OBJECTIVES: Hyperhomocysteinaemia (Hcy) is an independent risk factor for cardiovascular and cerebrovascular diseases. MicroRNA (miR)-18a-5p is closely related to cardiovascular diseases. This study aims to investigate the effects of miR-18a-5p on homocysteine (Hcy)-induced myocardial cells injury. METHODS: H9c2 cells were transfected with miR-18a-5p mimic/miR-18a-5p mimic negative control (NC) or combined with Hcy for intervention, and untreated cells were set as a control group. The transfection efficiency was verified by real-time RT-PCR, and cell counting kit-8 (CCK-8) assay was used to determine cell viability. Flow cytometry was used to detect apoptosis and reactive oxygen species (ROS) levels. Western blotting was performed to measure the protein levels of microtubule-associated protein 1 light chain 3 (LC3)-I, LC3-II, Beclin1, p62, Bax, Bcl-2, and Notch2. Dual luciferase reporter assay was used to detect the interaction of miR-18a-5p with Notch2. RESULTS: Compared with the control, treatment with Hcy or transfection with miR-18a-5p mimic alone, or combined treatment with Hcy and miR-18a-5p mimic/miR-18a-5p mimic NC significantly reduced the H9c2 cell viability, promoted apoptosis and ROS production, up-regulated the expressions of Bax and Beclin, down-regulated the expressions of Bcl-2, p62, and Notch2, and increased the ratio of LC3-II/LC3-I (all P<0.05). Compared with the combined intervention of miR-18a-5p mimic NC and Hcy group, the above indexes were more significantly changed in the combined intervention of miR-18a-5p mimic and Hcy group, and the difference between the 2 groups was statistically significant (all P<0.05). There is a targeted binding between Notch2 and miR-18a-5p. CONCLUSIONS MiR-18a-5p could induce autophagy and apoptosis via increasing ROS production in cardiomyocytes, and aggravate Hcy-induced myocardial injury. Notch2 is a target of miR-18a-5p.
Apoptosis/genetics* ; Autophagy/genetics* ; bcl-2-Associated X Protein ; MicroRNAs/metabolism* ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Reactive Oxygen Species ; Rats ; Animals ; Myocytes, Cardiac/drug effects* ; Homocysteine/adverse effects* ; Hyperhomocysteinemia

Objective:In order to develop an appropriate care service system and care security system for the elderly in urban communities, it is necessary to gain a comprehensive understanding of their needs and utilization of care services, as well as the cost of care and the factors that influence it.This will provide a theoretical basis for developing effective countermeasures.Methods:A stratified random cluster sampling method was utilized to conduct a questionnaire survey on individuals aged 60 and above in the Xuzhou urban community.The survey aimed to gain insight into the needs, utilization, and expenditure of care services for the elderly.To analyze the factors influencing care expenditure, a single factor χ2 test and Tobit regression model were employed. Results:In our survey of 1 623 elderly individuals, it was found that 32.4%(526 people)had been bedridden for more than one day in the past year and were unable to care for themselves.Of the elderly who are bedridden, 393 individuals(74.7%)have received care services from professional institutions, with a focus on medical care(312 people, 79.4%)and rehabilitation care(95 people, 24.2%).In terms of financial expenditures, 91.7% of respondents(1 489 people)reported spending zero yuan in the past year, while 6.0%(96 people)spent between 1 and 4 999 yuan.Only 1.0%(17 people)reported spending between 5 000 and 9 999 yuan, and 1.3%(21 people)spent 10 000 yuan or more.The findings from the univariate analysis revealed that various factors, including marriage, age, medical expenses, and life satisfaction had a significant impact on the care expenses of the elderly(all P<0.05).Furthermore, the Tobit regression model demonstrated that certain variables were particularly influential in determining care expenses.Specifically, elderly individuals with higher monthly income(Me=3.114), advanced age(Me=3.458), knowledge of care insurance(Me=7.647), disability(Me=10.998), no spouse(Me=14.387), and dementia(Me=20.473)had significantly higher care expenses. Conclusions:The survey conducted in Xuzhou suggests that the demand for care services is high, yet the utilization rate remains low, leading to a significant burden of care costs.To address these challenges, we must prioritize the care needs of disabled, mentally retarded, and advanced-age elderly individuals.We should also focus on enhancing medical and rehabilitation care services, improving the overall quality of elderly care, and promoting the development of a comprehensive elderly care service system and care security system that caters to the specific needs and financial constraints of the elderly population.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION ClinicalTrials.gov, NCT04563936.
Humans ; Male ; Antineoplastic Agents, Hormonal/therapeutic use* ; East Asian People ; Gonadotropin-Releasing Hormone/agonists* ; Goserelin/therapeutic use* ; Prostate-Specific Antigen ; Prostatic Neoplasms/drug therapy* ; Testosterone

