Objective To explore risk factors of sodium-dependent glucose transporters 2 （SGLT2） inhibitor-associated euglycemic diabetic ketoacidosis （euDKA） and to construct a risk prediction model. Methods A retrospective analysis was performed on the clinical data of type 2 diabetes patients treated with SGLT2 inhibitors in Dongnan Hospital of Xiamen University from January 2020 to December 2023, including age, gender and course of diabetes. The risk factors of SGLT2 inhibitor-associated euDKA were analyzed by univariate analysis and multivariate Logistic regression, and a prediction model was established. According to the receiver's operating characteristic （ROC） curve, the area under the curve （AUC） and the optimal critical value of the prediction model were determined. The prediction model was subjected to both internal and external validation. Results A total of 119 patients with type 2 diabetes treated with SGLT2 inhibitors were included in this study. Among them, there were 98 cases without euDKA （non-euDKA group）and 21 cases with euDKA （euDKA group）. Multivariate Logistic regression analysis showed the DKA history (OR=114.153), appetite or diet decreased three days before admission (OR=21.774), elevated neutrophil count (OR=2.056) and pre-hospital adjustment of hypoglycemic agents (OR=45.745) were independent factors to increase risks of euDKA associated with SGLT2 inhibitors （P<0.05）. Surgical history before admission was an independent factor to reduce this risk （OR=0.007, P<0.05）. By establishing the calculation formula of the prediction model = neutrophil count+6.571 （DKA history）−6.874 （surgical history before admission）+4.273 （appetite or diet decreased three days before admission）+5.302 （pre-hospital adjustment of hypoglycemic drugs）, the ROC curve was drawn. The AUC of the ROC of the prediction model was 0.982 （95%CI: 0.961-1.000, P<0.001）, with accuracy of 94.96%, sensitivity of 0.905, specificity of 0.959 and a critical value of 7.405. The AUC of ROC curve after the model’s ten-fold cross validation was 0.930. And the accuracy of the external validation of the prediction model was 85.29%. Conclusion The DKA history, appetite or diet decreased three days before admission, elevated neutrophil count and pre-hospital adjustment of hypoglycemic agents increased the risk of SGLT2 inhibitor-associated euDKA, while the surgical history before admission reduced this risk. The risk prediction model constructed on this basis could better predict the risk of SGLT2 inhibitor-associated euDKA.

ObjectiveTo investigate the changes in coagulation system in acute decompensated cirrhosis （ADC） patients with or without sepsis and the association of these changes with short-term prognosis. MethodsA prospective study was conducted among 116 ADC patients who were hospitalized in Nanfang Hospital from January 2021 to July 2023， among whom there were 86 patients with sepsis and 30 patients without sepsis， and 54 patients with sepsis alone who had no chronic liver disease were enrolled as control group. Thromboelastography （TEG） and other conventional coagulation parameters were used to comprehensively evaluate the coagulation function of patients. The data including TEG results and short-term prognosis were collected， and a correlation analysis was performed. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. The Spearman correlation coefficient was calculated to investigate the correlation between different variables. The Logistic regression model was used to perform the univariate and multivariate analyses. ResultsFor the ADC patients with sepsis， the lungs and bloodstream were the main infection sites， and bacteria were the main pathogenic microorganism. TEG results showed that compared with the patients with sepsis alone， the patients with ADC and sepsis had a significant reduction in median maximum amplitude （MA）， a significant increase in coagulation time （K time）， and a significant reduction in α angle （all P<0.05）； the patients with ADC and sepsis had a significantly longer reaction time （R time） than those with ADC alone （P=0.02）， and the patients with sepsis alone had a significantly longer R time than those with ADC and sepsis （P=0.04）. There was no correlation between MA and platelet count in the patients with ADC and sepsis （r=-0.133， P=0.057）， while there was a significant correlation between MA and platelet count in the patients with sepsis alone （r=0.595， P=0.001）. SOFA score was negatively correlated with MA in sepsis patients with or without ADC （r=-0.503 and -0.561， both P<0.001）， and for the patients with ADC and sepsis， R time， K time， and α angle were weakly correlated with SOFA score and had a relatively strong correlation with APTT （all P<0.05）. The patients with ADC alone all survived within 90 days， and compared with the death group， the patients with sepsis alone who survived had significantly higher values of MA and α angle （all P<0.05）； there was a significant difference in α angle on day 90 between the survival group and the death group， no matter whether the patients were comorbid with ADC or not （both P<0.01）， while for the patients with ADC and sepsis， there was no significant difference in MA value on day 90 between the survival group and the death group （P>0.05）. ConclusionFor ADC patients comorbid with sepsis， coagulation function assessment and monitoring should be taken seriously in clinical practice， and TEG parameters and SOFA score should be monitored when necessary to develop individualized treatment regimens.

