Trajectories of Human Milk Gangliosides during the First Four Hundred Days and Maternal-to-Offspring Transfer of Gangliosides: Results from a Chinese Cohort Study.

BACKGROUND: Gangliosides are crucial for early-life cognition and immunity development. However, limited data exist on gangliosides within the Chinese population, and maternal-to-fetal/infant ganglioside transport remains unclear. OBJECTIVES: This study aimed to investigate gangliosides concentrations and trajectories in Chinese human milk during the first 400 d of lactation, and seek to understand gangliosides transmission between mother and offspring. METHODS: This study involved 921 cross-sectional participants providing human milk samples across 0-400 d of lactation and 136 longitudinal participants offering maternal plasma, cord plasma, and human milk samples within the first 45 d postpartum. Ultrahigh-performance liquid chromatography-tandem mass spectrometry was used for the quantification of gangliosides. RESULTS: Human milk GM3 (Neu5Acα2-3Galß1-4GlcßCer) concentration increased from 2.29 ± 1.87 to 13.93 ± 4.82 µg/mL, whereas GD3 (Neu5Acα2-8Neu5Acα2-3Galß1-4GlcßCer) decreased from 17.94 ± 6.41 to 0.30 ± 0.50 µg/mL during the first 400 d postpartum (all P < 0.05). Consistent results were observed in cross-sectional and longitudinal participants. GD3 concentration gradually increased from maternal plasma (1.58 µg/mL) through cord plasma (2.05 µg/mL) to colostrum (21.35 µg/mL). Significant positive correlations were observed between maternal and cord plasma for both GM3 (r = 0.30, P < 0.001) and GD3 (r = 0.35, P < 0.001), and maternal plasma GD3 also correlated positively with colostrum concentrations (r = 0.21, P = 0.015). Additionally, in maternal and cord plasma, gangliosides were mainly linked with 16- and 18-carbon fatty acids. However, human milk GM3 showed a broad spectrum of fatty acid chain lengths, whereas GD3 was primarily tied to very long-chain fatty acids (≥20 carbon). CONCLUSIONS: We identified an increase in GM3 and a decrease in GD3 concentration in human milk, with GD3 notably more concentrated in cord plasma and colostrum. Importantly, ganglioside concentrations in maternal plasma positively correlated with those in cord plasma and colostrum. Our findings contribute to the existing Chinese data on gangliosides and enhance understanding of their transmission patterns from mother to offspring. This trial was registered at chictr.org.cn as ChiCTR1800015387.

Correlation between serum trimethylamine-N-oxide and body fat distribution in middle-aged and older adults: a prospective cohort study.

BACKGROUND: Trimethylamine-N-oxide (TMAO) is linked with obesity, while limited evidence on its relationship with body fat distribution. Herein, we investigated the associations between serum TMAO and longitudinal change of fat distribution in this prospective cohort study. METHODS: Data of 1964 participants (40-75y old) from Guangzhou Nutrition and Health Study (GNHS) during 2008-2014 was analyzed. Serum TMAO concentration was quantified by HPLC-MS/MS at baseline. The body composition was assessed by dual-energy X-ray absorptiometry at each 3-y follow-up. Fat distribution parameters were fat-to-lean mass ratio (FLR) and trunk-to-leg fat ratio (TLR). Fat distribution changes were derived from the coefficient of linear regression between their parameters and follow-up duration. RESULTS: After an average of 6.2-y follow-up, analysis of covariance (ANCOVA) and linear regression displayed women with higher serum TMAO level had greater increments in trunk FLR (mean ± SD: 1.47 ± 4.39, P-trend = 0.006) and TLR (mean ± SD: 0.06 ± 0.24, P-trend = 0.011). Meanwhile, for women in the highest TMAO tertile, linear mixed-effects model (LMEM) analysis demonstrated the annual estimated increments (95% CI) were 0.03 (95% CI: 0.003 - 0.06, P = 0.032) in trunk FLR and 1.28 (95% CI: -0.17 - 2.73, P = 0.083) in TLR, respectively. In men, there were no similar significant observations. Sensitivity analysis yielded consistent results. CONCLUSION: Serum TMAO displayed a more profound correlation with increment of FLR and TLR in middle-aged and older community-dwelling women in current study. More and further studies are still warranted in the future. TRIAL REGISTRATION: NCT03179657.

Level of empowerment of hospitalized patient in Taiwan clinical practice.

