Objective To investigate the expression characteristics of poly(rC)-binding protein 1(PCBP1)in gastric cancer tissues and their clinical significances by bioinformatics analysis combined with experimental verification,and to identify its relationship with STIP1 homology and U-Box containing protein 1(STUB1).Specifically,this study aims to verify the expression patterns of PCBP1 and STUB1 in gastric cancer and determine their relationships with clinicopathological features by immunohistochemistry to provide a theoretical framework as well as potential intervention strategies for gastric cancer.Methods Data of PCBP1 expression in gastric cancer and adjacent tissues were obtained from TIMER 2.0 online analysis website.KEGG pathway enrichment analysis was performed using gastric cancer data(STAD)in the TCGA(the Cancer Genome Atlas)database,and its potential mechanism was determined.The main regulatory factor STUB1 was found in the fer-roptosis regulatory pathway.Subsequently,PCBP1 and STUB1 expressions in 33 cases of gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemistry.The collected cases were grouped according to different degrees of differentiation,age,gender,tumor size,depth of tumor invasion,TNM stage and pathological morphology.The positive expression rates of PCBP1 and STUB1 were observed.The correlation between the two proteins and the correlation between clinical and pathological features were analyzed by c2 test.Finally,the relationship between PCBP1 and STUB1 and malignancy of gastric cancer was further explored.Results Immunohistochemical results showed that the positive expression rate of PCBP1 in cancer tissues was 69.7%,which was significantly higher than that in adjacent tissues(48.5%).The positive expression rate of STUB1 in cancer tissues was 39.4%,which was lower than that in adjacent tissues(54.5%),statistically significant difference(P<0.05).The positive expression rate of PCBP1 was correlated with tumor differentiation,lymph node metastasis and Lauren classification(P<0.05),but not with patient's age,gender,depth of inva-sion,clinical stage,nerve infiltration,and intravascular tumor thrombus(P>0.05).The positive expression rate of STUB1 was correlated with tumor differentiation,depth of invasion,lymph node metastasis and Lauren classification(P<0.05).The Spearman correlation coefficient between PCBP1(cancer)and STUB1(cancer)was-0.413,with P=0.017(P<0.05),indicating that there was a significant negative correlation between them.Conclusion PCBP1 participates in the malignant progression of gastric cancer by regulating the main regulator STUB1 in the ferroptosis pathway.Theoretically,it provides a new insight into molecular mechanism as well as a potential therapeutic strategy for treating gastric cancer.

BACKGROUND:With the increasing demand for orthopedic implants,the search for materials with good biocompatibility and degradability has become a research hotspot.Magnesium-lithium-gadolinium(Mg-Li-Gd)alloy has good degradability,biocompatibility,and mechanical properties,providing ideal supporting conditions for fracture healing.OBJECTIVE:To evaluate the effects of Mg-Li-Gd alloy implants on bone healing in rats.METHODS:A circular half-defect model was made on the lateral side of the right mid-femoral segment in 28 SD rats,and the rats were randomly divided into two groups.The stainless steel group was fixed with a stainless steel intramedullary nail,and the magnesium alloy group was fixed with an Mg-Li-Gd alloy intramedullary nail,with 14 rats in each group.At 2,8,and 14 weeks after surgery,right femur X-ray and Micro-CT examinations,as well as hematoxylin-eosin staining,immunohistochemical staining,and western blot assay were performed.RESULTS AND CONCLUSION:(1)X-ray film:At 2 weeks after surgery,the osteotomy lines of both groups were clear,the density of the intramedullary nail in the magnesium alloy group was close to that of bone tissue,and the density of the intramedullary nail in the stainless steel group was higher than that of bone tissue.At 8 weeks after surgery,the osteotomy lines of both groups were blurred,and the intramedullary nail in the magnesium alloy group had corroded and degraded.At 14 weeks after surgery,the osteotomy lines of both groups disappeared,and the intramedullary nail in the magnesium alloy group further corroded and degraded.