Objective: To investigate the trend of gastric cancer disease burden in Wenzhou City, Zhijiang Province from 2014 to 2023, so as to providing evidence for prevention and control strategies. Methods: Data on incidence and mortality of gastric cancer among household registered residents in Wenzhou City from 2014 to 2023 were collected through the Wenzhou Chronic Disease Monitoring and Management Information System, and the crude incidence and crude mortality were calculated. The disease burden of gastric cancer was evaluated by calculating years of life lost (YLL), years lived with disability (YLD), and disability-adjusted life years (DALY) using the World Health Organization's disease burden methodology. Trends in YLL rate, YLD rate and DALY rate of gastric cancer from 2014 to 2023 were analyzed using the average annual percent change (AAPC). Results: A total of 28 122 cases of gastric cancer and 17 080 deaths were reported in Wenzhou City from 2014 to 2023. The crude incidence and crude mortality were 34.13/105 and 20.73/105, respectively. The YYL, YLD and DALY caused by gastric cancer were 181 816.78, 53 198.41, and 235 015.198 person-years, and the YLL rate, YLD rate and DALY rate were 2.21, 0.64 and 2.85 person-years per 1 000 people, respectively. The YLL rate and DALY rate showed a downward trend (AAPC=-4.608% and -2.552%,both P<0.05), while the YLD rate showed an upward trend (AAPC=4.657%, P<0.05). The DALY rate of gastric cancer in men was 3.82 person-years per 1 000 people, and that in women was 1.83 person-years per 1 000 people, with a downward trend (AAPC=-2.924% and -1.647%, both P<0.05). The DALY rate of gastric cancer was relatively low in the 15 to <45 years age group, increased starting from the age of 45 years, and peaked in the ≥70 years age group, reaching 14.09 person-years per 1 000 peoples. The DALY rate of gastric cancer among residents aged 15 to <45 years, 45 to <70 years and ≥70 years showed a downward trend (AAPC=-3.626%, -5.450% and -4.404%, all P<0.05). Conclusions From 2014 to 2023, the DALY rate of gastric cancer in Wenzhou City demonstrated a sustained decline, primarily driven by a the loss of life years due to premature death. Males and older people continue had a heavier disease burden. It is recommended to implement targeted prevention and control measures to reduce the disease burden of gastric canceron among residents.

Objective To analyze the risk factors for chronic mountain sickness(CMS)in young male migrants living in high-altitude areas and to construct a diagnostic model and evaluate its diagnostic efficacy.Methods From June 10 to December 29,2023,a cross-sectional study was conducted on young male migrants subjected with convenience sampling who had been living in high-altitude areas(4 500～5 000 m)for 6 months or longer.Their demographic data were collected and blood samples were collected for laboratory test.According to the Qinghai Score for Chronic Mountain Sickness,they were divided into CMS group and non-CMS group.Then the participants were randomly divided into a training set and a test set in a ratio of 8∶2.Independent risk factors for CMS occurrence were screened out,through random forest variable importance ranking,univariate and multivariable logistic regression analysis,and a diagnostic model was constructed based on these factors.Receiver operating characteristic(ROC)curve analysis,calibration curve analysis,clinical decision curve analysis,and influence curve analysis were used to comprehensively evaluate the diagnostic performance of the model.Results According to the inclusion and exclusion criteria,308 out of 376 participants were finally subjected,and 17.53%of them were diagnosed with CMS.The major clinical symptoms of the CMS patients were dyspnea or palpitations(79.63%)and sleep disorders(85.19%).Further analysis revealed that creatine kinase-MB/creatine kinase(CK-MB/CK,OR=2.17,95%CI:1.43～3.28),high-altitude residence time(OR=2.44,95%CI:1.08～5.54),and body mass index(BMI,OR=1.62,95%CI:1.05～2.50)were 3 major independent risk factors for CMS.The area under the curve(AUC)value of the CMS diagnostic model in the training set and test set was 0.821(95%CI:0.756～0.886)and 0.821(95%CI:0.700～0.944),the specificity was 66.30%and 73.90%,the sensitivity was 89.50%and 81.20%,respectively,indicating good discrimination ability.Hosmer-Lemeshow goodness-of-fit test showed consistency between predicted results and actual observations(χ2=10.029,P=0.263;χ2=4.477,P=0.812).Clinical decision curve analysis demonstrated that within the threshold probability range from 0.1 to 0.7,the net benefit of the model exceeded both full intervention and no intervention strategies.The influence curve analysis showed high consistency between the model predictions and actual incidence when the threshold probability exceeded 0.4.These two analyses together confirmed the clinical application value of the model.Conclusion CK-MB/CK,high-altitude residence time and BMI are independent risk factors for CMS,and their diagnostic model helps identify potential individuals at risk for CMS.Early intervention can prevent the harm of CMS to the health of young men migrating to high-altitude areas.