To analyze the epidemiological characteristics of COVID-19 in Fujian Province from the 49th week of 2022 to the 5th week of 2023,after further optimization of China's COVID-19 prevention and control measures on December 7,2022(the 49th week of 2022),this study used multi-dimensional surveillance data to dynamically assess population infection levels and their changing trends.The aim of the study was to provide a scientific basis for early warning of epidemic risk,medical resource allocation,and evalu-ation of socio-economic impact.A multi-source data surveillance system was constructed,encompassing surveillance of fever clinics at medical institutions(weekly collection of visits,positive nucleic acid and antigen test results,inpatients,and severe cases in sec-ondary or above hospitals),population nucleic acid test monitoring(weekly person-times and positivity rates of single-tube tests from the provincial system),sentinel hospital monitoring(weekly proportion of influenza-like illness visits at 18 sentinel hospitals and re-lated viral testing data),and monitoring of novel coronavirus variants(weekly systematic collection of genomic sequences of local and imported cases).Line charts were plotted weekly,and time series analysis,molecular epidemiological methods,and an improved SEIAR model were used to simulate epidemic spread.During the study period,the COVID-19 epidemic in Fujian Province exhibited three distinct stages.In the infection peak stage(52nd week of 2022),the provincial fever clinic visits reached 606 893 person-times,and a 49.2%positivity rate in population single-tube nucleic acid tests and 63.8%positivity rate in sentinel hospital monitoring were observed.In the medical load peak stage(2nd week of 2023),274 460 inpatients and 28 487 severe cases were recorded.In the epidemic decline stage(4th to 5th weeks of 2023),fever clinic visits decreased by 96.3%with respect to the peak,the single-tube nucleic acid test positivity rate decreased to 6.3%,and the sentinel hospital COVID-19 nucleic acid test positivity rate was 6.4%.All 508 sequenced local cases were Omicron variants,predominantly BA.5.2 and its sub-lineages(67.4%).Among 56 imported se-quenced cases,BA.5.2 and its sub-lineages accounted for 50.0%,and 16.1%comprised nine variants of interest including XBB and BQ.The model predicted the infection peak in the 52nd week of 2022,whereas the hospitalization peak lagged by approximately 10.6 days.Multi-source data monitoring revealed a three-stage development of the COVID-19 epidemic in Fujian.The BA.5.2 strain was dominant during the epidemic.The combination of multi-source monitoring data and modeling provides important references for epi-demic prevention and control,and highlights the need to improve the monitoring system in follow-up.

