BACKGROUND:At present,the biological functions and molecular changes of bone marrow mesenchymal stem cells in the tumor microenvironment of acute myeloid leukemia are still unclear. OBJECTIVE:To explore the changes in the biological function of bone marrow mesenchymal stem cells in acute myeloid leukemia and the role of acute myeloid leukemia conditioned medium by bioinformatics and experiment. METHODS:Differential genes were screened from GEO data sets,and enrichment analysis was performed.The protein-protein interaction network was constructed and the Hub gene was obtained.Bone marrow mesenchymal stem cells from patients with acute myeloid leukemia and healthy donors were cultured.Bone marrow mesenchymal stem cells from healthy donors were treated with acute myeloid leukemia conditioned culture solution.Each group was subjected to the adipogenic differentiation,osteogenic differentiation,staining of β-galactosidase,detection of the cell cycle,and validation of Hub genes. RESULTS AND CONCLUSION:(1)Gene expression data of bone marrow mesenchymal stem cells from acute myeloid leukemia patients and healthy donors were obtained from GSE84881,and 184 up-regulated genes and 140 down-regulated genes were screened.(2)The biological functions of enrichment mainly include cell cycle,adipocyte differentiation,cell metabolism,and MYC pathway.According to the Degree algorithm,10 up-regulated Hub genes and 10 down-regulated Hub genes were selected.(3)The cell in vitro experiment found that:compared with the control group,the surface antigen of acute myeloid leukemia mesenchymal stem cells did not change,but it showed enhanced lipid differentiation ability,weakened osteogenic differentiation ability,increased β-galactosidase positive cell number,altered cell morphology,arrested cell cycle,increased LGALS3 expression,and decreased MYC expression.Mesenchymal stem cells from healthy donors showed similar changes after being cultured in acute myeloid leukemia conditioned medium.(4)The results show that biological function of mesenchymal stem cells is altered in the acute myeloid leukemia microenvironment,which provides new insights into the interaction between mesenchymal stem cells and tumor cells.

Objective To explore the role and mechanism of tannic acid in renal ischemia-reperfusion injury(IRI)in mice.Methods Male C57BL/6J mice were randomly divided into sham operation group(Sham group),blank control group(Sham+TA group),experimental group(IRI group)and treatment group(IRI+TA group),with 20 mice in each group.The survival of mice after renal IRI was observed 48 h after surgery.Serum and renal tissue samples were collected from mice 24 h after IRI(5 mice per group),and the levels of blood urea nitrogen and serum creatinine were detected.The levels of inflammatory factors and ferroptosis-related indicators in renal tissue were detected.The pathological damage of renal tissue was assessed.The protein expression levels of glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family 4(ACSL4)in renal tissue were detected.Molecular docking software was used to explore the binding activity of tannic acid with nuclear factor E2-related factor 2(Nrf2)and to verify the expression of Nrf2 and heme oxygenase-1(HO-1).Results Compared with the IRI group,the postoperative survival rate of mice in the IRI+TA group was higher(0 vs.60%),the levels of serum creatinine and blood urea nitrogen were decreased,the levels of interleukin(IL)-6,IL-1β,and tumor necrosis factor(TNF)-α in renal tissue were decreased,the renal tissue injury was improved,the levels of malondialdehyde and ferrous ions in renal tissue were reduced,the level of glutathione was increased,the expression of GPX4 was increased,and the expression of ACSL4 was decreased(all P<0.05).Tannic acid may form a suitable spatial complement with Nrf2,with a binding energy of-8.7 kcal/mol,indicating a strong binding ability of tannic acid with Nrf2.The protein levels of Nrf2 and HO-1 in the renal tissue of mice in the IRI+TA group were upregulated.Conclusions Tannic acid may bind to Nrf2 protein,activate the Nrf2/HO-1 pathway to inhibit ferroptosis,and alleviate renal IRI in mice.

Factors affecting male fertility include lifestyle,psychology,environment.and so on.Pathogenic microorganisms in the genitourinary system can also lead to decline of male fertility.However,doctors tend to ignore the effects of immune responses and oxidative stress caused by pathogenic microorganisms on fertility,thus delaying the optimal time of treatment.This paper reviews the relationship between bacteria(such as Escherichia coli,Helicobacter pylori),viruses((severe acute respiratory syndrome coronavirus 2,human papilloma virus),and other pathogenic microorganisms(mycoplasma and chlamydia)and male infertility,and summarizes the latest research progress,aiming to provide guidance for the multidimensional treatment and to provide new ideas for the prevention of male infertility.

