Improving sarcopenia in older adults: a systematic review and meta-analysis of randomized controlled trials of whey protein supplementation with or without resistance training.

OBJECTIVES: The aim of the study was to comprehensively analyze the effects of whey protein (WP)-enriched supplement intake with or without resistance training (RT) in older patients, either from the community or hospital, who were diagnosed with sarcopenia according to the EWGSOP or AWGS criteria. METHODS: This meta-analysis study was registered in PROSPERO (CRD42023407885). We searched the PubMed, Embase, Web of Science, and Cochrane Library databases for RCTs up to June 1, 2023. Standardized mean differences (SMD) with 95% confidence intervals (CI) were used to estimate the pooled results. RESULTS: Ten RCT studies, including 1154 participants, were included and analyzed. The primary outcomes were the changes in muscle mass, strength, and physical performance. In WP group versus (vs.) Isocaloric placebo (PLA)/Routine consultation (RC) group, WP significantly increased the appendicular skeletal muscle mass index (SMD: 0.47, 95%CI: 0.23, 0.71), appendicular skeletal muscle mass (SMD: 0.28, 95%CI: 0.11, 0.45) and gait speed (SMD: 1.13, 95%CI: 0.82, 1.44) in older patients with sarcopenia. In WP with RT group vs. PLA/ RC group, there was significant increase in handgrip strength (SMD: 0.67, 95%CI: 0.29, 1.04). In addition, in the secondary outcomes, WP significantly reduced interleukin-6, significantly increased insulin-like growth factor-1 and albumin, promoted participants' intake of total energy and protein, enhanced activities of daily living scores in patients, and had no significant effect on BMI, weight, or fat mass. CONCLUSION: This review confirms that WP can improve various aspects of older adult with sarcopenia, thereby enhancing their overall physical condition. More studies should be conducted to validate this result and further explore the effects of WP and RT in patients with sarcopenia.

A state-of-the-art review of functional magnetic resonance imaging technique integrated with advanced statistical modeling and machine learning for primary headache diagnosis.

Primary headache is a very common and burdensome functional headache worldwide, which can be classified as migraine, tension-type headache (TTH), trigeminal autonomic cephalalgia (TAC), and other primary headaches. Managing and treating these different categories require distinct approaches, and accurate diagnosis is crucial. Functional magnetic resonance imaging (fMRI) has become a research hotspot to explore primary headache. By examining the interrelationships between activated brain regions and improving temporal and spatial resolution, fMRI can distinguish between primary headaches and their subtypes. Currently the most commonly used is the cortical brain mapping technique, which is based on blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI). This review sheds light on the state-of-the-art advancements in data analysis based on fMRI technology for primary headaches along with their subtypes. It encompasses not only the conventional analysis methodologies employed to unravel pathophysiological mechanisms, but also deep-learning approaches that integrate these techniques with advanced statistical modeling and machine learning. The aim is to highlight cutting-edge fMRI technologies and provide new insights into the diagnosis of primary headaches.

Untargeted lipidomic analysis and network pharmacology for parthenolide treated papillary thyroid carcinoma cells.

BACKGROUND: With fast rising incidence, papillary thyroid carcinoma (PTC) is the most common head and neck cancer. Parthenolide, isolated from traditional Chinese medicine, inhibits various cancer cells, including PTC cells. The aim was to investigate the lipid profile and lipid changes of PTC cells when treated with parthenolide. METHODS: Comprehensive lipidomic analysis of parthenolide treated PTC cells was conducted using a UHPLC/Q-TOF-MS platform, and the changed lipid profile and specific altered lipid species were explored. Network pharmacology and molecular docking were performed to show the associations among parthenolide, changed lipid species, and potential target genes. RESULTS: With high stability and reproducibility, a total of 34 lipid classes and 1736 lipid species were identified. Lipid class analysis indicated that parthenolide treated PTC cells contained higher levels of fatty acid (FA), cholesterol ester (ChE), simple glc series 3 (CerG3) and lysophosphatidylglycerol (LPG), lower levels of zymosterol (ZyE) and Monogalactosyldiacylglycerol (MGDG) than controlled ones, but with no significant differences. Several specific lipid species were changed significantly in PTC cells treated by parthenolide, including the increasing of phosphatidylcholine (PC) (12:0e/16:0), PC (18:0/20:4), CerG3 (d18:1/24:1), lysophosphatidylethanolamine (LPE) (18:0), phosphatidylinositol (PI) (19:0/20:4), lysophosphatidylcholine (LPC) (28:0), ChE (22:6), and the decreasing of phosphatidylethanolamine (PE) (16:1/17:0), PC (34:1) and PC (16:0p/18:0). Four key targets (PLA2G4A, LCAT, LRAT, and PLA2G2A) were discovered when combining network pharmacology and lipidomics. Among them, PLA2G2A and PLA2G4A were able to bind with parthenolide confirmed by molecular docking. CONCLUSIONS: The changed lipid profile and several significantly altered lipid species of parthenolide treated PTC cells were observed. These altered lipid species, such as PC (34:1), and PC (16:0p/18:0), may be involved in the antitumor mechanisms of parthenolide. PLA2G2A and PLA2G4A may play key roles when parthenolide treated PTC cells.