Objective To develop a reagent for detecting of 17α-hydroxyprogesterone(17α-OHP)in dried blood spots on filter paper fixed on vascular stent by Auto TRFIA-4 automatic fluorescence immunoanalyzer and evaluate its performance.Methods The microwell plate was coated with the sheep anti-rabbit IgG antibody as microwell reaction plate,the rabbit anti-human 17α-OHP antibody was diluted as intermediate antibody,and the 17α-OHP-bovine serum albumin conjugate was labeled by europium as europium marker.The concentration of 17α-OHP in dried blood spots on filter paper fixed on blood spots stent was quantitatively detected by Auto TRFIA-4 automatic fluorescence immunoanalyzer.The analysis sensitivity,accuracy,linearity,precision,specificity and stability were evaluated,and whether they met the requirements of the formulated industry standards were evaluated.A total of 227 neonatal heel blood filter paper samples from newborns who were born 72 hours after birth and within 7 days and fully breastfeeding were selected for reagent comparison test.The consistency was analyzed by χ2 test,Kappa test,t test,linear correlation analysis,regression analysis,Bland-Altman method analysis and predictive bias analysis of medical decision level,P<0.05 indicated statistically significant difference.Results The optimal coating concentration of sheep anti-rabbit IgG antibody was 3 μg/ml.The optimal dilution ratio of rabbit anti-human 17α-OHP antibody was 1∶1 500.The optimal dilution ratio of 17α-OHP europium marker mother liquor was 1∶2 500.The limit of blank,limit of detection,limit of quantification was 0.75,1.08 and 1.99 nmol/L,respectively.The relative deviations of the standard check test were within±15.00%,and the average recovery rate was 92.36%.The linear correlation coefficient was 0.997 1 in the range of 2.00 to 300.00nmo/L.The intra-assay and inter-assay coefficients of variation were all within 10.00%.The cross-reactivity rates of 100.00 ng/ml progesterone,17α-hydroxypreg nenolone and 11-deoxycortisol were within 0.089%to 0.64%.The performance of stability test met the requirements.The total coincidence rate was 100%compared with the results of contrast reagent.The quantitative results were highly correlated with the contrast reagent(r=0.999 4,tr=452.02,P<0.05).Conclusion The self-developed reagent has the advantages of high sensitivity,good accuracy,wide linear range,good precision,high specificity and good stability,which meets the requirements of the formulated industry standards,and has high correlation and consistency with the result of contrast reagent,which meets the needs of clinical detection.

To analyze the epidemiological characteristics of COVID-19 in Fujian Province from the 49th week of 2022 to the 5th week of 2023,after further optimization of China's COVID-19 prevention and control measures on December 7,2022(the 49th week of 2022),this study used multi-dimensional surveillance data to dynamically assess population infection levels and their changing trends.The aim of the study was to provide a scientific basis for early warning of epidemic risk,medical resource allocation,and evalu-ation of socio-economic impact.A multi-source data surveillance system was constructed,encompassing surveillance of fever clinics at medical institutions(weekly collection of visits,positive nucleic acid and antigen test results,inpatients,and severe cases in sec-ondary or above hospitals),population nucleic acid test monitoring(weekly person-times and positivity rates of single-tube tests from the provincial system),sentinel hospital monitoring(weekly proportion of influenza-like illness visits at 18 sentinel hospitals and re-lated viral testing data),and monitoring of novel coronavirus variants(weekly systematic collection of genomic sequences of local and imported cases).Line charts were plotted weekly,and time series analysis,molecular epidemiological methods,and an improved SEIAR model were used to simulate epidemic spread.During the study period,the COVID-19 epidemic in Fujian Province exhibited three distinct stages.In the infection peak stage(52nd week of 2022),the provincial fever clinic visits reached 606 893 person-times,and a 49.2%positivity rate in population single-tube nucleic acid tests and 63.8%positivity rate in sentinel hospital monitoring were observed.In the medical load peak stage(2nd week of 2023),274 460 inpatients and 28 487 severe cases were recorded.In the epidemic decline stage(4th to 5th weeks of 2023),fever clinic visits decreased by 96.3%with respect to the peak,the single-tube nucleic acid test positivity rate decreased to 6.3%,and the sentinel hospital COVID-19 nucleic acid test positivity rate was 6.4%.All 508 sequenced local cases were Omicron variants,predominantly BA.5.2 and its sub-lineages(67.4%).Among 56 imported se-quenced cases,BA.5.2 and its sub-lineages accounted for 50.0%,and 16.1%comprised nine variants of interest including XBB and BQ.The model predicted the infection peak in the 52nd week of 2022,whereas the hospitalization peak lagged by approximately 10.6 days.Multi-source data monitoring revealed a three-stage development of the COVID-19 epidemic in Fujian.The BA.5.2 strain was dominant during the epidemic.The combination of multi-source monitoring data and modeling provides important references for epi-demic prevention and control,and highlights the need to improve the monitoring system in follow-up.

