Based on the trinity life view of ''physique， Qi， and spirit''， Chaihu Jia Longgu Mulitang treats the patient's physical symptoms， disorders of Qi movement， and disorders of consciousness， covering the overall treatment and comprehensive nursing of physique， Qi， and spirit. It is widely applied and recognized for its efficacy in modern clinical practice. This paper explored the treatment effect of Chaihu Jia Longgu Mulitang from the trinity life view of ''physique， Qi， and spirit''. This formula mainly targeted patients with Qi deficiency caused by cold， leading to a syndrome of Qi stagnation and water retention in the Triple Energizer Meridian of Hand Lesser Yang （TE）， as well as fire-heat syndrome in the Large Intestine Meridian of Hand Yang Brightness （LI） and Stomach Meridian of Foot Yang Brightness （ST）， accompanied by disorder of nutrient-blood and subsequent spirit and soul unrest. Accurately judging the imbalance of the patient's physique， Qi， and spirit and using an appropriate combination of medicinals can achieve balance among the three to achieve the best effect. The treatment strategy of Chaihu Jia Longgu Mulitang is as follows： For disorders of Qi movement， such as Qi deficiency， Qi stagnation， and gastrointestinal fire-heat， Ginseng Radix et Rhizoma and Bupleuri Radix-Scutellariae Radix， and Rhei Radix et Rhizoma are used in combination. For physical symptoms such as water retention and disorder of nutrient-blood， Poria-Pinelliae Rhizoma-Zingiberis Rhizoma Recens， as well as Cinnamomi Ramulus-Jujubae Fructus are used in combination. Finally， Os Draconis-Ostreae Concha-Plumbum Rubrum is used to calm the spirit and soothe the soul. According to existing research， Chaihu Jia Longgu Mulitang has shown good efficacy in treating a variety of complex clinical diseases. This article provides a comprehensive interpretation of Chaihu Jia Longgu Mulitang from the perspective of the trinity life view of ''physique， Qi， and spirit''， offering new insights for clinical syndrome differentiation， treatment， and prescription.

Metastasis is the leading cause of death from cutaneous melanoma. Identifying metastasis-related targets and developing corresponding therapeutic strategies are major areas of focus. While functional genomics strategies provide powerful tools for target discovery, investigations at the protein level can directly decode the bioactive epitopes on functional proteins. Aptamers present a promising avenue as they can explore membrane proteomes and have the potential to interfere with cell function. Herein, we developed a target and epitope discovery platform, termed functional aptamer evolution-enabled target identification (FAETI), by integrating affinity aptamer acquisition with phenotype screening and target protein identification. Utilizing the aptamer XH3C, which was screened for its migration-inhibitory function, we identified the Chondroitin Sulfate Proteoglycan 4 (CSPG4), as a potential target involved in melanoma migration. Further evidence demonstrated that XH3C induces cytoskeletal rearrangement by blocking the interaction between the bioactive epitope of CSPG4 and integrin α4. Taken together, our study demonstrates the robustness of aptamer-based molecular tools for target and epitope discovery. Additionally, XH3C is an affinity and functional molecule that selectively binds to a unique epitope on CSPG4, enabling the development of innovative therapeutic strategies.

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.
Transcription Factors/genetics* ; Humans ; Chromatin/genetics* ; Animals ; Binding Sites ; Mice ; DNA Footprinting/methods*

Objective:To investigate the efficacy and safety of separated R-CHOP in older patients with newly diagnosed diffuse large B-cell lymphoma(DLBCL).Methods:A total of 137 patients aged 65-80 years newly diagnosed with DLBCL between April 2013 and September 2022 at The First Affiliated Hospital of Zhengzhou University were enrolled.The patients were assigned into separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups based on their different chemotherapy regimens.All individuals were treated in 21-day cycles for 4-8 cycles.The short-term and long-term efficacies and adverse reactions of the treatments were compared among the three groups,and factors influencing progression-free survival(PFS)and overall survival(OS)were analyzed.Results:The overall response rates(ORR)of patients in the separated R-CHOP,full-dose R-CHOP,and reduced R-CHOP-like groups were 89.7%,90.3%,and 86.1%,respectively,with no significant differences among them.The complete respond rate(CRR)of the separated R-CHOP group(64.1%)was significantly higher than that of the reduced R-CHOP-like group(33.3%)(P=0.008)but not significantly different from that of the full-dose R-CHOP group(66.1%).Survival curve analysis revealed no significant differences in PFS and OS between the separated and full-dose R-CHOP groups.Although the separated R-CHOP group showed improved PFS compared with the reduced R-CHOP-like group(P=0.036),there was no statistical difference in OS between these two groups.Multivariate analysis revealed that the international prognostic index(IPI)and separated R-CHOP had significant effects on PFS in patients with DLBCL(all P<0.05),whereas only IPI had a significant effect on OS(P<0.001).The incidence of leukopenia and grade 3-4 leukopenia in the separated R-CHOP group was significantly lower than that in the full-dose R-CHOP group(P=0.007,P=0.012),but there was no significant difference with the reduced R-CHOP-like group in this regard.Conclusions:In older patients with newly diagnosed DLBCL,separated R-CHOP showed good efficacy both in the short and long terms and had acceptable safety and tolerability profiles.

