Causal relationship between sarcopenia with osteoarthritis and the mediating role of obesity: a univariate, multivariate, two-step Mendelian randomization study.

BACKGROUND: Recent genetic evidence supports a causal role for sarcopenia in osteoarthritis, which may be mediated by the occurrence of obesity or changes in circulating inflammatory protein levels. Here, we leveraged publicly available genome-wide association study data to investigate the intrinsic causal relationship between sarcopenia, obesity, circulating inflammatory protein levels, and osteoarthritis. METHODS: In this study, we used Mendelian randomization analyses to explore the causal relationship between sarcopenia phenotypes (Appendicular lean mass [ALM], Low hand-grip strength [LHG], and usual walking pace [UWP]) and osteoarthritis (Knee osteoarthritis [KOA], and Hip osteoarthritis [HOA]). Univariable Mendelian randomization (UVMR) analyses were performed using the inverse variance weighted (IVW) method, MR-Egger, weighted median method, simple mode, and weighted mode, with the IVW method being the primary analytical technique. Subsequently, the independent causal effects of sarcopenia phenotype on osteoarthritis were investigated using multivariate Mendelian randomization (MVMR) analysis. To further explore the mechanisms involved, obesity and circulating inflammatory proteins were introduced as the mediator variables, and a two-step Mendelian randomization analysis was used to explore the mediating effects of obesity and circulating inflammatory proteins between ALM and KOA as well as the mediating proportions. RESULTS: UVMR analysis showed a causal relationship between ALM, LHG, UWP and KOA [(OR = 1.151, 95% CI: 1.087-1.218, P = 1.19 × 10-6, PFDR = 7.14 × 10-6) (OR = 1.215, 95% CI: 1.004-1.470; P = 0.046, PFDR = 0.055) (OR = 0.503, 95% CI: 0.292-0.867; P = 0.013, PFDR = 0.027)], and a causal relationship between ALM, UWP and HOA [(OR = 1.181, 95% CI: 1.103-1.265, P = 2.05 × 10-6, PFDR = 6.15 × 10-6) (OR = 0.438, 95% CI: 0.226-0.849, P = 0.014, PFDR = 0.022)]. In the MVMR analyses adjusting for confounders (body mass index, insomnia, sedentary behavior, and bone density), causal relationships were observed between ALM, LHG, UWP and KOA [(ALM: OR = 1.323, 95%CI: 1.224- 1.431, P = 2.07 × 10-12), (LHG: OR = 1.161, 95%CI: 1.044- 1.292, P = 0.006), (UWP: OR = 0.511, 95%CI: 0.290- 0.899, P = 0.020)], and between ALM and HOA (ALM: OR = 1.245, 95%CI: 1.149- 1.348, P = 7.65 × 10-8). In a two-step MR analysis, obesity was identified to play a potential mediating role in ALM and KOA (proportion mediated: 5.9%). CONCLUSIONS: The results of this study suggest that decreased appendicular lean mass, grip strength, and walking speed increase the risk of KOA and decreased appendicular lean mass increases the risk of HOA in patients with sarcopenia in a European population. Obesity plays a mediator role in the occurrence of KOA due to appendicular lean body mass reduction.

[Effect of different delivery modes on the level of protein, glucose and blood lipids in cord artery and vein blood].