Prognostic and clinicopathologic significance of PLIN2 in cancers: A systematic review with meta-analysis.

The relationship between PLIN2 expression and prognosis, and clinicopathological significance of various cancers has been extensively studied, but the results are not completely consistent. This review followed the guidelines for systematic reviews of prognostic factors studies and was reported under the Preferred Reporting Program for Systematic Reviews and Meta-Analysis (PRISMA). We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Academia for relevant articles up to September 2, 2022, and calculated the pooled hazard ratios (HR) with 95% confidence intervals (CI) to determine the association between PLIN2 expression and the prognosis of various cancers. The meta-analysis ultimately included 17 studies. The quality of all included cohort studies was evaluated using the Quality in Prognosis Studies (QUIPS) tool, and an adaptation of Grading of Recommendations Assessment, Development and Evaluation (GRADE) method was used to assess the certainty of the results. High expression of PLIN2 was associated with poorer overall survival (HR = 1.65; 95% CI = 1.14, 2.38; P = 0.008), metastasis-free survival (HR = 1.48; 95% CI = 1.12, 1.94; P = 0.005), progression-free survival (HR = 2.11; 95% CI = 1.55, 2.87; P < 0.0005) and recurrence-free survival/relapse-free survival (HR = 2.21; 95% CI = 1.64, 2.98; P < 0.0005) in cancers. The clinicopathological parameters of digestive system malignancies suggested that high expression of PLIN2 was notably associated with distant metastasis ( + ) (odds ratio (OR) = 3.37; 95% CI = 1.31, 8.67; P = 0.012), lymph node metastasis ( + ) (OR = 1.61; 95% CI = 1.01, 2.54; P = 0.004), and tumor stage (III-IV) (OR = 1.96; 95% CI = 1.24, 3.09; P = 0.006). In summary, overexpression of PLIN2 is significantly associated with a poor prognosis in various human cancers, especially in respiratory and digestive malignancies. Thus, PLIN2 expression may be a potential prognostic biomarker in cancer patients.

A First for Human Vaccinology: GMP Compliant Radiation Attenuation of Plasmodium falciparum Sporozoites for Production of a Vaccine Against Malaria.

