Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Objective:To explore the relationship between serum urea nitrogen to creatinine ratio (UCR) and cardiac function in elderly patients with severe pneumonia.Methods:A prospective selection of 100 elderly patients with severe pneumonia admitted to Group Wanbei General Hospital of Wanbei Coal Power from May 2020 to April 2023 was conducted as the case group, and an additional 50 patients who underwent health examinations in the hospital during the same period were selected as the control group. Serum urea nitrogen (BUN), creatinine (Cr), UCR value, myocardial injury indexes: cardiac troponin I (cTnI), N-terminal pro-brain natriuretic peptide (NT-ProBNP), creatine kinase (CK), creatine kinase isoenzyme MB (CK-MB), and cardiac function indexes: left ventricular ejection fraction (LVEF), cardiac output (CO), stroke volume (SV) and cardiac output index (CI) were detected in the two groups. The patients in the case group were divided into two subgroups based on the occurrence of heart failure during hospitalization: the heart failure subgroup and the normal heart function subgroup. The serum UCR, myocardial injury and cardiac function indexes were compared between the case group and the control group. The general data, myocardial injury and cardiac function indexes were compared between the heart failure group and the normal heart function group. The relationship between serum UCR and cardiac function in patients with severe pneumonia was analyzed by bivariate Pearson correlation. Logistic regression model was used to analyze the influencing factors of cardiac dysfunction in patients with severe pneumonia, and using receiver operating characteristic (ROC) curve to analyze the value of serum UCR in predicting cardiac dysfunction in patients with severe pneumonia.Results:The values of BUN, UCR, cTnI, NT-ProBNP, CK and CK-MB in the case group were higher than those in the control group: (8.72 ± 1.14) μmol/L vs. (6.41 ± 0.76) μmol/L, 125.00 ± 19.75 vs. 86.12 ± 12.02, 0.04 (0.03, 0.05) μg/L vs. 0.04 (0.03, 0.05) μg/L, (185.49 ± 20.59) ng/L vs. (147.76 ± 20.85) ng/L, (104.78 ± 14.98) U/L vs. (99.33 ± 15.07) U/L, (31.59 ± 6.23) U/L vs. (29.13 ± 5.76) U/L. The values of Cr, LVEF, CO, SV and CI in the observation group were lower than those in the control group: (70.22 ± 5.76) μmol/L vs. (74.75 ± 5.12) μmol/L, (59.72 ± 2.41)% vs. (61.78 ± 2.16)%, (3.93 ± 0.43) L/min vs. (4.53 ± 0.62) L/min, (59.82 ± 6.12) ml vs. (62.23 ± 7.22) ml, (2.95 ± 0.30) L/(min·m 2) vs. (3.06 ± 0.33) L/(min·m 2), with a statistical significant difference ( P<0.05). In the case group, 21 patients had heart failure during hospitalization, accounting for 21.00%. The pneumonia severity index score on admission in the heart failure subgroup was higher than that in the normal heart function subgroup: (172.76 ± 9.18) points vs. (168.24 ± 8.81) points. The serum BUN and UCR levels were higher than those in the normal heart function subgroup: (9.51 ± 0.79) mmol/L vs. (8.51 ± 1.13) mmol/L, 141.62 ± 9.89 vs. 120.59 ± 19.39. The serum Cr level was lower than that in the normal heart function subgroup: (67.26 ± 5.34) μmol/L vs. (71.00 ± 5.65) μmol/L, with a significant statistical difference ( P<0.05). There was no significant statistical difference in other data between the two subgroups ( P>0.05). The bivariate Pearson correlation analysis showed that serum UCR was positively correlated with cardiac function indicators cTnI, NT-ProBNP, CK and CK-MB levels in severe pneumonia ( r = 0.40, 0.27, 0.32 and 0.33; P<0.05), and negatively correlated with LVEF, CO, SV and CI levels ( r = - 0.37, - 0.21, - 0.25 and - 0.21; P<0.05). Univariate and multivariate Logistic regression analysis showed that the occurrence of cardiac dysfunction in elderly patients with severe pneumonia may be related to the pneumonia severity index score on admission and the abnormal expression of serum BUN, UCR and Cr levels ( P<0.05). ROC curve analysis found that the area under the curve for predicting the occurrence of cardiac dysfunction during hospitalization in severe pneumonia patients with serum UCR on admission was 0.85 (95% CI 0.77 to 0.92), which had certain predictive value. Conclusions:Elderly patients with severe pneumonia are accompanied by a certain degree of elevated serum UCR levels, and the higher the serum UCR level, the more severe the cardiac function damage and the greater the risk of cardiac dysfunction.

