A novel autoantibody signatures for enhanced clinical diagnosis of pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease that requires precise diagnosis for effective treatment. However, the diagnostic value of carbohydrate antigen 19 - 9 (CA19-9) is limited. Therefore, this study aims to identify novel tumor-associated autoantibodies (TAAbs) for PDAC diagnosis. METHODS: A three-phase strategy comprising discovery, test, and validation was implemented. HuProt™ Human Proteome Microarray v3.1 was used to screen potential TAAbs in 49 samples. Subsequently, the levels of potential TAAbs were evaluated in 477 samples via enzyme-linked immunosorbent assay (ELISA) in PDAC, benign pancreatic diseases (BPD), and normal control (NC), followed by the construction of a diagnostic model. RESULTS: In the discovery phase, protein microarrays identified 167 candidate TAAbs. Based on bioinformatics analysis, fifteen tumor-associated antigens (TAAs) were selected for further validation using ELISA. Ten TAAbs exhibited differentially expressed in PDAC patients in the test phase (P < 0.05), with an area under the curve (AUC) ranging from 0.61 to 0.76. An immunodiagnostic model including three TAAbs (anti-HEXB, anti-TXLNA, anti-SLAMF6) was then developed, demonstrating AUCs of 0.81 (58.0% sensitivity, 86.0% specificity) and 0.78 (55.71% sensitivity, 87.14% specificity) for distinguishing PDAC from NC. Additionally, the model yielded AUCs of 0.80 (58.0% sensitivity, 86.25% specificity) and 0.83 (55.71% sensitivity, 100% specificity) for distinguishing PDAC from BPD in the test and validation phases, respectively. Notably, the combination of the immunodiagnostic model with CA19-9 resulted in an increased positive rate of PDAC to 92.91%. CONCLUSION: The immunodiagnostic model may offer a novel serological detection method for PDAC diagnosis, providing valuable insights into the development of effective diagnostic biomarkers.

Associations of plasma glycerophospholipid profile with modifiable lifestyles and incident diabetes in middle-aged and older Chinese.

AIMS/HYPOTHESIS: Glycerophospholipid (GPL) perturbance was linked to the pathogenesis of diabetes in animal studies but prospective studies in humans are rare, particularly in Asians. We aimed to investigate the associations between plasma GPLs and incident diabetes and to explore effects of lifestyle on the associations in a Chinese population. METHODS: The study included 1877 community-dwelling Chinese individuals aged 50-70 years (751 men and 1126 women), free of diabetes at baseline and followed for 6 years. A total of 160 GPL species were quantified in plasma at baseline by using high-throughput targeted lipidomics. Log-Poisson regression was used to assess the associations between GPLs and incidence of diabetes. RESULTS: Over the 6 years of follow-up, 499 participants (26.6%) developed diabetes. After multivariable adjustment, eight GPLs were positively associated with incident diabetes (RRper SD 1.13-1.25; all false-discovery rate [FDR]-corrected p < 0.05), including five novel GLPs, namely phosphatidylcholines (PCs; 16:0/18:1, 18:0/16:1, 18:1/20:3), lysophosphatidylcholine (LPC; 20:3) and phosphatidylethanolamine (PE; 16:0/16:1), and three reported GPLs (PCs 16:0/16:1, 16:0/20:3 and 18:0/20:3). In network analysis, a PC-containing module was positively associated with incident diabetes (RRper SD 1.16 [95% CI 1.06, 1.26]; FDR-corrected p < 0.05). Notably, three of the diabetes-associated PCs (16:0/16:1, 16:0/18:1 and 18:0/16:1) and PE (16:0/16:1) were associated not only with fatty acids in the de novo lipogenesis (DNL) pathway, especially 16:1n-7 (Spearman correlation coefficients = 0.35-0.62, p < 0.001), but also with an unhealthy dietary pattern high in refined grains and low in fish, dairy and soy products (|factor loadings| ≥0.2). When stratified by physical activity levels, the associations of the eight GPLs and the PC module with incident diabetes were stronger in participants with lower physical activity (RRper SD 1.24-1.49, FDR-corrected p < 0.05) than in those with the median and higher physical activity levels (RRper SD 1.03-1.12, FDR-corrected p ≥ 0.05; FDR-corrected pinteraction < 0.05). CONCLUSIONS/INTERPRETATION: Eight GPLs, especially PCs associated with the DNL pathway, were positively associated with incident diabetes in a cohort of Chinese men and women. The associations were most prominent in participants with a low level of physical activity.

