OBJECTIVE To analyze the occurrence characteristics and risk factors of adverse drug reactions （ADR） of gemcitabine for injection in national centralized volume-based procurement （hereinafter referred to as “centralized procurement”）， and provide reference for clinical safe drug use. METHODS A retrospective study was conducted to collect the relevant case reports of gemcitabine for injection reported to the National Adverse Drug Reaction Monitoring System by Inner Mongolia Autonomous Region from January 2022 to December 2023； basic information of patients， drug use status， patient outcomes， rational drug use and other information were collected， and the occurrence characteristics of ADRs with leukopenia， myelosuppression， neutropenia， thrombocytopenia and liver dysfunction were analyzed. Univariate analysis and multivariate Logistic regression were used to analyze the correlation of gender， age， combination of antitumor drugs， original malignant tumor and drug dose with ADR. RESULTS A total of 315 cases reports （315 patients） of gemcitabine-induced ADR were included in this study， with a male-to-female ratio of 1.42∶1 and age of （61.17±9.13） years. The primary malignant tumor was pancreatic cancer （73 cases， 23.17%）. Leukopenia， myelosuppression and nausea were the most common ADR， followed by neutropenia， thrombocytopenia， liver dysfunction and so on. The severity grade of ADR was mainly 1-2， and the outcome of most ADR was good. Multivariate Logistic regression analysis showed that combination of antitumor drugs was a risk factor for myelosuppression and neutropenia （RR＝2.154， 95%CI： 1.218- 3.807， P＝0.008； RR＝3.099， 95%CI： 1.240-7.744， P＝0.016）； gender （female） was a risk factor for leukopenia and liver dysfunction （RR＝0.508， 95%CI： 0.302-0.853， P＝0.010； RR＝0.301， 95%CI： 0.102-0.887， P＝0.029）. In terms of drug use rationality， there were 143 cases （45.40%） of drug 126.com use in accordance with the indications of the label， and 172 cases （54.60%） of off-label drug use. Among them， the primary malignant tumors were bladder cancer， bile duct cancer and ovarian cancer， which ranked the top three off-label drug use. CONCLUSIONS The ADR caused by gemcitabine in Inner Mongolia is mainly in the blood and digestive systems. The severity of ADRs is mainly classified as 1-2 levels， and most ADRs have good outcomes. Gender （female） and combination medication are risk factors for gemcitabine-induced ADR. Appropriate chemotherapy regimen should be selected according to the patient’s condition and physical condition， and ADR monitoring in blood and digestive systems should be strengthened during medication of gemcitabine.

BACKGROUND:Fibromyalgia syndrome,as a common rheumatic disease,is related to central sensitization and immune abnormalities.However,the specific mechanism has not been elucidated,and there is a lack of specific diagnostic markers.Exploring the possible pathogenesis of this disease has important clinical significance. OBJECTIVE:To screen the potential diagnostic marker genes of fibromyalgia syndrome and analyze the possible immune infiltration characteristics based on bioinformatics methods,such as weighted gene co-expression network analysis(WGCNA),and machine learning. METHODS:Gene expression profiles in peripheral serum of fibromyalgia syndrome patients and healthy controls were obtained from the gene expression omnibus(GEO)database.The differentially co-expressed genes were screened in the expression profile by differential analysis and WGCNA analysis.Least absolute shrinkage and selection operator(LASSO)and support vector machine-recursive feature elimination(SVM-RFE)machine learning algorithm were further used to identify hub biomarkers,and draw receiver operating characteristic curve(ROC)to evaluate the accuracy of diagnosing fibromyalgia syndrome.Finally,single sample gene set enrichment analysis(ssGSEA)and gene set enrichment analysis(GSEA)were used to evaluate the immune cell infiltration and pathway enrichment in patients with fibromyalgia syndrome. RESULTS AND CONCLUSION:Eight down-regulated differentially expressed genes(DEGs)were obtained after differential analysis of the GSE67311 