC group (31.9% vs. 17.8%), primarily due to an increase in CD4⁺ T cells (46.77% vs. 41.19%), while CD8⁺T cells were significantly decreased (19.73% vs. 22.07%). Notably, the proportions of CD4⁺ programmed cell death 1 (PD-1)⁺ T and CD8⁺PD-1⁺ T cells were elevated, with CD8⁺PD-1⁺ T cells showing a significant positive correlation with the severity of liver inflammation (r=0.41). Furthermore, the mitochondrial mass (MM) of CD4⁺ T cells was significantly increased in PBC patients, whereas no significant changes were observed in the MM of CD8⁺ T cells or the mitochondrial membrane potential (MMP) of CD3⁺ T cells. Additionally, the plasma levels of cytokines, such as IL-4, IL-8, IL-10 and IFN-α, were abnormally elevated. The plasma levels of IL-5 and IL-1β were negatively correlated with the stage of liver fibrosis in patients with PBC (r=-0.52). Conclusion The overactivation and proliferation of CD4⁺ T cells, along with the suppression of CD8⁺ T cell function and increased PD-1 expression leads to T cell exhaustion, indicating significant immunological alterations in PBC patients. These changes are closely associated with the disease progression. Additionally, cytokines are likely involved in the immune regulation process of PBC and may influence the pathogenic mechanisms of the disease. Regular monitoring of lymphocyte subsets and cytokine levels can help assess the immune status and disease activity in patients with PBC, thereby guiding the individualized treatment strategies.
Humans ; Male ; Female ; Middle Aged ; Liver Cirrhosis, Biliary/blood* ; Retrospective Studies ; T-Lymphocyte Subsets/immunology* ; Aged ; Cytokines/blood* ; Adult ; CD8-Positive T-Lymphocytes/immunology*

The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Objective To investigate the clinical features of hospitalized children with pertussis.Methods The clinical data of 87 hospitalized children with pertussis admitted to Women and Children's Hospital Affiliated to Xiamen University from January 2019 to December 2022 were retrospectively analyzed.According to the age of the children,they were divided into group A(≤3 months of age,35 cases),group B(4-12 months of age,36 cases)and group C(>12 months of age,16 cases).The clinical features of children at different ages were compared.Results The majority of children with pertussis were<1 year old(81.61%),and August was the month of high incidence.Spastic cough(72.41%)was the main clinical manifestation.Other manifestations included redness or cyanosis,vomiting after coughing,crow echo,etc.There were statistically significant differences in the incidence of spastic cough,redness or cyanosis and the contact history of patients with chronic cough among three groups(P<0.05).There were significant differences in the incidence of pneumonia and the average length of hospital stay among three groups(P<0.05).There was significant difference in C-reactive protein level among three groups(P<0.05).Among 87 children with pertussis,37 cases(42.53%)were infected with other pathogens,among which virus infection was the most common.The treatment is effective with macrolides and compound sulfamethoxazole.Conclusion Pertussis is more common in infants under 1 year of age,and the incidence is high in August.Chronic cough patients with close contact may be the source of infection.Spastic cough is the main clinical symptom of children;the younger,the more common symptoms such as spastic cough,redness and cyanosis,the higher incidence of pneumonia and the longer hospital stay.

Objective To compare the safety and comfort of patients with or without postoperative gastric tube placement after esophageal cancer surgery, and analyze the cost and nursing time of gastric tube placement. Methods The patients with esophageal cancer undergoing minimally invasive surgery in West China Hospital of Sichuan University in 2021 were enrolled. The patients were divided into a gastric tube indwelling group and a non gastric tube indwelling group according to whether the gastric tube was indwelled after the operation. The safety and comfort indicators of the two groups were compared. Results A total of 130 patients were enrolled. There were 66 patients in the gastric tube indwelling group, including 53 males and 13 females, aged 61.80±9.05 years and 64 patients in the non gastric tube indwelling group, including 55 males and 9 females, aged 64.47±8.00 years. Six patients in the non gastric tube indwelling group needed to place gastric tube 1 to 3 days after the operation due to their condition. There was no statistical difference in the incidence of postoperative complications between the two groups (P>0.05). The subjective comfort of patients in the gastric tube indwelling group was significantly lower than that in the non gastric tube indwelling group (P<0.001), and the incidence of foreign body sensation in the throat of patients in the gastric tube indwelling group was higher than that in the non gastric tube indwelling group (P<0.001). The average nursing time in the gastric tube indwelling group was about 59.58 minutes, and the average cost of gastric tube materials and nursing was 378.24 yuan per patient. Conclusion No gastric tube used after operation for appropriate esophageal cancer patients will not increase the incidence of postoperative complications (pulmonary infection, anastomotic leakage, chylothorax), but can increase the comfort of patients, save cost and reduce nursing workload, which is safe, feasible and economical.

