OBJECTIVE To establish a full-cycle management model for type 2 diabetes mellitus （T2DM） patients led by clinical pharmacists. METHODS Based on literature research， a basic framework and items of full-cycle management model led by clinical pharmacists were initially formulated. The Delphi method was adopted to conduct questionnaire inquiries among 26 experts to determine the specific implementation items of the model. The analytic hierarchy process （AHP） method was used to determine the weight values of items at all levels， and the reliability and validity of the model items were analyzed. RESULTS The recovery rates of the two rounds of expert consultation questionnaires were 86.67% and 100%， respectively， and the expert authority coefficient was 0.88. Kendall’s concordance coefficients of the tertiary-level items were 0.064 and 0.084， respectively， and the P values from the χ 2 tests were all less than 0.05； the consistent ratios of the judgment matrices for all levels of AHP model were all less than 0.1. The established full-cycle management led by clinical pharmacists comprised three primary-level items （pharmacy service pathway for T2DM patients during hospitalization， pharmacy management pathway for hypoglycemia in T2DM inpatients， and the pharmacy follow-up pathway for T2DM discharged patients， with weights of 0.098， 0.568 and 0.334， respectively）， twelve secondary-level items （e.g. pharmaceutical care during hospitalization for 1 to 2 days， admission assessment and education， with weights ranging from 0.143 to 0.333） and thirty-seven tertiary-level items （e.g. assessment of medication compliance， verification of the medication plan for discharge， with weights ranging from 0.068 to 0.750）. Cronbach’s α coefficients for primary-level items and the overall questionnaire were 0.762， 0.879， 0.928 and 0.951， respectively. The item-level and scale-level content validity indexes were 0.967 and 0.808， respectively. CONCLUSIONS A full-cycle management model for T2DM patients led by clinical pharmacists has been constructed successfully， demonstrating high scientificity and reliability.

Nasopharyngeal carcinoma （NPC） is a malignant tumor originating from the mucosal epithelium of the nasopharynx. In recent years， its incidence and mortality rates have shown a continuous upward trend， and there is still a lack of therapeutic regimens with both favorable efficacy and safety in clinical practice. Mitogen-activated protein kinase （MAPK） signaling pathway plays a key regulatory role in biological processes such as cell proliferation， differentiation， apoptosis and invasion. It is widely involved in the occurrence and progression of NPC， and serves as an important target in the research field of anti-NPC therapy. This article systematically elaborates on the mechanism of action of the MAPK signaling pathway in NPC， and reviews the research status regarding the anti-NPC effect of active components of traditional Chinese medicine （TCM） and TCM compound prescriptions by regulating this signaling pathway. The results show that TCM active components， including flavonoids （luteolin， maackiain， baicalein， etc.）， alkaloids （picrasidine Ⅰ， tetrandrine， etc.）， terpenoids （bakuchiol， cantharidic acid）， as well as traditional Chinese medicine compound formulas （such as Biyan jiedu capsules and Yiqi jiedu formula） can exert effects including inducing autophagy and apoptosis of NPC cells， promoting pyroptosis， reversing drug resistance， blocking epithelial-mesenchymal transition， weakening cell stemness and arresting cell cycle progression by regulating the MAPK signaling pathway， thereby inhibiting the occurrence and development of NPC through multiple pathways.