dataset according to the conditions of log2|(FC)|>0 and P<0.05.After WGCNA analysis,497 genes were included in the module(MEdarkviolet)with the highest positive correlation(r=0.22,P=0.04),and 19 genes were included in the module(MEsalmon2)with the highest negative correlation(r=-0.41,P=6×10-5).After intersecting DEGs and the module genes of WGCNA,seven genes were obtained.Four genes were screened out by LASSO regression algorithm and five genes were screened out by SVM-RFE machine learning algorithm.After the intersection of the two,three core genes were identified,which were germinal center associated signaling and motility like,integrin beta-8,and carboxypeptidase A3.The areas under the ROC curve of the three core genes were 0.744,0.739,and 0.734,respectively,indicating that they have good diagnostic value and can be used as biomarkers for fibromyalgia syndrome.The results of immune infiltration analysis showed that memory B cells,CD56 bright NK cells,and mast cells were significantly down-regulated in patients with fibromyalgia syndrome compared with the control group(P<0.05),and were significantly positively correlated with the above three biomarkers(P<0.05).The enrichment analysis suggested that there were nine fibromyalgia syndrome enrichment pathways,mainly related to olfactory transduction pathway,neuroactive ligand-receptor interaction,and infection pathway.The above results showed that the occurrence and development of fibromyalgia syndrome are related to the involvement of multiple genes,abnormal immune regulation,and multiple pathways imbalance.However,the interactions between these genes and immune cells,as well as their relationships with various pathways need to be further investigated.

Objective: To explore differences in the factors influencing parents and teachers assessments of preschool children s mental health using the Strengths and Difficulties Questionnaire (SDQ), so as to provide reference for promoting children s mental health. Methods: A retrospective analysis was conducted on the SDQ survey data of 14 763 middle and senior kindergarten children in Nanshan District, Shenzhen, from March to June 2023. Chi square χ 2 tests were used to analyze differences in mental health assessments between parents and teachers. Multivariate Logistic regression was employed to examine the factors influencing parental assessments, and Kappa coefficients were used to evaluate the consistency between parent and teacher evaluations. Results: The positive rate of mental health problems reported by parents (7.2%) was significantly higher than that reported by teachers (6.2%) ( χ 2=254.27, P <0.01). Gender differences revealed that parents reported a lower positive rate for boys (7.9%) compared to teachers (8.5%), whereas for girls, the parental positive rate (6.4%) was higher than that reported by teachers (3.8%) ( χ 2=163.59, 81.26, all P <0.01). Age related differences showed that parental positive rates for 4, 5, and 6 year olds (8.5%, 7.4%, 5.8%) were consistently higher than teachers assessments (6.3%, 6.7%, 5.4%) ( χ 2=41.23, 157.53, 63.67, all P <0.05). Univariate analysis of parental assessments indicated higher positive rates among boys (7.9%), 4 year olds (8.5%), mothers aged 20-35 ( 6.6 %), mothers with high school education or below (9.8%), fathers aged 23-40 (6.4%), fathers with high school education or below (10.3%), and children exposed to secondhand smoke (7.9%) ( χ 2=23.56-235.24, all P <0.01). Multivariate Logistic regression identified lower parental education levels and exposure to secondhand smoke as significant risk factors for abnormal SDQ assessments by parents ( χ 2=2.05, 1.62, 3.15, all P <0.05). The Kappa coefficients for parent-teacher agreement across SDQ subscales and total difficulties ranged from 0.04 to 0.12 (all P <0.01). Conclusions Parental education level and exposure to secondhand smoke are significant factors influencing preschool children s mental health. Differences exist between parental and teacher assessments of children s mental health, and incorporating teacher evaluations can provide a more comprehensive understanding of preschoolers psychological well being.

