ObjectiveTo explore the mechanism of Shenmai injection in improving cisplatin resistance in non-small cell lung cancer （NSCLC） based on the endoplasmic reticulum stress through protein kinase R-like endoplasmic reticulum kinase （PERK）/activated transcription factor 4 （ATF4）/C/EBP homologous protein （CHOP） signaling pathway. MethodsBALB/c nude mice bearing cisplatin-resistant human lung cancer cell line （A549/cisplatin） were randomly divided into four groups： Blank control group （0.9% sodium chloride）， cisplatin group （5 µg·g^-1cisplatin）， Shenmai injection group （5.2 mg·g^-1 Shenmai injection）， and combination therapy group （5.2 mg·g^-1 Shenmai injection +5 µg·g^-1cisplatin）. The drug intervention lasted for 4 weeks， and the changes in body weight and tumor volume were monitored. Hematoxylin-eosin （HE） staining was performed to observe tumor tissue pathology. Transmission electron microscopy （TEM） was used to assess the morphology of the endoplasmic reticulum. Immunohistochemical assay was conducted to measure the positive expressions of PERK， ATF4， and CHOP in tumor tissues. Western blot quantified the protein expression of immunoglobulin heavy chain binding protein （BIP）， PERK， phosphorylated PERK （p-PERK）， eukaryotic translation initiation factor 2α （eIF2α）， phosphorylated eIF2α （p-eIF2α）， ATF4， CHOP， B-cell lymphoma -2 （Bcl-2）， and Bcl-2 Associated X protein （Bax）. A549/cis cells were divided into blank group： Blank control group （normal culture medium）， cisplatin group （23.3 µmol·L^-1 cisplatin）， Shenmai Injection group （20 g·L^-1 Shenmai injection）， and combination therapy group （20 g·L^-1 Shenmai injection+23.3 µmol·L^-1 cisplatin）. Cell counting kit-8 （CCK-8） method was used to detect cell viability， TEM was used to observe the morphology of endoplasmic reticulum， and Western blot was used to detect endoplasmic reticulum stress and apoptosis-related proteins. ResultsCompared with the cisplatin group， the combination therapy group showed increased body weight （P<0.05）， decreased tumor volume （P<0.05）， and expanded endoplasmic reticulum in tumor cells. The positive expressions of PERK， ATF4， and CHOP increased （P<0.05）. Western blot revealed elevated protein expression levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP， and Bax （P<0.05）， while Bcl-2 expression decreased （P<0.05）. As shown in the in vitro experiment， compared with the cisplatin group， the combination therapy group exhibited a reduced cell survival rate （P<0.05）. TEM revealed increased endoplasmic reticulum dilation and vesicular degeneration. Western blotting showed increased protein levels of BIP， p-PERK/PERK， p-eIF2α/eIF2α， ATF4， CHOP and Bax （P<0.05）， with decreased Bcl-2 expression （P<0.05）. ConclusionShenmai injection combined with cisplatin has a synergistic antitumor effect in NSCLC， which may be attributed to the activation of endoplasmic reticulum stress response mediated by the PERK/eIF2α/ATF4/CHOP signaling pathway and the induction of tumor cell apoptosis.

: To analyze the prevalence of anemia and iron deficiency among primary and secondary school students in Rural Nutrition Improvement Program areas of Guizhou Province in 2023, and to explore the related factors, so as to provide evidence for Rural Nutrition Improvement Program optimization. Methods: In September 2023, a stratified random cluster sampling strategy was used to select 40 rural compulsory education schools with rural nutrition improvement program in five counties of Guizhou Province. School level questionnaire was employed to collect information of basic characteristics and school meal implementation. A total of 7 826 primary and secondary school students aged 6-16 underwent anthropometry and hemoglobin (Hb) determination; serum ferritin (SF) was additionally measured in a random subsample of 1 795 pupils. Students in Grade 3 and above also completed a questionnaire covering demographic characteristics, dietary behaviours and nutrition knowledge. Group comparisons were conducted by Chi square test or Fisher s exact test, and multivariable Logistic regression models were constructed to identify factors associated with anemia and iron deficiency. Results: The overall Hb level was (133.21±12.95)g/L, with an anemia prevalence of 7.17%. The overall SF level was (69.58±59.01)μg/L, with an iron deficiency prevalence of 2.73%. Multivariable analysis showed that stunting ( OR =1.88), school menus without nutrient calculation ( OR =1.61) and absence of menu planning software in the current semester ( OR =2.34) independently increased anemia risk, whereas obesity reduced it ( OR =0.54) (all P <0.05). Girls ( OR =4.16) and Grades 7-9 ( OR =5.93) increased iron deficiency risk (both P <0.05). Compared with rarely eating fresh vegetables, students with consuming <3 kinds per day ( OR =0.08) or exactly 3 kinds per day ( OR =0.06) had lower iron deficiency risks (both P <0.05). Conclusions Anemia and iron deficiency are prevalent among primary and secondary school students in Guizhou. Targeted intervention measures should be implemented for key populations to enhance the effectiveness of nutrition improvement program.

