Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective:To investigate the impact of lifestyle, apolipoprotein E (ApoE) gene, and their interaction on the risk for cognitive frailty in the elderly population in China.Methods:The study participants were from the Chinese Longitudinal Healthy Longevity Survey. The information about their lifestyles were collected by questionnaire survey, and a weighted lifestyle score was constructed based on β coefficients associated with specific lifestyles to assess the combined lifestyle. ApoE genotypes were assessed by rs429358 and rs7412 single nucleotide polymorphisms. Cognitive frailty was assessed based on cognitive function and physical frailty. Cox proportional hazards regression model was used to analyze the association of lifestyle and ApoE gene with the risk for cognitive frailty and evaluate the multiplicative and additive interactions between lifestyle and ApoE gene. Results:A total of 5 676 elderly persons, with median age [ M ( Q1, Q3)] of 76 (68, 85) years, were included, in whom 615 had cognitive frailty. The analysis by Cox proportional hazards regression model indicated that moderate and high levels of dietary diversity could reduce the risk for cognitive frailty by 18% [hazard ratio ( HR)=0.82, 95% CI: 0.68-1.00] and 28% ( HR=0.72, 95% CI: 0.57-0.91), respectively; moderate and high levels of physical activity could reduce the risk by 31% ( HR=0.69, 95% CI: 0.56-0.85) and 23% ( HR=0.77, 95% CI: 0.64-0.93), respectively. Healthy lifestyle was associated with a 40% reduced risk for cognitive frailty ( HR=0.60, 95% CI: 0.46-0.78). ApoE ε4 allele was associated with a 26% increased risk for cognitive frailty ( HR=1.26, 95% CI: 1.02-1.56). No multiplicative or additive interactions were found between lifestyle and ApoE gene. Conclusions:Dietary diversity and regular physical activity have protective effects against cognitive frailty in elderly population. Healthy lifestyle can reduce the risk for cognitive frailty in elderly population regardless of ApoE ε4 allele carriage status.

Objective To explore the application of dual-source CT derived fractional flow reserve(FFR)for percutaneous coronary intervention(PCI)in patients with coronary heart disease.Methods A retrospective study was conducted on 68 coronary heart disease patients admitted from January 2022 to June 2022.Whether PCI was carried out was dependent on coronary angiography in control group(n=34)and dual-source CT derived FFR in research group(n=34).The two groups were compared for general data,length of diseased blood vessels,number of stents,hospitalization expenses and incidence of adverse reactions.Results The differences in age,smoking history,diabetes,hypercholesterolemia and angina pectoris between two groups were trivial(P＞0.05).After treatment,research group had less number of stents,lower hospitalization costs,and shorter diseased blood vessels than control group(P＜0.05).The 6-month follow-up showed that the total incidences of adverse reactions in research group and control group were 17.65％and 58.82％(P＜0.05).Conclusion Using dual-source CT derived FFR to guide PCI can reduce the number of stents and hospitalization costs,and lower the incidence of cardiovascular adverse reactions.

ObjectiveTo investigate the therapeutic effect of antidiabetic drug canagliflozin （CGLZ） on adriamycin-induced nephrotic syndrome （NS） in rats， and the evaluation of contrast-enhanced ultrasound （CEUS） combined with color Doppler flow imaging （CDFI） during the treatment. MethodsA total of 56 male SD rats were randomly divided into normal group （NG）， model group （MG）， prednisone （PAT） group （PG）， low-dose single CGLZ group （LSCG）， high-dose single CGLZ group （HSCG）， low-dose CGLZ + PAT group （LUCG） and high-dose CGLZ + PAT group （HUCG）， with 8 rats in each group. The NS model in rats was induced by injecting adriamycin twice into the tail vein， and then the NS rats were treated by intragastric administration daily for 6 weeks with reference of PAT. Twenty-four hour urine total protein （24 h-UTP） was assessed one day before the start of oral administration and at the end of 2， 4 and 6 weeks after oral administration， respectively. CDFI and CEUS were performed on the right renal artery at the end of 6 weeks after oral administration， and the blood of abdominal aorta was taken for serological test the next day. ResultsCompared with those detection index of NG rats， the 24-hour UTP of MG rats increased （P＜0.01）， the serum ALB decreased and TG， TC， LDL increased （P＜0.01）， and CDFI shows that RRCT was thinner （P＜0.01） and the renal artery blood flow indicators RA-PI， RA-RI， RA-S/D all increased （P＜0.05）， and CEUS image shows that the TIC curve parameters TTP， AT， AUC all increased and DPI decrease in MG rats （P＜0.01）. After drug treatment， compared with those detection index of MG rats， 24 h-UTP decrease in LSCG after 2 weeks （P＜0.01）， and decrease significantly in all drug groups after 6 weeks （P＜0.01）； the serological test results show that the serum ALB in all CGLZ groups increased （P＜0.05）， TG decrease in LSCG （P＜0.01）， TC and LDL also decrease in LUCG after 6 weeks （P＜0.05）； CDFI shows that the RRCT thinning degree in all CGLZ is reduced （P＜0.01）， and the RA-PI in LSCG， RA-RI in PG， and RA-S/D in PG， LSCG， HSCG and LUCG rats all decreased （P＜0.05）； CEUS shows that the TTP， AT and AUC of renal TIC curve in drug treatment groups all decreased （P＜0.01）， and the DPI in PG， HSCG， LUCG and HUCG rats increased （P＜0.01）. ConclusionsCGLZ has the effect of treating NS， and the small dose is the best. CEUS combined with CDFI can be used to evaluate the renal morphology and hemodynamic changes of NS model rats before and after drug treatment， which is helpful to guide clinical application.

