Objective To explore the short-term efficacy and safety of programmed death receptor-1(PD-1)antibody combined with chemoradiotherapy in early high-risk nasal extranodal natural killer/T cell lymphoma(ENKTCL,Nomogram modified risk index ≥1).Methods This study was a prospective phase Ⅱclinical study.A total of 20 patients with stage Ⅰ/Ⅱ nasal ENKTCL initially treated in the Affiliated Hospi-tal of Guizhou Medical University from June 2021 to December 2023 were selected as the study subjects.They were given 3 cycles of PD-1 antibody+P-Gemox(pegaspargase+gemcitabine+oxaliplatin)regimen induced immunochemotherapy and 3 cycles of PD-1 antibody concurrent immunoradiotherapy,14 d/cycle.The com-plete response(CR)rate after 3 cycles of induced immunochemotherapy,CR rate after treatment,objective re-sponse rate(ORR)after 3 cycles of induced immunochemotherapy and ORR after comprehensive treatment,occurrence of adverse reactions and plasma Epstein-Barr virus DNA copy number were observed.Results Af-ter 3 cycles of induction immunochemotherapy,the CR rate was 35.0％(7/20)and ORR was 90.0％(18/20).After the concurrent immunoradiotherapy,the CR rate was 95.0％(19/20)and ORR was 100.0％(20/20).The adverse reactions were mainly the grade 1/2.the immune-related adverse reactions included 9 ca-ses of grade 1/2 hypothyroidism(45.0％),4 cases of grade 1 capillary vessel hyperplasia(20.0％),1 case(5.0％)of grade 2 infusion reaction,and no immune myocarditis occurred.All 7 cases of positive EBV DNA turned to negative after 3 cycles of induced immunochemotherapy.Conclusion PD-1 antibody combined with P-Gemox in the radiotherapy of early high-risk ENKTCL has a high short-term remission rate with good tol-erance for treatment.

Objective To investigate the expression of pepsin in vocal cord polyps and vocal cord cancer,and to compare the difference of pepsin expression.Methods From May 2020 to December 2021,27 patients with vocal cord polyp,27 patients with vocal cord cancer and 23 healthy volunteers were selected.RSI and RFS scoring scales were used for scoring,pepsin detection kit was used for saliva pepsin detection,and immunohistochemical methods were used to detect the expression of pepsin in vocal cord tissues of patients with vocal cord polyps and vocal cord cancer.Results The RSI score,RFS score and pepsin test kit results of vocal cord polyp group and vocal cord canc-er group were higher than those of non-vocal cord disease group,and the differences of the three indexes were statis-tically significant(P＜0.05).RSI score,pepsin detection kit results and pepsin immunohistochemistry results of vocal cord polyp group showed no significant difference compared with vocal cord cancer group(P＞0.05).The RFS score of vocal cord polyp group was significantly different from that of vocal cord cancer group(P＜0.05).Conclusion Pepsin may be an important pathogenic factor of vocal cord polyp and vocal cord cancer,and play an im-portant role in the occurrence of these two diseases.The difference of pepsin expression in vocal cord polyp and vo-cal cord cancer suggests that pepsin may have different pathogenesis.

OBJECTIVE To investigate the effects of CYP3A5 gene polymorphism and Wuzhi capsule （WZ） on early postoperative tacrolimus exposure and adverse reactions in renal transplant patients. METHODS A total of 132 patients who underwent renal transplantation and received tacrolimus + mycophenolic acids + prednisone after operation in our hospital from September 2021 to September 2023 were selected and divided into four groups according to genotypes （CYP3A5*1 or CYP3A5*3/*3） and with or without WZ （“ +WZ” meant drug combination， “ +NO WZ” meant without combination）. The blood trough concentration/daily dose （c0/D） values of the four groups were analyzed on the 14th day， 1 month and 3 months after renal transplantation. The incidence of acute rejection and the incidence of tacrolimus-related adverse reactions within 3 months after transplantation were compared among 4 groups. RESULTS On the 14th day， 1 month and 3 months after surgery （except for the CYP3A5*1+WZ group）， c0/D values of CYP3A5*1 genotype patients were significantly lower than those of CYP3A5*3/*3 genotype patients regardless of whether they were treated with WZ additionally （P＜0.05）. Within 3 months after surgery， although there was no significant difference in the incidence of acute rejection and tacrolimus-related adverse reactions among the four groups （P＞ 0.05）， the incidence of hyperglycemia in patients with CYP3A5*3/*3 was higher （41.67%）. CONCLUSIONS CYP3A5 gene polymorphism is significantly related to tacrolimus c0/D in kidney transplant patients. Under the premise of c0 monitoring of tacrolimus， patients with CYP3A5*1 genotype should be given WZ as soon as possible after surgery to accelerate tacrolimus to reach the therapeutic concentration range， while CYP3A5*3/*3 genotype is not recommended to be given WZ because of the higher risk of hyperglycemia.