Objective:To analyze the validity of an enhanced nutrition management model for all pregnant women in reducing the incidence of macrosomia.Methods:This retrospective cohort study utilized data from the Beijing Birth Cohort database established by Beijing Obstetrics and Gynecology Hospital, Capital Medical University. A total of 73 193 pregnant women who underwent regular prenatal examinations and delivered at the hospital between January 2018 and December 2023 were consecutively included. From 2018 to 2020, all participants received nutrition education, and high-risk pregnancies predisposed to macrosomia were referred to nutrition clinics for further follow-up. From 2021 to 2023, obstetricians participated in nutritional assessments and gestational weight gain guidance, with repeated nutrition evaluations and education provided during early, mid, and late pregnancy. A multidisciplinary team (obstetrics and nutrition departments) collaborated to implement an enhanced nutrition management model for all pregnant women. General data, parity, gestational age at delivery, neonatal birth weight, and clinical information were collected. Annual incidences of macrosomia and low birth weight were calculated. Chi-square tests and variance analysis were used to analyzed yearly changes in macrosomia rates and evaluate the impact of the two-phase management strategies on macrosomia incidence, thereby to explore the validity of an enhanced nutrition management model for all pregnant women in reducing the incidence of macrosomia.Results:The number of deliveries included annually from 2018 to 2023 was 14 578, 15 413, 11 496, 11 146, 10 396, and 10 164, respectively. Maternal pre-pregnancy body mass indices in 2022 to 2023 were higher than those in 2018 to 2021 [(22.26±3.50) and (22.23±3.65) vs (21.87±3.27), (21.82±3.31), (21.86±3.34) and (21.94±3.39) kg/m2, respectively (all P<0.05)]. Neonatal birth weights in 2021 to 2022 were lower than those in 2018 to 2020 [(3 271±514) and (3 270±513) vs (3 323±504), (3 314±500), and (3 315±510) g], and the birth weight in 2023 was further reduced compared to that in 2018 to 2022 [(3 236±506) vs (3 323±504), (3 314±500), (3 315±510), (3 271±514) and (3 270±513) g] (all P<0.05). The incidence of macrosomia in 2021 to 2022 was lower than those in 2018 to 2020 (5.55%, 5.75% vs 6.97%, 6.68%, 6.67%), and the incidence in 2023 further decreased compared to those in 2018 to 2022 (4.16% vs 6.97%, 6.68%, 6.67%, 5.55%, 5.75%) (all P<0.05). Conclusion:The enhanced nutrition management model for all pregnant women effectively reduces the incidence of macrosomia, demonstrating significant clinical value for widespread implementation.