AIM:To investigate the immunosuppressive effects of M2-like tumor-associated macrophages(M2-TAMs)on CD8+T cells within the tumor microenvironment of esophageal cancer.METHODS:Multiplex fluores-cence immunohistochemistry was used to analyze the distribution of immune cells in esophageal cancer tissues.An in vitro co-culture system was established,and flow cytometry along with Calcein-AM/PI staining was employed to assess the im-pact of M2-TAMs on CD8+T cell function.The GEPIA database was utilized to evaluate the prognostic significance of PDCD1 expression in esophageal cancer patients and to analyze the correlations between gene expressions.Immunohisto-chemistry(IHC)was performed to detect the expression of TGF-β1 in esophageal cancer tissues.Flow cytometry and en-zyme-linked immunosorbent assay(ELISA)were used to measure PD-1,IFN-γ and TNF-α expression in CD8+T cells fol-lowing treatment with a TGF-β1 inhibitor.RESULTS:Compared with early-stage(stage I)esophageal cancer patients,the patients with advanced disease(stages Ⅱ to Ⅳ)exhibited dynamic changes in the infiltration of CD4+T cells,CD8+T cells,Tregs,and M2-TAMs within tumor tissues,with significant correlations observed among these cell populations(P<0.05).The distribution of M2-TAMs and Tregs was positively correlated with poor prognosis(P<0.05),while that of CD8+T cells was negatively correlated(P<0.05).In contrast,CD4+T cell infiltration showed no significant association with clinical outcomes(P>0.05).Co-culture of CD8+T cells with M2-TAMs resulted in significant downregulation of CD107a,granzyme B,IFN-γ and TNF-α expression(P<0.01).Additionally,M2-TAM-treated CD8+T cells co-cultured with esophageal cancer cells led to reduced apoptosis of cancer cells.High expression of PDCD1 was significantly associated with poor prognosis(P<0.05),and significant correlations were observed between CD8A and PDCD1 expression,as well as between TGF-β1 and CD274 gene expression(P<0.01).TGF-β1 was also significantly associated with CD163+macro-phage infiltration and the progression of esophageal cancer(P<0.05).Treatment with a TGF-β1 inhibitor in the M2-TAM and CD8+T cell co-culture system significantly down-regulated PD-1 expression and increased the secretion of IFN-γ and TNF-α(P<0.01).CONCLUSION:The TGF-β1 derived from M2-TAMs inhibits the antitumor activity of CD8+T cells in the esophageal cancer microenvironment,suggesting potential therapeutic targets for overcoming immunosuppression in esophageal cancer.

Objective:To investigate the inflammatory indicator levels and influencing factors on middle-aged and elderly male residents at different residential distances from a uranium mine in Guangdong, so as to provide scientific data for the health risk assessment of the residents therein.Methods:With stratified sampling method, two groups of the permanent middle-aged and elderly male residents were randomly sampled within < 10 km and 10-20 km of the uranium mine, along with the basic demographic characteristics and lifestyle information collected through face-to-face questionnaire survey. Both height and weight of the respondents were measured using standard method and their body mass indexes (BMI) were calculated. Through collection of the venous blood, the levels of a wide range of inflammatory indicators were measured, such as C-reactive protein (CRP), complement C3, complement C4, leukocytes, lymphocytes, neutrophils, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and others. Multiple linear regression was used to analyze the influencing factors on the levels of inflammation indicators.Results:A total of 867 middle-aged and elderly male residents were included in this study, including one group of 431 residents within the 10-20 km at an average age of 51.54±5.37, and a second group of 436 residents within <10 km at an average age of 52.05±5.24. The result of multiple linear regression showed a positive correlation of the distance groups with complement C4 level ( β=0.014, 95% CI: 0.001-0.027) and lymphocyte number ( β=0.086, 95% CI: 0.003-0.168) ( t=2.07, 2.04, P<0.05). The ages of middle-aged and elderly male residents around the uranium mine was positively correlated ( t=2.50, P<0.05) with the levels of complement C4 ( β=0.018, 95% CI: 0.004-0.031), and negatively correlated ( t=-3.25, -2.97, P<0.05) with the levels of TNF-α ( β=-63.022, 95% CI: -101.114 to -24.929) and IL-6 ( β=-14.694, 95% CI: -24.396 to -4.992). Smoking was positively correlated ( t=4.29, 4.81, 3.19, P<0.05) with leukocytes number ( β=0.630, 95% CI: 0.341-0.918), lymphocytes number ( β=0.226, 95% CI: 0.134-0.319) and neutrophils number ( β=0.372, 95% CI: 0.143-0.601), and negatively correlated ( t=-2.07, -1.98, P<0.05) with the levels of TNF-α ( β=-43.551, 95% CI: -84.778 to -2.324) and IL-6 ( β=-10.603, 95% CI: -21.103 to -0.102). BMI was positively correlated ( t=8.60, 3.62, 3.18, 4.01, 2.10, P<0.05) with complement C3 level ( β=0.108, 95% CI: 0.084-0.133), complement C4 level ( β=0.026, 95% CI: 0.012-0.039), leukocytes number ( β=0.433, 95% CI: 0.166-0.699), lymphocyte number ( β=0.175, 95% CI: 0.089-0.261), and neutrophil number ( β=0.226, 95% CI: 0.014-0.438). Fruit consumption ( β=0.017, 95% CI: 0.001-0.034) was positively correlated with complement C4 levels ( t=2.10, P<0.05). Conclusions:This study showed no significant correlation between the inflammatory index levels of middle-aged and elderly male residents around the uranium mine and uranium mining. Age, smoking, BMI and fruit consumption were the influencing factors on the levels of inflammatory indicators of middle-aged and elderly male residents.

