Objective To investigate the relationship between thyroid function and brain volume in patients with Alzheimer's disease(AD).Methods A total of 64 AD patients(AD group)and 36 patients with mild cognitive impairment(MCI group)admitted in our department from January 2020 to March 2022 were enrolled in this study.Another 19 healthy individuals who had no cogni-tive impairment or psychiatric disorders were enrolled and served as normal control group.Their levels of free triiodothyronine(FT3),free thyroxine(FT4)and thyroid stimulating hormone(TSH)were detected by electrochemical luminescence assay.Results FT3 level was significantly decreased in the MCI group and AD group than the normal control group[2.50(2.28,2.60)ng/L and 2.07(1.97,2.30)ng/L vs 2.76(2.55,2.93)ng/L,P＜0.05],and the decrease in the AD group was more obvious than that in the MCI group.The volumes of the midbrain,pons,medulla oblon-gata,hippocampus,amygdala and temporal lobe were significantly smaller in the AD group than the MCI group(P＜0.05,P＜0.01).Spearman correlation analysis and multivariate linear regres-sion analysis showed that in the AD patients,FT3 and FT4 levels were positively while TSH level was negatively correlated with the volumes of both right and left hippocampus and amygdala(P＜0.05,P＜0.01),and TSH level was also negatively correlated with the left temporal lobe volume(P＜0.05).Conclusion Thyroid dysfunction is associated with reduced brain volume in AD patietns,and may contribute to the progression of AD cognitive dysfunction and brain atrophy.

The management of antibiotic-resistant, bacterial biofilm infections in skin wounds poses an increasingly challenging clinical scenario. Pseudomonas aeruginosa infection is difficult to eradicate because of biofilm formation and antibiotic resistance. In this study, we identified a new benzothiazole derivative compound, SN12 (IC₅₀ = 43.3 nmol/L), demonstrating remarkable biofilm inhibition at nanomolar concentrations in vitro. In further activity assays and mechanistic studies, we formulated an unconventional strategy for combating P. aeruginosa-derived infections by targeting the two-component (Gac/Rsm) system. Furthermore, SN12 slowed the development of ciprofloxacin and tobramycin resistance. By using murine skin wound infection models, we observed that SN12 significantly augmented the antibacterial effects of three widely used antibiotics-tobramycin (100-fold), vancomycin (200-fold), and ciprofloxacin (1000-fold)-compared with single-dose antibiotic treatments for P. aeruginosa infection in vivo. The findings of this study suggest the potential of SN12 as a promising antibacterial synergist, highlighting the effectiveness of targeting the two-component system in treating challenging bacterial biofilm infections in humans.

Aristolochic acid (AA), extracted from Aristolochiaceae plants, plays an essential role in traditional herbal medicines and is used for different diseases. However, AA has been found to be nephrotoxic and is known to cause aristolochic acid nephropathy (AAN).AA-induced acute kidney injury (AKI) is a syndrome in AAN with a high morbidity that manifests mitochondrial damage as a key part of its pathological progression. Melatonin primarily serves as a mitochondria-targeted antioxidant. However, its mitochondrial protective role in AA-induced AKI is barely reported. In this study, mice were administrated 2.5 mg/kg AA to induce AKI. Melatonin reduced the increase in Upro and Scr and attenuated the necrosis and atrophy of renal proximal tubules in mice exposed to AA. Melatonin suppressed ROS generation, MDA levels and iNOS expression and increased SOD activities in vivo and in vitro. Intriguingly, the in vivo study revealed that melatonin decreased mitochondrial fragmentation in renal proximal tubular cells and increased ATP levels in kidney tissues in response to AA. In vitro, melatonin restored the mitochondrial membrane potential (MMP) in NRK-52E and HK-2 cells and led to an elevation in ATP levels. Confocal immunofluorescence data showed that puncta containing Mito-tracker and GFP-LC3A/B were reduced, thereby impeding the mitophagy of tubular epithelial cells. Furthermore, melatonin decreased LC3A/B-II expression and increased p62 expression. The apoptosis of tubular epithelial cells induced by AA was decreased. Therefore, our findings revealed that melatonin could prevent AA-induced AKI by attenuating mitochondrial damage, which may provide a potential therapeutic method for renal AA toxicity.