Objective To analyze the disease burden and trends of bladder cancer in China and globally from 1992 to 2021.  Methods Using the GBD 2021 database, the incidence, prevalence, mortality, and disability-adjusted life years (DALYs) rates of bladder cancer in China and globally from 1992–2021 were analyzed. Average annual percentage change (AAPC) was calculated using Joinpoint regression. Subgroup analyses by sex and age were conducted, and a Bayesian age-period-cohort (BAPC) model was used to predict trends in age-standardized incidence rate (ASIR) and age-standardized mortality rate (ASMR) for the next 15 years.  Results In 2021, China reported 106 000 new cases (ASIR: 5.14/100 000), 571 000 prevalent cases (age-standardized prevalence rate, ASPR: 26.61/100 000), 43 000 deaths (ASMR: 2.34/100 000), and a DALY rate of 45.31/100 000. From 1992–2021, China showed upward trends in ASIR and ASPR but declines in ASMR and DALYs, while global ASIR, ASMR, and DALYs decreased overall with slow ASPR growth. The peak cases in China and globally were both concentrated in the 65-79 age group, with a significantly higher burden on males than females. In China, smoking-related ASMR and ASDR exceeded global averages and rose, whereas high glucose-related indexes were lower and declined. Projections for 2021–2036 indicated that the global incidence and mortality rates would be rising, but ASIR/ASPR would be declining, while in China, the incidence rate would continue to rise, and the mortality rate will stabilize, with a significant increase in ASIR and a gradual decrease in ASPR.  Conclusion From 1992 to 2021, the incidence of bladder cancer in China has shown a continuous upward trend and is projected to persist in the future, with significant gender and age differences. Particular attention should be given to elderly males aged 85-89. The disease burden of bladder cancer attributable to smoking continues to rise, highlighting the urgent need to strengthen tobacco control policies.

Objective: To investigate the damaging effects of red blood cell supernatant (RBC-S) stored for different durations (7 d, 14 d, and 28 d) on vascular endothelial cells, and to explore the underlying mechanisms using bioinformatics analysis, so as to provide references for optimizing red blood cell transfusion strategies. Methods: Human umbilical vein endothelial cells (HUVECs) were co-cultured with RBC-S stored for 7, 14 and 28 days, designated as the 7 d group, 14 d group and 28 d group respectively, which were collectively defined as the experimental groups. Cell damage was evaluated by cell proliferation assay (Cell Counting Kit8, CCK8), lactate dehydrogenase (LDH) release assay, 4′, 6diamidino2phenylindole (DAPI) staining, and flow cytometry for apoptosis and reactive oxygen species (ROS) levels. The damage degree of RBC-S on vascular endothelial cells was assessed by statistical analysis of damage data among different groups. Since the damage effect reached a plateau at all time points, the 28 d storage group was selected as the representative for further mechanistic studies. Transcriptomic analysis was performed to explore the role of frizzled class receptor 1 (FZD1) and Wnt signaling pathway in red blood cell storagerelated endothelial dysfunction. Results: Compared with the control group, the storage groups treated with 7 d, 14 d, and 28 d RBC-S showed significantly decreased cell proliferation rates [control group 100%, 7 d group (69.51±2.30)%, 14 d group (74.54±2.89)%, 28 d group (73.59±2.36)%, P<0.05], significantly reduced numbers of DAPI-stained cell nuclei [control group (213±12.5) per field, 7 d group (140.33±17.04) per field, 14 d group (152.00±23.72) per field, 28 d group (144.33±19.09) per field, P<0.05] and significantly increased LDH release [control group (1), 7 d group (8.33±1.41), 14 d group (9.23±0.83), 28 d group (9.16±0.60), P<0.05]. There was no significant difference in the degree of damage caused by RBC-S among different storage groups (P>0.05). With the prolongation of storage time, free hemoglobin (FHb) gradually increased [control group (not detected), 7 d (16.57±6.38) mg/L, 14 d (76.80±22.83) mg/L, 28 d (286.97±29.02) mg/L, P<0.05]. The apoptotic rate (20.53±2.94)% and ROS relative intensity (5.13±0.91) in the 28 d storage group were significantly higher than those in the control group (P<0.05). Transcriptomic analysis showed that FZD1 played a key role in vascular endothelial dysfunction induced by red blood cell storage and was closely related to the Wnt signaling regulatory network. Conclusion: RBC-S stored for 7 d, 14 d, or 28 d can all significantly damage vascular endothelial cells, and the damaging effect reaches a plateau at 7 d of storage. Mechanistic investigation of the 28 d group indicated that the downregulation of the FZD1/Wnt signaling pathway may play a critical role in vascular endothelial dysfunction induced by red blood cell storage, providing a theoretical basis for further optimizing red blood cell storage and transfusion strategies.