PURPOSE: In the health-care system within hospitals, Taiwanese patients usually play the role of passively cooperating with health-care professionals. Therefore, patients rarely make their own treatment decisions. This study evaluated the level of patient education and patient satisfaction in relation to empowerment level in Taiwan. METHODS: A cross-sectional survey by a self-administered structured questionnaire was carried out with 618 inpatients from the four hospitals. Statistical analyses were then conducted. Analysis of covariance and post-hoc comparison was used to compare differences between the level of patient empowerment, age, and education as covariates in the model. RESULTS: This study found that 21.2% and 35.6% of participants were highly empowered and well empowered, respectively. Years of education is a significant covariate in the counselling domain of patient education. Even after controlling for age and education level, the counselling, answer question and justifying action, providing information scores remain significant for all levels after adjusting for the effects of degree of patient empowerment. Patients with higher empowerment also having more-sufficient patient education, indicating a tendency toward higher patient satisfaction. Patient education and counselling practices in Taiwan's clinical practice could be improved to enhance patient empowerment and ensure health-care systems are person-centred. CONCLUSIONS: To move more toward highly patient empowerment, we suggest that health-care professionals advocate a patient-empowerment approach and to provide more counselling related to patients' illnesses and possible treatments.

Exogenous Melatonin Regulates Plant-Disease Interaction by Inducing Maize Resistance and Decreasing the Pathogenicity of Fusarium graminearum.

Plants cannot avoid environmental challenges and are constantly threatened by diverse biotic and abiotic stresses. However, plants have developed a unique immune system to defend themselves against the invasion of various pathogens. Melatonin, N-acetyl-5-methoxytryptamine has positive physiological effects in plants that are involved in disease resistance. The processes underlying melatonin-induced pathogen resistance in plants are still unknown. The current study explores how melatonin regulates the plant-disease interaction in maize. The results showed that 400 µM melatonin strongly reduced the disease lesion on maize stalks by 1.5 cm and corn by 4.0 cm caused by Fusarium graminearum PH-1. Furthermore, after treatment with melatonin, the plant defense enzymes like SOD significantly increased, while POD and APX significantly decreased compared to the control. In addition, melatonin can also improve maize's innate immunity, which is mediated by melatonin treatments through the salicylic acid signaling pathway, and up-regulate the defense-associated expression of PR1, LOX1, OXR, serPIN, and WIPI genes in maize. Melatonin not only inhibits the disease in the maize stalks and corn, but also down-regulates the deoxynivalenol (DON) production-related expression of genes Tri1, Tri4, Tri5, and Tri6 in maize. Overall, this study sheds new light on the mechanisms by which melatonin regulates antioxidant enzymes and defense-related genes involved in plant immunity to effectively suppress plant diseases.

Identification of the changes in the platelet proteomic profile of elderly individuals.

Background: Platelet hyperreactivity is a risk factor for thrombosis in elderly patients with cardiovascular diseases. However, the mechanism of platelet hyperactivation has not been elucidated. This study aims to investigate alterations in the proteomes of platelets and their correlation with platelet hyperreactivity among elderly individuals. Methods: This study included 10 young (28.1 ± 1.9 years), 10 middle-aged (60.4 ± 2.2 years), and 10 old (74.2 ± 3.0 years) subjects. Washed platelets were used in the present study. Platelet samples were analysed by using data-independent acquisition (DIA) quantitative mass spectrometry (MS). Results: The results showed that the platelet proteomic profile exhibited high similarity between the young and middle-aged groups. However, there were significant differences in protein expression profiles between the old group and the young group. By exploring the dynamic changes in the platelet proteome with ageing, clusters of proteins that changed significantly with ageing were selected for further investigation. These clusters were related to the initial triggering of complement, phagosome and haemostasis based on enrichment analysis. We found that platelet degranulation was the major characteristic of the differentially expressed proteins between the old and young populations. Moreover, complement activation, the calcium signalling pathway and the nuclear factor-κB (NF-κB) signalling pathway were enriched in differentially expressed proteins. Conclusions: The present study showed that there are obvious differences in the protein profiles of the elderly compared with young and middle-aged populations. The results provide novel evidence showing changes in platelet hyperactivity and susceptibility to thrombosis in the elderly population.

Impact of early refined nursing program on prognosis of middle-aged and elderly patients with cognitive dysfunction combined with cerebral infarction.

