BackgroundPatients with schizophrenia experience low quality of life， and internalized stigma is considered an important indicator for quality of life， while the mediating role of self-esteem and severity of negative symptoms in the relationship between internalized stigma and quality of life remains underexplored. ObjectiveTo examine the mediating role of self-esteem and severity of negative symptoms in the relationship between internalized stigma and quality of life， so as to provide references for improving their quality of life. MethodsA total of 342 patients with schizophrenia who were hospitalized in 6 hospitals in Xiangyang City， Siping City and Changchun City from April to September 2023 were included， and all of whom met the diagnostic criteria for schizophrenia according to the International Classification of Diseases， tenth edition （ICD-10）. Internalized Stigma of Mental Illness Scale （ISMI）， Schizophrenia Quality of Life Scale （SQLS）， Self-Esteem Scale （SES） and negative symptom subscale of Positive and Negative Symptom Scale （PANSS） were administered to all patients. Spearman correlation analysis was adopted to determine correlations between the different scales. A structural equation modeling was constructed using Amos 28.0， and Bootstrap method was employed to verify the mediating effect of self-esteem and negative symptom severity in the association between internalized stigma and quality of life. ResultsA total of 309 patients （90.35%） completed questionnaires in this study. The ISMI score of schizophrenia patients was positively correlated with both SQLS score and the PANSS negative symptom subscale score （r=0.612， 0.492， P<0.01）， while was negatively correlated with SES score （r=-0.513， P<0.01）. The SQLS score was negatively associated with the SES score （r=-0.555， P<0.01） and positively associated with PANSS negative symptom subscale score （r=0.672， P<0.01）. The SES score was negatively correlated with PANSS negative symptom subscale score （r=-0.433， P<0.01）.The total effect value of internalized stigma on quality of life was 0.746 （95% CI： 0.680~0.806）. Self-esteem and severity of negative symptoms independently mediated the relationship between internalized stigma and quality of life， and the indirect effect values were 0.151 （95% CI： 0.062~0.254） and 0.126 （95% CI： 0.047~0.205）， accounting for 20.24% and 16.89% of the total effect， respectively. In addition， a chained mediation effect of self-esteem and quality of life was also demonstrated， the indirect effect value was 0.102 （95% CI： 0.049~0.165）， accounting for 13.67% of the total effect）. ConclusionInternalized stigma in patients with schizophrenia patients can not only directly affect the quality of life， but also indirectly affect the quality of life of patients through either separate or chained mediation of self-esteem and the severity of negative symptoms. ［Funded by Hubei Provincial Undergraduate Innovation and Entrepreneurship Project （number， S202410519027）］

The purpose of this study was to clarify the effect of Huotan Jiedu Tongluo Decoction on atherosclerosis(AS) injury in ApoE~(-/-) mice by regulating the ferroptosis pathway. Seventy-five ApoE~(-/-) mice were randomly divided into model group, low-, medium-, and high-dose of Huotan Jiedu Tongluo Decoction groups, and evolocumab group(n=15), and 15 C57BL/6J mice were selected as the blank group. Mice in the blank group were fed with a normal diet, and those in the other groups were fed with a high-fat diet to induce AS. From the 9th week, mice in Huotan Jiedu Tongluo Decoction groups were administrated with Huotan Jiedu Tongluo Decoction at corresponding doses by gavage, and those in the blank group and the model group were given an equal volume of distilled water. Mice in the evolocumab group were treated with evolocumab 18.2 mg·kg~(-1 )by subcutaneous injection every 2 weeks. After 8 weeks of continuous intervention, oil red O staining and hematoxylin-eosin(HE) staining were employed to observe the lipid deposition and plaque formation in the aortic root. Masson staining was used to evaluate the collagen content in the aortic root. The serum levels of total cholesterol(TC), triglycerides(TG), high-density lipoprotein cholesterol(HDL-C), and low-density lipoprotein cholesterol(LDL-C) were determined by biochemical kits. The levels of Fe~(2+), superoxide dismutase(SOD), malondialdehyde(MDA), and glutathione(GSH) in the aorta were measured by colorimetry. The protein and mRNA levels of nuclear factor erythroid 2-related factor 2(Nrf2), glutathione peroxidase 4(GPX4), solute carrier family 7 member 11(SLC7A11), and acyl-CoA synthetase long chain family member 4(ACSL4) in the aorta were detected by Western blot and RT-qPCR, respectively. The expression of Nrf2, GPX4, and SLC7A11 was localized by immunofluorescence. The results showed that low-, medium-, and high-dose Huotan Jiedu Tongluo Decoction reduced the plaque formation of aortic root and increased the collagen content in AS mice. At the same time, Huotan Jiedu Tongluo Decoction improved the lipid metabolism by lowering the levels of TC, LDL-C, and TG and elevating the level of HDL-C in the serum. Huotan Jiedu Tongluo Decoction enhanced the antioxidant capacity by elevating the levels of GSH and SOD and lowering the level of MDA in the aorta and inhibiting the accumulation of Fe~(2+) in the aorta. In addition, Huotan Jiedu Tongluo Decoction up-regulated the protein and mRNA levels of Nrf2, GPX4, and SLC7A11, while down-regulating the protein and mRNA levels of ACSL4. In summary, Huotan Jiedu Tongluo Decoction can effectively alleviate AS lesions in ApoE~(-/-) mice by activating the Nrf2/GPX4 pathway, reducing lipid peroxidation, and inhibiting ferroptosis.
Animals ; Ferroptosis/drug effects* ; Atherosclerosis/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/genetics* ; Mice ; Mice, Inbred C57BL ; Apolipoproteins E/metabolism* ; Male ; Phospholipid Hydroperoxide Glutathione Peroxidase/genetics* ; Signal Transduction/drug effects* ; Humans ; Mice, Knockout

