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 study the safety and efficiency of endovascular treatment in pediatric severe cerebral venous sinus thrombosis(CVST).Methods:This was a case series study.Data of pediatric severe CVST patients who received endovascular treatment in the Department of Neurointerventional, the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2023 were retrospectively analyzed.The technical success rate, periprocedural complications, neurologic and radiologic outcomes were collected to study the safety and efficacy of endovascular treatment in pediatric severe CVST.Results:A total of 15 patients were included in this study, including 6 males(40.0%) and 9 females(60.0%) with a mean age of(14.60±2.26) years.The modified Rankin Scale score(mRS) before endovascular treatment was(3.47±1.06) points, and the time from onset to endovascular treatment was 17(12-26) days.Thirteen patients(86.7%) received mechanical thrombectomy through catheter aspiration and/or stent-retriever thrombectomy followed or not followed by intrasinus thrombolysis(IST), and 2 patients(13.3%) received IST only.The technical success rate was 100%.Three patients(20.0%) had periprocedural complications.Ten patients(66.7%) had mRS≤2 points at discharge.Twelve patients(80.0%) had valuable neurologic and radiologic follow-ups with a duration of 9.5(3.5-19.0) months, and they all had mRS≤2 points.Among the 12 patients, 8(66.7%) had good cerebral venous recanalization.Conclusions:Endovascular treatment is technically feasible in pediatric severe CVST patients, with acceptable safety and efficacy.

Objective: To investigate the clinicopathologic features of primary adrenal NK/T cell lymphoma (PANKL). Methods: Six cases of PANKL were collected at Henan Provincial People's Hospital from January 2000 to December 2021. The clinicopathologic features including morphology, immunophenotype, treatment and prognosis were retrospectively analyzed, and relevant literature was reviewed. Results: There were two males and four females. The median age was 63 years (ranged from 57 to 68 years). The tumors involved bilateral adrenal glands in 4 cases and unilateral adrenal gland in 2 cases. The main clinical symptom was low back pain without obvious cause. Serum lactate dehydrogenase (LDH) is elevated in five cases. The imaging feature was rapidly enlarging mass initially confined to unilateral/bilateral adrenal glands. Morphologically, the lymphoid cells were mainly medium-sized with a diffuse growth pattern. Coagulative necrosis and nuclear fragmentation were common. Angioinvasion was seen. Immunophenotypically, the neoplastic cells were positive for CD3, CD56 and TIA-1 while CD5 was negative in 5 cases. All cases were positive for EBER by in situ hybridization with more than 80% proliferative activity by Ki-67. Four cases received chemotherapy, one case underwent surgery, and one case underwent surgery with chemotherapy. Follow-up was done in 5 cases; one case was lost to follow-up. Three patients died with a median survival of 11.6 months (3-42 months). Conclusions: PANKL is rare with highly aggressive clinical presentation and poor prognosis. Accurate diagnosis entails correlation of histomorphology, immunohistochemistry, EBER in situ hybridization and clinical history.
Male ; Female ; Humans ; Middle Aged ; Aged ; Retrospective Studies ; Lymphoma, T-Cell, Peripheral/pathology* ; Killer Cells, Natural/pathology* ; Prognosis ; Immunophenotyping

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Four triterpenoids were isolated and purified from the 95% ethanol extract of Maytenus guangxiensis by silica gel column chromatography, Sephadex LH-20 column chromatography, MCI column chromatography and preparative RP-HPLC. Their structures were determined from their physicochemical properties and spectral data. They were identified as maytguanone A (1), maytguanone B (2), 11α-methoxyurs-12-ene-1β,3β-diol (3), lup-20(29)-ene-3β,11α-diol (4). Compounds 1 and 2 are new triterpenoids, along with compounds 3 and 4 were isolated from M. guangxiensis for the first time. The cytotoxicity of compounds 1, 3 and 4 was evaluated using the MTT procedure with three cancer cell lines. The results show that compound 3 displayed good inhibitory effects against HeLa, with an IC₅₀ of 10.68 μmol·L^-1.