BACKGROUND: Cerebral infarction is a local or extensive necrosis of brain tissue. Subsequently, the corresponding neurological deficits appear. The incidence of cerebrovascular diseases in China is increasing gradually. After the onset of cerebrovascular disease, the most common sequelae include movement disorders, language disorders, and cognitive dysfunction. AIM: To investigate the effect of early refined nursing program on the prognosis of middle-aged and elderly patients with cerebral infarction combined with cognitive dysfunction. METHODS: A retrospective study was conducted to divide 60 patients with cerebral infarction and cognitive impairment into an experimental group (n = 32) and a control group (n = 28). The experimental group received early intensive care every day, and the control group received daily routine care. The scores of the Mini-Mental State Examination (MMSE) and the Trail Making Test (TMT), as well as the latency and amplitude of the event-related potential P300, were used as main indicators to evaluate changes in cognitive function, and changes in BDNF, TGF-ß, and GDNF expression were used as secondary indicators. RESULTS: Both groups experienced notable enhancements in MMSE scores, with the experimental group demonstrating higher scores than the control group (experimental: 28.75 ± 2.31; control: 25.84 ± 2.87). Moreover, reductions in TMT-A and TMT-B scores were observed in both groups (experimental: TMT-A 52.36 ± 6.18, TMT-B 98.47 ± 10.23; control: TMT-A 61.48 ± 7.92, TMT-B 112.63 ± 12.55), with the experimental group displaying lower scores. P300 Latency decreased (experimental: 270.63 ms ± 14.28 ms; control: 285.72 ms ± 16.45 ms), while amplitude increased (experimental: 7.82 µV ± 1.05 µV; control: 6.35 µV ± 0.98 µV) significantly in both groups, with superior outcomes in the experimental cohort. Additionally, the levels of the growth factors BDNF, TGF-ß1, and GDNF surged (experimental: BDNF 48.37 ng/mL ± 5.62 ng/mL, TGF-ß1 52.14 pg/mL ± 4.28 pg/mL, GDNF 34.76 ng/mL ± 3.89 ng/mL; control: BDNF 42.58 ng/mL ± 4.73 ng/mL, TGF-ß1 46.23 pg/mL ± 3.94 pg/mL, GDNF 30.25 ng/mL ± 2.98 ng/mL) in both groups, with higher levels in the experimental group. CONCLUSION: For middle-aged and elderly patients with cerebral infarction and cognitive dysfunction, early refined nursing can significantly improve their cognitive function and prognosis.

Concentration and composition of odd-chain fatty acids in phospholipids and triacylglycerols in Chinese human milk throughout lactation.

Human milk represents the gold standard for infant nutrition, with approximately 50% of the energy in human milk derived from lipids. Odd-chain fatty acids (OCFAs) have been recognized as a category of bioactive milk fatty acids in recent research; however, limited data exist on OCFAs in human milk. This study collected human milk samples spanning the postpartum period from 0 to 400 days. Phospholipids containing OCFAs (PL-OCFAs) were determined in 486 human milk samples using hydrophilic liquid chromatography-electrospray ionization-triquadrupole-mass spectrometry. Triacylglycerols containing OCFAs (TAG-OCFAs) were analyzed in 296 human milk samples using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. The average total concentration of PL-OCFA ranged from 30.89 ± 14.27 mg L-1 to 93.48 ± 36.55 mg L-1 during lactation, and the average total TAG-OCFA content ranged from 103.1 ± 147.15 mg L-1 to 965.41 ± 651.67 mg L-1. Despite the lower absolute concentration of PL-OCFA, its relative concentration (8.75%-11.75%) was significantly higher than that of TAG-OCFA (0.37%-1.85%) throughout lactation. PC-OCFA, SM-OCFA and PE-OCFA are major sub-classes of PL-OCFA. Furthermore, C17:0 was the major chain length in both PL-OCFA and TAG-OCFA, followed by C15:0. C17:1 was characteristic of TAG-OCFA, while long-chain fatty acids C19:0, C21:0 and C23:0 were characteristic of PL-OCFA. Our findings highlighted the importance of bioactive lipids in human milk, suggesting that OCFAs could be targeted in future studies in relation to the health and development of infants.

Phyllanthus emblica Linn: A comprehensive review of botany, traditional uses, phytonutrients, health benefits, quality markers, and applications.