ObjectiveTo analyze the quantity-quality transfer of standard decoction of Ginseng Radix et Rhizoma（GRR） decoction pieces produced by fresh and traditional cutting， and to provide reference for quality control and application development of the decoction pieces produced by fresh cutting. MethodTen batches of representative GRR decoction pieces produced by fresh and traditional cutting and their standard decoctions were prepared by standard process， and high performance liquid chromatography（HPLC） fingerprint of the standard decoction was established and performed on an Agilent EC-C₁₈ column（4.6 mm×150 mm， 2.7 μm） with acetonitrile（A）-0.1% phosphoric acid aqueous solution（B） as the mobile phase for gradient elution（0-23 min， 18%-21%A； 23-35 min， 21%-28%A； 35-80 min， 28%-32%A）， and the detection wavelength was 203 nm. Then similarity evaluation， principal component analysis（PCA） and partial least squares-discriminant analysis（PLS-DA） of fingerprint of the standard decoction were performed to screen the differential components with variable importance in the projection（VIP） value>1. Quantitative analysis was carried out on the screened known differential components， and combined with the indicators of the dry extract rate and the transfer rate， to explore the differences in the quantity-quality transfer between the standard decoction of GRR decoction pieces produced by fresh and traditional cutting. ResultThe fingerprint similarity of the standard decoction of GRR decoction pieces produced by fresh and traditional cutting was more than 0.950， and 18 common peaks were identified， including 9 identified common peaks. The results of PCA and PLS-DA showed that there were some differences in the contents of index components between the two standard decoctions. The contents of ginsenoside Rg₁， Re and Ro in GRR decoction pieces produced by fresh cutting were higher than those in traditional decoction pieces， while the contents of ginsenoside Rb₁， Rc ， Rb₂ and Rd were lower than those in traditional decoction pieces. The contents of ginsenoside Rg₁， Re， Rb₁ and Ro in the standard decoction of GRR decoction pieces produced by fresh cutting were higher than those in the standard decoction of traditional decoction pieces， while the contents of ginsenoside Rc ， Rb₂ and Rd were comparable between the two standard decoctions. Compared with the standard decoction of the traditional decoction pieces， the average transfer rates of ginsenoside Rg₁， Rb₁， Rc， Rb₂ and dry extract rate of the standard decoction of GRR decoction pieces produced by fresh cutting were significantly increased（P<0.05）， and the average transfer rate of ginsenoside Re and Rd also increased， but the difference was not statistically significant. ConclusionThe dry extract rate， content and transfer rate of index components of standard decoction of GRR decoction pieces produced by fresh cutting are better than those of the standard decoction of traditional decoction pieces， which can provides data support for the subsequent clinical application of fresh cutting products.