ObjectiveTo analyze the traditional Chinese medicine （TCM） patterns in patients with spasmodic torticollis and provide reference for standardized differentiation and clinical treatment. MethodsA cross-sectional study was conducted in the spasmodic torticollis outpatient clinic and dystonia ward of the First Teaching Hospital of Tianjin University of Traditional Chinese Medicine from June 2022 to December 2023. The general information including gender， age， duration of disease and type， and the TCM four examinations data such as symptoms， tongue manifestation and pulse manifestation of 198 patients with spasmodic torticollis were obtained by means of on-site questionnaires. Descriptive frequency analysis， factor analysis， and cluster analysis were performed， and the distribution of major TCM patterns were summarized based on the clinical information. ResultsA total of 198 patients with spasmodic torticollis were included， of which 89 （44.95%） were male and 109 （55.05%） were female， with an average age of 40.70±0.96 years and an average course of disease of 24.78±2.32 months. A total of 296 symptoms/signs were obtained， with a cumulative frequency of 6756 times， of which 58 symptoms/signs had a frequency ≥20%， and the top three were neck and back stiffness （83.84%）， condition related to emotions （74.75%） and irritability （72.73%）. Factor analysis of 58 symptoms/signs showed that factor rotation converged after 51 iterations， resulting in 20 common factors with a cumulative contribution of 64.03%. The top three syndrome elements related to the location of the disease were liver， channels， tendons and bones， and those related nature of the disease were dominated by qi stagnation， blood stasis and yin deficiency. The cluster analysis of the 20 common factors showed that the main TCM patterns were internal stirring of liver wind syndrome， liver-kidney yin deficiency syndrome， turbid phlegm obstruction syndrome， and pathogen congested in the channels syndrome. Among the 198 patients， 81 were diagnosed with internal stirring of liver wind syndrome， 60 with liver-kidney yin deficiency syndrome， 37 with turbid phlegm obstruction syndrome， and 20 with pathogen congested in the channels syndrome.There was no statistically significant difference in the distribution of TCM patterns among patients of different genders， age groups， and duration of disease （P＞0.05）. ConclusionSpasmodic torticollis is mainly located in the liver， mostly with internal stirring of liver wind syndrome， liver-kidney yin deficiency syndrome， turbid phlegm obstruction syndrome， and pathogen congested in the channels syndrome.

Objective To explore the correlation between brachial and ankle pulse wave conduction velocity(baPWV)and cardiac structure and function in patients with type 2 diabetes mellitus(T2DM).Methods A total of 443 patients with T2DM who were treated in The Endocrinology Department of Gansu Provincial People's Hospital were enrolled in this study from June 2022 to October 2023.All the patients were divided into simple T2DM group(T2DM,baPWV<1400 cm/s,n=221)and atherosclerosis group(AS,baPWV≥1400 cm/s,n=222)based on baPWV.The cardiac ultrasound diagnostic instrument was used to record left ventricular ejection fraction(LVEF),end diastolic left ventricular diameter(LVd),end diastolic interventricular septal thickness(IVSd),end diastolic left ventricular posterior wall thickness(LVPWd),ratio of early to late diastolic peak velocity of mitral valve annulus(E/A),and ratio of early diastolic peak velocity of mitral valve orifice to early diastolic peak velocity of mitral valve annulus(E/E').Results Age,DM duration,SBP,DBP,HbA1c,TG,ABI,LVEF,IVSd,LVPWd,E/A<1,E/E'＞14,were higher in AS group than in T2DM group(P<0.05 or P<0.01).Spearman correlation analysis shows that E/A<1 was positively correlated with age,DM duration,BMI,SBP,DBP,and ABI(P<0.05 or P<0.01),while negatively correlated with baPWV(P<0.01).Pearson correlation analysis shows that LVPWd was positively correlated with age,DM duration,BMI,SBP,DBP,baPWV,and Scr(P<0.05 or P<0.01).Logistic regression analysis shows that baPWV,ABI,and SBP were the influencing factors for left ventricular diastolic dysfunction.The analysis of the working characteristic curve of the subjects shows that the area under the curve of baPWV,SBP and ABI for predicting left ventricular diastolic dysfunction is 0.647,0.643,and 0.624,with the best cutoff points being 1398.5 cm/s,125.5 mmHg,and 1.107.Conclusions baPWV is closely related to cardiac structure and function in T2DM patients.As baPWV increases,the risk of left ventricular diastolic insufficiency and hypertrophy rises.