Objective To investigate the protective effect of curcumin (Cur) against arsenic-induced neuroimmune toxicity and the underlying molecular mechanisms in vivo. Methods Eighty SPF female C57BL/6 mice were randomly assigned to four groups: a control group, an arsenic-treated group, a Cur-treated group and an arsenic+Cur group, with 20 mice in each group. The control group received distilled water; the arsenic-treated group was given 50 mg/L NaAsO₂ in the drinking water; the Cur-treated group was gavaged with 200 mg/kg of curcumin for 45 days; and the arsenic+Cur group received distilled water and was gavaged with 200 mg/kg of curcumin. Y-maze and Morris water maze experiments were conducted to assess the learning and memory ability of the mice. Western blot analysis was used to detect protein levels of blood-brain barrier tight junction proteins zonula occludens protein 1(ZO-1) and claudin 5, T lymphocyte subpopulation CD4 and CD8, Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway-related molecules JAK2 and STAT3. Real-time PCR was used to assess the mRNA levels of CD4⁺ T lymphocyte subsets type 1 T helper (Th1), Th2, Th17 and regulatory T cells (Treg) transcription factors and cytokines in hippocampus. Results Compared with the control group, the arsenic-treated group showed a significantly decreased correct rate, increased latency to reach the platform on the third and fifth days, and reduced times of crossing the platform. The expression of ZO-1 and claudin 5 protein decreased significantly, and the protein levels of CD4 and CD8 were up-regulated. The mRNA levels of Th1, Th17, and Treg transcription factor T-box expressed in T cell(T-bet), retinoid-related orphan receptor gamma t(RORγt), and forkhead box protein 3(FOXP3) in the arsenic-treated group were decreased. Th1 and Th17 cytokines interferon γ(IFN-γ) and interleukin 17(IL-17) were markedly decreased. In contrast, the mRNA levels of the Th2 transcription factor GATA binding protein 3(GATA3) and cytokine IL-4 in arsenic-treated group were higher than those in the control group. Furthermore, the protein levels of phosphorylated JAK2 (p-JAK2) and phosphorylated STAT3 (p-STAT3) increased. Compared with the arsenic-treated group, the arsenic+Cur group demonstrated a significantly increased correct rate, decreased latency to reach the platform on the third and fifth days, and increased times of crossing the platform. The protein expression levels of ZO-1 and claudin 5 increased significantly, and the protein levels of CD4 and CD8 were down-regulated. The mRNA levels of Th2 transcription factor GATA3 and cytokine IL-4 were decreased. The mRNA levels of Th17 transcription factor RORγt and cytokine IL-17 were markedly increased. Furthermore, the protein levels of p-JAK2 and p-STAT3 decreased. Conclusion Through inhibiting the JAK2/STAT3 signaling pathway, curcumin could improve arsenic-induced decline in learning and memory abilities in mice, reverse the destruction of blood-brain barrier permeability of innate immune system components in arsenic-exposed mice, and antagonize arsenic-induced increase in the number of renal CD4 and CD8 molecule as well as the imbalance of CD4⁺ T lymphocyte subsets (Th1, Th2, Th17 and Treg), ultimately counteracting arsenic-induced neurotoxicity.
Animals ; Janus Kinase 2/genetics* ; STAT3 Transcription Factor/genetics* ; Female ; Curcumin/pharmacology* ; Signal Transduction/drug effects* ; Mice, Inbred C57BL ; Mice ; Arsenic/toxicity*