Different Isocaloric Meals and Adiposity Modify Energy Expenditure and Clinical and Metabolomic Biomarkers During Resting and Exercise States in a Randomized Crossover Acute Trial of Normal-Weight and Overweight/Obese Men.

BACKGROUND: Few studies have assessed the integrative effects of diet, BMI, and exercise on postprandial changes in energy and circulating metabolic profiles. OBJECTIVES: We aimed to assess the collective effects of 3 isocaloric meals high in carbohydrate (74.2% energy), fat (64.6% energy), or protein (39.5% energy) on energy expenditure and clinical and metabolomic biomarkers under resting and exercise conditions in normal-weight and overweight/obese men. METHODS: This crossover controlled acute trial included 20 normal-weight (BMI, 18.5 to <24 kg/m2) and 20 overweight/obese (BMI ≥24 kg/m2) men aged 18-45 years. Each of 3 test meals was provided for 2 continuous days: a resting day without exercise, followed by an exercise day with a bicycling exercise of 50% maximal oxygen consumption (postprandial 90-120 minutes). Energy expenditure (exploratory outcome of primary interest) was measured using indirect calorimetry. Fasting and postprandial 2-hour serum clinical and metabolomic biomarkers (secondary interest) were measured. Mixed models were used to examine the effects of meal, time, and/or BMI category. RESULTS: On the resting day, no significant between-meal differences were detected for energy expenditure. However, high-carbohydrate and high-fat meals induced the highest postprandial 2-hour increase in glucose (0.34 ± 0.15 mmol/L) and triglyceride (0.95 ± 0.09 mmol/L), respectively, while the high-protein meal reduced glucose (-0.48 ± 0.08 mmol/L) and total cholesterol (-0.01 ± 0.03 mmol/L; all Pmeal values < 0.001). On the exercise day, a high-carbohydrate meal significantly promoted the carbohydrate oxidation rate but suppressed the fat oxidation rate (Pmeal < 0.05), while its postprandial glucose response was attenuated by bicycling (-0.31 ± 0.03 mmol/L; Pexercise < 0.001). We identified 69 metabolites as key features in discriminating between the 3 meals, and overweight/obese men had more varieties of metabolites than normal-weight men. CONCLUSIONS: Three isocaloric meals induced unique postprandial changes in clinical and metabolomic biomarkers, while exercise prevented the hyperglycemia induced by a high-carbohydrate meal. Overweight/obese men were more responsive to the meal challenges than normal-weight men. This trial was registered at clinicaltrials.gov as NCT03231618.

Different Isocaloric Meals and Adiposity Modify Energy Expenditure and Clinical and Metabolomic Biomarkers During Resting and Exercise States in a Randomized Crossover Acute Trial of Normal-Weight and Overweight/Obese Men.

BACKGROUND: Few studies have assessed the integrative effects of diet, BMI, and exercise on postprandial changes in energy and circulating metabolic profiles. OBJECTIVES: We aimed to assess the collective effects of 3 isocaloric meals high in carbohydrate (74.2% energy), fat (64.6% energy), or protein (39.5% energy) on energy expenditure and clinical and metabolomic biomarkers under resting and exercise conditions in normal-weight and overweight/obese men. METHODS: This crossover controlled acute trial included 20 normal-weight (BMI, 18.5 to <24 kg/m2) and 20 overweight/obese (BMI ≥24 kg/m2) men aged 18-45 years. Each of 3 test meals was provided for 2 continuous days: a resting day without exercise, followed by an exercise day with a bicycling exercise of 50% maximal oxygen consumption (postprandial 90-120 minutes). Energy expenditure (exploratory outcome of primary interest) was measured using indirect calorimetry. Fasting and postprandial 2-hour serum clinical and metabolomic biomarkers (secondary interest) were measured. Mixed models were used to examine the effects of meal, time, and/or BMI category. RESULTS: On the resting day, no significant between-meal differences were detected for energy expenditure. However, high-carbohydrate and high-fat meals induced the highest postprandial 2-hour increase in glucose (0.34 ± 0.15 mmol/L) and triglyceride (0.95 ± 0.09 mmol/L), respectively, while the high-protein meal reduced glucose (-0.48 ± 0.08 mmol/L) and total cholesterol (-0.01 ± 0.03 mmol/L; all Pmeal values < 0.001). On the exercise day, a high-carbohydrate meal significantly promoted the carbohydrate oxidation rate but suppressed the fat oxidation rate (Pmeal < 0.05), while its postprandial glucose response was attenuated by bicycling (-0.31 ± 0.03 mmol/L; Pexercise < 0.001). We identified 69 metabolites as key features in discriminating between the 3 meals, and overweight/obese men had more varieties of metabolites than normal-weight men. CONCLUSIONS: Three isocaloric meals induced unique postprandial changes in clinical and metabolomic biomarkers, while exercise prevented the hyperglycemia induced by a high-carbohydrate meal. Overweight/obese men were more responsive to the meal challenges than normal-weight men. This trial was registered at clinicaltrials.gov as NCT03231618.