Helicobacter pylori(Hp)is a common Gram-negative bacillus causing gastrointestinal infec-tions.It mainly exists on the surface of gastric epithelial cells and in mucus and is associated with gastric ulcers,gastric cancer,and gastric mucosa-associated lymphomas.Studies have shown that Hp can induce or exacerbate certain extragastric diseases and is associated with the occurrence of coronavirus disease 2019.It is hypothesized that Hp may be indirectly or directly involved in the occurrence and development of diseases by stimulating the production of inflammatory cytokines or inducing cross-immune reactions.In addition,Hp can enter Candida to release toxins continuously and play a role in escaping the recognition of the host immune system and the bacteri-cidal effect of drugs.This article reviews the research progress in Hp-associated extragastric diseases in recent years,aiming to draw the attention of clinical workers to Hp-associated extragastric diseases and enrich the knowledge about Hp infection for formulating countermeasures to avoid the aggravation or triggering of other disea-ses by Hp.

Objective To explore the correlation between moderate to severe bronchopulmonary dysplasia (BPD) and early breastfeeding in preterm infants with a gestational age of ≤32 weeks. Methods A retrospective analysis was conducted on the clinical data of 220 preterm infants with a gestational age of ≤32 weeks. The preterm infants were dividedinto moderate to severe BPD group (37 cases) and control group (183 cases) based on whether moderate to severe BPD occurred or not. The clinical characteristics, breastfeeding volume, and mother's own milk (MOM) feeding rate were compared between the two groups, and the relationship between breastfeeding and the occurrence of moderate to severe BPD in preterm infants was analyzed. Results Univariate analysis showed that the moderate to severe BPD group had a higher proportion of infants with birth weight < 1 500 g, gestational age < 28 weeks, vaginal delivery, Apgar score ≤ 7 at 1 minute after birth, and mechanical ventilation time ≥ 7 days compared to the control group(P < 0.05). The duration of intravenous nutrition was longer in the moderate to severe BPD group (P < 0.05). The moderate to severe BPD group had lower breast milk intake from 0 to 7 days after birth, MOM intake, MOM feeding rate, and breast milk intake from 8 to 14 days after birth compared to the control group (P < 0.05). Multivariate Logistic regression analysis showed that a high volume of breastfeeding from 0 to 7 days after birth was an independent protective factor for the occurrence of moderate to severe BPD in preterm infants (OR=0.865, 95%CI, 0.767 to 0.976, P < 0.05). Gestational age < 28 weeks (OR=5.238, 95%CI, 1.158 to 23.686, P < 0.05), and mechanical ventilation time ≥7 days (OR=22.386, 95%CI, 6.769 to 74.030, P < 0.05) were independent risk factors for the occurrence of moderate to severe BPD in preterm infants. Conclusion Early breastfeeding after birth can significantly reduce the risk of moderate to severe BPD in preterm infants with a gestational age of ≤32 weeks, and clinical measures should be actively implemented to promote early breastfeeding.

Objective:To investigate the correlation between adiponectin gene polymorphism and osteoporosis in patients with differentiated thyroid after thyroid stimulating hormone (thyroid stimulating hormone, TSH) suppression therapy.Methods:A total of 79 patients who underwent resection of thyroid cancer and TSH suppression therapy were collected as research objects. After 5 years of follow-up, the bone mineral density of the patients was measured, and they were divided into normal bone mass group and osteoporosis group. The general data of the two groups of patients were compared, and the distribution frequencies of rs1063539, rs266729, rs3774261, and rs710445 genotypes in the two groups of patients were analyzed. The differences in bone mineral density of patients with different genotypes of rs1063539, rs266729, rs3774261, and rs710445 were analyzed. To explore the risk factors of osteoporosis in patients treated with TSH suppression after differentiated thyroid surgery.Results:General data analysis showed that the family history of osteoporosis ( P=0.021) and preoperative thyroid hormone status ( P=0.022) were significantly different between the two groups (all P<0.05). The genotype frequency deviations of rs1063539, rs266729, rs3774261, and rs710445 conformed to the Hardy-Weinberg equilibrium law. The distribution of the three genotypes of rs1063539 locus was significantly different between the two groups, and the bone mineral density T value of rs1063539 CC+CG genotype (-3.68±0.61) was significantly lower than that of GG type (-3.14±0.47) ( t=3.142, P=0.003). Logistic regression analysis showed that no family history of osteoporosis was a protective factor for osteoporosis in patients with TSH suppression after thyroid cancer surgery ( OR: 0.258, OR 95%CI: 0.082-0.773, P=0.020). Preoperative hyperthyroidism ( OR: 2.203, OR 95%CI: 1.134-4.541, P=0.025) and rs1063539 CC+CG genotype ( OR: 4.392, OR 95%CI: 1.248-17.652, P=0.027) were the risk factors inducing osteoporosis. Conclusion:Adiponectin rs1063539 gene polymorphism is associated with bone mineral density in patients, and rs1063539 CC+CG genotype can increase the risk of osteoporosis in patients treated with TSH suppression after differentiated thyroid surgery.