Objective:To utilize the left ventricular myocardial work（LVMW）technique for early identification of myocardial damage in patients with fabry disease（FD）.Methods:In an observational cross-sectional study，35 patients with FD who visited the Second Hospital of Hebei Medical University from February 2023 to April 2024 were included. They were categorized into two groups based on left ventricular mass index（LVMI）：the non-left ventricular hypertrophy group（LVH-FD group，14 cases）and the left ventricular hypertrophy group（LVH+FD group，21 cases）. Further gender-stratified analysis was performed on parameters related to left ventricular global longitudinal strain（LVGLS）and LVMW. Additionally，for the FD group with normal LVGLS，a comparison of their LVMW-related parameters was made with a control group. A control group consisting of 28 healthy subjects from the same period was selected for comparison. The LVGLS，global work index（LVGWI），global constructive work（LVGCW），global wasted work（LVGWW），and global work efficiency（LVGWE）of the three groups were analyzed using two-dimensional speckle tracking and non-invasive myocardial work techniques，and intergroup comparisons of these parameters were performed. Pearson's linear correlation was applied to analyse the correlation between LVGWI，LVGWE and LVMI.Results:① According to the LVMI grouping results，compared with the control group，the LVH-FD group showed decreased LVGWI（ P<0.05），while the LVH+FD group exhibited reductions in LVGLS，LVGWI，and LVGWE（all P<0.05）. Compared to the LVH-FD group，the LVH+FD group demonstrated lower LVGLS，LVGWI，and LVGWE（all P<0.05）. ② Gender subgroup analysis revealed that in the female subgroup，no statistically significant differences were observed in LVGLS，LVGWI，and LVGWE between the female control group and the female LVH-FD group（all P>0.05）. However，the female LVH+ FD group showed decreased LVGLS，LVGWI，and LVGWE compared to both the female control group（all P<0.05）and the female LVH-FD group（all P<0.05）. In the male subgroup，compared to the male control group，the male LVH-FD group had reduced LVGWI（ P<0.05）but no significant differences in LVGLS or LVGWE（both P>0.05）. The male LVH+ FD group displayed lower LVGLS，LVGWI，and LVGWE compared to both the male control group（all P<0.05）and the male LVH- FD group（all P<0.05）. ③Compared with the control group，the LVGLS-normal FD group had a reduced LVGWI（ P<0.05），while there were no statistically significant differences in LVGLS，LVGWE，LVGCW，and LVGWW between these two groups（all P>0.05）. ④LVGWI and LVGWE were negatively correlated with LVMI（ r=-0.617，-0.707；both P<0.001）. Conclusions:LVMW can detect early cardiac dysfunction in patients with FD and is of guiding value for their clinical management.

Objective To explore the mechanism of Yizhu Wendan Decoction in treating eczema through GEO database combined with network pharmacology and experimental verification.Methods TCMSP,BATMAN-TCM and ETCM databases were used to screen the active components of Yizhu Wendan Decoction.Disease target information related to eczema was collected through GEO database.The drug-component-target network and PPI network were constructed by intersections of active component targets and disease targets.GO and KEGG pathway enrichment analyses were performed using DAVID database.CCK-8 method was used to screen out the optimal intervention concentration of freeze-dried powder of Yizhu Wendan Decoction.HaCaT cells were divided into control group,model group,Yizhu Wendan Decoction low concentration group,Yizhu Wendan Decoction high concentration group,si-IL-17RA group,si-IL-17RA+Yizhu Wendan Decoction low concentration group,si-IL-17RA+Yizhu Wendan Decoction high concentration group,Dexamethasone group,si-IL-17RA+Dexamethasone group.Each group was given relevant intervention.The expressions of chemokines and inflammatory factors were detected by qPCR.EdU and Annexin V-FITC/PI double staining were used to detect cell proliferation and apoptosis.Western blot was performed to detect the expressions of proteins related to apoptosis,skin barrier and IL-17 signaling pathway.Results By using databases,180 active components of Yizhu Wendan Decoction were obtained.Combined with GEO database microarrays related to eczema(GSE6012 and GSE57225),8 potential targets of Yizhu Wendan Decoction in the treatment of eczema were obtained.KEGG enrichment pathway mainly involved IL-17 signaling pathway,lipid and atherosclerotic,TNF signaling pathway,fluid shear stress and atherosclerotic,etc.When Yizhu Wendan Decoction freeze-dried powder concentration was 100 μg/mL,cell viability was the strongest.Yizhu Wendan Decoction could significantly inhibit the mRNA expressions of chemokines and inflammatory factors CCL17,CCL22,IL-1β,TNF-α,IL-6,IFN-γ,and increase the mRNA expression of IL-4 in eczema.It promoted the proliferation of HaCaT cells,increased the protein expression of Bcl-2,and reduced the protein expressions of Bad and Cleaved Caspase-3,thus inhibiting HaCaT cells apoptosis;promoted the protein expressions of FLG and LOR,and reduced the expression of MMP9,MMP1,CCL2,FOSL1,IL-17RA proteins in IL-17 signaling pathway.Conclusion Yizhu Wendan Decoction can treat eczema with multiple components,multiple pathways and multiple targets,promote the proliferation of HaCaT cells,inhibit their apoptosis,and restore the skin barrier.Its mechanism may be related to inhibiting the activation of IL-17 signaling pathway.