Popliteal Artery Injury After Fracture and/or Dislocation of the Knee: Risk Stratification for Revascularization Outcome.

BACKGROUND: Managing complex knee trauma involving both vascular and osseous injuries is challenging, yet the available guidelines for efficient popliteal artery injury management after high-velocity blunt knee trauma remain conflicting and inconsistent. In this study, the authors aim to identify the risk factors associated with delayed limb amputation and ischemic muscular sequela postrevascularization. Furthermore, we propose a treatment algorithm to improve the limb salvage rate. METHODS: Patients who presented with traumatic popliteal artery injury resulting in vessel occlusion or rupture, followed by fracture and/or dislocation of the knee from January 2008 to December 2013, were included for retrospective review. RESULTS: Overall delayed amputation rate was 24% (7/29) and 16% (4/25) after successful revascularization. Mangled Extremity Severity Score is higher in the delayed amputation group than the limb-salvaged group (P = 0.02). Higher-impact force (P = 0.03), ischemic limb on presentation (P = 0.03), prolonged ischemia time (P = 0.04), unstable hemodynamics (P = 0.01), longer operation time (P = 0.04), and prolonged intensive care unit stay (P = 0.03) are risk factors of delayed amputation. Longer ischemia time (P = 0.04) and length of popliteal artery injury (P = 0.02) are associated with ischemic muscular sequela. CONCLUSIONS: Mangled Extremity Severity Score is a reliable predictor of limb salvage. An algorithmic approach may improve the outcome of popliteal artery injury after high-velocity blunt knee trauma.

The Effect of Narrow-Band Ultraviolet B Irradiation on the Vascularized Composite Allotransplantation Rat Model.

INTRODUCTION: Vascularized composite allotransplantation (VCA) allows functional and esthetic reconstruction for patients with complex anatomical defects. However, acute and chronic graft rejections are significant obstacles to VCA. Ultraviolet light is an oncogenic environmental hazard. However, ultraviolet B (UVB) has an immunomodulation effect. Therefore, this study aims to elucidate the impact of UVB irradiation on the VCA rat model. METHODS: The rat vascularized bone marrow allotransplantation model was used. A vascularized bone marrow from a Brown Norway rat (RT1Ac) was transplanted into a Lewis rat (RT1Ab). The allograft and surrounding abdominal skin were exposed to narrow-band ultraviolet B (NB-UVB) (311 nm) radiation with an energy of 1350 mJ/cm2 3 times a week until the end of the study period. There were 5 study groups: syngeneic transplantation (group 1), allogeneic transplantation (group 2), allogenic transplantation-NB-UVB (group 3), allogenic transplantation-antilymphocyte serum (ALS)-tacrolimus (group 4), and allogenic transplantation-antilymphocyte serum-tacrolimus-NB-UVB (group 5). RESULTS: Group 5 had decreased graft survival compared with group 4. In the donor cell chimerism analysis, donor cell chimerism decreased significantly after UVB irradiation and was unresponsive to the administered immunosuppressants. After UVB irradiation, the CD8 T-cell ratio was increased, and the regulatory T-cell ratio was decreased. CONCLUSIONS: The preliminary data showed that NB-UVB irradiation of the VCA rat model may decrease graft survival. However, further studies are needed to elucidate the possible mechanisms of this phenomenon.