ObjectiveTo analyze and determine the differential components of freeze-dried and sun-dried Panacis Quinquefolii Radix（PQR）， and to compare the differences in their pro-angiogenic activities. MethodFingerprints of freeze-dried and sun-dried PQR were established based on ultra performance liquid chromatography（UPLC）， and chemometrics methods such as principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were combined to determine the differential saponin composition of the two decoction pieces， and six representative saponins were selected and their contents in freeze-dried and sun-dried PQR were determined by UPLC. Transgenic zebrafish line Tg（fli1a∶EGFP） embryos fertilized for 24 h were selected， and different doses of 70% methanol extracts of freeze-dried and sun-dried PQR（10， 30 mg·L^-1） were used to intervene in normal zebrafish and in a zebrafish model of intersegmental vascular（ISV） injury induced by vascular endothelial growth factor（VEGF） receptor tyrosine kinase inhibitor Ⅱ（PTK787）， then the development of subintestinal vein（SIV） and ISV of zebrafish was observed， SIV diameter， mean number of crossings and mean number of germinations were determined， and the ISV vascular index was calculated， in order to compare the pro-angiogenic activities of the two decoction pieces. ResultThe similarity of the fingerprints of freeze-dried and sun-dried PQR decoction pieces was>0.950， and 17 common peaks were identified， of which 6 common peaks were designated as peak 6（ginsenoside Rg₁）， peak 7（ginsenoside Re）， peak 8（ginsenoside Rb₁）， peak 11（ginsenoside Rc）， peak 13（ginsenoside Rb₂）， and peak 16（ginsenoside Rd）， respectively. A total of 11 differential saponin components were screened by PCA and OPLS-DA， indicating that there were some differences in the contents of the components in the two decoction pieces. The results of determination showed that the contents of ginsenosides Rg₁， Re， Rb₁ and Rb₂ in freeze-dried PQR were higher than those in sun-dried PQR， while the contents of ginsenosides Rc and Rd were lower than those in sun-dried PQR（P<0.05， P<0.01）. In the study of the pro-angiogenic effect on normal zebrafish embryos， compared with the blank group， and the SIV vessel diameter， mean germination rate and mean crossover rate were significantly higher in the high-dose groups of freeze-dried and sun-dried PQR（P<0.01）， and the vessel diameter， mean numbers of crossings and germinations in the freeze-dried PQR group were higher than those of the sun-dried PQR group（P<0.05）. In the study of the pro-angiogenic effect on zebrafish embryos with ISV injury， the development of ISV in the model group was significantly inhibited when compared with the blank group， compared with the model group， different dose groups of freeze-dried and sun-dried PQR could promote the growth and sprouting of ISV， and the number of normal blood vessels in the freeze-dried PQR group was significantly higher than that in the sun-dried PQR group at the same dosage（P<0.05）. ConclusionFreeze-drying can effectively avoid the loss and secondary transformation of ginsenosides in PQR， and its angiogenic activity is better than that of sun-dried PQR， which can provide a reference for the production and development of high-quality PQR decoction pieces.

To construct a high-quality Panax ginseng cDNA library, transcription factors binding to the P. ginseng PgD14 gene promoter were screened by yeast one-hybrid, and proteins interacting with the P. ginseng Pgpht2-1 gene-encoded protein were screened by yeast two-hybrid. In this study, root tissues of P. ginseng were used as materials. Gateway technology was used to construct the P. ginseng yeast one-hybrid library, and duplex-specific nuclease(DSN) homogenization technology was used to construct the P. ginseng yeast two-hybrid library. The pAbAi-PgD14-Pro961 vector was used as bait to screen candidate transcription factors that might bind to the PgD14 gene promoter from the yeast one-hybrid library, and the pGBKT7-Pgpht2-1 vector was used as bait to screen candidate proteins that might interact with the Pgpht2-1 gene-encoded protein from the yeast two-hybrid library. The yeast one-hybrid library had a size of 1.20×10~7 CFU, a recombination rate of 100%, and an average inserted fragment length of more than 1 000 bp. The yeast two-hybrid library had a size of 1.832×10~5 CFU, a recombination rate of 100%, and an average inserted fragment length of about 1 000 bp. The recombinant vectors pAbAi-PgD14-Pro961 and pGBKT7-Pgpht2-1 were transformed into Y1HGold and AH109 strains, respectively, and interacting proteins were screened by yeast one-hybrid and yeast two-hybrid. As a result, 54 transcription factors that could bind to the PgD14 gene promoter of P. ginseng and 42 proteins that may interact with the protein encoded by the Pgpht2-1 gene were identified. This study successfully constructed the P. ginseng yeast one-hybrid and yeast two-hybrid cDNA libraries, laying a foundation for subsequent studies on the functions of the P. ginseng PgD14, Pgpht2-1, and other genes.
Panax/metabolism* ; Two-Hybrid System Techniques ; Plant Proteins/metabolism* ; Gene Library ; Plant Roots/chemistry* ; Protein Binding ; Transcription Factors/metabolism* ; Promoter Regions, Genetic