Hydrogen (H

Objective: To observe the changes in nutrition indicators and the effect on chemotherapy complications as well as the safety of enteral nutrition by way of providing enteral nutrition support for children with acute lymphoblastic leukemia (ALL) at the stage of induction chemotherapy. Methods: From November 2016 to September 2017, 60 children with newly diagnosed ALL at the Hematology Oncology Center of Beijing Children′s Hospital were enrolled in this study.They were randomly divided into an experimental group and a control group, 30 cases for each group.The experimental group was given a high-calorie diet, high-quality protein, and high-medium-chain trigly-ceride enteral nutrition on the basis of a conventional low-fat diet, and the duration lasted the whole induction treatment of ALL children; while the control group was given a low-fat diet routinely.By analyzing relevant indicators before induction chemotherapy (D0), chemotherapy day 15 (D15), and after chemotherapy (D33), the changes in nutritional status and the effect on chemotherapy complications in 2 groups were investigated. Results: There was no significant difference in the body mass index (BMI) and the thickness of triceps skinfold between 2 groups before and after chemotherapy (all P>0.05). The upper arm circumference increased after chemotherapy in the experimental group[before treatment: (15.80±2.63) cm, after treatment: (16.27±2.57) cm], while that of the control group decreased slightly[before chemotherapy: (17.19±3.71) cm, after chemotherapy: (17.15±3.64) cm], and the difference between 2 groups was statistically significant (P<0.05). After chemotherapy, the total protein levels in two groups decreased[the experimental group: (64.52±4.85) g/L, the control group: (61.97±4.65) g/L] which was significantly different from that before chemotherapy [the experimental group: (68.17±6.37) g/L, the control group: (68.08±5.14) g/L] (P<0.01). The total protein level of the experimental group after chemotherapy was significant higher than that in the control group (P<0.05). Both albumin levels in 2 groups increased after chemotherapy [(42.45±4.32) g/L in the experimental group and (41.15±3.73) g/L in the control group], and there was a significant difference between 2 groups before chemotherapy [(39.54±3.26) g/L in the experimental group and (40.01±4.37) g/L in the control group] (P<0.05). The level of prealbumin increased after chemotherapy in both groups [(324.57±64.328) mg/L in the experimental group and (293.07±69.09) mg/L in the control group] compared with that before chemotherapy [(121.10±35.13) mg/L in the experimental group and(131.20±52.77) mg/L in the control group]. The change was statistically significant (P<0.01). The albumin level in the experimental group before chemotherapy was lower than that in the control group after chemotherapy, but it was higher than that in the control group after chemotherapy.Protein differences were statistically significant (P<0.05). The reduction rate of elemental iron in the experimental group after chemotherapy was lower than that in the control group, but it was not statistically significant (P>0.05). Elemental zinc was not significantly different compared with the control group.The incidence of neutropenia after chemotherapy in ALL children was higher (37/60 cases, 61.67%). The recovery of neutropenia after chemotherapy in the experimental group was better than that in the control group.After chemotherapy, the severity of anemia in the experimental group was lighter than that in the control group.The amount of blood transfusion required and amount of transfusion per capita were less than those in the control group (54 person-times vs.74 person-times, 2.45 times vs.3.08 times). The total number of transfused blood products was less than that of the control group (78 person-times vs.101 person-times), but none of the findings above were statistically significant (all P>0.05). The degree of hepatic damage in the experimental group decreased after chemotherapy, but there was no significant change in the control group.The initial activated partial thromboplastin time(APTT) prolongation in the trial group was more than that in the control group (5 cases vs.3 cases), and less than the control group (0 case vs.1 case) after chemotherapy.The frequency of fever in the experimental group during chemotherapy was less than that in the control group (6 cases vs.8 cases), and the average time of fever was shorter than that in the control group (2.8 d vs.4.1 d). None of the above findings were statistically significant (all P>0.05). During the course of chemotherapy, 0 pancreatitis occurred in the experimental group, and 1 pancreatitis occurred in the control group.There was no difference in remission rates between 2 groups of chemotherapy for 15 days and chemotherapy for 33 days. Conclusions The nutritional status of children with ALL was reduced after initial induction chemotherapy.Enteral nutrition support was helpful to maintain the nutritional status for children at the initial stage of chemotherapy, high-calorie diet, high-quality protein, and high-medium-chain triglyceride enteral nutrition support improves blood system tolerance to chemotherapy and reduces chemotherapy complications.