Phyllanthus emblica Linn is not only an edible fruit with high nutritional value, but also a medicinal plant with multiple bioactivities. It is widely used in clinical practice with functions of clearing heat, cooling blood, digesting food, strengthening stomach, promoting fluid production, and relieving cough. This review summarized a wide variety of phytonutrients, including nutritional components (mineral elements, amino acids, vitamins, polysaccharides, unsaturated free fatty acids) and functional components (phenolic acids (1-34), tannins (35-98), flavonoids (99-141), sterols (142-159), triterpenoids (160-175), lignans (176-183), alkaloids (184-197), alkanes (198-212), aromatic micromolecules (213-222), other compounds (223-239)). The isolated compounds and the various extracts of P. emblica Linn presented a diverse spectrum of biological activities such as anti-oxidant, anti-cancer, anti-inflammatory, anti-bacterial, hepatoprotective, hypoglycemic, anti-atherosclerosis, neuroprotective, enhancing immunity, anti-fatigue, anti-myocardial fibrosis. The quality markers of P. emblica Linn were predicted and analyzed based on traditional medicinal properties, traditional efficacy, plant genealogy and chemical component characteristics, biogenic pathway of chemical components, measurability of chemical components, transformation characteristics of polyphenolic components, homologous characteristics of medicine and food, compound compatibility environment, and clinical applications. This review also summarized and prospected applications of P. emblica Linn in beverages, preserved fruits, fermented foods, etc. However, the contents of mechanism, structure-activity relationship, quality control, toxicity, extraction, processing of P. emblica Linn are not clear, and are worth further studies in the future.

Serum S-adenosylhomocysteine, rather than homocysteine, is associated with hepatocellular carcinoma survival: a prospective cohort study.

BACKGROUND: Emerging evidence suggested that S-adenosylhomocysteine (SAH) may be a better serum biomarker for cardiovascular disease than homocysteine (Hcy). However, the role of SAH in hepatocellular carcinoma (HCC) prognosis remains unclear. OBJECTIVES: We aimed to prospectively explore the relationships between serum SAH and related metabolites [Hcy, S-adenosylmethionine (SAM)] with HCC survival, and to evaluate the effect modifications by gene polymorphisms in one-carbon metabolism key enzymes. METHODS: We included 1080 newly diagnosed patients with HCC from the Guangdong Liver Cancer Cohort. Serum SAH, Hcy, and SAM were measured utilizing high-performance liquid chromatography-tandem mass spectrometry. Gene polymorphisms in one-carbon metabolism key enzymes were identified using kompetitive allele-specific polymerase chain reaction. Primary outcomes were liver cancer-specific survival (LCSS) and overall survival (OS). Hazard ratios (HRs) and 95% confidence intervals (CIs) were computed using multivariate Cox proportional hazards models. RESULTS: After a median follow-up of 3.6 y, 601 deaths occurred, with 552 (92%) attributed to HCC. Multivariable analysis revealed that patients in the highest quartile of serum SAH concentrations were significantly associated with worse survival compared with those in the lowest quartile, with HRs of 1.58 (95% CI: 1.19, 2.10; P-trend = 0.002) for LCSS and 1.54 (95% CI: 1.18, 2.02; P-trend = 0.001) for OS. There were no significant interactions between serum SAH concentrations and genetic variants of one-carbon metabolism key enzymes. No significant associations were found between serum Hcy, SAM concentrations, and SAM/SAH ratio with LCSS or OS. CONCLUSIONS: Higher serum SAH concentrations, rather than Hcy, were independently associated with worse survival in patients with HCC, regardless of the genetic variants of one-carbon metabolism key enzymes. These findings suggest that SAH may be a novel metabolism-related prognostic biomarker for HCC.