ObjectiveTo investigate the effect and mechanism of Shuangshen Ningxin capsules （SSNX） in regulating the nuclear factor-κB （NF-κB） and mitogen-activated protein kinase （MAPK） pathways to inhibit inflammation and alleviate myocardial ischemia-reperfusion injury （MIRI） in rats. MethodsThe 45 healthy male Sprague-Dawley （SD） rats were divided into sham operation group， model group， and SSNX capsules group （90 mg·kg^-1）. The left anterior descending coronary artery was ligated to establish the MIRI model. Cardiac function was evaluated by echocardiography， and microvascular reperfusion was analyzed using contrast echocardiography. Myocardial inflammation and injury were assessed by hematoxylin and eosin （HE） staining， immunohistochemistry， and TdT-mediated dUTP nick end labeling （TUNEL）. The expression levels of cardiac inflammatory cytokines， including interleukin-1α （IL-1α）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） were detected by enzyme-linked immunosorbent assay （ELISA）. Core differentially expressed genes （DEGs） and enriched pathways were screened by transcriptome sequencing. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to verify the mRNA expression of Toll-like receptor 2 （TLR2）， chemokine （C-X-C motif） ligand 1 （CXCL1） and prostaglandin-endoperoxide synthase 2 （PTGS2）， as well as the protein expression of Caspase-3， cleaved Caspase-3， p-NF-κB/NF-κB， phosphorylated extracellular signal-regulated kinase 1/2 （p-ERK1/2/ERK1/2） and p-p38 MAPK/p38 MAPK. ResultsCompared with the sham operation group， the ejection fraction （EF）， fractional shortening （FS）， stroke volume （SV） and cardiac output （CO） of the model group were significantly decreased （P<0.01）， the peak time of myocardial perfusion was prolonged （P<0.01）， hypoxia-inducible factor （HIF）-1α and α-smooth muscle actin （SMA） expression increased （P<0.01）， the concentrations of inflammatory factors IL-1α， IL-6， TNF-α， TLR2， CXCL1 and PTGS2 increased （P<0.01）， and the expression of cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins was significantly increased （P<0.01）. SSNX could improve cardiac function （P<0.05， P<0.01）， and significantly shorten the peak time of myocardial perfusion （P<0.01）. Moreover， it could also down-regulate HIF-1α and a-SMA expression （P<0.05， P<0.01）， and reduce the concentrations of IL-1α， IL-6， TNF-α （P<0.01）， and the mRNA expression of TLR2， CXCL1 and PTGS2 （P<0.01）. Additionally， SSNX inhibited the apoptosis rate （P<0.01） and significantly reduced the expression of Cleaved Caspase-3， p-NF-κB/NF-κB， p-ERK1/2/ERK1/2 and p-p38 MAPK/p38 MAPK proteins （P<0.01）. ConclusionSSNX can alleviate cardiac inflammation by regulating the NF-κB and MAPK signaling pathways， thereby effectively preventing and alleviating myocardial reperfusion injury.