Early combined rehabilitation intervention to improve the short-term prognosis of premature infants.

BACKGROUND: To explore the clinical effect of early combined rehabilitation intervention on premature infants in the neonatal intensive care unit (NICU). METHODS: Premature infants with gestational ages less than 32 weeks or birth weights less than 1500 g were included in the present study.The participants were divided into the intervention group and control group. All infants received the current routine treatment based on the clinical guidelines, and the intervention group was additionally treated by visual and auditory stimulation, oral motor function, respiratory function and neurodevelopmental training. The following clinical outcomes were compared: durations of oxygen supplementation and indwelling gastric tube use; incidences of retinopathy of prematurity (ROP) and neonatal necrotizing enterocolitis (NEC); Sliverman scores; incidences of bronchopulmonary dysplasia (BPD) and intraventricular haemorrhage; days of hospitalization; and neurodevelopmental outcomes. Datas were analysed using the following statistical tests: the chi-square test, the independent samples or paired t test, repeated measures ANOVA, and the Wilcoxon rank sum test. RESULTS: Compared with those in the control group, premature infants in the intervention group had shorter durations of oxygen supplementation and indwelling gastric tube use, fewer hospitalization days and lower incidences of ROP, BPD, and NEC.The intervention group had lower Sliverman scores and higher Ballard neuromuscular scores than the control group. CONCLUSION: Early combined rehabilitation intervention can improve the short-term clinical outcomes of premature infants.

Associations among circulating sphingolipids, ß-cell function, and risk of developing type 2 diabetes: A population-based cohort study in China.

BACKGROUND: Animal studies suggest vital roles of sphingolipids, especially ceramides, in the pathogenesis of type 2 diabetes (T2D) via pathways involved in insulin resistance, ß-cell dysfunction, and inflammation, but human studies are limited. We aimed to evaluate the associations of circulating sphingolipids with incident T2D and to explore underlying mechanisms. METHODS AND FINDINGS: The current study included 826 men and 1,148 women who were aged 50-70 years, from Beijing and Shanghai, and without T2D in 2005 and who were resurveyed in 2011. Cardiometabolic traits were measured at baseline and follow-up surveys. A total of 76 sphingolipids were quantified using high-coverage targeted lipidomics. Summary data for 2-sample Mendelian randomization were obtained from genome-wide association studies of circulating sphingolipids and the China Health and Nutrition Survey (n = 5,731). During the 6-year period, 529 participants developed T2D. Eleven novel and 3 reported sphingolipids, namely ceramides (d18:1/18:1, d18:1/20:0, d18:1/20:1, d18:1/22:1), saturated sphingomyelins (C34:0, C36:0, C38:0, C40:0), unsaturated sphingomyelins (C34:1, C36:1, C42:3), hydroxyl-sphingomyelins (C34:1, C38:3), and a hexosylceramide (d18:1/20:1), were positively associated with incident T2D (relative risks [RRs]: 1.14-1.21; all P < 0.001), after multivariate adjustment including lifestyle characteristics and BMI. Network analysis further identified 5 modules, and 2 modules containing saturated sphingomyelins showed the strongest associations with increased T2D risk (RRQ4 versus Q1 = 1.59 and 1.43; both Ptrend < 0.001). Mediation analysis suggested that the detrimental associations of 13 sphingolipids with T2D were largely mediated through ß-cell dysfunction, as indicated by HOMA-B (mediation proportion: 11.19%-42.42%; all P < 0.001). Moreover, Mendelian randomization evidenced a positive association between a genetically instrumented ceramide (d18:1/20:1) and T2D (odds ratio: 1.15 [95% CI 1.05-1.26]; P = 0.002). Main limitations in the current study included potential undiagnosed cases and lack of an independent population for replication. CONCLUSIONS: In this study, we observed that a panel of novel sphingolipids with unique structures were positively associated with incident T2D, largely mediated through ß-cell dysfunction, in Chinese individuals.

The prevalence and clinical characteristics of tick-borne diseases at One Sentinel Hospital in Northeastern China.