AIM: To compare the changes in axial length of myopic patients of different ages after wearing orthokeratology lenses with increased compression factor(ICF)or conventional compression factor(CCF)for 2 a.METHODS: Retrospective study. A total of 141 myopia patients(141 right eyes)aged 8 to 15 years who fitted with orthokeratology lenses in the General Hospital of Foshan Aier Eye Hospital from July 2020 to July 2021 were continuously included. They were divided into the CCF group(70 cases, 70 eyes)and the ICF group(71 cases, 71 eyes). The patients in the CCF group were fitted with orthokeratology lens of 0.75 DS CCF, while patients in the ICF group were fitted with orthokeratology lens of 1.25 D ICF. Taking 12 years old as a boundary, these two groups were divided into 8-11 years old and 12-15 years old group. The uncorrected visual acuity(UCVA), horizontal corneal curvature(K1)and corneal staining were recorded for all subjects after wearing lenses for 1 d, 1 wk, 1, 6 mo, 1 and 2 a. The axial length(AL)was recorded after wearing lenses for 6 mo, 1 and 2 a, and the complication and corneal epithelial staining were observed during lens wearing.RESULTS:The improvement of UCVA in the ICF group was faster than that in the CCF group, which were statistical significant after wearing lenses for 1 d, 1 wk and 1 mo, respectively(all P<0.001); however, there was no statistical significance between the two groups after 6 mo, 1 and 2 a(all P>0.05); K1 of the ICF group decreased faster than that of the CCF group, and there were statistical significance at 1 d, 1 wk, and 1 mo after wearing lenses(all P<0.05); there was no statistical significance at 6 mo, 1 and 2 a(all P>0.05). The axial length growth of patients aged 8-11 years old in the ICF group and CCF group was 0.35±0.17 and 0.48±0.26 mm, respectively(P=0.010), after wearing lenses for 2 a, and the axial length growth of patients aged 12-15 years old in the ICF group and CCF group was 0.16±0.15 and 0.31±0.29 mm, respectively(P=0.011). During the follow-up period, corneal spotting occurred in 6 eyes(8.5%)in the ICF group, and 7 eyes(10%)in the CCF group(P>0.05), all of which were grade 1 spotting.CONCLUSION:Wearing ICF orthokeratology lens is more effective than wearing CCF lenses in controlling the growth of axial length, with faster shaping and more obvious improvement in UCVA, especially for the prevention of high myopia in children under 12 years. Therefore, young children can give priority to wearing lenses that increase the compression factor, and for children over 12 years old, the compression factor of the lens can be selectively increased according to the wearer's eye habits, health status of ocular surface and visual function.

This article reports a rare case of proliferative glomerulonephritis with monoclonal immunoglobulin deposits. The patient, a middle-aged woman, exhibited clinical manifestations including nephrotic syndrome, microscopic hematuria, renal insufficiency, hyperglycemia, and bilateral diabetic retinopathy. Notably, monoclonal bands were absent in both blood and urine immunofixation electrophoresis. Renal biopsy revealed membranoproliferative glomerulonephritis, with immunofluorescence revealing exclusive petal-like deposition of IgG3 subtype along the capillary loop. Electron microscopy demonstrated segmental thickening of the glomerular basement membrane, along with electron dense deposits in the subendothelial and mesangial areas, lacking discernible substructure. The diagnosis comprised proliferative glomerulonephritis with monoclonal immunoglobulin deposition concurrent with diabetic nephropathy. Subsequent sequential treatment with daratumumab and cyclophosphamide over 6 months led to partial remission of nephrotic syndrome, normalization of renal function, and significant improvement of anemia. During the 24-month follow-up period, no serious adverse reactions occurred.

