Idiopathic pulmonary fibrosis （IPF）， as a progressive lung disease， has a poor prognosis and no reliable and effective therapies. IPF is mainly treated by organ transplantation and administration of chemical drugs， which are ineffective and induce side effects， failing to meet the clinical needs. Therefore， developing safer and more effective drugs has become an urgent task， which necessitates clear understanding of the pathogenesis of IPF. The available studies about the pathogenesis of IPF mainly focus on macrophage polarization， epithelial-mesenchymal transition （EMT）， oxidative stress， and autophagy， while few studies systematically explain the principles and links of the pathogeneses. According to the traditional Chinese medicine theory， Qi deficiency and blood stasis and Qi-Yang deficiency are the key pathogeneses of IPF. Therefore， the Chinese medicines or compound prescriptions with the effects of replenishing Qi and activating blood， warming Yang and tonifying Qi， and eliminating stasis and resolving phlegm are often used to treat IPF. Modern pharmacological studies have shown that such medicines play a positive role in inhibiting macrophage polarization， restoring redox balance， inhibiting EMT， and regulating cell autophagy. However， few studies report how Chinese medicines regulate the pathways in the treatment of IPF. By reviewing the latest articles in this field， we elaborate on the pathogenesis of IPF and provide a comprehensive overview of the mechanism of the active ingredients or compound prescriptions of Chinese medicines in regulating IPF. Combining the pathogenesis of IPF with the modulating effects of Chinese medicines， we focus on exploring systemic treatment options for IPF， with a view to providing new ideas for the in-depth study of IPF and the research and development of related drugs.

Objective:To observe the projections from tyrosine hydroxylase(TH)positive neurons in locus coerule-us(LC)to tachykinin-1(TAC1)neurons in paraventricular nucleus of the thalamus(PVT),and morphologically determine whether they are involved in transmission and modulation of nociceptive information.Methods:TAC1-ires-Cre mice were hybridized with Rosa26:CAG-LSL-tdTomato(Ai9)mice.And spared nerve injury(SNI)induced neu-ropathic pain model was established with TAC1-ires-Cre::Ai9 mice to observe the colocalization of TAC1 and Fos and the close appositions between TAC1/FOS double-labeled neurons and TH positive axonal terminals.The distribution of the TH positive neurons and FG retrogradely labeled neurons were observed in the LC after Fluorogold(FG)was injec-ted into the PVT.Finally,the coexistences of TH positive neurons and RV labeled neurons in the LC were observed after injection of RV-mediated retrograde tracing system.Results:TAC1 positive neurons were shown with red fluores-cence in TAC1-ires-Cre::Ai9 mice.TAC1/FOS double-labeled neurons were found in the PVT of the SNI model.Some TAC1/FOS double labeled neurons made close appositions with TH positive axonal terminals.FG retrogradely labeled neurons were observed in the LC after FG injected into the PVT,and some of the FG labeled neurons coexisted with TH positive neurons.Using RV retrograde transsynaptic tracing virus,the results showed that presynaptic neurons of TAC1 positive neurons in the PVT were found in the LC,and most of the presynaptic neurons were TH positive neu-rons.Conclusion:TH positive neurons in the LC project to TAC1 positive neurons of the PVT,forming LCTH+-PVTTAC1+neural circuit,which were activated by nociceptive information.It demonstrates that this pathway plays a role in pain transmission or regulation.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

[Objective] To explore the cellular composition and gene expression characteristics of adrenocortical adenoma (ACA) based on single-nuclear RNA sequencing. [Methods] The postoperative resection samples of 2 ACA cases treated at our hospital during Jul.and Aug.2022 were collected.The cellular composition was isolated and identified with single-nuclear RNA sequencing, the adrenal cortical subgroups were subdivided with specific cortical cell subgroup markers, and the characteristic gene expression profile was studied. [Results] The main components of ACA were adrenal cortical cells (78.62%), endothelial cells (1.91%), fibroblasts (3.09%), macrophages (14.34%), and T cells (2.05%). Subdivision of cortical cells revealed a group of undefined cells (1.08%), in addition to zona glomerulosa (ZG) cells (1.77%), zona fasciculata (ZF) cells (94.98%), and zona reticularis (ZR) cells (2.17%). These undefined cells were characterized by high expression of intercellular adhesion molecule 1, growth arrest and DNA damage inducing proteins β, tumor necrosis factor α inducing protein 3 and CD36 molecules.According to correlation analysis of the gene expression, these undefined cells were similar to the ZF cells.DEGs enrichment analysis indicated that the metabolic process enrichment index was the highest in biological processes.Reactome GO enrichment analysis revealed that the immune system cytokine signaling response was the most significant.KEGG signaling pathway analysis showed that Th17 cell differentiation pathway was the mostly enriched.DEGs were found to be most closely related to viral infection by DO enrichment analysis. [Conclusion] This study reveals for the first time the gene expression profile characteristics of cell subset in ACA, which can provide reference to explore the mechanism of ACA.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective:To investigate the effect of construction and practice of problem-based learning(PBL)case database based on post competency for postgraduates majoring in Clinical Pharmacy.Methods:Through collective discussion,the case theme selection,case design and teaching process were clarified,and the case database was constructed.Students in grade 2021 received the traditional teaching method and students in grade 2022 received case-based teaching method.The teaching effect was evaluated according to the training objectives.Results:Compared with students in grade 2021,the students in grade 2022 showed an improvement trend in various evaluation indicators such as stimulating learning interest,literature review ability,problem analysis ability,problem-solving ability,team collaboration ability,and final exam score(P＜0.05).Conclusion:The PBL teaching method based on post competency case is conducive to improving the practical ability to find,analyze and solve practical problems in practical work of postgraduates majoring in Clinical Pharmacy.