Objective To investigate the impact of the artificial intelligence iterative reconstruction (AIIR) algorithm on image quality in chest computed tomography (CT) at different radiation doses, and assess its value in reducing radiation dose during chest CT examinations. Methods A simulated chest phantom was scanned with 12 groups of tube voltages and milliampere-seconds, and the radiation dose was recorded for each group. The images of each group were reconstructed using seven methods: AIIR with noise levels 1-5, KARL iterative reconstruction, and filtered back projection (FBP). The CT values and standard deviations of soft tissue, thoracic vertebrae, pulmonary nodules, and the mediastinum were measured, with standard deviation representing image noise. Subjective evaluation of image quality was performed. The Friedman test was used to compare CT values among the seven reconstruction groups, a linear mixed model was employed for statistical analysis of image noise, and the Friedman test was also used for comparing subjective evaluation scores. Results The reconstruction algorithm, tube voltage, milliampere-seconds, and their interactions all showed statistically significant effects on image noise for the four tissues (F = 2.041-391.283, P < 0.05). Among the reconstruction algorithms, noise reduction capability decreased in the following order: AIIR levels 1-5, KARL, and FBP. The interaction between the reconstruction algorithm and tube voltage or milliampere-seconds indicated that AIIR exhibited improved noise reduction efficacy under low tube voltage and low milliampere-second conditions (|t| = 1.892-8.245, P < 0.05). In terms of subjective evaluation of image quality, there was no statistically significant difference among AIIR levels 3-5 (|Z| ≤ 0.567, P > 0.05), and the score of AIIR level 3 was significantly higher than those of AIIR level 1, AIIR level 2, FBP, and KARL level 2 (|Z| = 3.449-5.906, P < 0.05). Conclusion The AIIR reconstruction algorithm significantly reduced image noise in chest CT examinations. For improving image quality while maintaining image realism, AIIR level 3 is recommended, which can reduce the radiation dose by more than 75%. Furthermore, AIIR showed superior performance in noise reduction under low tube voltage and low milliampere-second conditions, demonstrating significant potential for reducing radiation dose.

Objective To evaluate the cost-effectiveness of inclisiran injection treatment in patients with atherosclerotic heart disease(ASCVD)in China.Methods From the perspective of China's health system,according to the Markov model,patients with ASCVD were divided into inclisilan injection group and placebo group,and both groups were treated with convention-al lipid-lowering drugs.The study period was 25 years.The rate parameters,cost parameters,and effectiveness parameters were de-rived from the ORION-18 trial and other literature.Effects were expressed as quality-adjusted life-years(QALYs).The incremental cost-effectiveness ratio(ICER)was used to evaluate the economy of inclisilan injection.One-way sensitivity analysis and probabil-ity sensitivity analysis were used to verify the reliability of the results.Results The treatment effect of the inclisilan injection group was higher(10.02 QALYs),and the cost of the placebo group was lower(255 179 yuan).The ICER of the two groups was 137 850 yuan per QALY gained,and using 257 094 yuan per capita by 2022 as the threshold,the treatment would be economically advantageous.Sensitivity analysis supported this result.Conclusion At present,the additional use of inclisilan injection can get a better treatment effect,and it has economic advantages under the threshold of three times GDP per capita in China.