Objective: To analyze the clinical characteristics of children with Burkitt lymphoma (BL) and to summarize the mid-term efficacy of China Net Childhood Lymphoma-mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen. Methods: Clinical features of 436 BL patients who were ≤18 years old and treated with the CNCL-B-NHL-2017 regimen from May 2017 to April 2021 were analyzed retrospectively. Clinical characteristics of patients at disease onset were analyzed and the therapeutic effects of patients with different clinical stages and risk groups were compared. Survival analysis was performed by Kaplan-Meier method, and Cox regression was used to identify the prognostic factors. Results: Among 436 patients, there were 368 (84.4%) males and 68 (15.6%) females, the age of disease onset was 6.0 (4.0, 9.0) years old. According to the St. Jude staging system, there were 4 patients (0.9%) with stage Ⅰ, 30 patients (6.9%) with stage Ⅱ, 217 patients (49.8%) with stage Ⅲ, and 185 patients (42.4%) with stage Ⅳ. All patients were stratified into following risk groups: group A (n=1, 0.2%), group B1 (n=46, 10.6%), group B2 (n=19, 4.4%), group C1 (n=285, 65.4%), group C2 (n=85, 19.5%). Sixty-three patients (14.4%) were treated with chemotherapy only and 373 patients (85.6%) were treated with chemotherapy combined with rituximab. Twenty-one patients (4.8%) suffered from progressive disease, 3 patients (0.7%) relapsed, and 13 patients (3.0%) died of treatment-related complications. The follow-up time of all patients was 24.0 (13.0, 35.0) months, the 2-year event free survival (EFS) rate of all patients was (90.9±1.4) %. The 2-year EFS rates of group A, B1, B2, C1 and C2 were 100.0%, 100.0%, (94.7±5.1) %, (90.7±1.7) % and (85.9±4.0) %, respectively. The 2-year EFS rates was higher in group A, B1, and B2 than those in group C1 (χ²=4.16, P=0.041) and group C2 (χ²=7.21, P=0.007). The 2-year EFS rates of the patients treated with chemotherapy alone and those treated with chemotherapy combined with rituximab were (79.3±5.1)% and (92.9±1.4)% (χ²=14.23, P<0.001) respectively. Multivariate analysis showed that stage Ⅳ (including leukemia stage), serum lactate dehydrogenase (LDH)>4-fold normal value, and with residual tumor in the mid-term evaluation were risk factors for poor prognosis (HR=1.38,1.23,8.52,95%CI 1.05-1.82,1.05-1.43,3.96-18.30). Conclusions: The CNCL-B-NHL-2017 regimen show significant effect in the treatment of pediatric BL. The combination of rituximab improve the efficacy further.
Adolescent ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Burkitt Lymphoma/drug therapy* ; Child ; Disease-Free Survival ; Female ; Humans ; Lactate Dehydrogenases ; Lymphoma, B-Cell/drug therapy* ; Male ; Prognosis ; Retrospective Studies ; Rituximab/therapeutic use* ; Treatment Outcome

Carboxyl CoA ligases(CCLs) is an important branch of adenylate synthetase gene family, which mainly has two-step catalytic reactions. Firstly, in the presence of adenosine triphosphate, it can catalyze the pyrophosphorylation of carboxylateswith diffe-rent structures to form corresponding acyl adenosine monophosphate intermediates. Secondly, adenosine monophosphate was replaced by free electrons in the mercaptan group of enzyme A or other acyl receptors by nucleophilic attack to form thioesters. In this study, on the basis of the transcriptome database of Arnebia euchroma, two genes were selected, named AeCCL5(XP_019237476.1) and AeCCL7(XP_019237476.1). Bioinformatics analysis showed that their relative molecular weights were 60.569 kDa and 60.928 kDa, theoretical PI were 8.59 and 8.92, respectively. They both have transmembrane domains but without signal peptide. By multiple sequence alignment and phylogenetic tree analysis, we found that the similarity between AeCCLs and other plant homologous proteins was not high, and the substrate binding sites of AeCCLs were not highly conserved. The reasons might be that the sequence and structure need to adapt to the changes of new substrates in the process of evolution. In this study, the full-length of AeCCL5 and AecCCL7 were cloned into the expression vector pCDFDuet-1. The proteins of AeCCL5 and AeCCL7 with His-tag were expressed in Escherichia coli. The proteins of AeCCL5 and AeCCL7 were purified by nickel column. In vitro enzymatic reactions proved that both AeCCL5 and AeCCL7 can participate in the upstream phenylpropane pathway of shikonin biosynthesisby catalyzing 4-coumaric acid to produce 4-coumarin-CoA, and then to synthesis p-hydroxybenzoic acid, which is an important precursor of shikonin biosynthesis in A. euchroma.
Boraginaceae/genetics* ; Cloning, Molecular ; Coenzyme A ; Coenzyme A Ligases/genetics* ; Ligases ; Phylogeny