Objective To observe the value of FOLFOX-hepatic arterial infusion chemotherapy(HAIC)combined with programmed cell death receptor-1(PD-1)inhibitor+targeted drug for treating China liver cancer staging(CNLC)stageⅢa hepatocellular carcinoma(HCC).Methods Sixty-one patients with CNLC stage Ⅲa HCC who underwent PD-1 inhibitor+targeted drug treatment were retrospectively enrolled and divided into observation group(n=30)and control group(n=31)based on whether received FOLFOX-HAIC treatment or not.The general information,treatment strategy,adverse reactions and therapeutic effects were compared between groups,and the value of treatment strategy in observation group was analyzed.Results No significant difference of general information nor PD-1 inhibitor+targeted drug strategy was found between groups(both P＞0.05).Among 1-2 grade adverse reactions,the incidence of nausea,vomiting and abdominal pain in observation group were higher than those in control group(both P＜0.05),while no significant difference of the other 1-2 grade nor 3 grade adverse reactions was observed(all P＞0.05).The objective response rate(ORR),progression free survival(PFS)and overall survival(OS)of observation group were all higher than those of control group(all P＜0.05).Conclusion FOLFOX-HAIC combined with PD-1 inhibitor+targeted drug was more effective for treating CNLC stage Ⅲa HCC with acceptable safety.

The emergence of high virulent mutant strains of infectious bursal disease virus(IBDV)becomes a serious threat to the poultry industry.However,the live attenuated IBDV vaccine can potentially revert to a virulent strain.Therefore,it is a necessary to develop safe and effective IB-DV-associated vaccines.The construction of a recombinant Marek's disease(MD)vaccine strain,CVI988,expressing the IBDV VP2 protein,can protect against disease induced by both IBDV and Marek's disease virus(MDV).Here,the IBDV-VP2 gene was integrated into the UL55 locus of CVI988 by bacterial artificial chromosome(BAC)technique,resulting in the recombinant virus CVI988 BAC-VP2.The recombinant virus was characterized by PCR,IFA and subsequently the bi-ological properties of the recombinant virus were investigated.The results showed that the recom-binant virus CVI988 BAC-VP2 was successfully rescued.The VP2 protein stably expressed in chick-en embryo fibroblasts(CEF).The growth kinetics and plague size assays showed that there was comparable replication ability between recombinant virus and parental virus.This study provides the basis for the development of a low-cost vaccine against both IBDV and MDV infections.

Objective To develop an expert consensus on subcutaneous injection nursing for allergic asthma in children,standardize nursing practice to reduce the occurrence of related adverse reactions.Methods The clinical guideline,expert consensus,systematic review,evidence summary and original research on subcutaneous injection of monoclonal antibody drug for children with allergic asthma were comprehensively searched in domestic and foreign databases.The time limit for retrieval was from the establishment of databases until August 2023.Combined with clinical practice experience,the first draft of the consensus was formed.From December 2023 to February 2024,27 experts were invited to conduct 2 rounds of expert letter consultation,revise and improve the contents of the first draft,and expert demonstration was conducted,and finally a consensus final draft was formed.Results The effective recovery rate of the 2 rounds of letter consultation questionnaires was 100％;the authority coefficient of experts was 0.88;the judging basis coefficient was 0.93;the familiarity coefficient was 0.83.In the 2 rounds of correspondence,the Kendall concordant coefficients of expert opinions were 0.241 and 0.252,respectively(P＜0.001 for both).The consensus includes 6 parts,including personnel management,environmental layout,indications and contraindications,subcutaneous injection operation norms,identification and treatment of adverse reactions,and health education.Conclusion The consensus is strongly scientific and practical,and can provide guidance for nursing practice of subcutaneous injection of monoclonal antibodies in children with allergic asthma.

Objective To investigate the influencing factors of unplanned rehospitalization within one year after surgery among adult renal transplant recipients. Methods The clinical data of 299 recipients who underwent renal transplant surgery in the Department of Organ Transplantation of the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2022 were retrospectively analyzed. The recipients were divided into unplanned rehospitalization group and non-rehospitalization group based on whether they experienced unplanned rehospitalization within one year after surgery. Univariate analysis and binary Logistic regression analysis were performed to explore the influencing factors of unplanned rehospitalization within one year after renal transplantation. Results Among the 299 recipients, 102 experienced unplanned rehospitalization, with an incidence rate of 34.11%. Univariate analysis revealedstatistically significant differences were noted between the two groups in terms of gender, occupational status, preoperative underlying disease, rejection reactions, nosocomial infections, immunosuppressive medication regimens, serum creatinine, cystatin C, serum phosphorus, serum potassium, and initial hospitalization duration (P < 0.05). Binary Logistic regression analysis showed that having ≥3 kinds of preoperative underlying disease (OR=2.122, 95%CI, 1.198 to 3.759) and experiencing rejection reactions (OR=3.162, 95%CI, 1.217 to 8.218) were independent risk factors for unplanned rehospitalization within one year after renal transplantation (P < 0.05). Conclusion The rate of unplanned rehospitalization within one year after surgery is relatively high among adult renal transplant recipients. Having ≥3 preoperative underlying disease and experiencing rejection reactions are independent risk factors for unplanned rehospitalization within one year after surgery. Transplantation healthcare teams can develop corresponding strategies targeting these risk factors to reduce the rate of unplanned rehospitalization and alleviate the burden of disease.