Objective To investigate the predictive value of bone metabolism parameters on cardiac autonomic nervous system function in patients with type 2 diabetes mellitus(T2DM).Methods A total of 328 patients with T2DM hospitalized in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2022 to October 2023.According to the serum 25(OH)D level,all the participants were divided into<10 ng/ml group(n=80),10～20 ng/ml group(n=173),and 20～30 ng/ml group(n=75).Biochemical indicators,bone metabolic parameters,left ventricular mass(LVM)and left ventricular mass index(LVMI)were compared.Time domain indicators ofheart rate variability(HRV)in 24 h holter electrocardiogram,including the global standard deviation of normal sinus RR interval(SDNN),sinus RR interval mean standard deviation(SDANN),and normal continuous sinus RR interval difference root mean square(RMSSD).Meanwhile,adjacent RR interval difference>50 ms as a percentage of the total inter-period(PNN50),HRV triangle index,standard deviation of the difference between the length of the entire adjacent NN interperiod(SDSD),and 24 h holter electrocardiogram HRV time-domain relevant indicators were compared among the three groups.The influence of bone metabolism parameters on cardiac autonomic nervous function and their correlation were analyzed,and the optimal cutting point of cardiac autonomic nervous function was predicted by receiver operating characteristic(ROC)curve.Results SBP,heart rate(HR),FPG,PWV,PTH and β-CTX in groups of 10 ng/ml,10～20 ng/ml and 20～30 ng/ml decreased in turn(P<0.05),while HDL-C,ABI,25(OH)D,Ca2+and PNN50 decreased.Correlation analysis between Spearman and Pearson showed that 25(OH)D was positively correlated with SDNN,HRV triangle index,PNN50 and rMSSD(P<0.01).Logistic regression analysis showed that 25(OH)D,Ca2+and HR were the influencing factors of cardiac autonomic nervous dysfunction in patients with T2DM.The ROC curve analysis showed that the areas under the ROC curve of 25(OH)D,Ca2+and HR were 0.791,0.607 and 0.629,respectively,with sensitivity of 73.4%,53.2%and 38.7%,and specificity of 74.0%,93.6%and 81.4%,respectively.Conclusions 25(OH)D is the influencing factor of cardiac autonomic nervous dysfunction in patients with T2DM,and patients with high degree of deficiency are more prone to cardiac autonomic nervous dysfunction.

Objective:To explore the mechanisms of oxaliplatin resistance mediated by TET2 methylation in the treatment of acute lymphoblastic leukemia (ALL) using bioinformatics methods.Methods:The data on drug-resistant and sensitive cell lines related to oxaliplatin treatment for ALL were download using the Genomics of Drug Sensitivity in Cancer (GDSC) database (updated in December 2023); the drug-resistant cell lines were screened based on half maximal inhibitory concentration ( IC50) > 10 μmol/L, and the difference in IC50 between drug-resistant and sensitive cell lines were analyzed using Mann-Whitney U test. The cancer driver mutation genes in drug-resistant cell lines were retrieved using the Cancer Cell Line Encyclopedia (CCLE) database (updated in December 2023). Using the protein-protein interaction (PPI) network functional enrichment analysis (STRING) database (updated in June 2024), PPI network analysis was performed on cancer driver mutation genes with biological functions. A confidence threshold of ≥ 0.7 (high confidence) and an average network node degree above 4 (high average) were selected to screen for cancer driver mutation genes with significant biological functions. Using the microRNA Data Integration Portal (mirDIP) database (updated in June 2024), the coexpression data of microRNA (miRNA) and mutant target genes were queried, miRNA-target gene pairs were screened according to the highest score threshold of 1% miRNA and interaction score > 0.9, and the regulatory effect of miRNA on mutant genes was analyzed. DNA methylation data were download from the Methylation in Human Cancer (MethHC) database (updated in June 2024) and the methylSig R software package was used to analyze the differentially methylated regions (DMR) of DNA methylation between drug-resistant and sensitive cell lines; genes with P < 0.05 and absolute difference > 0.2 were selected, and they were divided into high methylation gene group and low methylation gene group. Spearman correlation analysis and Spearman rank test were performed for the degree