(2)Micro-CT:At 2 weeks after surgery,callus began to form in both groups;8 weeks after surgery,the stainless steel group entered the callus remodeling stage,and a relatively dense bone structure was formed at the bone defect site,and the magnesium alloy group showed obvious callus hyperplasia at the bone defect site.At 14 weeks after surgery,the stainless steel group showed a mature bone remodeling process,and thick cortical bone was formed at the bone defect site,and thinner cortical bone was formed in the magnesium alloy group.(3)Hematoxylin-eosin staining:At 2 weeks after surgery,a large number of osteoblasts,osteocytes,a small number of osteoclasts and trabecular structures were observed in the magnesium alloy group,while relatively few osteoblasts and osteocytes were observed in the stainless steel group.At 8 weeks after surgery,a large number of osteoblasts,osteocytes,and mature trabecular structures were observed in the magnesium alloy group,while a large number of osteocytes and lamellar bones were observed in the stainless steel group.At 14 weeks after surgery,lamellar bones were observed in the magnesium alloy group,while mature bone tissue was observed in the stainless steel group.(4)Immunohistochemical staining and western blot assay:At the same time point,the expression levels of bone morphogenetic protein 2,osteocalcin,and RUNX2 proteins in the magnesium alloy group were higher than those in the stainless steel group.(5)The results showed that compared with stainless steel materials,Mg-Li-Gd alloy had no obvious advantage in promoting the formation of fracture healing structure.

BACKGROUND:With the increasing demand for orthopedic implants,the search for materials with good biocompatibility and degradability has become a research hotspot.Magnesium-lithium-gadolinium(Mg-Li-Gd)alloy has good degradability,biocompatibility,and mechanical properties,providing ideal supporting conditions for fracture healing.OBJECTIVE:To evaluate the effects of Mg-Li-Gd alloy implants on bone healing in rats.METHODS:A circular half-defect model was made on the lateral side of the right mid-femoral segment in 28 SD rats,and the rats were randomly divided into two groups.The stainless steel group was fixed with a stainless steel intramedullary nail,and the magnesium alloy group was fixed with an Mg-Li-Gd alloy intramedullary nail,with 14 rats in each group.At 2,8,and 14 weeks after surgery,right femur X-ray and Micro-CT examinations,as well as hematoxylin-eosin staining,immunohistochemical staining,and western blot assay were performed.RESULTS AND CONCLUSION:(1)X-ray film:At 2 weeks after surgery,the osteotomy lines of both groups were clear,the density of the intramedullary nail in the magnesium alloy group was close to that of bone tissue,and the density of the intramedullary nail in the stainless steel group was higher than that of bone tissue.At 8 weeks after surgery,the osteotomy lines of both groups were blurred,and the intramedullary nail in the magnesium alloy group had corroded and degraded.At 14 weeks after surgery,the osteotomy lines of both groups disappeared,and the intramedullary nail in the magnesium alloy group further corroded and degraded.(2)Micro-CT:At 2 weeks after surgery,callus began to form in both groups;8 weeks after surgery,the stainless steel group entered the callus remodeling stage,and a relatively dense bone structure was formed at the bone defect site,and the magnesium alloy group showed obvious callus hyperplasia at the bone defect site.At 14 weeks after surgery,the stainless steel group showed a mature bone remodeling process,and thick cortical bone was formed at the bone defect site,and thinner cortical bone was formed in the magnesium alloy group.(3)Hematoxylin-eosin staining:At 2 weeks after surgery,a large number of osteoblasts,osteocytes,a small number of osteoclasts and trabecular structures were observed in the magnesium alloy group,while relatively few osteoblasts and osteocytes were observed in the stainless steel group.At 8 weeks after surgery,a large number of osteoblasts,osteocytes,and mature trabecular structures were observed in the magnesium alloy group,while a large number of osteocytes and lamellar bones were observed in the stainless steel group.At 14 weeks after surgery,lamellar bones were observed in the magnesium alloy group,while mature bone tissue was observed in the stainless steel group.(4)Immunohistochemical staining and western blot assay:At the same time point,the expression levels of bone morphogenetic protein 2,osteocalcin,and RUNX2 proteins in the magnesium alloy group were higher than those in the stainless steel group.(5)The results showed that compared with stainless steel materials,Mg-Li-Gd alloy had no obvious advantage in promoting the formation of fracture healing structure.