Objective To prepare a multifunctional mesoporous silica-based nanocarrier system(MMSN@Gem)with gemcitabine and investigate its effect on bladder cancer cells BIU-87.Methods The multifunctional meso-porous silica-based nano drug-carrying system was prepared by a modified method.Transmission electron microsco-py,high-performance liquid chromatography,and thermal imaging were used to characterize the morphology,drug-carrying and photothermal properties of MMSN@Gem.The effect of MMSN@Gem on BIU-87 bladder cancer cells was detected by in vitro experiments.Results MMSN@Gem exhibited a well-defined spherical morphology with an average particle size of(102.48±1.03)nm with a drug loading capacity of 25.04％±0.17％,and an average zeta potential of(-24.84±0.07)mV.The photothermal conversion efficiency was 40.7％which significantly enhanced the release of Gem under near-infrared irradiation.In vitro studies showed that MMSN@Gem significantly inhibited BIU-87 cell activity,induced apoptosis of BIU-87 cells,reduced migration and invasion ability,and enhanced its uptake by BIU-87 cells.Conclusions MMSN@Gem exhibits excellent photothermal properties,enhances cellular uptake efficiency,inhibits the proliferation and migration of BIU-87 cells,and promotes apoptosis,providing a promising drug delivery system for the clinical treatment of bladder cancer.

The safe and reliable maternal fetal monitor can provide comprehensive physiological monitoring for pregnant women and fetuses,and effectively reduce maternal and infant mortality.In the current stage,in addition to the general requirements of medical electrical equipment applicable to maternal fetal monitor in China,there is no particular standard for maternal fetal monitor.The common practice in the industry is to refer to and learn from the particular standards of multi-parameter monitor and ultrasonic Doppler fetal monitor.Based on this,the particular standards applicable to the maternal fetal monitor were researched,and the idea of formulating particular standards for the basic safety and essential performance requirements of the maternal fetal monitor were proposed to ensure the safety and effectiveness of the monitor.

Objective:To investigate the perioperative impact of closure of mesenteric fissure in laparoscopic right hemicolectomy.Methods:The prospective randomized controlled trial was conducted. The clinical data of 320 patients who underwent laparoscopic right hemicolectomy in 11 medical centers, including The First Affiliated Hospital of China Medical University et al, from November 2022 to August 2023 were selected. Based on block randomization, patients were alloca-ted into the mesenteric fissure non-closure group and the mesenteric fissure closure group. Observa-tion indicators: (1) grouping of the enrolled patients; (2) intraoperative conditions; (3) postopera-tive conditions. Measurement data with skewed distribution were represented as M( Q1, Q3) and com-parison between groups was conducted using the Mann-Whitney U test. Count data were represen-ted as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test or Fisher's exact probability. Comparison of ordinal data was conducted using the rank sum test. Comparison of visual analog scores was analyzed using generalized estimating equations. Results:(1) Grouping of the enrolled patients. A total of 320 patients with colon cancer were screened for eligibility, including 156 males and 164 females, aged 68(59,73)years. All the 320 patients were allocated into the mesenteric fissure non-closure group with 164 cases and the mesenteric fissure closure group with 156 cases. There was no significant difference in the age, body mass index, American Society of Anesthesiologist score, maximum tumor diameter, anastomosis location, anastomosis method, surgical approach, range of lymph node dissection, tumor staging between the two groups ( P>0.05) and there was a significant difference in the sex between them ( P<0.05). (2) Intraoperative conditions. There was no significant difference between the mesenteric fissure closure group and the mesenteric fissure non-closure group in the volume of intraoperative blood loss, operation time, conversion to laparotomy, intraoperative complication ( P>0.05). Three patients in the mesenteric fissure non-closure group were converted to laparotomy. One patient in the mesenteric fissure closure group was converted to laparotomy, and 2 cases with intraoperative complication were mesenteric hematoma. (3) Postoperative conditions. There was no significant difference between the mesenteric fissure non-closure group and the mesenteric fissure closure group in the overall postoperative complications ( χ2=0.28, P>0.05). There was no significant difference in the occurrence of postoperative intestinal obstruction, abdominal distension, ascites, pleural effusion, gastric paralysis, anastomotic bleeding, anastomotic leakage, or surgical wound infection between the two groups ( P>0.05). There was no significant difference between the two groups in the reoperation, postoperative gastric tube replacement. There was no significant differ-ence in time to postoperative first flatus, time to postoperative initial liquid food intake, time to post-operative resumption of bowel movements, duration of postoperative hospital stay, total hospital expenses between the two groups ( Z=-0.01, 0.43, 1.04, -0.54, -0.36, P>0.05). One patient in the mesenteric fissure non-closure group received reoperation. No perioperative internal hernia or death occurred in either group. The visual analog score decreased with time in both groups. There was no significant difference in the visual analog score between the mesenteric fissure closure group and the mesenteric fissure non-closure group [ β=-0.20(-0.53,0.13), P>0.05]. Conclusion:Compared with closure of mesenteric fissure, non-closure of mesenteric fissure during laparoscopic right hemi-colectomy dose not increase perioperative complications or postoperative management risk.