Ionizing radiation (UV, X-ray and É£) administered at an appropriate dose to pathogenic organisms can prevent replication while preserving metabolic activity. We have established the GMP process for attenuation by ionizing radiation of the Plasmodium falciparum (Pf) sporozoites (SPZ) in Sanaria® PfSPZ Vaccine, a protective vaccine against malaria. Mosquitoes raised and infected aseptically with Pf were transferred into infected mosquito transport containers (IMTC) and É£-irradiated using a 60Co source. PfSPZ were then extracted, purified, vialed, and cryopreserved. To establish the appropriate radiation conditions, the irradiation field inside the IMTCs was mapped using radiochromic film and alanine transfer dosimeters. Dosimeters were irradiated for times calculated to provide 120-170 Gy at the minimum dose location inside the IMTC and regression analysis was used to determine the time required to achieve a lower 95% confidence interval for 150 Gy. A formula incorporating the half-life of 60Co was then used to construct tables of irradiation times for each calendar day. From the mapping studies, formulae were derived to estimate the minimum and maximum doses of irradiation received inside the IMTC from a reference dosimeter mounted on the outside wall. For PfSPZ Vaccine manufacture a dose of 150 Gy was targeted for each irradiation event, a dose known to completely attenuate PfSPZ. The reference dosimeters were processed by the National Institute of Standards and Technology. There have been 587 irradiation events to produce PfSPZ Vaccine during 13 years which generated multiple lots released for pre-clinical studies and clinical trials. The estimated doses at the minimum dose location (mean 154.3 ± 1.77 Gy; range 150.0-159.3 Gy), and maximum dose location (mean 166.3 ± 3.65 Gy, range 155.7 to 175.3 Gy), in IMTCs were normally distributed. Overall dose uniformity was 1.078 ± 0.012. There was no siginifcant change in measured dose over 13 years. As of January 2022, 21 clinical trials of PfSPZ Vaccine have been conducted, with 1,740 volunteers aged 5 months to 61 years receiving 5,648 doses of PfSPZ Vaccine totalling >5.3 billion PfSPZ administered. There have been no breakthrough infections, confirming the consistency and robustness of the radiation attenuation process.

Relationship between the ideal cardiovascular health behaviors and factors and newonset heart failure / 中华心血管病杂志

Objective: To explore the relationship between the ideal cardiovascular health behaviors and factors and newonset heart failure. Methods: It was a prospective cohort study. People who attended the 2006-2007 physical examination of Kailuan Group Company and with complete data of cardiovascular behaviors and related factors were eligible for this study. A total of 95 167 participants who were free of valvular heart diseases, congenital heart diseases and a prior history of heart failure were included. Basic cardiovascular health score (CHS) of each participant was calculated. Participants were divided into 3 groups according to CHS. Group 1:CHS<8 (n=26 640), Group 2:8≤CHS<10 (n=35 230), Group3:CHS≥10 (n=33 297). The general clinical data and laboratory test results were collected. The outcome was defined as the first occurrence of heart failure at the end of followup(December 31, 2016). Cox regression model was used to determine the association between baseline CHS and the risk of newonset heart failure. Results: After a median followup of 10.3 years, the incidence of newonset heart failure in the group of CHS<8,8≤CHS<10,CHS≥10 were 2.7%(729/26 640), 1.8%(651/35 230) and 1.1%(360/33 297),respectively. After adjustment for age, sex, history of myocardial infarction, history of atrial fibrillation, income, alcohol consumption, education and the use of antihypertensive, cholesterol-lowering, glucose-lowering medications, compared with the group of CHS<8, the Cox regression model showed that HRs of the group of 8≤CHS<10 and CHS≥10 were 0.68 (95%CI 0.61-0.75), 0.49 (95%CI 0.43-0.55), respectively. Cox regression analysis after removing each single cardiovascular behavior or factor showed that the HR value range ability was as follows:systolic blood pressure(HR=0.78,95%CI 0.74-0.82), body mass index(HR=0.78,95%CI 0.74-0.82), fasting blood glucose (HR=0.77,95%CI 0.73-0.81), total cholesterol(HR=0.76,95%CI 0.72-0.80), physical exercise(HR=0.72,95%CI 0.69-0.76), smoking(HR=0.75,95%CI 0.71-0.79) and salt intake(HR=0.73,95%CI 0.69-0.77). Conclusion: CHS is negatively associated with the risk of newonset heart failure, and there is a dose-response relationship between the two indexes.

Impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging / 中华心血管病杂志

Objective: To investigate the impact of change of ideal cardiovascular behavior and related factors on healthy vascular aging(HVA). Methods: This study was a multi-center cross-sectional survey. Six thousand three hundred and sixteen participants who underwent at least 2 healthy examinations from 2006 to 2015 at 11 hospitals, including Kailuan Hospital and so on, and examined brachial-ankle pulse wave velocity (baPWV) during 2010 and 2016, with available information about cardiovascular behavior and factors were included. The cardiovascular health score (CHS) was calculated. Basic CHS was collected from the first examination. The second CHS derived from the healthy examination in the same year of baPWV examination. Change of cardiovascular health score (ΔCHS) was calculated. Participants were defined into 5 groups according to ΔCHS, namely ΔCHS≤-2 (n=2 166), ΔCHS=-1 (n=1 284), ΔCHS=0 (n=1 187), ΔCHS=1 (n=860), and ΔCHS≥2 (n=819). Participants' characteristics, value of baPWV and proportion of HVA were compared among different groups. Multiple logistic regression analysis was used to investigate the association between ΔCHS and HVA. The ΔCHS was recalculated and included in multiple logistic regression analysis model again after each component of the cardiovascular health metrics was removed separately in order to investigate effects of removal factors on HVA by observing changes in effect values. Results: The percentage of the participants with HVA in the group of ΔCHS≤-2, ΔCHS=-1, ΔCHS=0, ΔCHS=1 and ΔCHS≥2 were 23.3%(505/2 166), 27.8%(357/1 284), 28.7%(341/1 187),31.9%(274/860) and 33.9%(278/819), respectively. After adjustment for age, sex, income, education, alcohol consumption and the basic CHS, a significant positive association between ΔCHS and proportion of participants with HVA was observed (OR=1.50, 95%CI 1.44-1.56). Multiple regression analysis after removing each single cardiovascular behavior or factor showed that the OR value decreased as follow systolic blood pressure (OR=1.04, 95%CI 1.00-1.09), fasting blood glucose (OR=1.14, 95%CI 1.09-1.18), physical exercise (OR=1.16, 95%CI 1.11-1.21), salt intake (OR=1.17, 95%CI 1.12-1.22), body mass index (OR=1.18, 95%CI 1.13-1.23), smoking(OR=1.18, 95%CI 1.13-1.23) and total cholesterol (OR=1.20, 95%CI 1.16-1.24). Conclusion: The improvement of every ideal cardiovascular behavior and factor is associated with the increase of the proportion of HVA population.

Vitamin D prevents high glucose-induced human umbilical vein endothe-lial cell apoptosis by inhibition of prolyl isomerase 1-mediated mitochon-drial oxidative stress / 中国病理生理杂志

AIM:To observe the effects of vitamin D on the apoptosis ,prolyl isomerase 1(Pin1)protein ex-pression and activity ,mitochondrial translocation of p 66Shc,and reactive oxygen species(ROS)production in high glu-cose-cultured human umbilical vein endothelial cells(HUVECs),and to explore the role of vitamin D receptor(VDR)in these processes.METHODS:HUVECs were treated with high glucose(33 mmol/L)in the presence or absence of vita-min D or Pin1 inhibitor juglone.The cell apoptosis was measured by flow cytometry and TUNEL staining.Intracellular ROS levels were examined by flow cytometry and fluorescence microscopy.The protein levels of Pin1,p66Shc,p-p66Shc,mito-chondria to cytoplasm ratio of p66Shc,and caspase-3 in HUVECs were measured by Western blot.Pin1 activity in HU-VECs lysate was assessed by a commercial kit.Knockdown of VDR by siRNA was conducted to evaluate the role of VDR in the regulatory effects of vitamin D on Pin 1 protein expression and activity in HUVECs under high-glucose condition.RE-SULTS:Vitamin D suppressed the apoptosis and intracellular ROS generation of HUVECs induced by high glucose(P<0.05).Vitamin D inhibited high glucose-induced upregulation of Pin1 protein expression and activity(P<0.05).Vita-min D inhibited the phosphorylation and mitochondrial translocation of p 66Shc and caspase-3 protein expression induced by high glucose(P<0.05).Knockdown of VDR by siRNA abolished the inhibitory effects of vitamin D on high glucose-in-duced upregulation of Pin 1 protein expression and activity.CONCLUSION:Vitamin D alleviates high glucose-induced endothelial cell apoptosis by inhibition of Pin 1 protein expression and activity ,and attenuation of p66Shc-mediated mito-chondrial oxidative stress ,which are dependent on VDR activation.

Optimizing Intradermal Administration of Cryopreserved Plasmodium falciparum Sporozoites in Controlled Human Malaria Infection.