Objective To investigate the expression characteristics of poly(rC)-binding protein 1(PCBP1)in gastric cancer tissues and their clinical significances by bioinformatics analysis combined with experimental verification,and to identify its relationship with STIP1 homology and U-Box containing protein 1(STUB1).Specifically,this study aims to verify the expression patterns of PCBP1 and STUB1 in gastric cancer and determine their relationships with clinicopathological features by immunohistochemistry to provide a theoretical framework as well as potential intervention strategies for gastric cancer.Methods Data of PCBP1 expression in gastric cancer and adjacent tissues were obtained from TIMER 2.0 online analysis website.KEGG pathway enrichment analysis was performed using gastric cancer data(STAD)in the TCGA(the Cancer Genome Atlas)database,and its potential mechanism was determined.The main regulatory factor STUB1 was found in the fer-roptosis regulatory pathway.Subsequently,PCBP1 and STUB1 expressions in 33 cases of gastric cancer tissues and corresponding adjacent tissues were detected by immunohistochemistry.The collected cases were grouped according to different degrees of differentiation,age,gender,tumor size,depth of tumor invasion,TNM stage and pathological morphology.The positive expression rates of PCBP1 and STUB1 were observed.The correlation between the two proteins and the correlation between clinical and pathological features were analyzed by c2 test.Finally,the relationship between PCBP1 and STUB1 and malignancy of gastric cancer was further explored.Results Immunohistochemical results showed that the positive expression rate of PCBP1 in cancer tissues was 69.7%,which was significantly higher than that in adjacent tissues(48.5%).The positive expression rate of STUB1 in cancer tissues was 39.4%,which was lower than that in adjacent tissues(54.5%),statistically significant difference(P<0.05).The positive expression rate of PCBP1 was correlated with tumor differentiation,lymph node metastasis and Lauren classification(P<0.05),but not with patient's age,gender,depth of inva-sion,clinical stage,nerve infiltration,and intravascular tumor thrombus(P>0.05).The positive expression rate of STUB1 was correlated with tumor differentiation,depth of invasion,lymph node metastasis and Lauren classification(P<0.05).The Spearman correlation coefficient between PCBP1(cancer)and STUB1(cancer)was-0.413,with P=0.017(P<0.05),indicating that there was a significant negative correlation between them.Conclusion PCBP1 participates in the malignant progression of gastric cancer by regulating the main regulator STUB1 in the ferroptosis pathway.Theoretically,it provides a new insight into molecular mechanism as well as a potential therapeutic strategy for treating gastric cancer.