Objective:Progressive bone resorption and destruction is one of the most critical clinical features of middle ear cholesteatoma,potentially leading to various intracranial and extracranial complications.However,the mechanisms underlying bone destruction in middle ear cholesteatoma remain unclear.This study aims to explore the role of parathyroid hormone-related protein(PTHrP)in bone destruction associated with middle ear cholesteatoma. Methods:A total of 25 cholesteatoma specimens and 13 normal external auditory canal skin specimens were collected from patients with acquired middle ear cholesteatoma.Immunohistochemical staining was used to detect the expressions of PTHrP,receptor activator for nuclear factor-kappa B ligand(RANKL),and osteoprotegerin(OPG)in cholesteatoma and normal tissues.Tartrate-resistant acid phosphatase(TRAP)staining was used to detect the presence of TRAP positive multi-nucleated macrophages in cholesteatoma and normal tissues.Mono-nuclear macrophage RAW264.7 cells were subjected to interventions,divided into a RANKL intervention group and a PTHrP+RANKL co-intervention group.TRAP staining was used to detect osteoclast formation in the 2 groups.The mRNA expression levels of osteoclast-related genes,including TRAP,cathepsin K(CTSK),and nuclear factor of activated T cell cytoplasmic 1(NFATc1),were measured using real-time polymerase chain reaction(real-time PCR)after the interventions.Bone resorption function of osteoclasts was assessed using a bone resorption pit analysis. Results:Immunohistochemical staining showed significantly increased expression of PTHrP and RANKL and decreased expression of OPG in cholesteatoma tissues(all P<0.05).PTHrP expression was significantly positively correlated with RANKL,the RANKL/OPG ratio,and negatively correlated with OPG expression(r=0.385,r=0.417,r=-0.316,all P<0.05).Additionally,the expression levels of PTHrP and RANKL were significantly positively correlated with the degree of bone destruction in cholesteatoma(r=0.413,r=0.505,both P<0.05).TRAP staining revealed a large number of TRAP-positive cells,including multi-nucleated osteoclasts with three or more nuclei,in the stroma surrounding the cholesteatoma epithelium.After 5 days of RANKL or PTHrP+RANKL co-intervention,the number of osteoclasts was significantly greater in the PTHrP+RANKL co-intervention group than that in the RANKL group(P<0.05),with increased mRNA expression levels of TRAP,CTSK,and NFATc1(all P<0.05).Scanning electron microscopy of bone resorption pits showed that the number(P<0.05)and size of bone resorption pits on bone slices were significantly greater in the PTHrP+RANKL co-intervention group compared with the RANKL group. Conclusion:PTHrP may promote the differentiation of macrophages in the surrounding stroma of cholesteatoma into osteoclasts through RANKL induction,contributing to bone destruction in middle ear cholesteatoma.

Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe complications.Despite surgery being the primary treatment,the recurrence rate remains high.Therefore,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic approaches.This study aims to explore the involvement of N6-methyladenosine(m6A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear cholesteatoma. Methods:The m6A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m6A transcriptome microarray.Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear cholesteatoma.Methylated RNA immunoprecipitation(MeRIP)-PCR was used to validate the m6A modifications in cholesteatoma and normal skin tissues. Results:Compared with normal skin tissues,1 525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1 048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation of α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor activity.Hypomethylated lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA methylation.KEGG analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in cardiomyocytes.Hypomethylated lncRNAs were mainly involved in 4 pathways:Renal cell carcinoma,tumor necrosis factor signaling pathway,transcriptional misregulation in cancer,and cytokine-cytokine receptor interaction.Additionally,MeRIP-PCR confirmed the changes in m6A methylation levels in NR_033339,NR_122111,NR_130744,and NR_026800,consistent with microarray analysis.Real-time PCR also confirmed the significant upregulation of MAPK1 and NF-κB,key genes in the MAPK signaling pathway. Conclusion:This study reveals the m6A modification patterns of lncRNAs in middle ear cholesteatoma,suggests a direction for further research into the role of lncRNA m6A modification in the etiology of cholesteatoma.The findings provide potential therapeutic targets for the treatment of middle ear cholesteatoma.

Objective:To analyze the level and clinical significance of IL-18 and IL-18-binding protein (BP) in the bone marrow of patients with myelodysplastic syndrome (MDS) .Methods:A total of 43 newly diagnosed patients with MDS who were admitted to the Department of Hematology, Tianjin Medical University General Hospital, from July 2020 to February 2021 were randomly selected. The control group consisted of 14 patients with acute myeloid leukemia (AML) and 25 patients with iron-deficiency anemia (IDA). The levels of IL-18 and IL-18 BP in the bone marrow supernatant were measured, and their correlations with MDS severity, as well as the functionality of CD8 + T cells and natural killer cells, was analyzed. Results:The levels of IL-18, IL-18 BP, and free IL-18 (fIL-18) in the bone marrow supernatant of patients with MDS were higher than in the IDA group. The level of fIL-18 was linearly and negatively correlated with the MDS-International Prognostic Scoring System (IPSS) score. IL-18 receptor (IL-18Rα) expression on CD8 + T cells in the MDS group was lower than in the IDA group, and the levels of fIL-18 and IL-18Rα were positively correlated with CD8 + T-cell function in the MDS group. Conclusion:IL-18 BP antagonizes IL-18, leading to a decrease in fIL-18 in the bone marrow microenvironment of patients with MDS, affecting CD8 + T-cell function, which is closely related to MDS severity; therefore, it may become a new target for MDS treatment.