Objective:To evaluate the efficacy and safety of mild hypothermia for patients with severe traumatic brain injury (sTBI).Methods:PubMed, Embase, Cochrane Library, Web of Science, China Biology Medicine Disc, China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and VIP Database were searched for prospective randomized controlled researches on mild hypothermia and normothermia for patients with sTBI. The search time was from the establishment of the databases to February 2023. RevMan 5.3 software was used for Meta-analysis. The evaluation indicators included literature search results, basic characteristics and quality of the literature, poor prognosis rate and mortality at 6 and 12 months after treatment, incidence of pulmonary infection, arrhythmia, thrombocytopenia, intracranial infection, renal insufficiency, gastrointestinal ulcer/bleeding and electrolyte disorder during the treatment, and publication bias.Results:A total of 16 papers involving 2 640 patients were included, comprising 1 381 patients in the mild hypothermia group and 1 259 patients in the normothermia group. The poor prognosis rate in the mild hypothermia group was significantly lower than that in the normothermia group at 6 and 12 months after treatment ( RR=0.81, 95% CI 0.69, 0.95, P<0.01; RR=0.65, 95% CI 0.51, 0.84, P<0.01). There was no significant difference in the mortality between the two groups at 6 and 12 months after treatment ( RR=0.81, 95% CI 0.61, 1.08, P>0.05; RR=0.69, 95% CI 0.47, 1.03, P>0.05). In contrast with the the normothermia group, in the mild hypothermia group the incidence of pulmonary infection was significantly different ( RR=1.18, 95% CI 1.04, 1.34, P<0.01); the incidence of arrhythmia was not significantly different ( RR=1.35, 95% CI 0.73, 2.49, P>0.05); the incidence of thrombocytopenia was significantly different ( RR=1.78, 95% CI 1.34, 2.37, P<0.01); the incidence of intracranial infection was not significantly different ( RR=1.32, 95% CI 0.54, 3.23, P>0.05); the incidence of renal insufficiency was not significantly different ( RR=1.22, 95% CI 0.71, 2.09, P>0.05); the incidence of gastrointestinal ulcer/bleeding was not significantly different ( RR=0.98, 95% CI 0.73, 1.31, P>0.05); the incidence of electrolyte disorders was not significantly different ( RR=1.39, 95% CI 1.00, 1.94, P>0.05). The funnel plot was approximately symmetrical and the scattered points were concentrated in the narrow area in the upper part of the funnel plot, suggesting no publication bias. Conclusions:In comparison with normothermia for sTBI, mild hypothermia can not reduce the mortality at 6 and 12 months after treatment, but it can reduce the incidence of poor prognosis at 6 and 12 months after treatment. Moreover, mild hypothermia has no obvious effect on the incidence of arrhythmia, intracranial infection, renal insufficiency, gastrointestinal ulcer/bleeding, and electrolyte disorder, but it can increase the incidence of pulmonary infection and thrombocytopenia.

The timely use of screening tools to assess the palliative care needs of emergency patients can provide decision-making basis for patient referral and help patients receive palliative care in a timely manner.This paper reviews the palliative care needs screening tools for emergency patients at home and abroad,describes their development methods,scoring criteria and application status,compares and analyzes their characteristics and shortcomings.It aims to provide references for the localized development and application of palliative care needs screening tools in emergency patients.

Objective:To systematically evaluate the experience of home-based hospice care from two different perspectives of professional caregivers and family caregivers, and summarize the barriers faced by caregivers.Methods:This study was Meta-synthesis. Qualitative studies on the barriers of home-based hospice care among professional caregivers or family caregivers were electronically searched on China National Knowledge Infrastructure, WanFang Data, VIP, PubMed, Web of Science, Cochrane Library, Embase, CINAHL and Medline. The search period was from database establishment to October 3, 2023. The quality evaluation of literature was conducted using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center. The aggregation Meta-synthesis method was used to integrate the included article.Results:A total of ten articles were included, all had a quality evaluation level of B. Thirty-five results were extracted and summarized into eight new categories. Two integrated results were formed, including barriers to implementation of home-based hospice care by patients' family members (three categories) and barriers to implementation of home-based hospice care by professional caregivers (five categories) .Conclusions:Due to various factors such as external policies, organizations, and personnel, there are still many challenges in the practical development of home-based hospice care. Government and medical institutions can formulate or improve policies and service processes to address the obstacles to implementing home hospice care for different caregivers, and promote the development of home-based hospice care.