Objective:To investigate differential gene expression, enriched biological processes, and pathway differences between residents of a high-background radiation area (HBRA), Yangjiang, and a control area—Enping.Methods:Seven residents were selected from the HBRA (the HBRA group) and seven from the control area (the control group) using the two-stage random sampling method. The cumulative radiation dose for each individual was calculated based on the ambient gamma exposure levels. Peripheral blood samples were collected and analyzed via high-throughput sequencing to identify differentially expressed genes. Subsequent analyses included gene ontology (GO) for biological process (BP), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and gene set enrichment analysis (GSEA).Results:The median ages of the HBRA and control groups had no statistically significant difference ( P = 0.370). The cumulative external doses for the HBRA and control groups were (99.59±20.07) and (33.82±10.61) mSv, respectively. This difference was statistically significant ( t = -5.88, P = 0.001). High-throughput sequencing identified 1 224 differentially expressed genes in the HBRA group, including 32 senescence-related genes, compared to the control group. The result of GO-BP analysis showed that these genes were predominantly enriched in cell signaling, biosynthesis, localization, cell cycle regulation, and cellular stress responses. KEGG analysis revealed significant enrichment in the chemokine and MAPK signaling pathways, as well as in pathways related to the cell cycle, autophagy, and mitophagy. Furthermore, GSEA analysis confirmed that the differentially expressed genes were mainly related to cell cycle regulation and mitochondrial functions. Conclusions:Differentially expressed mRNAs are found in the peripheral blood of residents in the HBRA. These mRNAs are predominantly associated with key biological processes and pathways, including cell cycle regulation, chemokine and MAPK signaling pathways, and mitophagy.

Objective:To compare the analgesic effect of femoral triangle block and adductor canal block after total knee arthroplasty.Methods:Clinical studies comparing the analgesic efficacy of femoral triangle block and adductor canal block after total knee arthroplasty were retrieved from CNKI, Wanfang Data Knowledge Service Platform, VIP, Chinese Medical Journal Full-text Database, PubMed, Embase, and the Cochrane Library, with the retrieval time ranging from the establishment of the databases to October 2024. Data on knee pain scores, morphine consumption, quadriceps muscle strength, postoperative timed up-and-go test (TUGT), and postoperative complications were extracted. The modified Jadad scale was used to evaluate the methodological quality of the included literature. Meta-analysis was performed using Stata 18.0 statistical software.Results:A total of 670 patients from 9 randomized controlled trials were included in the meta-analysis. There were 333 patients in the femoral triangle block group, with an average age of 60.6-72.3 years, and there were 337 patients in the adductor canal block group, with an average age of 61.7-73.5 years. All the 7 English articles were of high quality, and the modified Jadad score was 6-7 points. Two Chinese articles were of low quality and the modified Jadad score was 3. The results of meta-analysis showed that there were no statistically significant differences between the two groups in postoperative morphine consumption [ SMD=0.13, 95% CI(-0.45, 0.71), P=0.658], postoperative 24h knee resting pain score [ SMD=-0.35, 95% CI(-1.48, 0.78), P=0.545], postoperative 48h knee resting pain score [ SMD=-0.56, 95% CI(-1.71, 0.60), P=0.347], postoperative 24h TUGT [ SMD=0.01, 95% CI(-0.27, 0.30), P=0.933], postoperative 48h TUGT [ SMD=0.04, 95% CI(-0.61, 0.69), P=0.905], and incidence of postoperative complications [ RR=1.17, 95% CI(0.56, 2.45), P=0.669]. The quadriceps strength of the adductor canal block group was greater than that of the femoral triangle block group at 24 h after operation, and the difference was statistically significant [ WMD=-0.73, 95% CI(-0.93, -0.53), P<0.001]. Conclusions:Both femoral triangle block and adductor canal block can effectively relieve pain after total knee arthroplasty. Patients with adductor canal block have better muscle strength recovery in the early postoperative period.