ObjectiveNonalcoholic fatty liver disease （NAFLD） is a metabolic stress liver injury. Ferroptosis is involved in the occurrence and development of NAFLD. Exploring the efficacy and mechanism of schisandrin B in treating NAFLD facilitates the development of strategies for the prevention and treatment of NAFLD. MethodsThe molecular structure of schisandrin B was obtained by searching against PubChem， and the related targets were predicted by SwissTargetPrediction. The active ingredients and their targets were retrieved from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the high-throughput experiment- and reference-guide database of traditional Chinese medicine （HERB）. GeneCards and FerrDb were searched for the targets of NAFLD and ferroptosis. The common targets were taken as the core targets， and the protein-protein interaction network of the core targets was established. DAVID was used for gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses. Finally， molecular docking was performed between schisandrin B and core targets， and the binding energy was calculated. C57BL/6 mice were fed with a methionine and choline-deficiency （MCD） diet for the modeling of NAFLD. Mice were randomized into normal， model， positive drug （essentiale）， and low- and high-dose schisandrin B groups. The body mass and liver index of mice were measured after drug administration. The levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in the serum and those of total cholesterol （TC）， triglyceride （TG）， malondialdehyde （MDA）， glutathione （GSH）， and Fe²⁺ in the liver homogenate were measured by biochemical assay kits. The pathological changes of the liver tissue were observed by hematoxylin-eosin （HE） and red oil O staining. Enzyme-linked immunosorbent assay was employed to determine the levels of interleukin （IL）-6， IL-1β， tumor necrosis factor （TNF）-α， and 4-hydroxynonenal （4-HNE） in the serum. Western blotting and real-time PCR were employed to determine the protein and mRNA levels， respectively， of solute carrier family 7 member 11 （SLC7A11）， solute carrier family 3 member 2 （SLC3A2）， glutathione peroxidase 4 （GPX4）， transferrin， and ferritin heavy chain （FTH） in the liver tissue. ResultsA total of 2 370， 2 547， and 1 451 targets of schisandrin B， NAFLD， and ferroptosis were obtained， in which 90 common targets were shared by the three. Enrichment analyses predicted 505 GO terms and 92 KEGG pathways. Molecular docking suggested that schizandrin B had strong binding affinity with the key targets of ferropstosis （SLC7A11 and SLC3A2）. Animal experiments showed that schizandrin B significantly decreased the liver index， lowered the levels of ALT， AST， TC， TG， IL-6， IL-1β， and TNF-α， alleviated hepatocyte ballooning and inflammatory cell infiltration， and reduced lipid accumulation in the liver of NAFLD mice. In addition， schisandrin B significantly lowered the levels of MDA， 4-HNE， and Fe²⁺， elevated the level of GSH， up-regulated the protein and mRNA levels of SLC7A11， SLC3A2， and GPX4， and down-regulated the protein and mRNA levels of transferrin in the liver tissue. ConclusionSchisandrin B can alleviate NAFLD by inhibiting ferroptosis in hepatocytes.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

ObjectiveTo obtain the gene sequences of major histocompatibility complex (MHC ) Ⅱgenes of Wuzhishan pigs, analyze their genetic information, and explore the biological functions of their MHC system. MethodsSpleen samples were collected from 3 adult male Wuzhishan pigs. Primers were designed according to MHCⅡ gene sequences, and the coding sequences of Wuzhishan pig MHCⅡ genes were amplified by RT-PCR. Sanger sequencing was performed to determine the full-length sequences. Bioinformatics tools were employed to analyze the physicochemical properties, phylogenetic relationships, conserved motifs, structural domains, chromosomal localization, and syntenic relationships of these genes. ResultsEight MHCⅡ genes were identified in Wuzhishan pigs, designated as SLA-DRA, SLA-DQA, SLA-DQB, SLA-DRB, SLA-DOB, SLA-DMB, SLA-DMA and SLA-DOA. The full-length sequences of these genes were determined by Sanger sequencing and subsequently deposited in GenBank under accession numbers PQ182796, PQ182797, PQ182798, PQ182799, PQ182800, PQ182801, PQ182802, and PQ164779. Phylogenetic analysis showed that the six MHCⅡ genes of Wuzhishan pigs clustered separately from their counterparts in Duroc, Meishan, Large White, and Bama pigs, indicating distinct evolutionary trajectories. Bioinformatics analysis demonstrated that most MHC Ⅱ proteins were hydrophobic, with molecular weights ranging from 27 700 to 30 000 Da. Genes within the same subregion shared conserved motifs. Specifically, four MHCⅡ proteins encoded by SLA-DQB, SLA-DRB, SLA-DOB, and SLA-DMB contained the MHCⅡβ conserved domain, while those encoded by the genes SLA-DRA, SLA-DQA, SLA-DMA, and SLA-DOA contained the MHCⅡα conserved domain. The eight MHCⅡ genes were scattered along the long arm of chromosome 7 in the Wuzhishan pigs, exhibiting syntenic relationships with three human genes and five Duroc pig genes. ConclusionThe MHCⅡ genes of Wuzhishan pigs may possess a unique evolutionary origin.