Objective To investigate the correlation between incidence rate of tinnitus and noise exposure time,age,hearing condition in noise exposure workers.Methods A total of 1 985 noise exposure workers (age between 20～60 years old;working length between 1 ～30 years) in a large dockyard were randomly selected as the subject of this study with 1 831 male workers and 154 female workers in average 36.3±8.25 years old.The average noise exposure time was 9.1±6.50 years and pure tone threshold of final candidates in sound-proofed environment was evaluated (at 0.25～8 kHz).The subjects were divided into four groups according to the subjective tinnitus level:mild tinnitus,moderate tinnitus,severe tinnitus and no tinnitus to analysis the correlation among incidence rate of tinnitus and noise exposure time,age,hearing condition,etc.Results Among all 1 985 subjects enrolled the occurrence rate of tinnitus was 20.55％ (408/1 985),with 367 acquired mild tinnitus(89.95％),39 acquired moderate tinnitus (9.56％) and 2 for severe tinnitus (0.49％).Mild tinnitus and moderate tinnitus showed a multi-step raising according to noise exposure time.Mild tinnitus increased continually with age while moderate tinnitus showed an accumulation in age group over 55 years old.Female was less likely to be annoyed by tinnitus than male.Conclusion Tinnitus can be early warning of auditory damage by noise exposure;older male group with longer noise exposure time is more vulnerable to tinnitus.Tinnitus acquired in noise environment is more likely to be mild.

Objective To establish reference interval of thyroid hormones in pregnant women in Urumqi,standardize the diagnostic criteria of thyroid diseases in pregnancy,assess the iodine nutrition and thyroid function at different stages of pregnancy,and provide evidence to guide iodine supplementation.Methods A cross-sectional survey was performed in 3 731 pregnant women in Urumqi from May 2015 to June 2016.1 206 of them were in the first trimester,1 125 in the second and 1 400 in the third.500 non-pregnant women were recruited as controls.Levels of serum thyrotrophin (TSH),free triiodothyrunine (FT3),free thyroxine (FT4),anti-thyroid peroxidase (anti-TPO) and antithyroglobulin (anti-TG) were measured,and urinary iodine levels were detected by arsenic-cerium catalytic spectrophotometry.Results There were statistically significant differences between the pregnant groups and the control group in FT3,FT4,and TSH levels (P＜0.05).The serum thyroid concentrations in each group were FT3 values:(4.64±1.15),(4.36±0.89),(3.89±0.92),(5.24±0.65) pmol/L;FT4:(16.49±2.78),(15.06±3.76),(12.38± 1.65),(17.56± 1.12) pmol/L;TSH:(1.98±0.65),(2.43 ±0.83),(3.15± 1.25),(2.13 ± 0.75) mU/L.The reference intervals of thyroid hormones in early,middle and late pregnancy (P2.5 to P97.5) were:FT3:3.24-7.58,3.16-5.47,3.05-4.28 pmol/L;FT4:13.36-22.58,12.04-19.77,12.78-20.03 pmoL/L;TSH:0.24-3.78,0.51-3.91,0.55-4.55 mU/L.The medians of anti-TG and anti-TPO at different stages of pregnancy were significantly different,with the first trimester being the lowest and the third trimester being the highest (P=0.07,0.04).The medians of urinary iodine in all four groups were 235.78 μg/L (controls),198.25 μg/L (first trimester),175.36 pg,/L (second trimester) and 141.24 μg/L (third trimester),showing a significant gestational age-dependent decrease (P =0.036).Changes in serum levels of TSH,FT3,FT4,anti-TG and anti-TPO seemed to be in accordance with changes of urinary iodine levels;yet the correlations were not statistically significant (P＞0.05).Conclusions Iodine nutritional status was closely related to gestational age.Abnormal TSH levels were mainly observed in the second and third trimesters,abnormal serum levels of FT3,FT4,anti-TG and anti-TPO in the first trimester,and iodine deficiency in the third trimester.Thyroid function and urinary iodine should be monitored at each trimester during pregnancy.