Hypoprothrombinemia-lupus anticoagulant syndrome(HLAS)is a rare disease in which patients present with varying degrees of bleeding and positive lupus anticoagulant with reduced prothrombin on laboratory tests.This article reports a case of HLAS in a middle-aged woman with recurrent gingival bleeding and epistaxis as the first presentation.After admission,tests revealed prolonged prothrombin time(PT),activated partial thromboplastin time(APTT),and reduced coagulation factor Ⅱ activity,and positive lupus anticoagulant(LA).Meanwhile,the patient had symptoms of dry mouth and dry eyes for a long time,and the examination of autoantibodies,tear secretion test and salivary gland emission computed tomography(ECT)were consistent with the diagnosis of Sjogren's syndrome.The final diagnosis was HLAS secondary to Sjogren's syndrome.After treatment with methylprednisolone and cyclophosphamide,the coagulation disorder gradually improved,and no recurrent bleeding occurred.HLAS is a rare clinical case,which reminds medical staff to be alert to the possibility of HLAS when encountering patients with unexplained prolonged APTT and PT and positive lupus anticoagulant.

Objective:To investigate the clinicopathological characteristics and survival of patients with lymphoplasmacytic lymphoma (LPL).Methods:The data of 33 newly diagnosed LPL patients in the First Affiliated Hospital of Dalian Medical University from July 2003 to May 2021 were retrospectively analyzed. The clinical characteristics, bone marrow cell morphology, immunophenotyping, chromosomal karyotype, gene mutation, treatment response and prognosis were analyzed, and Kaplan-Meier method was used to analyze the survival of patients.Results:The median age of onset of 33 patients was 66 years old (55-84 years old). There were 26 males (78.8%) and 7 females (21.2%). The common clinical manifestations were anemia (31 cases, 93.9%), enlarged lymph nodes (16 cases, 48.5%) and B symptoms (8 cases, 24.2%). All patients had bone marrow involvement and M protein, 23 of them (69.7%) were type IgM-κ, 8 cases (24.2%) were type IgM-λ, 1 case (3.0%) was type IgG-κ, and 1 case (3.0%) was type IgA-κ. Lymphocytes, lymphoplasmacytes or plasma cells was increased in bone marrow smear; 22 patients underwent immunophenotyping of bone marrow by flow cytometry, and all patients expressed B cell surface antigens (CD19 and CD20), 16 patients (72.7%) lost the expression of CD5 and CD10, 13 patients (59.1%) expressed or weakly expressed CD138 and 5 patients (22.7%) expressed CD38. Seven out of 23 cases (30.4%) who received chromosome examination had abnormal chromosomal karyotype. Fourteen out of 16 cases (87.5%) who received MYD88 L265P mutation detection harbored the mutation. Among 21 patients with evaluable efficacy, 18 patients (85.7%) responded to treatment, achieving partial remission or stable disease, but the rate of complete remission was low (14.3%, 3/21). The median follow-up time was 34 months (2-102 months), 1 case was lost. The median overall survival time was not reached, and the 3-year and 5-year overall survival rates were 79.2% and 67.9%, respectively.Conclusions:LPL is a rare indolent small B-cell lymphoma with a long course and a variety of manifestations, which is commonly seen in elderly men.Serological examination, bone marrow cell morphology and biopsy, immunophenotyping and MYD88 L265P mutation detection are important for the diagnosis and differential diagnosis.