Objective To investigate the role of the O-6-methylguanine-DNA methyltransferase (MGMT) gene-3′ untranslated region (UTR) microRNA-associated single nucleotide polymorphism (miRSNP) (rs7896488 G>A) in affecting miR-4297-targeted modulation of MGMT in senescence of lung cells with polymorphic genotypes induced by fractionated low dose ionizing radiation (LDIR). Methods i) MiRSNPs were predicted and screened using bioinformatics, and DNA from two types of lung cells, A549 cells and human bronchial epithelioid cells (HBE cells), was extracted for target gene sequencing. After co-transfection of pGL3c-MGMT-3′UTR-rs7896488 G>A reporter gene recombinant plasmid, pRL-TK Vector with micrON mimic NC #22 or micrON hsa-miR-4297 mimic (set up as the mimic NC group and the miR-4297 mimic group) in these two types of lung cells, dual luciferase reporter gene assay was performed. The relative expression of MGMT mRNA was detected by real-time fluorescence quantitative polymerase chain reaction, and the relative expression of MGMT protein was detected by Western blotting. ii) These two types of lung cells were randomly divided into the control group and irradiation group, which received either 0 or 100 mGy X-rays irradiation seven times. After irradiation, the cells were transfected with either micrON mimic NC #22 or micrON hsa-miR-4297 mimic, resulting in mimic NC + control group, miR-4297 mimic + control group, mimic NC + irradiation group, and miR-4297 mimic + irradiation group. Cells were collected for senescence-associated-β-galactosidase (SA-β-Gal) staining, and the relative expression of matrix metalloproteinase-9 (MMP-9) and chemokine (C-X-C motif) ligand-1 (CXCL-1) proteins was detected via Western blotting. Results i) The rs7896488 G>A was the miRSNP located in the conserved binding region targeted by miR-4297 in the MGMT gene 3′UTR. A549 cells were the rs7896488 GG wild-type homozygous genotype, while HBE cells were the rs7896488 GA heterozygous mutant genotype. In the miR-4297 mimic group, A549 and HBE cells carrying the rs7896488 G allele showed significantly lower dual-luciferase activity compared with that in the mimic NC group (both P<0.01). However, there was no significant difference in dual-luciferase activity between the two groups in both A549 and HBE cells carrying the rs7896488 A allele (both P>0.05). The relative expression levels of MGMT mRNA and MGMT protein of A549 cells in the miR-4297 mimic group were lower than those in the mimic NC group (both P<0.05). However, there was no significant difference in MGMT mRNA and MGMT protein of HBE cells between these two groups (both P>0.05). ii) The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of A549 cells in the miR-4297 mimic+irradiation group were higher than those in the mimic NC + control group, the miR-4297 mimic + control group, and the mimic NC + irradiation group (all P<0.05). The relative activity of SA-β-Gal and the relative expression of MMP-9 and CXCL-1 proteins of HBE cells in the miR-4297 mimic + irradiation group were higher than those in the mimic NC + control group and the miR-4297 mimic + control group (all P<0.05), while there was no significant difference compared with those in the mimic NC + irradiation group (all P>0.05). Conclusion MGMT-3′UTR-miRSNP rs7896488 G>A plays a role in LDIR-induced senescence of lung cells with different polymorphic genotypes by affecting miR-4297-targeted regulation of MGMT.