OBJECTIVE: To explore whether there are differences in the levels of protein, glucose and blood lipids in umbilical vein and umbilical artery blood of newborns with different delivery modes, and to evaluate their value as indicators of fetal intrauterine nutrition and nutritional support. METHODS: A total of 89 pairs of mothers and infants who were delivered in Danyang People's Hospital of Jiangsu Province from June to September 2021 were selected as the study subjects, including 38 cases of spontaneous delivery and 51 cases of cesarean section. The basic information of pregnant women, pregnancy information, newborn delivery and physical examination information were extracted from the medical record information system of the hospital. According to the mode of delivery, HITACHI 7600 automatic biochemical analyzer was used to measure the levels of protein, glucose and blood lipids in umbilical vein and umbilical artery blood, including total protein(TP), albumin(ALB), glucose(GLU), total cholesterol(TC), triglyceride(TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C). The data were statistically analyzed using IBM SPSS Statistics 26.0 statistical software. RESULTS: The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in the umbilical vein blood of the spontaneous delivery group were(56.40±5.83)g/L, (38.41±3.43)g/L, (4.55±1.53)mmol/L, (1.68±0.42)mmol/L, (0.25±0.11)mmol/L, (0.84±0.17)mmol/L and(0.69±0.23)mmol/L, respectively. The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in umbilical artery blood were(56.49±9.91)g/L, (37.72±4.77)g/L, (4.07±1.52)mmol/L, (1.60±0.42)mmol/L, (0.24±0.10)mmol/L, (0.80±0.18)mmol/L and(0.68±0.24)mmol/L, respectively. The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in umbilical vein blood of cesarean section group were(52.08±4.12)g/L, (36.12±2.13)g/L, (3.45±1.16)mmol/L, (1.61±0.39)mmol/L, (0.19±0.08)mmol/L, (0.82±0.18)mmol/L and(0.61±0.20)mmol/L, respectively. The levels of TP, ALB, GLU, TC, TG, HDL-C and LDL-C in umbilical artery blood were(51.49±7.59)g/L, (35.40±3.60)g/L, (3.09±1.15)mmol/L, (1.48±0.40)mmol/L, (0.19±0.08)mmol/L, (0.78±0.18)mmol/L and(0.60±0.20)mmol/L, respectively. The levels of TP, ALB, Glu and TG in cord vein blood and cord artery blood in spontaneous labor group were significantly higher than those in cesarean section group(P<0.05); The levels of Glu, TC, TG and HDL-C in cord vein blood were significantly higher in spontaneous labor group and cesarean section group than those in cord artery blood(P<0.05). CONCLUSION: The levels of protein, glucose and blood lipids in umbilical vein and umbilical artery blood were different among different delivery modes.

[Effect of different delivery modes on the level of cortical hormones in cord artery and vein blood].

OBJECTIVE: To investigate the difference of cortical hormones in cord artery and vein blood of newborns with different delivery modes. METHODS: A total of 65 pregnant women who delivered in the People's Hospital of Danyang City, Jiangsu Province from June to September 2021 were selected as the study subjects, including 26 cases of spontaneous delivery and 39 cases of cesarean section. The basic information of 65 pregnant women and newborns was collected by questionnaire survey. According to the mode of delivery, the levels of corticosteroids in umbilical vein and umbilical artery blood were determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS), including corticosterone, 11-desoxycorticosterone, aldosterone, cortisol, 11-deoxycortisol and cortisone. The data were statistically analyzed using IBM SPSS Statistics 26.0 statistical software. RESULTS: The levels of cortisol, 11-deoxycortisol, aldosterone, cortisol, 11-deoxycortisol and cortisone in the umbilical vein blood of the spontaneous delivery group were(2.44±1.87), (0.64±0.29), (0.49±0.35), (54.95±40.80), (3.20±1.23) and(142.27±57.42)ng/mL, respectively. The levels of corticosterone, 11-deoxycortisol, aldosterone, cortisol, 11-deoxycortisol and cortisone in umbilical artery blood were(4.51±4.47), (0.57±0.28), (0.42±0.29), (60.79±45.53), (2.69±1.25) and(123.10±46.32)ng/mL, respectively. The levels of corticosterone, 11-deoxycortisone, aldosterone, cortisol, 11-deoxycortisone and cortisone in umbilical vein blood of cesarean section group were(0.94±1.09), (0.47±0.14), (0.26±0.14), (22.63±19.82), (2.30±0.90) and(84.51±29.49)ng/mL, respectively. The levels of corticosterone, 11-deoxycortisol, aldosterone, cortisol, 11-deoxycortisol and cortisone in umbilical artery blood were(2.22±2.24), (0.43±0.17), (0.27±0.14), (30.09±25.93), (1.87±0.76) and(75.03±24.90)ng/mL, respectively. The levels of corticosterone, 11-desoxycorticosterone, aldosterone, cortisol, 11-deoxycortisol and cortisone in cord vein blood and cord artery blood in spontaneous labor group were significantly higher than those in cesarean section group(P<0.05). The levels of corticosterone and cortisol in cord vein blood were significantly lower in spontaneous labor group and cesarean section group than those in cord artery blood(P<0.05), the levels of 11-desoxycorticosterone, 11-deoxycortisol and cortisone in cord vein blood were significantly higher in spontaneous labor group and cesarean section group than those in cord artery blood(P<0.05). CONCLUSION: There are differences in the level of cortical hormones in cord artery and vein blood in different delivery modes.