Controlled human malaria infection (CHMI) is a powerful tool to evaluate malaria vaccine and prophylactic drug efficacy. Until recently CHMI was only carried out by the bite of infected mosquitoes. A parenteral method of CHMI would standardize Plasmodium falciparum sporozoite (PfSPZ) administration, eliminate the need for expensive challenge facility infrastructure, and allow for use of many P. falciparum strains. Recently, intradermal (ID) injection of aseptic, purified, cryopreserved PfSPZ was shown to induce P. falciparum malaria; however, 100% infection rates were not achieved by ID injection. To optimize ID PfSPZ dosing so as to achieve 100% infection, 30 adults aged 18-45 years were randomized to one of six groups composed of five volunteers each. The parameters of dose (1 × 10(4) versus 5 × 10(4) PfSPZ total dose per volunteer), number of injections (two versus eight), and aliquot volume per ID injection (10 µL versus 50 µL) were studied. Three groups attained 100% infection: 1 × 10(4) PfSPZ in 50 µL/2 doses, 1 × 10(4) PfSPZ in 10 µL/2 doses, and 5 × 10(4) PfSPZ in 10 µL/8 doses. The group that received 5 × 10(4) PfSPZ total dose in eight 10 µL injections had a 100% infection rate and the shortest prepatent period (mean of 12.7 days), approaching the prepatent period for the current CHMI standard of five infected mosquitoes.

Impact of resting heart rate on new-onset diabetes in population without hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the impact of resting heart rate (RHR) on new-onset diabetes (NOD) in population without hypertension.</p><p><b>METHODS</b>This prospective cohort study was performed in 2006 and 2007 and screened 101 510 participants. All subjects were employees of the Kailuan Group, a state-run coal mining company. The observation cohort included 48 926 subjects with normal fasting blood glucose (FBG) <7.0 mmol/L, no history of diabetes, complete FBG and RHR examination data, systolic blood pressure <140 mm Hg (1 mm Hg = 0.133 kPa) , diastolic blood pressure <90 mm Hg, no history of hypertension, and no use of hypoglycemic agents or antihypertensive drugs.We excluded participants without a health examination in 2008-2009 or 2010-2011 and those with incomplete examination data. A total of 29 910 participants were included in the final analysis. The observation population was divided into four groups according to RHR data collected during 2006-2007 health examinations: quartile 1 (RHR<63 beats/min) ; quartile 2 (63 beats/min ≤ RHR<70 beats/min) ; quartile 3 (70 beats/min ≤ RHR<75 beats/min) ; quartile 4 ( RHR ≥ 75 beats/min). Kaplan-Meier analysis was used to calculate the incidence of NOD. The relationship between RHR and NOD was estimated using Cox proportional hazard analysis.</p><p><b>RESULTS</b>The incidences of NOD/1000 person-years for the above quartiles of RHR were 11.22, 13.58, 13.96, and 17.55, respectively in the total observational population; the corresponding incidences were 12.17, 15.20, 16.08, 20.44, and 8.29, 9.38, 8.86, and 9.60 in men and women, respectively. Compared with quartile 1, Cox proportional hazard regression analysis showed that the other three RHR groups had an increased risk of NOD after adjusting for age, gender, systolic blood pressure, diastolic blood pressure, and other risk factors. The hazard ratio values for these groups were 1.20 (95%CI:1.04-1.40, P < 0.05), 1.25 (95%CI:1.07-1.45, P < 0.01) and 1.58 (95%CI:1.36-1.82, P < 0.01), respectively. Furthermore, after adjusted the FBG, risk of NOD was significantly higher in quartile 2 (HR = 1.21, 95%CI:1.04-1.40, P < 0.01) and quartile 4 (HR = 1.22, 95%CI:1.06-1.41, P < 0.01 compared that in quartile 1. After adjusting for the factors listed above, the influence of RHR on NOD was not significant in women (P > 0.05) , but there was still an increased risk of NOD in men compared with quartile 1 with hazard ratio values of 1.21 (95%CI:1.02-1.43, P < 0.05) , and 1.27 (95%CI:1.09-1.49, P < 0.01) for quartile 2 and quartile 4, respectively.</p><p><b>CONCLUSION</b>Higher RHR is linked with higher risk of NOD in population without hypertension.</p>

