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.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To analyze the clinical and genetic characteristics of children diagnosed with Noonan-syndrome associated with loose anagen hair (NS-LAH).Methods:A retrospective analysis was conducted on the clinical data of 5 children diagnosed with NS-LAH by the Endocrinology Department of the Capital Institute of Pediatrics from January 2018 to June 2024. This analysis encompassed the patients′ demographic information, clinical manifestations, distinguishing features, treatment regimens, and prognostic outcomes to elucidate their clinical characteristics. Additionally, whole-exome sequencing and Sanger sequencing were utilized to investigate the genetic etiology within the families, and the identified variations were interpreted according to the guidelines of the American College of Medical Genetics and Genomics.Results:Among the 5 NS-LAH patients, there were 3 boys and 2 girls, with ages at diagnosis ranging from 2.3 to 7.7 years old. All patients presented with short stature as a primary complaint. Birth histories were generally unremarkable, though case 2 and 5 of macrosomia were noted. In addition to the characteristic facial features of Noonan syndrome, short stature, and varying degrees of intellectual and motor developmental delay, all 5 patients exhibited sparse hair that was easily shed, as well as enlarged head circumferences. Four patients showed structural cardiac abnormalities, which included a case of hypertrophic cardiomyopathy, 2 cases of atrial septal defect, and 1 case of patent foramen ovale. Genetic analysis revealed heterozygous missense variantion in SHOC2 gene in 4 patients, comprising 3 cases with c.4A>G (p.S2G) and one case with c.519G>C (p.M173I). Additionally, one patient was found to have a heterozygous missense variantion c.146C>G (p.P49R) in PPP1CB gene. Three children were diagnosed with growth hormone deficiency and treated with growth hormone for 1.7, 2.7 and 0.5 years. This resulted in significant improvements in height, with annual increases of 11.8, 8.4 and 13.0 cm, respectively. Among the 4 patients with SHOC2 variantions, 2 developed systemic lupus erythematosus and 1 exhibited symptoms of arthritis.Conclusions:Growth failure is the primary complaint in patients with NS-LAH. Key characteristic findings include enlarged head circumference and sparse, loose hair. Growth hormone deficiency is commonly associated with NS-LAH, and growth hormone therapy is generally effective. Furthermore, patients carrying the classic variantion in SHOC2 (c.4A>G) may have an increased risk of developing autoimmune diseases.

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.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective To understand the instrument distribution and capacities of inter-laboratory comparisons among occupational medical examination (OME) institutions in Guangdong Province. Methods A total of 291 OME institutions in Guangdong Province that were within the validity period of filing in June 2024 and 101 OME institutions that participated in inter-laboratory comparisons in 2023 were selected as the study subjects. Their filing categories, instrument distribution and external quality assessment in laboratories were collected and analyzed. Results The location of 291 OME institutions distributed in 21 prefectural-level cities in the province, mainly in the Pearl River Delta (PRD) region, accounting for 68.4% of the total. The public hospitals, private medical institutions, the center for disease control and prevention and occupational disease prevention and treatment institutions (hereinafter referred to as "occupational prevention institutions") accounted for 61.2%, 28.5% and 10.3%, respectively. The filing rates for physical factors, chemical factors, and dust categories among OME institutions were 91.1%, 86.9%, and 86.6%, respectively. The average number of institutional instruments, from high to low, was 53.8, 38.8 and 38.2 per unit in occupational prevention institutions, private medical institutions and public hospitals, respectively. The passing rates of inter-laboratory comparisons among OME institutions of external quality assessment in laboratories among OME institutes in Guangdong Province, from high to low were occupational prevention institutions, public hospitals and private medical institutions (96.2% vs 86.8% vs 73.0%, P<0.05). Conclusion The regional distribution of OME institutes in Guangdong Province is unbalanced, mainly concentrated in the PRD region. Low overall level of OME capacity is found in public hospitals and private medical institutions. Leading by the occupational prevention institutions, public hospitals and private medical institutions should strengthen the development and investment in OME hardware, in order to improve the OME level.

Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

Objective To 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.Methods A 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.Results For 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).Conclusion For 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.

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.