Choline suppresses hepatocellular carcinoma progression by attenuating AMPK/mTOR-mediated autophagy via choline transporter SLC5A7 activation.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-associated death. Emerging evidence suggests that autophagy plays a critical role in HCC tumorigenesis, metastasis, and prognosis. Choline is an essential nutrient related to prolonged survival and reduced risk of HCC. However, it remains unclear whether this phenomenon is mediated by autophagy. Methods: Two HCC cell lines (HUH-7 and Hep3B) were used in the present study. Cell growth was evaluated by cell counting kit 8 (CCK-8), colony formation, and in vivo mouse xenografts assays. Cell motility was calculated by wound healing and transwell assays. Autophagosomes were measured by transmission electron microscope (TEM), and autophagy flux was detected by mRFP-GFP-labeled LC3 protein. The mRNA level of genes was measured by quantitative real-time polymerase chain reaction (qRT-PCR). The protein levels were detected by Western blotting (WB). Results: We found that choline inhibited the proliferation, migration, and invasion of HCC cells by downregulating autophagy in vitro and in vivo. Upregulated expression of the solute carrier family 5 member 7 (SLC5A7), a specific choline transporter, correlated with better HCC prognosis. We further discovered that choline could promote SLC5A7 expression, upregulate cytoplasm p53 expression to impair the AMPK/mTOR pathway, and attenuate autophagy. Finally, we found that choline acted synergistically with sorafenib to attenuate HCC development in vitro and in vivo. Conclusions: Our findings provide novel insights into choline-mediated autophagy in HCC, providing the foothold for its future application in HCC treatment.

Betaine alleviates cognitive impairment induced by homocysteine through attenuating NLRP3-mediated microglial pyroptosis in an m6A-YTHDF2-dependent manner.

Dementia, with homocysteine (Hcy) as an important risk factor, is a severe public health problem in the aging society. Betaine serves as a methyl donor and plays an important role in reducing Hcy. However, the effects and mechanisms of betaine on Hcy-induced cognitive impairment remain unclear. Firstly, SD rats were injected with Hcy (400 µg/kg) through vena caudalis, and betaine (2.5 % w/v) was supplemented via drinking water for 14 days. Betaine supplementation could attenuate Hcy-induced cognitive impairment in the Y maze and novel object recognition tests by repairing brain injury. Meanwhile, microglial activation was observed to be inhibited by betaine supplementation using immunofluorescence and sholl analysis. Secondly, HMC3 cells were treated with betaine, which was found to decrease the ROS level, ameliorate cell membrane rupture, reduce the release of LDH, IL-18 and IL-1ß, and attenuate the damage of microglia to neurons. Mechanistically, betaine alleviates cognitive impairment by inhibiting microglial pyroptosis via reducing the expressions of NLRP3, ASC, pro-caspase-1, cleaved-caspase-1, GSDMD, GSDMD-N, IL-18 and IL-1ß. Betaine treatment can increase SAM/SAH ratio, confirming its enhancement on methylation capacity. Furthermore, betaine treatment was found to enhance N6-methyladenosine (m6A) modification of NLRP3 mRNA, and reduced the NLRP3 mRNA stability through increasing the expression of the m6A reader YTH N6-methyladenosine RNA binding protein 2 (YTHDF2). Finally, silencing YTHDF2 could reverse the inhibitory effect of betaine on pyroptosis. Our data demonstrated that betaine attenuated Hcy-induced cognitive impairment by suppressing microglia pyroptosis via inhibiting the NLRP3/caspase-1/GSDMD pathway in an m6A-YTHDF2-dependent manner.

Associations of blood pressure change with change in foods' intake among adults with mild to moderate hypertension / 中华心血管病杂志

Objective: To explore the association between the intake and changes in various types of food and the changes in blood pressure in patients with mild to moderate hypertension. Methods: Mild to moderate hypertension participants with complete baseline and outcome data were included from DECIDE-Diet study, a multicenter, randomized controlled trial. Dietary records and blood pressure measurements at both 7-day run-in (baseline) and 28-day intervention phases were collected for enrolled participants. Blood pressure change was defined as the difference between blood pressure at the end of trial and the baseline blood pressure. Baseline intake of food was the average daily intake during the run-in period, and the intake increment was defined as the difference between the average intake during the trial period and the average intake during the run-in period. After adjusting for age, sex, study center, intervention groups, baseline body mass index (kg/m2), antihypertension medication use, and baseline total calorie intake, a linear regression model was used to analyze the associations of the before-after-intervention change in blood pressure with baseline intake and intake increment of foods. Results: A total of 258 patients with mild to moderate hypertension were included, including 133 males, aged (56.5±9.9) years. (1) After adjusting for confounding factors, there was no significant association between baseline intake of food and baseline blood pressure (all P>0.05). The blood pressure change was negatively associated with baseline intakes of tubers, vegetables, and vegetable oils but positively with baseline intake of meats; and was negatively associated with intake increment of whole grains and fish (all P<0.05). (2) The multiple linear regression analysis showed that baseline intake of vegetables (β=-0.021, P=0.004), vegetable oils (β=-0.260, P=0.002), and increment in intake of fish (β=-0.128, P=0.026) were all significantly associated with changes in systolic blood pressure; baseline intake of vegetables (β=-0.017, P=0.002), vegetable oils (β=-0.182, P=0.001), dairy products (β=0.021, P=0.022), and increment in intake of fish (β=-0.092, P=0.010) were all significantly associated with changes in diastolic blood pressure. Conclusion: Increasing the intake of whole grains, vegetables, vegetable oils, and fish and decreasing the intake of meat may be beneficial for blood pressure control in patients with mild to moderate hypertension.