Northeastern China is a region of high tick abundance, multiple tick-borne pathogens and likely human infections. The spectrum of diseases caused by tick-borne pathogens has not been objectively evaluated in this region for clinical management and for comparison with other regions globally where tick-transmitted diseases are common. Based on clinical symptoms, PCR, indirect immunofluorescent assay and (or) blood smear, we identified and described tick-borne diseases from patients with recent tick bite seen at Mudanjiang Forestry Central Hospital. From May 2010 to September 2011, 42% (75/180) of patients were diagnosed with a specific tick-borne disease, including Lyme borreliosis, tick-borne encephalitis, human granulocytic anaplasmosis, human babesiosis and spotted fever group rickettsiosis. When we compared clinical and laboratory features to identify factors that might discriminate tick-transmitted infections from those lacking that evidence, we revealed that erythema migrans and neurological manifestations were statistically significantly differently presented between those with and without documented aetiologies (P < 0.001, P = 0.003). Twelve patients (6.7%, 12/180) were co-infected with two tick-borne pathogens. We demonstrated the poor ability of clinicians to identify the specific tick-borne disease. In addition, it is necessary to develop specific laboratory assays for optimal diagnosis of tick-borne diseases.

Effects of Systemic and Local Caffeine on Vessel Diameter, Anastomosis Patency, and Intimal Hyperplasia in the Rat.

BACKGROUND: The use of caffeine is not recommended prior to elective microsurgery due to its demonstrated negative effects on vessel anastomosis by the presumed sympathomimetic induction of vasoconstriction. In this study, we aimed to elucidate the systemic and local effects of caffeine on vessel diameter, anastomosis patency, and degree of intimal hyperplasia during the healing process. METHODS: Twenty-five rats were randomly assigned to five groups: (1) negative control, (2) preoperative systemic caffeine, (3) postoperative systemic caffeine, (4) perioperative systemic caffeine, and (5) a local caffeine group. Both the right and left femoral arteries were used. Ten anastomoses were performed per group. The arterial diameter was measured by micrometer, anastomosis patency was assessed surgically and histologically, and the histological examination was conducted 3 weeks postoperatively to determine intimal hyperplasia. RESULTS: The overall patency rate was 96%. Mild vasoconstriction was observed in the systemic caffeine groups (statistically insignificant); however, there were no negative effects on anastomosis patency. Local caffeine irrigation resulted in significant vasodilatation in the local caffeine group (p = 0.001); a similar effect was not observed in the other groups. There was a significant decrease in the intima/media ratio in the local caffeine group (p < 0.01), when compared with the control and systemic caffeine groups. No other intima/media ratio differences were observed among other comparison groups. CONCLUSION: The systemic administration of caffeine, although statistically insignificant, has an observable effect on vasoconstriction. However, it does not appear to have negative effects on anastomosis patency regardless of its application period (pre-, post-, or perioperatively). The local application of caffeine resulted in considerable vasodilatation as opposed to the vasoconstriction effect in the systemic caffeine groups. Decreased intimal hyperplasia at the anastomosis edge, and antifibrotic properties in the surgical field were also observed in this group. Histologically, the local caffeine group demonstrated an additional beneficial effect on anastomosis remodeling.

Phase I/II study of adjuvant immunotherapy with sentinel lymph node T lymphocytes in patients with colorectal cancer.

Although the development of multi-disciplinary management has improved the survival of colorectal cancer (CRC), the prognosis of metastatic CRC patients remains poor. Accumulating evidence has demonstrated that immunotherapy with cancer vaccines and adoptive T cell transfusions may improve outcomes as an adjuvant to current standard CRC treatment. In this phase I/II study, 71 CRC patients who underwent radical surgery (stage I-III, n = 46) or palliative surgery (stage IV with non-resectable synchronous metastases, n = 25) were included. In the first part of this study, sentinel lymph nodes (SLNs) were intraoperatively identified in 55 patients (46 with stage I-III CRC and 9 with stage IV CRC). SLN-T lymphocytes were expanded ex vivo for a median of 28.5 days (range 23-33 days). Thereafter, a median of 153 × 10(6) cells (range 20.7-639.0 × 10(6)) were transfused. No treatment-related toxicity was observed. In the second part of this study, the stage IV patients were routinely followed. The 24-month survival rate of the SLN-T lymphocyte group was significantly higher than that of the control group: 55.6 versus 17.5% (p = 0.02). The median overall survival of the SLN-T lymphocyte and control groups was 28 and 14 months, respectively. Our study showed that adjuvant SLN-T lymphocyte immunotherapy is feasible and safe for postoperative CRC patients. Additionally, this therapy may improve the long-term survival of metastatic CRC. Further investigation of the clinical efficacy and anti-tumor immunity is warranted.