Objective To explore the difference of transfer RNA-derived small RNA(tsRNA)expression profile before and after acute myocardial infarction(AMI)and the diagnostic value of tsRNA for AMI.Methods Age-and weight-matched male C57 mice(8-10 weeks)were randomly divided into MI group and Sham group,with 4 in each group.AMI model was surgically induced in mice in MI group.After 24 h of modeling,RNA was extracted from left ventricular myocardial tissue.After removing modifications,total RNA of each sample was sequentially ligated to 3'and 5'small RNA adapters.Subsequently,reverse transcription PCR was performed.cDNA was then synthesized and amplified.The amplified products corresponding to the size of 15-40 nt RNA were screened to construct a library for sequencing.The sequencing results were compared with the mature tRNA and tRNA precursor sequences in GtRNAdb database.Differentially expressed tsRNA profiles before and after AMI were obtained.The alterations of the cleaved patterns of tRNA corresponding to the same codon before and after AMI were analyzed.According to the profile of differentially expressed tsRNA before and after AMI,tsRNA only abundantly expressed in MI group were selected and verified in myocardial tissue and plasma of mice to explore the potential of these tsRNAs as diagnostic markers of AMI.Results tsRNA profile showed good repeatability within the same group and great distinctiveness between the different groups.After AMI occurred,the cleaved patterns of a variety of tRNAs changed,including tRNA Asn-GTT,Glu-TTC,Gly-ACC,Gly-GCC,His-GTG,Ile-AAT,Ile-GAT,Pro-TGG,Ser-AGA,and Trp-CCA.Compared with the Sham group,268 tsRNAs significantly up-regulated and 1 228 tsRNAs down-regulated in MI group,and 64 tsRNAs were uniquely expressed in MI group.tRF-Gly-CCC-2-31,tiRNA-Val-CAC-1-32,tiRNA-Val-AAC-2-32,tiRNA-Glu-TTC-2-32,and tiRNA-Lys-TTT-1-34 were specifically expressed in cardiac tissue on the 1st day post AMI.Among them,tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 showed specifically abundant levels in plasma from MI group and dynamically changed with AMI duration.Conclusions The expression profile of tsRNA is significantly different before and after AMI.tiRNA-Val-AAC-2-32 and tiRNA-Lys-TTT-1-34 are uniquely highly expressed in myocardial tissue and plasma from AMI mice,and might have the potential as diagnostic markers of AMI.

Objective:To explore the clinical characteristics of hemoglobin H (HbH) disease during pregnancy, and evaluate the impact of prepregnant anemia on maternal and fetal outcomes.Methods:Clinical data of 12 pregnant women, who were diagnosed with HbH disease by genetic testing in the Third Affiliated Hospital of Guangzhou Medical University from January 1, 2017, to December 31, 2022, were retrospectively collected. Thalassemia genotypes, general conditions before and during pregnancy, and perinatal outcomes were analyzed using descriptive analysis.Results:The 12 patients were categorized into moderate anemia (Hb<90 g/L, n=5) and mild anemia (Hb≥90 g/L and <110 g/L, n=7) groups according to the level of Hb before conception. In the moderate anemia group, with one deletional HbH disease and four non-deletional type, all had blood transfusion histories, and four developed severe anemia during pregnancy with four cases of fetal growth restriction. The mild anemia group comprised six deletional and one non-deletional genotype, with no severe anemia or transfusion requirement during pregnancy. In terms of maternal and fetal outcomes, two moderate anemia cases opted for pregnancy termination, while three delivered via cesarean section with two preterm infants having mild asphyxia and one full-term. In the mild anemia group, one case terminated due to intrauterine fetal death, and the remaining six continued the pregnancies, including two were delivered normally, one was assisted by forceps, and three through cesarean section. Among the six delivered cases, one was preterm birth, one infant was born with severe asphyxia and four mothers developed postpartum complications such as puerperal infection and postpartum hemorrhage. Conclusions:Clinical manifestations of HbH disease vary greatly. Individualized management should be offered based on the degree of anemia before pregnancy. For women with moderate anemia, close monitoring and appropriate intervention are required during pregnancy to improve both maternal and infant outcomes.