Objective:To understand the distribution and epidemiological characteristics of chronic lymphocytic leukemia (CLL) in Hunan Province.Methods:According to the audit methods and evaluation criteria specified by the National Cancer Registration Center, the registration data of CLL reported by 24 tumor registries was included. Through the research method of retrospective analysis, the selected registry data was calculated and analyzed according to the year, administrative division, urban and rural areas, gender and age.Results:A total of 104 newly diagnosed CLL patients were diagnosed in Hunan Province from 2014 to 2015, with an average annual morbidity of 0.39/100, 000. The morbidity in 2014 and 2015 was 0.39/100, 000 and 0.39/100, 000, respectively. The annual average morbidity in Zhuzhou was 0.8/100, 000, which was the highest among municipalities. The annual average morbidity in Kaifu District of Changsha was 1.65/100, 000, which was the highest among district-level administrative divisions. The morbidity of urban was higher than that of rural (Urban vs Rural, P=0.006). The male to female morbidity was 1.7∶1. The cases were mainly concentrated in the 61-70-year-old population, accounting for 33.65% of all cases (35/104). There were 64 patients died of CLL in Hunan Province from 2014 to 2015, and the average annual mortality was 0.24/100, 000. The mortality in 2014 and 2015 was 0.22/100, 000 and 0.26/100, 000, respectively. The average annual mortality in Hengyang was 0.53/100, 000, which was the highest among municipalities. The average annual mortality in Furong District of Changsha was 0.74/100, 000, which was the highest among district-level administrative divisions. The mortality of urban was higher than that of rural but with no significant difference ( P=0.006). The male to female mortality rate was 1.4∶1. The deaths were mainly concentrated in the 71-80-year-old population, accounting for 29.69% of all deaths (19/64). Conclusions:The morbidity of CLL in Hunan Province is much lower than that of European and American populations, and it mainly occurs in the elderly people. It is more common in men. The morbidity of urban is higher than that of rural and morbidity in Zhuzhou is the highest. The death of CLL patients was mainly in middle-aged and elderly population, with more males. The mortality of urban is slightly higher than that of rural and the mortality in Hengyang is the highest.

Objective:To explore the relationship between seizure cluster of temporal lobe epilepsy with hippocampal sclerosis (TLE-HS) and cortisol (COR) rhythm, and understand its mechanism from the perspective of neuroendocrine.Methods:Fifty-seven patients with unilateral TLE-HS were recruited from the Qinghai Provincial People′s Hospital from May 1st 2012 to December 31st 2020. According to the history of seizure clusters one month before admission, 27 patients were enrolled in seizure clusters group (SC group), 30 patients were included in without seizures cluster group (NSC group). The clinical characteristics were systematically analyzed and compared between the SC and NSC groups. Plasma COR levels were measured at 8:00, 16:00 and 24:00 (COR8, COR16 and COR0) on the same day, and bilateral magnetic resonance spectroscopy (MRS) diagnosis was performed in two groups. Independent sample t test, chi-square test, repeated analysis of variance, covariance analysis, and multivariate Logistic regression were used for statistical analysis. Results:Time effect, grouping effect and the interaction effect of the time and grouping in the level of COR were statistically significant. Covariance analysis excluded age as an influential factor, COR16, COR0 and the slope of COR8-16 in the SC group [(126.22±19.98) μg/L, (51.63±21.43) μg/L, -7.78±4.54] were higher than the NSC group [(97.70±18.55) μg/L, (31.90±10.73) μg/L, -12.40±4.16], and the difference was statistically significant ( F=5.587, 4.320, 4.013, all P<0.05). The slope of COR0-8 in the SC group (17.11±6.32) was lower than that in the NSC group (20.62±6.54), and the difference was statistically significant ( F=-2.065, P<0.05). There was no significant difference in lateralization of hippocampal sclerosis between the two groups, and there was no significant difference in the ratio of N-acetyl aspartic acid(NAA)/[choline(Cho)+creatinine(Cr)] in the unilateral hippocampal sclerosis zone of the two groups, but the NAA/(Cho±Cr) ratio of the contralateral hippocampus in the SC group (0.71±0.03) was lower than that in the NSC group (0.76±0.06),and the difference was statistically significant ( t=4.999, P=0.029). Multivariate Logistic regression analysis showed that COR16 ( OR=1.328, 95% CI 1.073-1.642, P=0.009), COR8-16 ( OR=3.657, 95% CI 1.404-9.525, P=0.008) were independent risk factors of seizure clusters in TLE-HS. Conclusion:COR rhythm disturbance may be the neuroendocrine basis of seizure clusters in patients with TLE-HS.