Objective To analyze the differential expressed genes(DEGs)in the lung tissues of rat model of high altitude pulmonary edema(HAPE)by using microarray analysis in order to provide new clues for molecular mechanism of HAPE.Methods Healthy male SD rats(8 weeks old,weighing 200±20 g)were randomized into normoxia control(NC)group,lipopolysaccharide(LPS)group,hypoxia group and hypoxia+low-dose LPS(HL)group.The rats of the LPS group and HL group were injected with 0.1 mL 0.05％LPS per 100 g body weight,and those of the NC group and the hypoxia group were administered with an equivalent volume of normal saline.The rats of the hypoxia group and the HL group were housed in a hypobaric chamber simulating an altitude of 5 000 m,and those of the NC group and the LPS group were raised simultaneously outside of the chamber.The wet/dry mass ratio(WDR)of lung tissue and total protein content in bronchoalveolar lavage fluid(BALF)were measured,and the histopathological changes of lung tissue was observed using HE staining.The total RNA was extracted from the lung tissues,and the mRNA expression profile was obtained with Affymetrix microarray followed by Gene Ontology(GO)analysis and Kyoto encyclopedia of genes and genomes(KEGG)pathway analysis with Metascape(http://metascape.org).Results The rats of the HL group showed significant congestion,edema,and widened alveolar septa.Compared with the NC group,the HL group had significantly increased lung WDR(P＜0.01)and total protein content in BALF(P＜0.05).Gene expression analysis revealed that there were 79 genes up-regulated and 59 genes down-regulated in the hypoxia group,473 genes up-regulated and 695 genes down-regulated in the LPS group,and especially,669 genes up-regulated and 1 253 genes down-regulated in the HL group.GO and KEGG pathway analyses revealed that the upregulated genes in the HL group were mainly enriched in biological processes,such as cytokine mediated signaling pathways,response to IL-1,regulation of inflammatory response,as well as signaling pathways,including cytokine-cytokine receptor interactions,TNF,NF-κB,IL-17,complement and coagulation cascades,etc.The down-regulated genes were mainly enriched in biological processes,such as extracellular matrix organization,regulation of endothelial cell migration,cell substrate adhesion,as well as signaling pathways,such as focal adhesion,Wnt,cGMP-PKG,PI3K-Akt,Rap1,etc.The mRNA expression of NF-κB,TNF-α,IL-1βand IL-6 was significantly up-regulated in the lung tissue of the HL group(P＜0.01).Conclusion Hypoxia+low-dose LPS is an effective procedure to establish a reliable model for HAPE in rats.Hypoxia can significantly aggravate LPS-induced inflammation and immune response,enhance the expression of inflammatory mediators,and thus promote the pathogenesis of HAPE.