Objective:To observe the clinical efficacy and safety of Tongren Niuhuang Qingxin Pills combined with telmisartan tablets in the treatment of hypertensive vertigo syndrome of phlegm-heat disturbance.Methods:Randomized controlled trial was conducted. Totally 80 patients with hypertension vertigo and phlegm-heat disturbance syndrome were selected from March 2021 to August 2022 at Beijing Tongrentang Hospital of Traditional Chinese Medicine as the observation objects. They were randomly divided into two groups using a random number table method, with 40 cases in each group. The control group received oral telmisartan tablets, while the experimental group received Tongren Niuhuang Qingxin Pills in addition to the control group. Both groups were treated for 28 days and followed up for 1 month. The patients' room blood pressure before and after treatment was measured, and TCM syndrome scores were evaluated. The dizziness assessment rating scale (DARS) was used to evaluate the severity of dizziness, adverse reactions during treatment were recorded, drug safety was observed, and clinical efficacy was evaluated.Results:The total effective rate of the experimental group was 85.0% (34/40), and that of the control group was 7.5% (3/40), with statistical significance between the two groups ( χ2=48.32, P<0.001). Compared with before treatment, the experimental group had SBP [(136.63 ± 6.01) mmHg vs. (159.30 ± 9.01) mmHg, t=-21.00] and DBP [(84.48 ± 4.36) mmHg vs. (95.30 ± 3.75) mmHg, t=-13.80] after treatment; after treatment, SBP [(137.34 ± 6.39) mmHg vs. (158.00 ± 10.06) mmHg, t=-5.28] and DBP [(86.08 ± 4.43) mmHg vs. (95.18 ± 6.61) mmHg, t=-8.09] decreased in the control group ( P<0.01), but there was no statistical significance between the two groups after treatment ( P>0.05). After treatment, the TCM syndrome scores in the experimental group (8.68 ± 3.39 vs. 15.12 ± 3.03, Z=-6.61) were lower than those in the control group ( P<0.001), and DARS score [(8.53 ± 3.93) vs. (12.20 ± 3.95), Z=-3.63] was lower than that in the control group ( P<0.001). After treatment, the therapeutic effect index of TCM syndromes in the experimental group improved compared to before treatment in the same group. The therapeutic effect index of each symptom, from high to low, was as follows: rotation of oneself or visual objects>numbness of limbs>dry stool>dizziness and dizziness>liking cold drinks>bitter and dry mouth>red urine>red tongue, yellow coating, and greasy tongue>vomiting sticky and turbid phlegm>tinnitus>smooth pulse. There were no significant adverse reactions during the treatment of the two groups. Conclusion:Tongren Niuhuang Qingxin Pills combined with telmisartan can reduce the blood pressure of patients with hypertensive vertigo syndrome of phlegm-heat disturbance, improve the vertigo symptoms and TCM syndromes of patients, and the efficacy evaluation is superior to that of telmisartan alone.

Objective:To investigate the correlations of myasthenia gravis (MG) susceptibility with STAT3 (rs744166 and rs1053005) and STAT4 (rs7574865) gene polymorphisms. Methods:A total of 149 MG patients admitted to Department of Neurology, Second Affiliated Hospital of Harbin Medical University from September 2019 to June 2022 were selected as MG group, and 148 subjects accepted physical examination in our hospital at the same period were selected as control group. Peripheral venous blood of all subjects was collected. Improved multiplex ligation detection reaction (imLDR) assay was used to detect the STAT3 (rs744166 and rs1053005) and STAT4 (rs7574865) gene polymorphisms. Differences in polymorphisms of various gene loci were compared between the MG group and control group, among subjects with different gender or age, between MG patients with and without thymoma, between AChR-Ab positive and AChR-Ab negative MG patients, and between patients with eye muscle MG and systemic MG. Results:(1) Compared with the control group, the MG group had significantly increased GT and TT genotype and T allele frequencies (37.2% vs. 57.0%; 10.1% vs. 11.4%; 28.7% vs. 39.9%), and decreased GG genotype and G allele frequencies (52.7% vs. 31.5%; 71.3% vs. 60.1%) at rs7574865 locus in STAT4 gene ( P<0.05). (2) Compared with male subjects in the control group, the male patients in MG group had significantly increased GT and TT genotype and T allele frequencies, and decreased GG genotype and G allele frequencies at rs7574865 locus in STAT4 gene ( P<0.05); compared with female subjects in the control group, the female patients in MG group had significantly increased GT and TT genotype frequencies and decreased GG genotype frequency at rs7574865 locus in STAT4 gene ( P<0.05). Compared with subjects≤50 years old in the control group, patients≤50 years old in the MG group had significantly increased GT and TT genotype and T allele frequencies, and decreased GG genotype and G allele frequencies at rs7574865 locus in STAT4 gene ( P<0.05); compared with subjects>50 years old in the control group, patients>50 years old in the MG group had significantly increased GT genotype frequency and decreased GG and TT genotype frequencies at rs7574865 locus in STAT4 gene ( P<0.05). (3) No significant differences in genotype and allele frequencies were noted between MG patients with and without thymoma, between AChR-Ab positive and AChR-Ab negative MG patients, or between patients with eye muscle MG and systemic MG ( P>0.05). Conclusion:MG susceptibility is associated with rs7574865 polymorphism of STAT4 gene; the male subjects or subjects≤50 years old with GT/TT genotype or T allele are susceptible to MG.