Associations of blood pressure change with change in foods' intake among adults with mild to moderate hypertension / 中华心血管病杂志

Objective: To explore the association between the intake and changes in various types of food and the changes in blood pressure in patients with mild to moderate hypertension. Methods: Mild to moderate hypertension participants with complete baseline and outcome data were included from DECIDE-Diet study, a multicenter, randomized controlled trial. Dietary records and blood pressure measurements at both 7-day run-in (baseline) and 28-day intervention phases were collected for enrolled participants. Blood pressure change was defined as the difference between blood pressure at the end of trial and the baseline blood pressure. Baseline intake of food was the average daily intake during the run-in period, and the intake increment was defined as the difference between the average intake during the trial period and the average intake during the run-in period. After adjusting for age, sex, study center, intervention groups, baseline body mass index (kg/m2), antihypertension medication use, and baseline total calorie intake, a linear regression model was used to analyze the associations of the before-after-intervention change in blood pressure with baseline intake and intake increment of foods. Results: A total of 258 patients with mild to moderate hypertension were included, including 133 males, aged (56.5±9.9) years. (1) After adjusting for confounding factors, there was no significant association between baseline intake of food and baseline blood pressure (all P>0.05). The blood pressure change was negatively associated with baseline intakes of tubers, vegetables, and vegetable oils but positively with baseline intake of meats; and was negatively associated with intake increment of whole grains and fish (all P<0.05). (2) The multiple linear regression analysis showed that baseline intake of vegetables (β=-0.021, P=0.004), vegetable oils (β=-0.260, P=0.002), and increment in intake of fish (β=-0.128, P=0.026) were all significantly associated with changes in systolic blood pressure; baseline intake of vegetables (β=-0.017, P=0.002), vegetable oils (β=-0.182, P=0.001), dairy products (β=0.021, P=0.022), and increment in intake of fish (β=-0.092, P=0.010) were all significantly associated with changes in diastolic blood pressure. Conclusion: Increasing the intake of whole grains, vegetables, vegetable oils, and fish and decreasing the intake of meat may be beneficial for blood pressure control in patients with mild to moderate hypertension.

The implementation and management of disease risk reduction claims in the European Union and the United States / 中华预防医学杂志

The improvement of food labeling can improve consumers' health awareness, reduce the burden of chronic diseases on the health and economy, and promote the development of the healthy food industry. Disease Risk Reduction Claim has been developed in European Union and the U.S. for over 20 years, with mature management methods and experience, but it is still lacking in China. Learning and drawing on the international management experience of food disease risk reduction claims can assist China to establish food disease risk reduction claims and improve the food health claims and labeling system.

The implementation and management of disease risk reduction claims in the European Union and the United States / 中华预防医学杂志

The improvement of food labeling can improve consumers' health awareness, reduce the burden of chronic diseases on the health and economy, and promote the development of the healthy food industry. Disease Risk Reduction Claim has been developed in European Union and the U.S. for over 20 years, with mature management methods and experience, but it is still lacking in China. Learning and drawing on the international management experience of food disease risk reduction claims can assist China to establish food disease risk reduction claims and improve the food health claims and labeling system.