Amino Acid Substitution ; Antineoplastic Agents/pharmacology* ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; Gastrointestinal Neoplasms/pathology* ; Humans ; MAP Kinase Signaling System/genetics* ; Mutation, Missense ; Receptor, ErbB-3/metabolism* ; Receptor, Fibroblast Growth Factor, Type 1/metabolism*

Objective: To detect the expression of P53, human epidermal growth factor receptor-2 (HER-2), and tumor endothelial marker 1 (TEM1) in gastric cancer tissues, analyze their correlation with clinical efficacy, and explore their potential roles as biomarkers for neoadjuvant chemotherapy. Methods: Sixty-three patients with gastric cancer who underwent fluorouracil-based neoadjuvant che-motherapy in The First Hospital of Lanzhou University from May 2015 to May 2017 were enrolled. Using immunohistochemistry, the expression of P53, Her2, and TEM1 was detected in 63 gastric cancer specimens before neoadjuvant chemotherapy. The efficacy of neoadjuvant chemotherapy was assessed by imaging. The relationship between the expression of P53, HER-2, and TEM1 and the effi-cacy of neoadjuvant chemotherapy was analyzed. Results: The total effective rate of neoadjuvant chemotherapy in 63 patients with advanced gastric cancer was 69.8%, with 2, 7, and 35 patients achieving complete remission, partial remission, and stable disease, re-spectively. Disease progression was noted in 19 patients. Univariate analysis revealed that patients positive for TEM1 and having high T stage had a poor response to neoadjuvant chemotherapy (P<0.05); furthermore, location, differentiation, and size of tumor; P53 posi-tivity (P=0.488); and Her-2 positivity (P=0.106) were not associated with the efficacy of neoadjuvant chemotherapy for gastric cancer. Multivariate analysis revealed that TEM1 positivity and a higher T stage could be factors that predicted the response to neoadjuvant chemotherapy in patients with advanced gastric cancer. Conclusions: TEM1, as a marker of tumor stroma, may be an important molec-ular biological indicator that predicts the poor response to neoadjuvant chemotherapy in patients with gastric cancer.

Objective To explore the correlation between the pathogenesis of coronary heart disease and the polymorphism of methylenetetrahydrofolate reductase ( MTHFR ) .Methods 130 cases of coronary heart disease diagnosed and treated in Heze Municiple Hospital from July 2015 to July 2017 were selected as observation group .At the same time,130 healthy people were selected as control group .The serum folate and homocysteine ( HCY) levels were compared between the two groups .At the same time, polymerase chain reaction -restriction fragment length polymorphism was used to analyze the MTHFR gene polymorphisms .The distribution of MTHFR gene polymorphism was compared between the two groups .Results The level of serum folic acid in the observation group was (5.76 ± 2.14)g/L,which was significantly lower than (7.34 ±2.43)g/L in the control group (t=5.64,P<0.05).The level of serum HCY in the observation group was (15.46 ±5.74)μmol/L,which was significantly higher than (10.28 ± 4.38)μmol/L in the control group (t=6.43,P<0.05).The frequencies of TT type,TC type and CC type of MTHFR gene in the observation group were 36.92％,46.92％and 16.15％,respectively.The frequencies of TT type,TC type and CC type of MTHFR gene in the control group were 21.54％,55.38％ and 23.08％,respectively.The frequency of TT type in the observation group was significantly higher than that of the control group (χ2 =8.25,P<0.05). There were no statistically significant differences in folic acid levels among different gene types in the observationgroup(t=1.31,0.55,0.73,all P>0.05),but the serum HCY level of TT type was significantly higher than that of CT type and CC type in the observation group (t=5.33,4.62,all P<0.05).Conclusion Serum folic acid level, HCY level and homozygous mutations of MTHFR gene type have certain relationship with the occurrence of coronary heart disease ,the body serum folic acid level and the distribution of MTHFR genotypes can affect the concentration of HCY,thus affecting the occurrence of coronary heart disease .