Objective　To identify the temporal-spatial distribution patterns and changing of hotspot areas of malaria importations, and high-risk importation areas for imported malaria in Jiangsu Province, in order to provide the scientific evidence for prevention of malaria reintroduction in China. Methods　Cases with imported malaria in Jiangsu Province from 2016 to 2022 were accessed from the National Notifiable Disease Report System and the Information Management System for Parasitic Disease Control in China. The county-level vector map of Jiangsu Province was obtained from the National Fundamental Geographic Information System, China. ArcGIS 10.7 software was utilized to create a thematic map depicting the distribution of imported malaria cases in Jiangsu Province at the county level. Global and local autocorrelation analysis was then conducted to investigate the spatiotemporal changes in malaria import hotspot counties. Results　There were a total of 1 189 cases with imported malaria reported in 77 counties (81.05%, 77/95) of Jiangsu Province from 2016 to 2022. The global spatial autocorrelation analysis showed that a global spatial cluster of imported malaria in Jiangsu was only identified in 2020 ( Moran's I =0.46, Z=4.37, P<0.01), but local spatial autocorrelation analysis found that a total 60 hotspot counties existed from 2016 to 2022. There are 23 counties in central Jiangsu (38.33%), and 20 counties in southern Jiangsu (33.33%), 17 counties in northern Jiangsu (28.33%). The distribution of hotspot counties exhibits continuity. For instance, Chongchuan District, which falls under the jurisdiction of Nantong City, has consistently emerged as a hotspot county for 2016-2021. Since 2020, two recurring hotspot counties emerged in northern Jiangsu and southern Jiangsu. These counties are Ganyu District, under the jurisdiction of Lianyungang City, and Lishui District, under the jurisdiction of Nanjing City. Conclusions　The spatial-temporal cluster of cases with imported malaria was identified at the county level in Jiangsu, that hotspot counties were consistently detected. It is essential to maintain the sustainability of malaria surveillance and response in hotspot counties which were new detected, and strengthen the capacity of surveillance and response in hotspot counties which were continually detected based on the spatial-temporal distribution characteristics and changing rules of imported malaria.

Objective To study NF1 gene variations in 10 suspected cases of neurofibromatosis type I(NF1)and their parents,thereby providing a basis for genetic counselling,clinical diagnosis,and treatment of this disease.Methods A total of 10 patients diagnosed with,or suspected of having NF1 at Northwest Women's and Children's Hospital from March to December 2023 were selected as study subjects.Whole exome sequencing(WES)was performed to analyse NF1 gene mutations in the patients and their parents,with the findings validated by Sanger sequencing.Results Pathogenic mutations were identified in 6 of the 10 families,with the remaining 4 cases showing no pathogenic gene mutations.In Family 1,a de novo mutation,c.6505A>T,was detected in the NF1 gene.In Family 2,a de novo mutation,c.6705-3C>A,was identified in the NF1 gene.In Family 3,a de novo mutation,c.6853delT,was detected in the NF1 gene.In Family 4,a de novo mutation,c.2446C>T,was found in the NF1 gene.In Family 5,a paternal mutation,c.6067T>A,was identified in the NF1 gene.In Family 6,a paternal mutation,c.2991_2993dup,was detected in the NF1 gene.Conclusion The identification of new mutation sites enriches the mutation spectrum of the NF1 gene.This study provides important guidance for genetic counselling and prenatal diagnosis,offering crucial information for families with reproductive needs.