Stiffness and Stress Distribution of Internal Fixation System for Long Bone Fractures / 医用生物力学

Objective To study distributions of stiffness and stress of each component in internal fixation system for long bone fractures composed of fractured bones (including callus) and bone plates,and propose a method for determining bending stiffness of fracture internal fixation implants. Methods Based on the linear bending theory and composite beam theory, the mechanical model of femoral shaft internal fracture fixing system composed of fractured bones and bone plate was constructed and verified with the finite element model based on artificial femur CT data. The relationship between stress and stiffness of the internal fixation system for long bone fractures was established. Results The three stages (slow-rapid-steady growth) for variation of fractured bone bending stiffness with callus elastic modulus obtained by calculation and analysis were consistent with the three stages of actual bone healing process, which proved accuracy of the theoretical calculation method. Changing patterns for the neutral axis position of internal fracture fixing system composed of fractured bones and bone plate were further obtained, namely, the neutral axis position was close to (away from) the central axis of bone plate when stiffness of bone plate increased (decreased). According to the stress required for fracture healing (0.72-0.80 MPa), the reasonable range for bending stiffness of bone plate was 0.99-4.20 kN·mm2. Conclusions When elastic modulus of the callus was 0.037.00 GPa, bending stiffness of the fractured bones increased rapidly, which was at the stage of bone bridge formation. When elastic modulus of the callus was above 7 GPa, the callus tended to mature. Based on the femur model in this study, when thickness of bone plate was 3.6-6.0 mm and elastic modulus of fractured bones was 3.013.5 GPa, the entire fractured bone section could be effectively stimulated. In this study, when bending stiffness of bone plate was 0.99-4.20 kN·mm2 during the generation stage of bone bridge, it was conducive to bone healing.

Radioactive I-125 seed implantation in treatment of TACE-refractory hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To study the use of radioactive I-125 seed implantation in the treatment of transarterial chemoembolization (TACE)-refractory hepatocellular carcinoma (HCC).Methods:A retrospective study was conducted on 70 patients with HCC who were initially treated with TACE between July 1, 2016 and August 31, 2019 at the Second Affiliated Hospital of Guangzhou Medical University. After these patients were found to be refractory to TACE, 29 patients were converted to radioactive I-125 seed implantation (the 125I seed group), and 41 patients were continued with TACE (the TACE group). The objective response rate, progression-free survival (PFS), overall survival (OS), total overall survival (TOS) of the two groups were compared. Results:There were 59 males and 11 females, aged (60.5±11.9 ) years in this study. At 1, 3, 6 months after treatment, the objective response rates of the 125I seed group were 20.7%, 40.7%, 34.6%, respectively, which were significantly higher than that of the TACE group of 2.6%, 3.3%, 5.0%, respectively. The PFS, OS, TOS in the 125I seed group were 7.6, 21.1, 32.1 months, respectively, which were significantly better when compared with the TACE group (3.5, 8.5, 14.8 months, respectively, all P<0.05). There was no significant difference in the embolization syndrome between the two groups [93.1%(27/29) vs 100.0%(41/41), P>0.05]. Child-Pugh B grading ( HR=0.311, 95% CI: 0.160-0.603, P=0.005) and TACE ( HR=0.308, 95% CI: 0.159-0.597, P=0.002) were independent risk prognostic factors for survival. Conclusion:This study showed better treatment efficacy and safety using radioactive I-125 seed implantation in TACE-refractory HCC and this treatment significantly improved survival of patients when compared with TACE alone.

Progress on Anticancer Effects of PD-1/PD-L1 Checkpoint Inhibitors / 中国药学杂志

This artical explained the biological action mechanism of PD-1/PD-L1 monoclonal antibodies through reactivating the immune response of T cells to tumor cells immune response, analyzed the detection reports on the targets, introduced the clinical manifestations and indications research results, and looked into their development potential in the field of anticancer therapy. It's important to rationally use PD-1/PD-L1 monoclonal antibodies to decrease immune-mediated adverse events as well as maximizing the therapeutic effect. Furthermore, we should not only see the accomplishment in anticancer therapy, but also gain insight into its development direction in the field of anticancer research based on the therapeutic idea of inducing autoimmune system to kill tumor cells.

Effects of obatoclax combined with gemcitabine on breast cancer cells under hypoxia condition / 中国应用生理学杂志