Objective:To systematically evaluate the safety of heavy metals in Dendrobii Officinalis Caulis and its rhizosphere soil and bedrock in epiphytic culture imitated wild rock fissure. The distribution characteristics of heavy metals in carbonate-black limestone-Dendrobii Officinalis Caulis system in the study area were analyzed. Method:Samples of biennial Dendrobii Officinalis Caulis， black calcareous soil and carbonate rocks were collected from fracture-epiphytic culture in karst area of Guizhou province. The contents of Cu， Pb， As， Cd in Dendrobii Officinalis Caulis， and Cu， Pb， As， Cd， Cr in soil and bedrock were determined by inductively coupled plasma-mass spectrometry （ICP-MS）. The detection conditions were as follows：plasma power of 1 550 W， feedback power of 2 W， sampling depth of 9 mm， atomization chamber temperature at 2 ℃， analysis mode of full quantitative， and double charge of <1.5%. Hg content in Dendrobii Officinalis Caulis was determined by atomic fluorescence spectrometry， and Hg content in soil and bedrock was determined by mercury analyzer. SPSS 26.0 software was used to analyze the test data. Result:The contents of Cu， Pb， As， Cd and Hg in Dendrobii Officinalis Caulis were all within the safety threshold. The contents of Pb， As， Cd， Hg and Cr in black calcareous soil were higher than the corresponding background values of Chinese soil （P<0.05， P<0.01）， Cd in black calcareous soil was slightly polluted， while Cr， Cu， As， Pb and Hg were clean. The contents of Cu， As， Pb， Cd， Hg and Cr in carbonate rocks were significantly lower than those in black calcareous soil （P<0.01）. The order of heavy metals in black calcareous soil affected by parent rock was Hg>Cd>Cu>As>Cr>Pb. The bioconcentration factor （BCF） of heavy metals in Dendrobii Officinalis Caulis was in the order of Cu>Cd>Pb=Hg>As， but the BCFs of these five heavy metals were all low （all <10%）. The contents of Cu， Pb， Cd and Hg in Dendrobii Officinalis Caulis increased slightly with the increase of heavy metal content in the rhizosphere soil， while the content of As decreased with the increase of As content in the rhizosphere soil. In addition to Cu content in Dendrobii Officinalis Caulis， the migration characteristics of Pb， As， Cd and Hg in the system of carbonate-black limestone-Dendrobii Officinalis Caulis showed consistency. Conclusion:The distribution characteristics of heavy metals in geotechnical plant system in the study area show obvious inheritance. The characteristics of high content， low activity and low pollution risk of heavy metals in black limestone soil and low BCF are the main factors affecting the safety threshold of five heavy metals in Dendrobii Officinalis Caulis.

Angiotensin-Converting Enzyme 2 ; COVID-19 ; Drug Repositioning ; Enzyme-Linked Immunosorbent Assay ; Humans ; Pharmaceutical Preparations ; SARS-CoV-2

Objective: To investigate the feasibility of endoscopic lateral neck dissection via the breast and transoral approaches (ELNDBTOA) for papillary thyroid carcinoma (PTC). Methods: From February 2015 to April 2019, 10 patients with PTC (cN1b) including 1 male and 9 females aged from 22 to 53 years old received ELNDBTOA in the General Surgery Department of Zhongshan Hospital, Xiamen University. Total thyroidectomy, the central lymph node dissection and the selective neck dissection (levels Ⅱ, Ⅲ and Ⅳ) were performed endoscopically via the breast approach, and then the residual lymph nodes were dissected via transoral approach. The medical records, operation time, blood loss, complications and postoperative follow-up outcomes were analyzed retrospectively. SPSS 22.0 software package was used for statistical processing of clinical data of patients. Results: All cases were successfully treated with ELNDBTOA without transfer to open surgery. The average operative time was (362.5±79.7) min, the blood loss was (23.0±14.9) ml, and the postoperative hospital stay was (5.1±1.3) days. The mean number of harvested cervical lymph nodes were (34.2±25.8), and the mean number of positive lymph nodes were (6.5±4.9). Lymph nodes were dissected by the further dissection via oral approach in 6 patients and a total of 9 lateral lymph nodes were havested from 2 of the 6 patients, with 3 positive lymph nodes. Two patients had transient skin numbness in the mandibular area and recovered within two weeks. One patient developed transient hypoparathyroidism and recovered within two months. No secondary bleeding, recurrent laryngeal nerve paralysis, chylous leakage, neck infection, permanent hypoparathyroidism or other complications were observed. The follow-up time was from 16 to 66 months with a median of 42.5 months, no tumor recurrence or metastasis occurred, and also no obvious deformity, abnormal sensation or movement in the chest, neck and mouth was observed. Conclusions: ELNBTOA is safe and feasible, with good cosmetic outcome.
Adult ; Female ; Humans ; Lymph Nodes ; Male ; Middle Aged ; Neck Dissection ; Retrospective Studies ; Thyroid Cancer, Papillary/surgery* ; Thyroid Neoplasms/surgery* ; Thyroidectomy ; Young Adult