of methylation and gene expression, and the key genes with P < 0.01 were screened to reveal the relationship between methylation degree and gene expression. Results:As a result of searching the GDSC database, there were a total of 9 drug-resistant cell lines and 17 sensitive cell lines related to oxaliplatin treatment for ALL; after Z-score normalization of IC50 data between drug-resistant and sensitive cell lines, the average rank of drug-resistant cell lines was 21, and the average rank of sensitive cell lines was 8.5, with a statistically significant difference ( Z = -4.08, P < 0.01). Eight cancer driver mutation genes with significant biological functions that lead to drug resistance of the cell lines were screened using the CCLE database and STRING database. According to the mirDIP database, there were a total of 12 pairs of miRNA-target gene pairs with miRNA-target gene interaction scores >0.9. miRNA had strong regulatory effects on the expressions of NRAS and MAP2K1 target genes. In the MethHC database, the β values (numerical value of increased methylation level) of DMR for genes such as TP53, RXRG and SGIP in drug-resistant cell lines were 0.151, 0.165 and 0.149, respectively, compared to those in sensitive cell lines, the differences were statistically significant (all P < 0.01). The degree of methylation of SGIP gene was negatively correlated with the relative expression level of SGIP mRNA ( r = -0.71, P < 0.01), and SGIP gene underwent high methylation at promoter site 143886940. The cg08321569 locus in the TET2 gene domain of drug-resistant cell lines exhibited persistent high methylation, with a methylation level of β = 0.89. This locus was located 1.2 kb downstream of the transcription start point of exon 4, and the degree of TET2 methylation was negatively correlated with the relative expression level of TET2b mRNA ( r = -0.81, P < 0.01). Conclusions:TET2 methylation may be an important factor for oxaliplatin resistance in the treatment of ALL.

Objective To investigate the effects of obesity-related indexes on cardiovascular autonomic nervous function in type 2 diabetes mellitus(T2DM)patients.Methods A total of 421 T2DM patients treated in the Department of Endocrinology of Gansu Provincial People's Hospital were enrolled in this study from October 2020 to October 2023.All the patients were divided into simple T2DM group with VFA<100 cm2(n=193)and obese group with VFA≥100 cm2(OB,n=228)according to visceral fat area(VFA).BMI,waist-to-height ratio(WHtR),waist-to-hip ratio(WHR),lipid accumulation index(LAP),visceral fat index(VAI),Chinese visceral fat index(CVAI),tapeness index(CI),body shape index(ABSI),and body roundness index(BRI)were calculated.Time domain parameters of heart rate variability(HRV)in 24 h holter electrocardiogram were recorded,including the global standard deviation(SDNN)of normal sinus RR interval,standard deviation of mean value of sinus RR interval(SDANN),root mean square difference(RMSSD)of normal continuous sinus RR interval.The percentage of adjacent RR interval difference>50 ms in total interval(PNN50),the HRV triangle index,the standard deviation of the difference of the entire adjacent NN interval length(SDSD).Results Compared with T2DM group,the OB group showed an increase in age,weight,BMI,WC,hip circumference(HC),neck circumference(NC),SBP,HbA1c,TG,SUA,CI,WHtR,WHR,VFA,SFA,VAI,LAP,CVAI,and BRI(P<0.05 or P<0.01),while a decrease in HDL-C(P<0.05).The SDNN,SDANN,SDSD,RMSSD,HRV trigonometric index,and PNN50 were lower in OB group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis showed that SDNN and HRV trigonometric index was negatively correlated with age,DM duration,HR,SBP,PWV,WHtR,TG,SUA,VAI,LAP,BRI,VFA,LAP,and CVAI(P<0.05 or P<0.01).Logistic regression analysis shows that age,VFA,and LAP are influencing factors for cardiac autonomic dysfunction.The analysis of the working characteristic curve of the subjects showed that the area under the curve of VFA,age,and LAP in predicting cardiovascular autonomic dysfunction was 0.680,0.614,and 0.577,with sensitivity of 87.5%,41.7%,and 61.8%,and specificity of 47.3%,73.6%,and 55.6%respectively.Conclusions BMI,HC,NC,WC,TG,SFA,CI,WHtR,WHR,LAP,BRI,VAI,CVAI and VFA are closely related to cardiovascular autonomic nervous function in T2DM patients.As VFA,Ageand LAP increase,the risk of cardiovascular autonomic dysfunction increases.