BACKGROUND:Although bone marrow mesenchymal stem cels from multiple myeloma patients present a variety of abnormalities, it is unclear how these abnormal mesenchymal stem cels influence the chemotactic function of myeloma cel lines.
OBJECTIVE:To investigate thein vitro effects of bone marrow mesenchymal stem cels from normal donors versus multiple myeloma patients on the chemotactic capacity of myeloma cel lines.
METHODS:In vitro cultured bone marrow mesenchymal stem cels derived from either normal donors (N-MSCs group) or newly-diagnosed multiple myeloma patients (MN-MSCs group) were directly co-cultured with U266 cels, in the presence or absence of bortezomib; and then harvested U266 cels were assayed for Transwel migration and mRAN expression of chemotaxis-related genes. U266 Transwel migration to conditioned medium derived from either N-MSCs or MN-MSCs was also tested.
RESULTS AND CONCLUSION:After co-cultured with N-MSCs or MN-MSCs, U266 cels harvested from MN-MSCs group showed increased spontaneous Transwel migration and up-regulated CCR1 mRNA level than those from N-MSCs group (P < 0.05), whatever bortezomib was present or not. However, there was no evident difference between U266 cel Transwel migration to conditioned medium derived from either MM-MSCs group or N-MSCs group. Our study implies that there may be some intrinsic aberrance in bone marrow mesenchymal stem cels derived from multiple myeloma patients, which can modulate the chemotactic migration of myeloma cel lines when they directly interact with each other.

OBJECTIVETo investigate the expression level and regulation mechanism of miR-720 as well as the association of miR-720 expression with leukemia biological characteristics.

METHODSExpression and promoter methylation of miR-720 were determined by quantitive PCR and pyrosequencing in 38 patients with AML and 20 normal controls. Lentivirous-mediated miR-702 overexpression was constructed in AML cell line kasumi-1. The cell proliferation, apoptosis, cycle, colony formation, migration and P53-mediated apoptosis pathway were determined.

RESULTSAML patients showed significantly lower miR-720 expression compared with normal controls (0.69±0.09 vs 3.00±0.46, P<0.01); The methylation level of miR-720 promoter region in AML patients were significantly higher than normal controls [(75.56±2.35)% vs (47.65±2.78)%, P<0.01]. miR-720 overexpression in kasumi-1 cells induced significantly increased cell apoptosis (P=0.017), elevated apoptosis sensitivity to etoposide (P=0.004), and reduced cell proliferation (P<0.01). miR-720 overexpression also induced reduced colony formation (P=0.005), cell cycle arrest in G(1)/G(0) phase and decreased migration ability in kasumi-1 cells. In addition, overexpression of miR-720 significantly induced increased cell apoptosis-related proteins including P53 and Bax, and activation of NF-κB signal transduction pathway. After kasumi-1 cells were treated with 1uM decitabine for 48 hours, miR-720 promoter methylation reduced significantly, and miR-720 expression significantly increased.

CONCLUSIONThe expression of miR-720 in AML patients reduced significantly, and DNA methylation-mediated epigenetic silencing of miR-720 contributed to maintain the malignant characteristics of AML.

Apoptosis ; Cell Line, Tumor ; Cell Proliferation ; DNA Methylation ; Epigenesis, Genetic ; Humans ; Leukemia, Myeloid, Acute ; genetics ; pathology ; MicroRNAs ; genetics ; Promoter Regions, Genetic