Manganese plays an important physiological role in the organism, and excessive manganese exposure can cause impairment of neurological and reproductive functions. Gonadotropin-releasing hormone secreted by the hypothalamus acts as an initiator to regulate reproductive functions, such as gonadal development, onset of puberty, and gonadal hormone release. But the mechanism by which manganese damages the hypothalamus leading to abnormal gonadotropin-releasing hormone release is still unclear yet. Kisspeptin, prostaglandin E₂, and nitric oxide may act as stimulators to increase the release of gonadotropin-releasing hormone, while the stimulatory or inhibitory effect of γ-aminobutyric acid on the release of gonadotropin-releasing hormone is controversial. Based on current research, manganese has been less studied with Kisspeptin, and studies with prostaglandin E₂, nitric oxide, and γ-aminobutyric acid mainly focused on inflammation, oxidative stress, and neurotransmitter transmission. Therefore, taking Kisspeptin, prostaglandin E₂, γ-aminobutyric acid, and nitric oxide as the breakthrough points, this paper introduced the mechanism of manganese affecting the release of gonadotropin-releasing hormone in the hypothalamus through the above four pathways, and proposed that the abnormal release of gonadotropin-releasing hormone in the hypothalamus may be one of the mechanisms by which manganese regulates reproductive function, providing a new direction for the prevention and treatment of manganese-induced reproductive damage in the future.

Excessive levels of cadmium (Cd) in soil exert serious negative impacts on soil ecosystems. Microorganisms are a common component of soil and show great potential for mitigating soil Cd. This review summarizes the application and remediation mechanisms of microorganisms, microbial-plants, and microbial-biochar in Cd-contaminated soil. Microorganisms such as Bacillus, Acinetobacter, Pseudomonas, and arbuscular mycorrhizal fungi (AMF) can change the biological validity of Cd through adsorption, mineralization, precipitation and dissolution. Different factors such as pH, temperature, biomass, concentration, and duration have significant effects on Cd bioavailability by microorganisms. Pseudomonas, Burkholderia, and Flavobacterium can promote the uptake of Cd²⁺ by hyperaccumulator through promotion and activation. Biochar, a soil amendment, possesses unique physicochemical properties and could act as a shelter for microorganisms in agriculture. The use of combined microbial-biochar can further stabilize Cd compared to using biochar alone.
Cadmium ; Ecosystem ; Soil Pollutants ; Charcoal/chemistry* ; Soil/chemistry*

Child ; Humans ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Mutation ; Neoplasms, Germ Cell and Embryonal/genetics*

OBJECTIVE: To detect the expression level of HK2 gene in the bone marrow of newly diagnosed patients with acute myeloid leukemia (AML) and investigate its influence on the clinical characteristics and prognosis. METHODS: The expression level of HK2 gene in the bone marrow of 90 newly diagnosed patients with AML that accompanying clinical characteristics and survival status were detected by RT-qPCR, and compared with 18 allogeneic hematopoietic stem cell transplantation (allo-HSCT) donors. The Chi-square test, Kaplan-Meier survival analysis, and Cox proportional hazards regression model were used to analyze the correlation of HK2 expression level with clinical characteristics and prognosis. RESULTS: Compared with allo-HSCT donors, the HK2 expression was significantly increased in newly diagnosed AML patients (P <0.01). Compared with patients with total response (OR, complete response + complete response with incomplete hematologic recovery) after 2 courses of induction chemotherapy, the expression of HK2 in patients without OR was significantly increased (P <0.05). There was a significant difference in the relative expression of HK2 between patients with and without OR after 2 courses of induction therapy (P <0.001). The median survival time of patients with high expression of HK2 was significantly shorter than that of patients with low expression of HK2 (P <0.05). The multivariate Cox proportional hazards regression analysis showed that prognostic stratification, the expression level of HK2, and whether two courses of induction therapy achieved OR were independent factors affecting the prognosis of AML patients (P <0.05). CONCLUSIONS Compared with allo-HSCT donors, the expression level of HK2 gene is increased in the bone marrow of newly diagnosed AML patients. The prognosis of patients with high expression of HK2 is poor. The expression level of HK2 is an independent factor affecting the prognosis of AML patients.
Humans ; Bone Marrow ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Leukemia, Myeloid, Acute/therapy* ; Prognosis ; Retrospective Studies ; Transplantation, Homologous/adverse effects*