OBJECTIVE: To review the research progress in the construction strategy and application of bone/cartilage immunomodulating hydrogels. METHODS: The literature related to bone/cartilage immunomodulating hydrogels at home and abroad in recent years was reviewed and summarized from the immune response mechanism of different immune cells, the construction strategy of immunomodulating hydrogels, and their practical applications. RESULTS: According to the immune response mechanism of different immune cells, the biological materials with immunoregulatory effect is designed, which can regulate the immune response of the body and thus promote the regeneration of bone/cartilage tissue. Immunomodulating hydrogels have good biocompatibility, adjustability, and multifunctionality. By regulating the physical and chemical properties of hydrogel and loading factors or cells, the immune system of the body can be purposively regulated, thus forming an immune microenvironment conducive to osteochondral regeneration. CONCLUSION Immunomodulating hydrogels can promote osteochondral repair by affecting the immunomodulation process of host organs or cells. It has shown a wide application prospect in the repair of osteochondral defects. However, more data support from basic and clinical experiments is needed for this material to further advance its clinical translation process.
Hydrogels ; Cartilage ; Bone and Bones ; Tissue Engineering/methods*

Objective:To compare the preservation effect of DX preservation solution and glycerin preservation solution on the corneal stromal lens.Methods:Sixty intact corneal stromal lens samples were collected during femtosecond small incision lenticule extraction (SMILE) from 60 myopic eyes of 30 subjects at Qingdao Eye Hospital of Shandong First Medical University from February 2019 to May 2019.The samples were randomized into DX preserved 1-day group, DX preserved 1-week group, glycerin preserved 1-day group, glycerin preserved 1-week group and glycerin preserved 2-week group according to the different preservation methods, with 10 samples in each group.No intervention was done in the samples of the normal control group.Trypan blue staining was used to count the number of dead cells in the corneal stromal lens.The morphological structure of the corneal stromal lens was examined with an optical microscope, and its ultrastructure was observed under the transmission electron microscope.This study adhered to the Declaration of Helsinki.Written informed consent was obtained from each patient prior to any medical intervention.The study protocol was approved by an Ethics Committee of Qingdao Eye Hospital of Shandong First Medical University (No.2019-30).Results:The number of dead cells was (53.1±14.2), (50.8±9.8), (70.4±13.6) and (172.8±31.7) and (182.8±14.2) cells/field in the DX preserved 1-day group, DX preserved 1-week group, glycerin preserved 1-day group, glycerin preserved 1-week group and glycerin preserved 2-week group, respectively, showing a significant difference among the five groups ( F=16.37, P<0.05). There was no significant difference between the DX preserved 1-day group and 1-week group ( P>0.05). The number of dead cells was significantly less in the glycerin preserved 1-day group than that of the glycerin preserved 1-week group and glycerin preserved 2-week group, and the number of dead cells was significantly increased in the glycerin preserved 1-week group compared with the DX preserved 1-week group (all at P<0.05). The arrangement of collagen fibers of the corneal stromal lens was regular and the cells were intact in the normal control group, DX preserved 1-day group and DX preserved 1-week group.The tissue edema, bare cell nuclei and loose collagen fibers were found in the samples in the glycerin preserved 1-day group.The corneal stromal lens was compact and the collagen fibers were dense and the nuclei were intact in the DX preserved 1-day group and DX preserved 1-week group.The distribution of the cells was sparse and the cell structure was abnormal under the transmission electron microscope in various glycerin preserved groups. Conclusions:The structure of corneal stromal lens can be well preserved for one week by DX storage solution.The preservation effect of DX solution is better for fresh human corneal stromal lens than glycerin solution.

Model informed precision dosing for warfarin is to provide individualized dosing by integrating information related to patient characteristics, disease status and pharmacokinetics /pharmacodynamics of warfarin, through mathematical modeling and simulation techniques based on the quantitative pharmacology. Compared with empirical dosing, it can improve the safety, effectiveness, economy, and adherence of pharmacotherapy of warfarin. This consensus report describes the commonly used modeling and simulation techniques for warfarin, their application in developing and adjusting dosing regimens, medication adherence and economy. Moreover, this consensus also elaborates the detailed procedures for the implementation in the warfarin pharmacy service pathway to facilitate the development and application of model informed precision dosing for warfarin.

Model informed precision dosing (MIPD) is a new concept to guide precision dosing for individual patient by modeling and simulation based on the available information about the individual patient, medications and the disease. Compared to the empirical dosing, MIPD could improve the efficacy, safety, economics and adherence of the pharmacotherapy according to the individual's pathophysiology, genotyping and disease progression. This consensus report provides a brief account of the concept, methodology and implementation of MIPD as well as clinical decision supporting systems for MIPD. The status and future advancing of MIPD was also discussed to facilitate the appropriate application and development of MIPD in China.