OBJECTIVE To investigate the protective effect of curcumin on Aβ1-42 damaged cells. METHODS SH-SY5Y cells were cultured with Aβ1-4210μmol · L-1 in the absence or presence of curcumin 1, 5 or 10 μmol · L-1. Cell viability was assayed by MTT. Cell membrane damage was detected by the concentration of lactate dehydrogenase (LDH) in culture medium. Cell apoptosis was measured by flow cytometry with Annexin Ⅴ-FITC/PI staining. Mitochondrial membrane potential was characterized by fluorescence of JC-1 dye. Enzymatic activity of caspases-9 and-3 was measured by colorimetric assay. Protein expression of caspase-3 was detected by Western blotting. RESULTS Compared with vehicle control, the cell viability, concentration of LDH and both early and late apoptosis in Aβ1-4210 μmol · L-1 damaged group were decreased(P<0.01). However, the cell viability, release of LDH and both early and late apoptosis in curcumin group were promoted compared with that in Aβ1-4210μmol·L-1 damaged group. Curcumin inhibited Aβ1-42-induced depolarization of mitochondrial membrane potential(P<0.01), and attenuated Aβ1-42-induced activation of both caspases9 and caspases3 in a concentration-dependent manner, respectively(r=0.990, P<0.01; r=0.996, P<0.01). There were no significant differences in the above detected indexes between curcumin 10 μmol · L-1 group and vehicle control group. CONCLUSION Curcumin inhibits Aβ1-42-induced cell damage and apoptosis by promoting mitochondrial membrane potential and depressing the activation of caspases.

Objective To explore the efficacy and safety of Solitaire stent arterial embolectomy in the treatment of acute cardiogenic cerebral embolism.Methods The data of 24 patients who underwent Solitaire stent arterial embolectomy,either alone or in combination with reorganization type tissue plasminogen activator (rt-PA) intravenous thrombolysis,to treat acute cardiogenic cerebral embolism in our hospital were collected.These results between October 2012 and March 2016 were compared with 21 control patients who were treated using only rtPA Ⅳ thrombolysis.The short-term efficacy,long-term clinical outcomes,complications,and mortality rate of these two groups were compared,and the clinical outcomes of these patients with posterior circulation infarction in the two groups were further assessed.Results The time between onset and rt-PA administration in the study group (median time:3.17 h) was significantly shorter than that in the control group (4.00 h,P＜0.05);rt-PA dose used in both two groups was 50 mg.NIHSS scores and Glasgow Coma scale scores at discharge,and modified Rankin scale (mRs) scores 3 and 6 months after treatment in the study group were significantly higher than those in the control group (P＜0.05).There were no significant differences in symptomatic intra-cerebral hemorrhage,high perfusion encephalopathy,incidence of hernia,or mortality between the two groups (P＞0.05).The mRS scores 3 months after treatment in patients with posterior circulation infarction (2) were significantly lower than those in the control group (3,P＜0.05).Conclusions As compared with simple venous thrombolytic therapy,Solitaire stent embolectomy can significantly improve short-term neurological function and long-term prognosis in patients with acute cardiogenic cerebral embolism,enhance their life quality,without increasing the complication incidence and mortality rate.It is safe and effective,and patients with posterior circulation infarction can also be treated by arterial embolectomy.

Taxol is one of the most important chemotherapeutic drugs against cancer. Taxol has been mainly extracted from the bark of yews for a long time. However, methods for the extraction of taxol from the bark of Taxus species were inefficient and environmentally costly. As a result of the high ecological toll exacted on trees with the potential for Pacific yew extinction, investigators began to look for other methods of taxol production. Recently, increasing efforts have been made to develop alternative means of taxol production, such as using complete chemical synthesis, semi-synthesis, Taxus spp. plant cell culture and microbe fermentation. Using microbe fermentation in the production of taxol would be a very prospective method for obtaining a large amount of taxol. Therefore, it is necessary to understand the molecular basis and genetic regulation mechanisms of taxol biosynthesis by endophytic fungi, which may be helpful to construct the genetic engineering strain with high taxol output. In this paper, the taxol biosynthesis pathway from Taxus cells and the advantages of taxol biosynthesis by endophytic fungi were discussed. The study on the isolation and biodiversity of taxol-producing endophytic fungi and the taxol biosynthesis related genes are also discussed.
Endophytes ; Fungi ; Industrial Microbiology ; Microorganisms, Genetically-Modified ; Neoplasms ; drug therapy ; Paclitaxel ; biosynthesis ; Taxus ; chemistry