Lactobacillus bulgaricus mutants decompose uremic toxins.

BACKGROUND/AIMS: We aim to obtain a probiotic strain from Lactobacillus bulgaricus by testing its capability to decompose uremic toxins to provide new intestinal bacteria for the treatment of chronic renal failure. METHODS: Original L. bulgaricus was cultured with the serum of uremic patients and then mutated by physical (ultraviolet) and chemical (diethyl sulfate) methods repeatedly. Using creatinine decomposition rate as an observed index, we selected the best strains which decreased the most concentration of the creatinine. We then tested its ability to decompose urea, uric acid, serum phosphate, parathyroid hormone, and homocysteine and its genetic stability. RESULTS: After inductive and mutagenic treatment, DUC3-17 was selected. Its decomposition rate of creatinine, urea nitrogen, uric acid, phosphorus, parathyroid hormone, and homocysteine were 17.23%, 36.02%, 9.84%, 15.73%, 78.26%, and 12.69%, respectively. The degrading capacity was sustained over five generations. CONCLUSIONS: After directional induction and compound mutation, L. bulgaricus has greater capacity to decompose uremic toxins, with a stable inheritance.

[Effect of jiaotai pill on pancreatic fat accumulation and islet cell apoptosis in rats with type 2 diabetes].

In this study, the rat type 2 diabetes mellitus (T2DM) model was established through tail vein injection with low dose of streptozotocin (STZ) and high fat diet for 8 weeks, and then treated with Jiaotai Pill. The oral glucose tolerance test (OGTT), fasting serum insulin (FINS), free fatty acid(FFA) levels and blood lipid were assayed. HOMA-IR was calculated. Pancreatic pathology was performed. And pancreatic triglyceride (TG) content was examined by the lipid extraction method. Pancreatic islet cell apoptosis were detected by terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL). According to the results, the model group showed abnormal OGTT, increased FINS, HOMA-IR, FFA, lipid disorder, obvious fat accumulation and significantly increased TG content in pancreatic tissues, and enhanced pancreatic islet cell apoptosis. Compared with the model group, the Jiaotai Pill group displayed improved OGTT, reduced FINS, HOMA-IR, FFA, recovered lipid disorder, decreased fat accumulation and significantly declined TG content in pancreatic tissues, and lowered pancreatic islet cell apoptosis. In summary, Jiaotai pill could effectively treat type 2 diabetes in rats. Its mechanism may be related to the reduction in pancreatic fat accumulation and islet cell apoptosis.

[Effects of steaming and baking on content of alkaloids in Aconite Lateralis Radix (Fuzi)].

To study the effect of steaming and baking process on contents of alkaloids in Aconite Lateralis Radix (Fuzi), 13 alkaloids were analyzed by UPLC-MS/MS equipped with ESI ion source in MRM mode. In steaming process, the contents of diester-diterpenoid alkaloids decreased rapidly, the contents of monoester-diterpenoid alkaloids firstly increased, reached the peak at 40 min, and then deceased gradually. The contents of aconine alkaloids (mesaconine, aconine and hypaconine) increased all the time during processing, while the contents of fuziline, songorine, karacoline, salsolionl were stable or slightly decreased. In baking process, dynamic variations of alkaloids were different from that in the steaming process. Diester-diterpenoid alkaloids were degraded slightly slower than in steaming process. Monoester-diterpenoid alkaloids, aconine alkaloids and the total alkaloids had been destroyed at different degrees, their contents were significantly lower than the ones in steaming Fuzi at the same processing time. This experiment revealed the dynamic variations of alkaloids in the course of steaming and baking. Two processing methods which can both effectively remove the toxic ingredients and retain the active ingredients are simple and controllable, and are valuable for popularization and application.

Evolution and Diversity of Medial Sural Artery Perforator Flap for Hand Reconstruction.