Ulcerative colitis is a chronic,non-specific inflammatory disease.The persistent damage to its intestinal epithelium is key to the development of the disease.In recent years,a new form of cell death has been identified by researchers-iron death-which is thought to be an important contributor to intestinal epithelial cell death.The occurrence of iron death is often associated with abnormal intracellular iron metabolism,reduced cystine/glutamate reverse transporter activity,abnormal lipid metabolism,voltage-dependent anion channel activation and overexpression of the Nrf2 gene.Iron death can lead to smaller mitochondria,increased membrane density and reduced number of cristae,unlike conventional cell death,which does not exhibit specific phenomena.Studies have found that TCM can alleviate iron death in intestinal epithelial cells by reducing intracellular iron content,inhibiting lipid reactive oxygen species production and regulating Nrf2 gene expression,thus acting as a treatment for ulcerative colitis.Therefore,Chinese medicine may become an important tool for the treatment of ulcerative colitis.This paper reviews the relationship between cellular iron death and ulcerative colitis and the research progress of Chinese medicine in treating ulcerative colitis through the iron death pathway.

Cardiovascular diseases (CVDs) are major disease burdens with high mortality worldwide. Early prediction of cardiovascular events can reduce the incidence of acute myocardial infarction and decrease the mortality rates of patients with CVDs. The pathological mechanisms and multiple factors involved in CVDs are complex; thus, traditional data analysis is insufficient and inefficient to manage multidimensional data for the risk prediction of CVDs and heart attacks, medical image interpretations, therapeutic decision-making, and disease prognosis prediction. Meanwhile, traditional Chinese medicine (TCM) has been widely used for treating CVDs. TCM offers unique theoretical and practical applications in the diagnosis and treatment of CVDs. Big data have been generated to investigate the scientific basis of TCM diagnostic methods. TCM formulae contain multiple herbal items. Elucidating the complicated interactions between the active compounds and network modulations requires advanced data-analysis capability. Recent progress in artificial intelligence (AI) technology has allowed these challenges to be resolved, which significantly facilitates the development of integrative diagnostic and therapeutic strategies for CVDs and the understanding of the therapeutic principles of TCM formulae. Herein, we briefly introduce the basic concept and current progress of AI and machine learning (ML) technology, and summarize the applications of advanced AI and ML for the diagnosis and treatment of CVDs. Furthermore, we review the progress of AI and ML technology for investigating the scientific basis of TCM diagnosis and treatment for CVDs. We expect the application of AI and ML technology to promote synergy between western medicine and TCM, which can then boost the development of integrative medicine for the diagnosis and treatment of CVDs.