Clostridium perfringens is a common Gram-positive anaerobic conditioned pathogen,widely existing in nature,which can cause diarrhea,gas gangrene,and other diseases.Antibiotics are used in the clinical treatment of Clostridium perfringens infection,but the bacteria will devel-op resistance through mutation,drug-resistant plasmid transmission,and other ways,so that Clos-tridium perfringens can survive under the environmental pressure of antibiotics.Therefore,it is very important to find and develop new preparations to replace antibiotics or as feed additives to target the removal of Clostridium perfringens from the body or to prevent infection.In this study,a virulent Clostridium perfringens phage vB_CPP_AT was isolated from sewage by double plate method.The morphology of the bacteriophage was observed by transmission electron microscope.The biological characteristics of the bacteriophage were analyzed by lytic spectrum,MOI,pH,and temperature tolerance.The results showed that the vB_CPP_AT belongs to the Podoviridae.It would grow explosively at 60 min with an optimal MOI of 0.1.The vB_CPP_AT only lyse Clos-tridium perfringens and the lytic rate was 40％(8/20).No cleavage reaction occurred with other bacteria tested.The phage had good thermal stability and acid-base tolerance.Genomic analysis re-vealed that the phage had double-stranded DNA with a total length of 16 790 bp,and 20 open read-ing frames.Genomic analysis of vBCPPAT showed that it was a new virulent phage of Clostridi-um perfringens.The results laid a foundation for the clinical treatment of Clostridium perfringens with phage.

Objective: To evaluate the caries preventive effect and economic outcome of an oral health promotion model in rural primary schools in Guangxi Zhuang Autonomous Region. Methods: In November 2015, a baseline survey was conducted on the caries prevalence of rural first graders in program areas, and then a program intervention was carried out on the first graders of target primary schools. The intervention methods included the distribution of oral health care products, oral health education, teacher training, etc. In 2020, the method of cluster random sampling was adopted to include the sixth graders who received the program intervention as first graders and were still available in 2020 as the intervention group. During this period, the sixth graders transferred from foreign schools who failed to receive the program intervention as first graders were included in the non-intervention group. The caries preventive effect was evaluated by analyzing the caries epidemiological data of 2 652 children aged 11-13 years, comparing the intervention and non-intervention group. The cost of the program was estimated by the structural analysis method. A decision tree model was established by TreeAge pro2019 and incorporated into the effect parameters and cost parameters for cost-effectiveness analysis and sensitivity analysis. Results : The prevalence of caries in the intervention group was 54.8%, and the mean DMFT was 1.36 ± 1.64, both of which were lower than those in the non-intervention group. The difference in prevalence and mean DMFT between the two groups was statistically significant (P < 0.05). It costs CNY 319.83 per child to reduce suffering from caries. The number of patients with caries in the intervention group was the most sensitive indicator of an economic effect. The probability of a cost-effectiveness advantage for the program was 92.2%. Conclusion This oral health promotion model used in rural schools demonstrated a caries preventive effect that was very likely economically advantageous. It is of practical significance to improve and promote this model in the Guangxi Zhuang Autonomous Region.

Objective:To describe the real experience of the elderly who has felt happy during the time they stayed at nursing homes, and discuss the meaning which is behind their experience during the COVID-19 pandemic, to provide scientific basis for improving their subjective well-being.Methods:Qualitative explanatory phenomenological analysis methods, and semi-structured in-depth interviews were used to interview 21 elderly people living in Guangzhou Songhe Nursing Home. Data analysis and subject extraction were carried out with reference to the Colaizzi 7-step analysis.Results:The real experience of subjective well-being of the elderly in nursing homes has six themes: be satisfied with the nursing home management service, be satisfied with harmonious interpersonal relationship, be satisfied with good health, be satisfied with family support, grateful and expectations for the social support system, be satisfied with and grateful for the epidemic prevention work during the COVID-19 epidemic.Conclusions:The elderly who live in a nursing home with perfect management and service, care for each other, are healthy, receive family and social support, are grateful, and understand family and social support will be more likely to feel happy. Improving the subjective well-being of the elderly in nursing homes requires the coordination and support of nursing homes, the elderly, families, society and other aspects.

Malnutrition and dehydration are prevalent in the elderly poplulation, and obesity is also a growing problem, which pose a serious challenge to the nutritional management in geriatrics. In order to better guide clinical practice, the European Society for Clinical Nutrition and Metabolism (ESPEN) published the practical guideline on clinical nutrition and hydration in geria-trics on March 5, 2022. This guideline provides 82 recommendations on clinical nutrition and hydration in geriatrics based on clinical practicability, covering basic problems and general prin-ciples, prevention and treatment of malnutrition/nutri-tional risk, prevention and treatment of specific diseases, as well as prevention and treatment of obesity, along with flow-charts, hoping to be convenient for doctors, nutritionists and nurses to use in clinical practice.