The free medial sural artery perforator (MSAP) flap is a recently popularized flap. It has evolved from a composite myocutaneous flap to a pedicled perforator flap for lower limb reconstruction. It is also a versatile free perforator flap for extremity and head and neck reconstruction. The diversity of the flap designs with options for harvest of non-vascularized grafts enhances the versatility for hand and upper limb reconstruction. The adjunctive use of endoscopy and indocyanine green fluorescence imaging studies can assist and demystify the flap anatomy. The authors present their experience using free MSAP flaps for complex mutilated hand and upper extremity reconstruction.

Appendiceal intussusception complicated by adenocarcinoma of the cecum: A case report.

BACKGROUND: Appendiceal intussusception is a pathological condition in which the appendix is inverted into the cecum, which may cause symptoms that resemble those of other gastrointestinal disorders and may induce intestinal obstruction. The rarity of this case presentation is the co-occurrence of appendiceal intussusception and cecal adenocarcinoma, a combination that to our knowledge has not previously been reported in the medical literature. This case provides new insights into the complexities of diagnosing and managing overlapping pathologies. CASE SUMMARY: A 25-year-old woman presented with persistent periumbilical pain and bloody stools. An initial biopsy showed cecal cancer; however, subsequent colonoscopy and computed tomography findings raised the suspicion of appendiceal intussusception, which was later confirmed postoperatively. This unique case was characterized by a combination of intussusception and adenocarcinoma of the cecum. The intervention included a laparoscopic right hemicolectomy, which led to the histopathological diagnosis of mucinous adenocarcinoma with appendiceal intussusception. The patient recovered well postoperatively and was advised to initiate adjuvant chemotherapy. This case highlights not only the importance of considering appendiceal intussusception in the differential diagnosis, but also the possibility of appendicitis and the atypical presentation of neoplastic lesions. CONCLUSIONS: Physicians should consider the possibility of appendiceal intussusception in cases of atypical appendicitis, particularly when associated with neoplastic presentation.

24-h urinary sodium and potassium excretions, plasma metabolomic profiles, and cardiometabolic biomarkers in the United States adults: a cross-sectional study.

BACKGROUND: High-sodium and low-potassium intakes are associated with a higher risk of hypertension and cardiovascular disease, but there are limited data on the circulating metabolomics profiles of 24-h urinary sodium and potassium excretions in free-living individuals. OBJECTIVES: We aimed to characterize the metabolomics signatures of a high-sodium and low-potassium diet in a cross-sectional study. METHODS: In 1028 healthy older adults from the Women's and Men's Lifestyle Validation Studies, we investigated the association of habitual sodium and potassium intakes measured by 2 to 4 24-h urine samples with plasma metabolites (quantified using liquid chromatography-tandem mass spectrometry) and metabolomic pathways. Our primary exposures were energy-adjusted 24-h urinary sodium excretion, potassium excretion, and sodium-to-potassium ratio, calculated based on energy expenditure derived from the doubly labeled water method. We then assessed the partial correlations of their metabolomics scores, derived from elastic net regressions, with cardiometabolic biomarkers. RESULTS: Higher sodium excretion was associated with 38 metabolites including higher piperine, phosphatidylethanolamine, and C5:1 carnitine. In pathway analysis, higher sodium excretion was associated with enhanced biotin and propanoate metabolism and enhanced degradation of lysine and branched-chain amino acids (BCAAs). Metabolites associated with higher potassium and lower sodium-to-potassium ratio included quinic acid and proline-betaine. After adjusting for confounding factors, the metabolomics score for sodium-to-potassium ratio positively correlated with fasting insulin (Spearman's rank correlation coefficient ρ = 0.27), C-peptide (ρ = 0.30), and triglyceride (ρ = 0.46), and negatively with adiponectin (ρ = -0.40), and high-density lipoprotein cholesterol (ρ = -0.42). CONCLUSIONS: We discovered metabolites and metabolomics pathways associated with a high-sodium diet, including metabolites related to biotin, propanoate, lysine, and BCAA pathways. The metabolomics signature for a higher sodium low-potassium diet is associated with multiple components of elevated cardiometabolic risk.

Enhancing immunogenicity and antiviral protection of inactivated porcine reproductive and respiratory syndrome virus vaccine in piglets.