OBJECTIVES: To explore the therapeutic effect of LuoFuShan Rheumatism Plaster (LFS) on neuropathic pain (NP) and its molecular mechanism. METHODS: Mouse models of sciatic nerve chronic constriction injury (CCI) were treated with low, medium, and high doses (2.2, 4.4, and 8.8 cm², respectively) of LFS by topical application for 14 consecutive days. The therapeutic effects were assessed by evaluating the mechanical withdrawal threshold (MWT), paw withdrawal latency (PWL), plasma IL-6 and TNF-α levels, and histopathology of the sciatic nerve. Network pharmacology and molecular docking were used to identify the key targets and signaling pathways. The key targets were verified by RT-qPCR and immunohistochemistry. The biosafety of LFS was evaluated by measuring the organ indices and damage indicators of the heart, liver, and kidneys. RESULTS: Compared with the CCI group, LFS dose-dependently increased MWT and PWL, reduced plasma IL-6 and TNF-α levels, and alleviated sciatic nerve inflammation in the mouse models. Network pharmacology identified 378 bioactive compounds targeting 279 NP-associated genes enriched in TLR and TNF signaling. Molecular docking showed that quercetin and ursolic acid in LFS could stably bind to TLR4 and TNF‑α. In the mouse models of sciatic nerve CCI, LFS significantly downregulated the mRNA expression levels of Tlr4 and Tnf-α in the spinal cord in a dose-dependent manner and lowered the protein expressions of TLR4 and TNF-α in the sciatic nerve. LFS treatment did not cause significant changes in the organ indices or damage indicators of the heart, liver and kidneys as compared with those in the CCI model group and sham-operated group. CONCLUSIONS LFS alleviates NP in mice by suppression of TLR4/TNF-α-mediated neuroinflammation with a good safety profile.
Animals ; Toll-Like Receptor 4/metabolism* ; Neuralgia/metabolism* ; Mice ; Signal Transduction/drug effects* ; Tumor Necrosis Factor-alpha/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Sciatic Nerve/injuries* ; Male ; Molecular Docking Simulation ; Disease Models, Animal ; Interleukin-6

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective To investigate the expression of lncRNA SNHG8 in placenta accrete(PA)and its effect on trophoblast invasion and migration.Methods qRT-PCR was used to detect the expression of lncRNA SNHG8 in placenta tissue of 30 cases in PA group and 30 cases in control group,and the correlation between lncRNA SNHG8 expression and prenatal ultrasound score of 30 cases in PA group was analyzed.Transwell and scratch assay were used to detect the effect of lncRNA SNHG8 interference on the invasion and migration of human chorionic trophoblast cells(HTR8/SVneo cells),and western blot was used to detect the expression of MMP-2 and MMP-9.The downstream targets of lncRNA SNHG8 were predicted by StarBase software,and the expression of lncRNA SNHG8 was detected in placental tissues of the two groups.Dual luciferase reporter assay was used to detect the targeting relationship between lncRNA SNHG8 and miR-542-3p.Results Compared with that of the control group,the expression of lncRNA SNHG8 was up-regulated in the placenta tissue of the PA group(P<0.05),and it was positively correlated with prenatal ultrasound score.Interference with lncRNA SNHG8 inhibited the invasion and migration of trophoblast cells(P<0.05);the protein expression of MMP-9 and MMP-2 also decreased signifi-cantly(P<0.05).Biological prediction indicates that miR-542-3p had a binding site with lncRNA SNHG8,and miR-542-3p expression was down-regulated in PA placental tissue(P<0.05).Dual luciferase reporter assay confirmed that lncRNA SNHG8 could target miR-542-3p.Compared with si-SNHG8+inhibitor-NC,co-transfection of si-SNHG8 and miR-542-3p inhibitor enhanced the invasion and migration ability of trophoblast cells(P<0.05).Conclusion lncRNA SNHG8 is highly expressed in PA and is related to the severity of PA.LncRNA SNHG8 promotes the invasion and migration of trophoblast by regulating the level of miR-542-3p.The study suggests that lncRNA SNHG8 plays an important role in the invasion and migration of PA trophoblast cells,which is expected to be a clinical diagnostic biomarker and therapeutic target.