Objective:To explore the distribution of integrons in Escherichia coli isolated from community patients with urinary tract infections and their relationship with the phylogenetic groups and antimicrobial resistance. Methods:From November 2015 to December 2018, 152 isolates of E. coli that collected without repetition from the urine samples of outpatients in nephrology of Fengxian District Central Hospital in Shanghai, were studied retrospectively. Bacterial identification and antimicrobial susceptibility analysis was carried out by Phoenix 100 automatic microbiological analyzer. Class 1, 2 integron integrase genes, variable regions of integrons and the phylogenetic groups of isolated E.coli were screened by PCR. The type of promoters and gene cassette arrays of variable regions were determined by sequencing. The relationship of intergon with the phylogenetic groups and antimicrobial resistance was also analyzed. Results:The resistance rate of 152 E. coli to ampicillin was 70.39% (107/152), and the resistance rates to other antibacterial drugs were all less than 40.00%. Among the 152 E. coli isolates, class 1 integron integrase gene intI1 was detected in 65 isolates (42.76%), 8 gene cassette arrays and 14 antimicrobial resistance gene cassettes were detected in 68 class 1 integrons. The most popular gene cassette array was dfrA17-aadA5 (51.47%, 35/68), while the variable regions of class 1 integrons were failed to detected in 12 intI1-positive isolates. Five variable region promoters were detected in 68 class 1 integrons, with the relative weak promoter PcH1 to be the most popular type (77.94%, 53/68). The gene cassette array arr- 2-cmlA5-bla OXA-10-aadA1 was also detected in this study. 65 intI1-positive isolates were mainly belonged to group B2 and D. The class 2 integron integrase gene intI2 was detected in 4 isolates (2.63%,4/152), and their variable region gene cassette arrays were all dfrA1-sat2-aadA1. Conclusions:Class 1 integrons were closely related to antimicrobial resistance in E. coli isolated from community patients with urinary tract infection. Most of the variable region promoters of class 1 integrons were relatively weak promoters. The distribution of each phylogenetic group in the intI1-positive isolates was consistent with the distribution of the overall isolates. The gene cassette array arr-2-cmlA5-bla OXA-10-aadA1 was detected in E. coli.

Objective To investigate the distribution of integrons in clinical isolates of carbapen-em-resistant Acinetobacter baumannii and their relationships to bacterial resistance to antimicrobial agents.Methods A total of 115 carbapenem-resistant Acinetobacter baumannii strains were isolated from clinical samples of patients from January to October, 2017. Phoenix 100 automatic microbiological analyzer was used for antimicrobial sensitivity analysis. Classes 1 and 2 integrase genes and carbapenemase-encoding genes, bla IMP , blaVIM , blaKPC , blaNDM and blaOXA-23 , were screened by PCR. The variable regions of integrons were amplified by long fragment PCR. The types of promoters and gene cassette arrays of variable regions were de-termined by sequencing and overlap PCR. Relationships between integrons and antimicrobial resistance were analyzed. Results The 115 isolates of carbapenem-resistant Acinetobacter baumannii were resistant to most commonly used antimicrobial agents, but sensitive to polymyxin E. All of the isolates carried blaOXA-23 gene and none of them were positive for blaIMP , blaVIM , blaKPC or blaNDM gene. Class 1 integrase gene intI1 was de-tected in 40 isolates (34. 8％ ), while class 2 integrase gene intI2 was not detected. Two gene cassette ar-rays of variable regions, aacA4-catB8-aadA1 (39 isolates) and aacC1-gacP-gacQ-aadA1a (23 isolates), were detected in intI1-positive isolates. Twenty-two isolates carried both aacA4-catB8-aadA1 and aacC1-gacP-gacQ-aadA1a. The upstream promoters of the variable regions were relatively strong promoters, PcH2 and PcS. The gene cassettes of the variable regions endowed bacteria with resistance to chloramphenicol and aminoglycoside antibiotics. The resistance rate of class 1 integron-positive isolates to compound sulfamethox-azole was higher than that of negative strains. However, their resistance rate to ampicillin/sulbactam was lower than that of negative strains. Conclusions Antimicrobial resistance in carbapenem-resistant Acineto-bacter baumannii was serious. Carbapenem resistance was associated with blaOXA-23 gene. The types of pro-moters of variable regions in class 1 integrons were all relatively strong promoters. Class 1 integrons were closely related to sulfonamides resistance.