OBJECTIVE: Porcine interferon-γ (poIFN-γ) and porcine granulocyte-macrophage colony-stimulating factor (poGM-CSF) are multifunctional cytokines that exhibit robust antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV). In this study, the immunoadjuvant effects of recombinant poIFN-γ-poGM-CSF fusion protein in inactivated PRRSV vaccine administered to piglets were assessed. ANIMALS: Twenty-eight 4-week-old specific pathogen-free piglets. METHODS: The experimental piglets were divided into control, highly pathologic PRRSV, PRRSV killed virus vaccine (KV), poIFN-γ-poGM-CSF, KV + 1.0 mg poIFN-γ-poGM-CSF, KV + 2.0 mg poIFN-γ-poGM-CSF, and KV + 4.0 mg poIFN-γ-poGM-CSF groups. A recombinant poIFN-γ-linker-poGM-CSF fusion gene was constructed via splicing by overlap extension PCR and prepared using an Escherichia coli expression system, after which its adjuvant activity in the context of PRRSV KV administration was assessed. RESULTS: This analysis revealed the successful construction of the poIFN-γ-linker-poGM-CSF fusion gene via splicing by overlap extension PCR, with recombinant poIFN-γ-linker-poGM-CSF successfully being prepared in E coli with a plasmid vector for expressing thioredoxin fusion proteins with an enterokinase site. Importantly, the coadministration of poIFN-γ-linker-poGM-CSF and PRRSV KV significantly increased neutralizing antibody titers, accelerated viral clearance, reduced clinical symptoms, and prevented highly pathogenic PRRSV infection. CLINICAL RELEVANCE: The recombinant poIFN-γ-poGM-CSF fusion protein is a promising candidate adjuvant for use in the context of swine immunization and viral challenge.

Effect of 1-year lifestyle intervention with energy-reduced Mediterranean diet and physical activity promotion on the gut metabolome and microbiota: a randomized clinical trial.

BACKGROUND: The health benefits of the Mediterranean diet (MedDiet) have been linked to the presence of beneficial gut microbes and related metabolites. However, its impact on the fecal metabolome remains poorly understood. OBJECTIVES: Our goal was to investigate the weight-loss effects of a 1-y lifestyle intervention based on an energy-reduced MedDiet coupled with physical activity (intervention group), compared with an ad libitum MedDiet (control group), on fecal metabolites, fecal microbiota, and their potential association with cardiovascular disease risk factors. METHODS: A total of 400 participants (200 from each study group), aged 55-75 y, and at high cardiovascular disease risk, were included. Dietary and lifestyle information, anthropometric measurements, blood biochemical parameters, and stool samples were collected at baseline and after 1 y of follow-up. Liquid chromatography-tandem mass spectrometry was used to profile endogenous fecal metabolites, and 16S amplicon sequencing was employed to profile the fecal microbiota. RESULTS: Compared with the control group, the intervention group exhibited greater weight loss and improvement in various cardiovascular disease risk factors. We identified intervention effects on 4 stool metabolites and subnetworks primarily composed of bile acids, ceramides, and sphingosines, fatty acids, carnitines, nucleotides, and metabolites of purine and the Krebs cycle. Some of these were associated with changes in several cardiovascular disease risk factors. In addition, we observed a reduction in the abundance of the genera Eubacterium hallii group and Dorea, and an increase in alpha diversity in the intervention group after 1 y of follow-up. Changes in the intervention-related microbiota profiles were also associated with alterations in different fecal metabolite subnetworks and some cardiovascular disease risk factors. CONCLUSIONS: An intervention based on an energy-reduced MedDiet and physical activity promotion, compared with an ad libitum MedDiet, was associated with improvements in cardiometabolic risk factors, potentially through modulation of the fecal microbiota and metabolome. This trial was registered at https://www.isrctn.com/ as ISRCTN89898870 (https://doi.org/10.1186/ISRCTN89898870).

Nutrition, DNA methylation and obesity across life stages and generations.

Obesity is a complex multifactorial condition that often manifests in early life with a lifelong burden on metabolic health. Diet, including pre-pregnancy maternal diet, in utero nutrition and dietary patterns in early and late life, can shape obesity development. Growing evidence suggests that epigenetic modifications, specifically DNA methylation, might mediate or accompany these effects across life stages and generations. By reviewing human observational and intervention studies conducted over the past 10 years, this work provides a comprehensive overview of the evidence linking nutrition to DNA methylation and its association with obesity across different age periods, spanning from preconception to adulthood and identify future research directions in the field.