BACKGROUND:Bone defects are caused by many factors,such as inflammation,tumor,trauma or bone diseases.Erythropoietin can promote the differentiation of mesenchymal stem cells into osteoblasts and osteoclasts and act on vascular endothelial cells to induce angiogenesis and accelerate the repair of bone and cartilage defects.Erythropoietin is a growth factor with potential application in bone tissue engineering construction. OBJECTIVE:To expound the application and potential mechanism of erythropoietin in bone tissue engineering. METHODS:The first author searched the related articles published in CNKI,WanFang,VIP,and PubMed databases from 2004 to 2022 by computer.Search terms were"erythropoietin,bone defect,bone regeneration,angiogenesis,osteogenesis,osteoblast,osteoclast,bone tissue engineering"in Chinese and English.Finally,64 articles were included for review. RESULTS AND CONCLUSION:(1)Erythropoietin can directly act on osteoblasts and osteoclasts in the bone marrow microenvironment by promoting the differentiation of mesenchymal stem cells into osteoblasts,osteoclasts,adipocytes,nerve cells and stromal cells.The activation of Wnt/β-catenin,hypoxia-inducible factor 1α/vascular endothelial growth factor,p38 MAPK and EphrinB2/EphB4 signaling pathways mediates the osteogenic differentiation of mesenchymal stem cells.(2)Erythropoietin can not only regulate the production of erythrocytes to alter the oxygen-carrying capacity of blood but also stimulate vascular endothelial cells to promote angiogenesis.The new blood vessels can carry oxygen,nutrients,growth factors,and bone progenitor cells necessary for osteogenesis to the osteogenic site,thereby promoting bone formation and fracture healing.(3)Currently,erythropoietin is being used as a growth factor with osteogenic and angiogenic effects in various types of scaffold materials such as chitosan,polycaprolactone,bioceramics,and nanofibers through various drug delivery methods.Erythropoietin,along with other growth factors such as bone morphogenetic protein-2 and bone morphogenetic protein-9,has been applied to the surface of scaffold materials to participate in the repair of bone defects.Erythropoietin has demonstrated excellent practicality in the construction of new tissue-engineered bone and has potential clinical application value.

BACKGROUND:Vibration environment can cause spinal injury,especially in patients with scoliosis.At present,there is no information about the inherent mode of the whole spine from T1 to the pelvis in scoliosis patients in the free state. OBJECTIVE:To analyze the dynamic characteristics of the whole spine in patients with scoliosis by the finite element method. METHODS:Based on CT scan images,a three-dimensional finite element model of the T1-pelvic total spine of an 11-year-old patient with thoracolumbar biflexion scoliosis was established,and the Cobb angles of thoracolumbar scoliosis were 36° and 24°,respectively.The mode analysis in the free state of the whole spine was carried out by the finite element method. RESULTS AND CONCLUSION:The fifteen-order free modes of the spine were extracted,and the dynamic characteristics of the scolio-curved spine were obtained.The resonance frequency distribution of the spine was concentrated.The thoracic vertebra was the most deformed in the whole spine model,and the amplitude of the thoracic vertebra was larger than that of the lumbar vertebra.Modal analysis was used to analyze the vibration characteristics of scoliosis patients in the vibration environment.It is of great significance to determine the natural frequency,vibration mode,and amplitude of scoliosis patients for analyzing the vibration characteristics of scoliosis.