To explore the effects of obatoclax(OBX) combined with gemcitabine(GEM) on breast cancer cells MCF-7 and BT-20 cell activity, migration, invasion and apoptosis under hypoxia condition. Breast cancer cells MCF-7 and BT-20 were divided into normal group, hypoxia group, GEM group, OBX+GEM group. Normal group: Cells were cultured at 37℃, 5% CO for 24 h and 48 h; Hypoxia group: Cells were cultured at 37℃, 1% O, 5% CO, 94% N for 24 h and 48 h; GEM group: Cells were cultured at 37℃, 1% O, 5% CO, 94% N, adding 10 μmol/L GEM for 24 h and 48 h; OBX + GEM group: Cells were cultured at 37℃, 1% O, 5% CO, 94% N, adding 10 μmol/L GEM and 50 nmol/L OBX for 24 h and 48 h. Western blot method was used to detect the expressions of HIF-1α in MCF-7 and BT-20 cells under normal oxygen and hypoxia condition. CCK-8 method was used to detect cancer cell activity, each group was provided with 15 compound holes. Scratch experiment was used to detect cells migration ability, each group was provided with 6 compound holes. Western blot method was used to detect the expressions of vimentin, E-Cadherin and p53 protein in cells of each group. Under hypoxia condition, the expression of HIF-1α in MCF-7 and BT-20 cells was much higher than that under normal oxygen(P＜0.05). Compared with hypoxia group, GEM could reduce MCF-7 and BT-20 cells migration ability(P＜0.01)and cell activity(P＜0.05), while decrease the expression of vimentin protein(P＜0.01)and promote the expressions of E-Cadherin (P＜0.01)and p53 protein(P＜0.01) in tumor cells under hypoxia condition. In OBX combined with GEM group, the cell activity and the migration ability of MCF-7 and BT-20 were reduced significantly(P＜0.01). The expression of vimentin in cells was further reduced(P＜0.01). The expressions of E-Cadherin(P＜0.01)and p53(P＜0.01) protein were increased significantly compared with GEM group. Under hypoxia condition, OBX combined with a low-dose of GEM can significantly inhibit the growth, migration and invasion of breast cancer cells, and enhance the pro-apoptotic effect of GEM, but the specific mechanism needs further study.

Mechanism of Xiaoyaosan in Improving Abnormal Lipid Metabolism and Steatohepatitis of Ovariectomized Rats / 中国实验方剂学杂志

Objective::To investigate the effect of Xiaoyaosan (XYS) on hepatic lipid metabolism and steatohepatitis in ovariectomized (OVX) female SD rats and its mechanism. Method::Forty female SD rats were randomly divided into sham surgery group, OVX group, low-dose XYS group (3 g·kg-1), and high-dose XYS group (9 g·kg-1). Bilateral ovaries of rats were excised to replicate the obesity model of ovariectomized rat. After 6 weeks of intragastric administration, the change rate of body mass in each group, the levels of blood lipids and liver function of rats were detected. Hematoxylin-eosin (HE) staining and oil red staining were used to observe the hepatocyte histomorphology and the intrahepatic fatty deposits. The expressions of hepatic proinflammatory cytokines and estrogen receptor beta (ERβ) were determined by quantitative real time polymerase chain reaction (Real-time PCR). Result::Compared with sham surgery group, the change rate of body mass of OVX group was significantly increased (2-6 weeks) with the changes in the course of drug administration and the levels of serum total cholesterol (TC), alanine aminotransferase (ALT) (P<0.05), aspartate amino transferase (AST) (P<0.01), low-density lipoprotein (LDL) (P<0.05) were markedly increased too (P<0.05, P<0.01). By histological method, in OVX group, the structure of hepatic cord became disordered, and there were new lipid droplets in hepatocyte cytoplasm, transcription levels of hepatic interleukin-1β (IL-1β) and interleukin-6 (IL-6) in OVX group were significantly increased (P<0.05). Compared with OVX group, the growth rate of body weight in low-dose and high-dose XYS group showed significant decreases with the increase of the cycle of drug administration (3-6 weeks). XYS significantly reduced levels of serum TC, ALT, AST, and LDL levels of OVX rats (P<0.05) in a dose-dependent manner, while serum triglyceride (TG), alkaline phosphatase (AKP) and high-density lipoprotein (HDL) levels in the four groups showed no statistical significance, XYS can improve hepatocyte structure and steatosis of OVX rats, XYS could reduce the transcription hepatic levels of IL-6 and IL-1β of OVX rats in a dose-dependent manner (P<0.05, P<0.01), but there was no significant difference in the transcription level of tumor necrosis factor-α (TNF-α) among groups, both low and high-dose XYS can increase the transcription hepatic level of ERβ in OVX group (P<0.05, P<0.01). Conclusion::XYS can improve the growth rate of body mass, the hepatic lipid metabolism abnormalities and steatohepatitis of OVX rats. The mechanism may be related to the elevated expression of hepatic ERβ by XYS, so as to inhibit the hepatic pro-inflammatory factors expressions.