OBJECTIVE To explore the pricing methods of multi-indication drugs suitable for China from the economic perspective. METHODS By sorting out the situation and pricing methods of multi-indication drugs in China’s health insurance negotiation in recent years， the experience of typical countries （Sweden， Germany， Britain， Italy， etc.） in the value measurement， access and management of multi-indication drugs were explored with 3 methods， namely， branded pricing， weighted average bidding pricing， and single bidding pricing under the risk sharing agreement. The advantages and disadvantages of the 2 types of multi-indication drug pricing methods， such as single bidding pricing and indication-based pricing， and conditions of use were explored， so as to put forward a pricing method suitable for multi-indication drugs in China. RESULTS＆＆CONCLUSIONS The pricing of multi-indication drugs by single bidding pricing mode has certain disadvantages at this stage， and should be supplemented and improved by agreement pricing. Based on international experience， China can explore a reasonable management mode of drug indications， adopt a pricing mode with agreement pricing as the main mode and multiple pricing modes as the coexisting mode， and promote the development of pharmacoeconomic evaluation and the improvement of drug use information collection mechanism.

Objective:To investigate the correlation between serum recombinant sclerostin (SOST) and dickkopf-related protein 1 (DKK-1) levels and bone metabolism indexes in patients with osteoporosis after differentiated thyroid cancer surgery.Methods:A total of 110 patients diagnosed with osteoporosis after differentiated thyroid cancer surgery were recruited as the study group, and another 110 patients without osteoporosis diagnosed after differentiated thyroid cancer surgery were recruited as the control group. The general data, bone mineral density, serum SOST, DKK-1 levels and bone metabolism indicators N-terminal propeptide of type I procollagen (PINP), bone alkaline phosphatase (BALP), beta-isomerized C-telopeptide (β-CTX), 25-hydroxyvitamin D3 [25- (OH) D3] levels were compared between the two groups. The correlation between serum SOST, DKK-1 levels and bone metabolism indexes was analyzed, and the risk factors affecting the formation of osteoporosis were explored.Results:The T value of bone mineral density in the study group (-3.27±0.92) was significantly lower than that in the control group (-1.23±0.27, t=22.32, P<0.001). The serum SOST (15.84±1.34, t=32.53, P<0.001) and DKK-1 (5.96±1.40, t=4.82, P<0.001) levels in the study group were significantly higher than those in the control group (SOST: 10.24±1.21, DKK-1: 5.05±1.40). The serum PINP (40.95±9.84, t=7.59, P<0.001), BALP (23.14±5.26, t=5.06, P<0.001) and β-CTX (1.07±0.54, t=4.96, P<0.001) in the study group were significantly higher than those in the control group (31.48±8.64, 19.64±4.99, 0.78±0.29), and the 25- (OH) D3 level (13.68±4.49) was significantly lower than that of the control group (18.31±5.72, t=6.68, P<0.001). Serum SOST was positively correlated with PINP ( r=0.33, P=0.001), BALP ( r=0.23, P=0.016) and β-CTX ( r=0.19, P=0.046), but not with 25- (OH) D3 ( r=-0.09, P=0.349). Serum DKK-1 was positively correlated with PINP ( r=0.19, P=0.044), BALP ( r=0.26, P=0.007) and β-CTX ( r=0.21, P=0.028), but not with 25- (OH) D3 ( r=-0.16, P=0.088). Serum SOST and DKK-1 levels were independent risk factors for osteoporosis (all P<0.05) . Conclusion:Serum SOST and DKK-1 levels are independent risk factors for the formation of osteoporosis, which are significantly positively correlated with bone metabolism indexes PINP, BALP, and β-CTX in patients with osteoporosis after differentiated thyroid cancer surgery.