Objective To investigate the predictive value of serum placental growth factor(PLGF)/soluble fms-like tyrosine kinase-1(sFlt-1),combined with the placental three-dimensional energy Doppler index(3D-PDI)in preeclampsia(PE).Methods From January 2021 to December 2022,120 pregnant women with PE risk factors were selected and followed up until 1 week after delivery.Serum PLGF and sFlt-1 levels were measured at routine prenatal check-ups at 14 to 20 weeks gestation.The PLGF/sFlt-1 ratio was calculated,and placental 3D-PDI was detected by ultrasound,including the vascularization index(VI),blood flow index(FI),and vascularization-blood flow index(VFI).Based on whether PE occurred after 20 weeks of pregnancy,cases were divided into PE(55 cases)and control groups(65 cases).The PE group was further divided into mild PE(35 cases)and severe PE groups(20 cases)based on the severity of the di-sease.The differences in PLGF/sFlt-1 and 3D-PDI between the groups were compared in terms of a statistical analysis of the correlation between PLGF,sFlt-1,and 3D-PDI.The receiver operating characteristic curve(ROC)was plotted,and the predictive value of each index on PE alone or in combination was analyzed.Results The systolic blood pressure(SBP),diastolic blood pressure(DBP),24 h protein-uria level,preterm birth rate,NICU admission rate,and preconception BMI in the PE group were higher than those in the control group(P＜0.05).The two groups had no differences in age,gestational age,pregnancy history,and fertility history(P＞0.05).The serum PLGF/sFlt-1 of the PE group was lower than that of the control group,and the serum PLGF/sFlt-1 of the severe group was lower than that of the mild group(P＜0.05).The 3D-PDI index of the PE group was lower than that of the control group,and the 3D-PDI index of the severe group was lower than that of the mild group(P＜0.05).Pearson's correlation analysis indicated that PLGF and VFI were signifi-cantly positively correlated(P＜0.01),and sFlt-1 was significantly negatively correlated with VFI(P＜0.01).ROC curve analysis showed that PLGF/sFlt-1,VI,FI,and VFI all had predictive value for PE and the value of VI,FI,and VFI jointly predicted PE,and was higher than that of various parameters(AUC = 0.951).Serum PLGF/sFlt-1,VI,FI,and VFI combined predicted the highest value(AUC=0.987).Conclusion In patients with PE,serum PLGF,sFlt-1,and placental VFI are significantly correlated.Serum PLGF/sFlt-1,placenta VI,FI,and VFI are reduced in early pregnancy,and the combined application of the four indicators has the highest efficacy in predicting PE,providing a possible reference for the early clinical screening or prediction of PE.

Objective To investigate the assessment of fetal lung maturity using main pulmonary artery accelerated systolic time(AT)/ejection time(ET)ratio in patients with severe preeclampsia.Methods A total of 65 pregnant women who were hospitalized in our hos-pital due to severe preeclampsia,from January 2021 to December 2022,and voluntarily underwent ultrasound examination were enrolled in this study.The patients were divided into early-onset(20 to 33+6 weeks gestation)severe preeclampsia group(group A,n= 30)and late-onset(34 to 40 weeks)severe preeclampsia group(group B,n= 35).Healthy pregnant women with gestational age-matched to groups A and B via ultrasound examination were selected as controls(n= 30 andn= 35,respectively).Fetal main pulmonary artery blood flow parameters were measured using ultrasound Doppler:AT,ET,AT/ET,and peak systolic flow rate(PSV).Amniotic fluid(approximately 15 mL)was collected immediately after delivery,and the lecithin/sphingomyelin(L/S)values were measured.The blood flow parameters of the main pulmonary artery of the fetuses in groups A and B were compared,and whether there was any difference between them and the control group was analyzed.The correlation between the blood flow parameters and amniotic fluid L/S was also analyzed.Results There were statistically significant differences in AT,ET,AT/ET,and PSV in the fetal main pulmonary artery between groups A and group B(P＜0.05),and all of them were smaller than those in the control group(P＜0.05).The AT/ET ratio of the fetal main pulmonary artery in groups A and B was positively correlated with amniotic fluid L/S(r= 0.821 and 0.383,respectively,P＜0.05).Receiver operating charac-teristic curve analysis showed that the area under the curve of AT/ET in the diagnosis of early-onset and late-onset preeclampsia was 0.839 and 0.833,respectively,and the sensitivity was 0.853 and 0.912,the specificity was 0.583 and 0.611,and the cut-off values were 0.185 and 0.255,respectively.The false positive rate was 5%.Conclusion The AT/ET value of the fetal main pulmonary artery can be used to make a preliminary diagnosis of severe preeclampsia and quantitatively assess fetal lung maturity,which can provide a new,simple,non-invasive,and reproducible assessment method for clinical practice.