Objective:By comparing the volume% (V% GGOs) of ground glass opacities (GGOs) in high resolution CT (HRCT) of patients with acute paraquat (PQ) poisoning at different time points, its value in the early prognosis of patients with PQ poisoning was analyzed. Methods:The data of patients with PQ poisoning admitted to Department of Respiratory and Critical Care Medicine of Chinese Armed Police Forces from June 2017 to December 2018 were prospectively analyzed. According to the follow-up results after poisoning at 90 days, the patients were divided into the survival group and death group. Three-dimensional reconstruction technology was used to calculate the change of V% GGOs on the 3rd, 5th, and 7th day after poisoning. Chi-square test and One-Way ANOVA of variance were used to compare sex, age, and time of poisoning between the two groups. The Student's t test was used to compare V% GGOs between the two groups at different time points. The receiver operating characteristic curve (ROC) was used to determine the guiding significance of the indicator on the prognosis of patients with PQ poisoning at different time points. Results:A total of 89 patients with PQ poisoning were included in the study, 49 in the survival group and 40 in the death group. There were no statistical differences between the two groups of patients in sex, age, poisoning time, oxygenation index, mean arterial pressure, total bilirubin, blood urea nitrogen, alanine aminotransferase, and aspartate aminotransferase at admission (all P>0.05). The blood PQ concentration (mg/L) in the death group was significantly higher than that in the survival group (6.35 ±0.51 vs 3.49 ±0.21, P= 0.013). On the 3rd, 5th and 7th day after admission, the V% GGOs was significantly higher than that in the survival group (3rd day: 0.062±0.020 vs 0.049±0.007, P= 0.013; 5th day: 0.292±0.130 vs 0.123±0.044, P<0.01; 7th day: 0.334±0.116 vs 0.138±0.034, P=0.019). The area under the ROC curve showed that the prognosis AUC of the 7th day V% GGOs after poisoning was 0.967, the sensitivity was 100% and the specificity was 83.33% when the threshold was 0.16, but the time point was late. On the 5th day after poisoning, the V% GGOs judged the prognosis AUC was 0.842, the sensitivity was 82.35% and the specificity was 89.47% when the threshold was 0.14. On the 3rd day after poisoning, the V% GGOs judged the prognosis AUC was 0.708, the sensitivity was 55.00% and the specificity was 78.95% when the threshold was 0.05. At this time, the sensitivity and specificity were lower than those on the 5th and 7th day. Conclusions:The proportion of ground glass opacity volume in patients with PQ poisoning can be used to evaluate their prognosis, and the best time point is the 5th day after poisoning.

Objective:To analyze the associations between prenatal and 1-year-old exposure to antibiotics and allergic symptoms in children aged 6-11 months and 18-23 months.Methods:In this study, a prospective birth cohort study was adopted. A total of 2 122 pregnant women were enrolled in Maternal and Child Health Care Center of Ma′anshan from June 2015 to June 2016, and they were followed up from the beginning of pregnancy to children′s 24 months of age. Excluding 564 pairs of mothers and children who were lost to follow-up or with incomplete information on the use of antibiotics and children′s allergic symptoms, a total of 1 558 pairs of mothers and children were included in the analysis of this study. The parents and children′s general demographic information, early-life antibiotic exposure and other data were collected, the information about allergic symptoms in children aged 6-11 months and 18-23 months were investigated by reference to the "International Study of Asthma and Allergies in Childhood (ISAAC)". The univariate and multivariate binary unconditional logistic regression model was used to was used to estimate associations between the effects of early-life antibiotic exposure on allergic symptoms in 2-year-old children.Results:The antibiotic usage rate of pregnant women during pregnancy was 3.4% (53), and the antibiotic usage rates of children between 0 to 2 months, 3 to 5 months, and 6 to 11 months were separately 15.2%(237), 15.5%(242) and 17.3%(269). The total prevalence of allergic diseases in children aged 6 to 11 months was 24.1% (375 children), and the total prevalence of allergic diseases in children aged 18 to 23 months was 22.0% (342 children). After adjust parental (maternal) education level, family monthly income per capita, parental (maternal) allergy history, parental (maternal) age at pregnancy, mother′s Body Mass Index (BMI) before pregnancy, exposure to second-hand smoke during pregnancy, delivery method, child gender, birth weight, preterm birth, the use of antibiotics when children were 3-5 months old ( RR=1.61,95% CI:1.19-2.17) and 6-11 months old ( RR=1.43,95% CI:1.06-1.93) were the risk factors for allergic symptoms at 6-11 months of age; and the use of antibiotics when children were 0-2 months old (RR=1.41, 95% CI: 1.03-1.95), 3-5 months old ( RR=1.54, 95% CI: 1.12-2.11) and 6-11 months old ( RR=1.58, 95% CI: 1.17-2.14) were the risk factors for allergic symptoms at 18-23 months of age. Conclusion:Children′s exposure to antibiotics within 1 year of age was a risk factor for allergic symptoms in children aged 6-11 months and 18-23 months, children should avoid unnecessary antibiotic use in infancy.