CT radiographic study of different paths of iliac screw path / 中国骨伤

<p><b>OBJECTIVE</b>To investigate the best effective and accepted path of iliac screws for lumbar sacral spine and pelvis to provide reference for reconstruction.</p><p><b>METHODS</b>From Feb. 2009 to Aug. 2009, radiographic data of 50 patients were selected for various reasons, pelvic CT scanning and three-dimensional reconstruction and no positive performance, included 28 males and 22 females with an average age of 41.2 years old, ranging from 19 to 65 years. Designed four paths, in path A, B, C, CLIC (crossing point of Chiotic line and posterior iliac crest, located 24 mm on the top of posterior superior iliac spine) was the starting point for the path in the direction of the upper edge of the acetabulum, anterior inferior iliac spine, acetabulum center; in path D, the posterior superior iliac spine was starting point to direct anterior inferior iliac spine. The length of the screw channel and two narrow points in the screw channel of the bone plate thickness data of each different path were measured and analyzed.</p><p><b>RESULTS</b>The path A (CLIC point to the upper edge of the acetabulum) and the path B (CLIC point to the AIIS) and the path D (PSIS to AIIS) had correspond length of the screw channel, but the thickness of iliac of path A was thicker than that of path B and D. The iliac thickness of path A (CLIC point to the upper edge of the acetabulum) and the path C (CLIC point to the acetabular center) has no significant difference, but the channel length of path A was significant longer than that of path C.</p><p><b>CONCLUSION</b>Path A from the CLIC point to the direction of the upper edge of acetabular ilium nail route was the longest path and the iliac bone plate was the most thick, and able to accommodate the relatively longest and most coarse iliac screw, but also bear the greatest tension. It is the best iliac nail route.</p>

The primary study on the relationship between hemoglobin, erythrocyte protoporphrin and altitude / 实用儿科临床杂志

Objective To ssarch for the relationship between hemoglobulin (Hb),erythrocyte protoporphyrin (EP) and the altitude.Methods The altitudes of Guinan and Maduo county in Qinghai province are respectively 3200m and 4300m. The 122 healthy students aged from 7 to 14 years old were selected, Hb and EP of them were respectively determined by the methods of ferric cyanation and fluorospectrophotometry. The statistical treatment was carry out by t test and matched-pair t test.Results The Hb levels of the healthy children aged from 7 to 14 years old in Guinan and Maduo county are respectively 133 .6?10.1 and 152.8?14.0 g/L (t = 12.31, p＜0.001), the EP levels of them are respectively 320.7 ? 114.9 and 347.8 ? 123.6 ?g/L (t = 1.77, P＞0.05), the value of EP/Hh of them are respectively 2.4 ?0 .9 and 2 .3?0.8 (t = 1.12, p＞0.05). The result of matched-pair t test shows that there are not sexural difFerence for Hb, EP and EP/Hb (P＞0.05).Conclusion Along with the increasing of altitude, the Hb and EP levels of the healthy Children aged from 7 to 14 years old are obviously increased and on sexural difference.

The observation on the relationship between iron deficiency and altitude hypoxia / 实用儿科临床杂志

Background Since the measurement method establishment of serum ferritin abroad in early period of theseventies, the iron deficiency had been divided into two types: the non-anemia and anemia types. In orderto go step further studies, we must ertablish the bemoglobin targets of the two types. Methods One hurdred and fifty-two children in experimontal group, from 6 to 7 years old, and allcome from Qinghai province. There are 29 children in Xining city, 24 in Guide, 26 in Gongbe, 40 in Gui-nan and 33 in Maduo countics. There are 36 health children aged from 6 to 7 years old in the controlgroup, and all comes from Beijing. The Hb, RBC, HCT, HCTW and FEP wcre determined. Results The three targets correlating with Hb (Hb, MCH and MCHC); correlating with RBC (RBC,HCT and MCV); the two targets correlating with RBC_weight (HCTW and CMCW) and correlating withFEP of RBC(FEP and MCEP) have very significant difference between experimental group and control group. Conclusion The determination values of the 10 targets are not same in children in different districts,and the values of all the target: are increased on different degree along with the increase in altitude of ele-vation. There is very important significance on the studies of iron deficiency and altitude hypoxia to establish the normal values of the 10 targets.