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

Objective: To explore the value of vector angle of Lorenz plots(LPs) and the role of combining B-line slope in improving the diagnostic efficiency of arrhythmia． Methods: LPs of 119 cases with ventricular premature contraction (VPC group ) ，97 cases with supraventricular premature contraction(SPC group) ，52 cases with type II°I atrioventricular block ( Ⅱ ° Ⅰ group) and 54 cases with type Ⅱ ° Ⅱ atrioventricular / sinoatrial block ( Ⅱ ° Ⅱ group) were retrospectively analyzed．The B-line slope and vector angle were measured，and the differences between groups were compared. Receiver operating characteristic curve was used to analyze the diagnostic efficacy of B-line slope，vector angle and their combination between groups ，and MedCalc software was used for statistical comparison．The consistency of intra-observer and inter-observer measurements of B-line slope and vector angle was evaluated using Intra group correlation coefficient (ICC) and Bland-Altman plot. Results: There were significant differences between VPC group and SPC group，and between Ⅱ ° Ⅰ group and II°II group (P＜0. 05) ．The area under the curve (AUC) of B-line slope，vector angle，and the combination of the two in distinguishing ventricular and supraventricular premature contraction were 0. 81，0. 84 and 0. 87 respectively，and the AUC in distinguishing type Ⅱ ° Ⅰ and type Ⅱ ° Ⅱ atrioventricular / sinoatrial block were 0. 76，0. 78 and 0. 80 respectively．The ICC of vector angle was better than B-line slope (Intra-observer 0. 99 vs 0. 98，Inter-observer 0. 97 vs 0. 96) ． Conclusion Vector angle can be used to identify the type of arrhythmia，and has good intraobserver and interobserver consistency．Its combination with B-line slope has the highest accuracy in diagnosing arrhythmia，providing a new reference for clinical diagnosis and treatment.

Objective     To analyze the changes of perioperative symptoms of lung cancer patients by using patient-reported outcomes at different time points. Methods    A total of 109 patients who underwent thoracoscopic lung cancer resection in the department of thoracic surgery of our hospital from March to April 2021 were selected, including 55 (50.46%) males and 54 (49.54%) females. The mean age was 55.19±12.12 years. The postoperative symptom scale for lung cancer patients was used to investigate the changes of symptoms before surgery, 1 day after surgery, the day of discharge, and 30 days after surgery. Results     The mean hospital stay was 6.89±2.25 days. None of the patients reported any clinical symptoms related to lung cancer before surgery. The most prominent symptoms 1 day after surgery were pain (3.33±0.96 points), nausea (2.81±1.18 points), dizziness (2.00±0.85 points), fatigue (1.89±0.79 points) and shortness of breath (1.79±1.37 points). The patients with dizziness, nausea, fatigue and other symptoms gradually decreased, and the symptoms were relieved significantly (P<0.05). However, the symptoms of conscious pain, cough and shortness of breath lasted for a long time. At 30 days after surgery, 70.64%, 64.22% and 33.03% of patients felt pain, cough and shortness of breath, respectively, and the degree of cough was aggravated (P<0.001). Conclusion     Pain, cough, dizziness, shortness of breath and fatigue are the core postoperative symptoms of lung cancer patients. Most postoperative adverse symptoms can be effectively controlled in a short period of time, but pain, cough and shortness of breath still present persistent characteristics, which deserve further study.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

OBJECTIVE: To explore the short-term efficacy and adverse reactions of orelabrutinib combined with high-dose methotrexate (HD-MTX) in the first-line treatment of elderly high-risk primary central nervous system lymphoma (PCNSL), as well as the survival of patients. METHODS: Twenty-five elderly patients with high-risk primary central nervous system diffuse large B-cell lymphoma admitted to Fujian Provincial Hospital from June 2016 to June 2022 were enrolled in this study, and complete clinical data from all patients were collected retrospectively, and the cut-off for follow-up was December 2022. 15 patients had received temmozolomide combined with HD-MTX regimen for at least four cycles, sequential lenalidomide maintenance therapy, while 10 patients had received orelabrutinib combined with HD-MTX regimen for at least four cycles, sequential orelabrutinib maintenance therapy. The short-term efficacy and adverse reactions of the two groups of patients after treatment were observed. Kaplan-Meier was used to analyze the progression-free survival (PFS) and time to progression (TTP). RESULTS: The objective response rate (ORR) and 2-year median FPS of orelabrutinib combined with HD-MTX regimen group were similar to the temozolomide combined with HD-MTX regimen group (ORR: 100% vs 66.7%; 2-year median PFS: 16 months vs 15 months, P>0.05). The 2-year median TTP of the orelabrutinib+HD-MTX regimen group was better than that of the temozolomide+HD-MTX regimen group (not reached vs 12 months, P<0.05). There were no significant differences in adverse reactions such as gastrointestinal reactions, bone marrow suppression, liver and kidney damage, cardiotoxicity, pneumonia and bleeding between these two groups (P>0.05). CONCLUSION For elderly patients with high-risk PCNSL, orelabrutinib combined with HD-MTX has reliable short-term efficacy, good safety, and tolerable adverse reactions, which is worthy of clinical promotion.
Humans ; Aged ; Methotrexate/adverse effects* ; Retrospective Studies ; Temozolomide/therapeutic use* ; Central Nervous System Neoplasms/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Central Nervous System