Objective:To further improve the awareness of the clinical feature of acute diquat poisoning.Methods:A retrospective analysis was performed on 4 cases of acute diquat poisoning with epileptoid seizure as the main clinical manifestation, which were admitted and diagnosed by the Characteristic Medical Center of Chinese People's Armed Police Force from January 1, 2017 to December 31, 2019. Take "Diquat" or "Deiquat" or "Reward" as keyword search for CNKI, Pubmed, and EMbase in both Chinese and English. The date of literature retrieval was from the database founding to December 31, 2019.Results:Of the 4 patients, 3 were male and 1 female, with an average age of 28 years (22-33 years) . The estimated dose was 8-20 g. All patients were treated with gastric lavage, catharsis, fluid replacement, blood perfusion, and in the early stage of treatment of epileptic seizures, the initial routine antiepileptic drugs had poor effect. Then propofol and midazolam were injected into the treatment. The epilepsy was relieved, but the condition deteriorated rapidly, and the patients died eventually. The literature search retrieved 3 patients in the 3 literatures included in the study were analyzed, and their clinical course was similar to that of 4 cases in the center. Necropsy was performedon all 3 patients, and the results were cerebral edema, diffuse cerebral edema, and hemorrhage around the basal ganglia.Conclusion:Acute diquat poisoning can cause epileptic seizures. Once it occurs, the disease progresses rapidly and the prognosis is poor. The combination of large dose of sedative drugs can be used to treat epilepsy in order to improve the prognosis.

Objective:To analyze the associations between prenatal and 1-year-old exposure to antibiotics and allergic symptoms in children aged 6-11 months and 18-23 months.Methods:In this study, a prospective birth cohort study was adopted. A total of 2 122 pregnant women were enrolled in Maternal and Child Health Care Center of Ma′anshan from June 2015 to June 2016, and they were followed up from the beginning of pregnancy to children′s 24 months of age. Excluding 564 pairs of mothers and children who were lost to follow-up or with incomplete information on the use of antibiotics and children′s allergic symptoms, a total of 1 558 pairs of mothers and children were included in the analysis of this study. The parents and children′s general demographic information, early-life antibiotic exposure and other data were collected, the information about allergic symptoms in children aged 6-11 months and 18-23 months were investigated by reference to the "International Study of Asthma and Allergies in Childhood (ISAAC)". The univariate and multivariate binary unconditional logistic regression model was used to was used to estimate associations between the effects of early-life antibiotic exposure on allergic symptoms in 2-year-old children.Results:The antibiotic usage rate of pregnant women during pregnancy was 3.4% (53), and the antibiotic usage rates of children between 0 to 2 months, 3 to 5 months, and 6 to 11 months were separately 15.2%(237), 15.5%(242) and 17.3%(269). The total prevalence of allergic diseases in children aged 6 to 11 months was 24.1% (375 children), and the total prevalence of allergic diseases in children aged 18 to 23 months was 22.0% (342 children). After adjust parental (maternal) education level, family monthly income per capita, parental (maternal) allergy history, parental (maternal) age at pregnancy, mother′s Body Mass Index (BMI) before pregnancy, exposure to second-hand smoke during pregnancy, delivery method, child gender, birth weight, preterm birth, the use of antibiotics when children were 3-5 months old ( RR=1.61,95% CI:1.19-2.17) and 6-11 months old ( RR=1.43,95% CI:1.06-1.93) were the risk factors for allergic symptoms at 6-11 months of age; and the use of antibiotics when children were 0-2 months old (RR=1.41, 95% CI: 1.03-1.95), 3-5 months old ( RR=1.54, 95% CI: 1.12-2.11) and 6-11 months old ( RR=1.58, 95% CI: 1.17-2.14) were the risk factors for allergic symptoms at 18-23 months of age. Conclusion:Children′s exposure to antibiotics within 1 year of age was a risk factor for allergic symptoms in children aged 6-11 months and 18-23 months, children should avoid unnecessary antibiotic use in infancy.