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

Humans ; Consensus ; Hypersensitivity ; Desensitization, Immunologic/adverse effects* ; Immunotherapy/adverse effects* ; Injections, Subcutaneous ; Allergens

OBJECTIVE: To evaluate the feasibility and tolerability of metoprolol standard dosing pathway (MSDP) in Chinese patients with acute coronary syndrome (ACS). METHODS: In this multicenter, prospective, open label, single-arm and interventional study that was conducted from February 2018 to April 2019 in fifteen Chinese hospitals. A total of 998 hospitalized patients aged ≥ 18 years and diagnosed with ACS were included. The MSDP was applied to all eligible ACS patients based on the standard treatment recommended by international guidelines. The primary endpoint was the percentage of patients achieving the target dose at discharge (V2). The secondary endpoints included the heart rate and blood pressure at V2 and four weeks after discharge (V4), and percentage of patients experiencing bradycardia (heart rate < 50 beats/min), hypotension (blood pressure < 90/60 mmHg) and transient cardiac dysfunction at V2 and V4. RESULTS: Of the 998 patients, 29.46% of patients achieved the target dose (≥ 95 mg/d) at V2. The total population was divided into two groups: target group (patients achieving the target dose at V2) and non-target group (patients not achieving the target dose at V2). There was significant difference in the reduction of heart rate from baseline to discharge in the two groups (-4.97 ± 11.90 beats/min vs. -2.70 ± 9.47 beats/min, P = 0.034). There was no significant difference in the proportion of bradycardia that occurred in the two groups at V2 (0 vs. 0, P = 1.000) and V4 (0.81% vs. 0.33%, P = 0.715). There was no significant difference in the proportion of hypotension between the two groups at V2 (0.004% vs. 0.004%, P = 1.000) and V4 (0 vs. 0.005%, P = 0.560). No transient cardiac dysfunction occurred in two groups during the study. A total of five adverse events (1.70%) and one serious adverse event (0.34%) were related to the pathway in target group. CONCLUSIONS In Chinese ACS patients, the feasibility and tolerability of the MSDP have been proved to be acceptable.

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

OBJECTIVE: Osteosarcoma(OS) and Ewing's sarcoma (EWS) are the two most common primary malignant bone tumors in children. The aim of the study was to identify key genes in OS and EWS and investigate their potential pathways. METHODS: Expression profiling (GSE16088 and GSE45544) were obtained from GEO DataSets. Differentially expressed genes were identified using GEO2R and key genes involved in the occurrence of both OS and EWS were selected using venn diagram. Gene ontology and pathway enrichment analyses were performed for the ensembl. Protein-protein interaction (PPI) networks were established by STRING. Further, UCSC was used to predict the transcription factors of the cell division cycke 5-like(CDC5L) gene, and GEPIA was used to analyze the correlation between the transcription factors and the CDC5L gene. RESULTS: The results showed that CDC5L gene was the key gene involved in the pathogenesis of OS and EWS. The gene is mainly involved in mitosis, and is related to RNA metabolism, processing of capped intron-containing pre-mRNA, mRNA and pre-mRNA splicing. CONCLUSION CDC5L, as a key gene, plays a role in development of OS and EWS, which may be reliable targets for diagnosis and treatment of these primary malignant tumors.
Bone Neoplasms/pathology* ; Cell Cycle Proteins/genetics* ; Child ; Computational Biology ; Gene Expression Profiling ; Humans ; Osteosarcoma/genetics* ; RNA-Binding Proteins/genetics* ; Sarcoma, Ewing/genetics*