[Meta analysis of the validity of image-based dietary assessment method based on energy and macronutrients].

OBJECTIVE: Meta-analysis was used to study the validity of image-based dietary assessment(IBDA) in evaluating energy and macronutrients intake, and compared with three traditional method: weighed food record(WFR), 24-hour dietary recall(24-HDR) and double-labeled water(DLW). METHODS: Studies were retrieved and collected from various databases including China National Knowledge Infrastructure(CNKI), WanFang Database, VIP Database, PubMed, Web of Science, Cochrane Library and Embase, screened according to the inclusion and exclusion criteria. After extracting the data, all the data were Meta-analyzed through RevMan 5.4. RESULTS: A total of 24 studies were included. Meta-analysis showed that, comparison of IBDA method and traditional method in energy intake assessment[MD=-54.71 kcal/d(95%CI-118.81-9.39), P=0.09], comparison of carbohydrate intake assessment[MD=-2.77 g(95%CI-8.86-3.31), P=0.37], comparison of protein intake assessment[MD=0.00 g(95%CI-2.09-2.09), P>0.05], comparison of fat intake assessment[MD=0.10 g(95%CI-2.06-2.25), P=0.93], these differences were not statistically significant. Subgroup analysis showed that, IBDA method compared with the 24-hour dietary review method in protein intake(P=0.01), the difference was statistically significant. IBDA method overestimated protein intake by about 7.3% on average compared with the 24-hour dietary review method. CONCLUSION: There was no significant difference between IBDA method and traditional method in the assessment of energy and macronutrient intakes.

Identification and distribution of HIV type 1 genetic diversity and protease inhibitor resistance-associated mutations in Shanghai, P. R. China.

OBJECTIVE: To investigate the genetic diversity of the HIV-1 circulating in Shanghai and to analyze the mutations in the protease (PR) gene associated with resistance to protease inhibitors (PIs). DESIGN: The genetic diversity of HIV-1 and PI resistance-associated mutations was studied in 40 Shanghai HIV-1-seropositive treatment-naive residents. The patients studied were exposed to the infection mainly through contaminated blood products (hemophiliacs) (n = 17) and sexual contacts (n = 19). Samples from 2 injecting drug users (IDUs) and 2 children born to HIV-1 infected mothers were also analyzed. METHODS: HIV-1 partial gag, pol, and env genes in infected plasma samples were amplified by reverse transcriptase polymerase chain reaction, sequenced, and phylogenetically analyzed. Analysis of PI resistance-associated amino acid substitution in PR was performed. RESULTS: HIV-1 genes in 38 of the 40 plasma samples were successfully amplified and analyzed. Polymerase chain reaction amplification was successful for 16/17 hemophilia patients and 18/19 sexually infected individuals. While all the 16 hemophilia patients infected through contaminated blood products were infected with subtype B', the 18 patients infected through sexual contact were infected with several subtypes including subtype A (n = 2), B (n = 4), B' (n = 1), C (n = 2), CRF08_BC (n = 1), CRF01_AE (n = 7), and intersubtype recombinant CRF01_AE/B (n = 1). The 2 IDUs were infected with CRF08_BC and the 2 children born to HIV-1 infected mothers were infected with subtype B' and CRF01_AE. PI resistance-associated amino acid substitutions were found at 1 codon in primary and 7 codons in secondary regions of the PR gene. Amino acid substitutions were more frequently found in the B/B' sequences (69%) than in the non-B sequences (31%). Substitutions characteristic with the subtype B/B' sequences mainly among hemophiliacs included L63P (87%), A71V/T (27%), and V77I (93%) while those that characterized the non-B sequences mainly found among heterosexuals included M36I (69%) and K20R (19%). CONCLUSION: This study reveals the presence of multiple HIV-1 subtypes and recombinants infecting Shanghai residents. The broad HIV-1 diversity is being introduced into this city through heterosexual contacts. This study also reveals that viruses infecting these treatment-naive patients have acquired both primary or secondary mutations in their PR genes. These studies should provide the basis for further epidemiologic surveys of HIV-1 subtypes and set strategies for treatment intervention and vaccine programs.