This study aims to decipher the mechanism underlying the effect of Shaofu Zhuyu Decoction on endometriosis(EMT)-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis based on mitogen-and stress-activated protein kinase 1/2(MSK1/2).We employed a random number table to randomly assign SPF female non-pregnant rats into the sham group, and treated the rest rats with autologous transplantation+refrigerator freezing for the modeling of the syndrome of cold coagulation and blood stasis.The modeled rats were then randomly assigned into the control group and high-, medium-and low-dose Shaofu Zhuyu Decoction groups.The rats in the low-, medium-, and high-dose decoction groups were respectively administrated with 9, 4.5, and 2.3 g·kg~(-1) decoction through gavage once a day for 2 consecutive weeks, and those in the control group were administrated with 0.24 mg·kg~(-1) gestrinone through gavage once every 3 days for 2 weeks.After that, the size of ectopic focus in each rat was measured via laparotomy.Enzyme-linked immunosorbent assay(ELISA) was adopted to determine the expression of interleukin(IL)-6, IL-10, prostaglandin E2(PGE2), tumor necrosis factor-α(TNF-α).Western blot was employed to determine the protein levels of MSK1/2 and dual-specificity phosphatase 1(DUSP1) and real-time quantitative polymerase chain reaction(RT-PCR) to determine the mRNA levels of the two genes in rat eutopic endometrial tissue.Compared with the sham group, the model group showed increased levels of IL-6, PGE2, and TNF-α while decrease level of IL-10 in the serum(P<0.01).Compared with the model group, the high-and medium-dose decoction groups and the gestrinone group had declined levels of IL-6, PGE2, and TNF-α while risen level of IL-10 in the serum(P<0.01).The model group had lower protein levels and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the sham group(P<0.01). The high-and medium-dose decoction groups and the gestrinone group had higher protein and mRNA levels of MSK1/2 and DUSP1 in the eutopic endometrial tissue than the model group(P<0.01).The results indicated that Shaofu Zhuyu Decoction can regulate the abnormal expression of pro-inflammatory cytokines TNF-α, IL-6, and PGE2 and anti-inflammatory cytokines IL-10 and DUSP1 via MSK1/2 to alleviate EMT-associated dysmenorrhea in rats with the syndrome of cold coagulation and blood stasis.
Animals ; Female ; Rats ; Anti-Inflammatory Agents/therapeutic use* ; Cytokines ; Dinoprostone ; Drugs, Chinese Herbal/therapeutic use* ; Dual-Specificity Phosphatases ; Dysmenorrhea/genetics* ; Endometriosis/genetics* ; Gestrinone/therapeutic use* ; Interleukin-10 ; Interleukin-6 ; Mitogen-Activated Protein Kinase 8/therapeutic use* ; Mitogens/therapeutic use* ; RNA, Messenger ; Tumor Necrosis Factor-alpha/metabolism*

OBJECTIVES: Although hysteroscopic adhesiolysis (HA) is the main treatment for intrauterine adhesion (IUA), postoperative management of IUA remains challenging because there is no consensus on how to mitigate the high rate of postoperative adhesions reformation. This study aims to compare the effectiveness and safety of 2 types of intrauterine stents with different thickness and hardness in treating moderate-to-severe IUA. METHODS: A retrospective clinical study was conducted in the Third Xiangya Hospital of Central South University from November 2020 to July 2021. A total of 191 patients with moderate-to-severe IUA who received surgical treatment and placed intrauterine stents after HA to prevent recurrence of postoperative adhesions were included. According to the hardness and thickness of the intrauterine stents, the participants were divided into a case group (placed the novel thin intrauterine stent, n=62) and a control group (placed the conventional stent, n=129). After 2-3 menstrual cycles, a second-look hysteroscopy was performed, and the intrauterine stents were removed. The postoperative efficacy [the reduction of American Fertility Society (AFS) scores, the adhesions reformation rate, the changes in menstrual pattern, and the pregnancy rate during the follow-up], safety (the adverse events), and applicability (the difficulty of stent removal) were compared between the 2 groups. RESULTS: No significant differences in preoperative clinical characteristics were observed between the 2 groups (all P>0.05). The menstrual volume of all patients was increased after the treatment. The reduction of AFS scores and the menstruation recovery rate were not significantly different between the 2 groups (P=0.519 and P=0.272, respectively). Notably, there was no case of displacement in the case group, while the displacement rate of the control group was 2.3% (P=0.552). Moreover, there was no significant difference in abdominal pain or postoperative abnormal vaginal bleeding between the 2 groups (P=0.823 and P=0.851, respectively). However, the difficulty rate of removing the thinner stents was significantly lower than that of removing the traditional stent (21.0% vs 38.8%, P=0.014). During the follow-up for half a year of the postoperative period, the pregnancy rate did not differ significantly in the case and control groups (45.0% vs 34.6%, P=0.173). CONCLUSIONS The novel intrauterine stent shows noninferior efficacy and had a good safety profile compared with conventional stents in treating moderate-to-severe IUA. Importantly, it was more convenient to be removed without increasing the rate of displacement and detachment. Therefore, it could reduce the amount of damage to the endometrium and has higher applicability than conventional stents.
Humans ; Retrospective Studies ; Tissue Adhesions ; Uterus/pathology*