Circadian Rhythm Disruption in Hepatocellular Carcinoma Investigated by Integrated Analysis of Bulk and Single-Cell RNA Sequencing Data.

Circadian rhythms are essential regulators of a multitude of physiological and behavioral processes, such as the metabolism and function of the liver. Circadian rhythms are crucial to liver homeostasis, as the liver is a key metabolic organ accountable for the systemic equilibrium of the body. Circadian rhythm disruption alone is sufficient to cause liver cancer through the maintenance of hepatic metabolic disorder. Although there is evidence linking CRD to hepatocarcinogenesis, the precise cellular and molecular mechanisms that underlie the circadian crosstalk that leads to hepatocellular carcinoma remain unknown. The expression of CRD-related genes in HCC was investigated in this study via bulk RNA transcriptomic analysis and single-cell sequencing. Dysregulated CRD-related genes are predominantly found in hepatocytes and fibroblasts, according to the findings. By using a combination of single-cell RNA sequencing and bulk RNA sequencing analyses, the dysregulated CRD-related genes ADAMTS13, BIRC5, IGFBP3, MARCO, MT2A, NNMT, and PGLYRP2 were identified. The survival analysis using the Kaplan-Meier method revealed a significant correlation between the expression levels of BIRC5 and IGFBP3 and the survival of patients diagnosed with HCC.

Cathelicidin Antimicrobial Peptide Acts as a Tumor Suppressor in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is associated with high rates of metastasis and recurrence, and is one of the most common causes of cancer-associated death worldwide. This study examined the protein changes within circulating exosomes in patients with HCC against those in healthy people using isobaric tags for a relative or absolute quantitation (iTRAQ)-based quantitative proteomics analysis. The protein levels of von Willebrand factor (VWF), cathelicidin antimicrobial peptide (CAMP), and proteasome subunit beta type-2 (PSMB2) were altered in HCC. The increased levels of VWF and PSMB2 but decreased CAMP levels in the serum of patients with HCC were validated by enzyme-linked immunosorbent assays. The level of CAMP (the only cathelicidin found in humans) also decreased in the circulating exosomes and buffy coat of the HCC patients. The serum with reduced levels of CAMP protein in the HCC patients increased the cell proliferation of Huh-7 cells; this effect was reduced following the addition of CAMP protein. The depletion of CAMP proteins in the serum of healthy people enhances the cell proliferation of Huh-7 cells. In addition, supplementation with synthetic CAMP reduces cell proliferation in a dose-dependent manner and significantly delays G1-S transition in Huh-7 cells. This implies that CAMP may act as a tumor suppressor in HCC.

Investigate the improvement of facial skin texture with the VISIA system after total thyroidectomy.

BACKGROUND: During clinical practice we have noticed that some patients with hyperthyroidism have finer skin with less wrinkles, pores, and spots after thyroidectomy, and the improvement can be observed within a few weeks after the operation. However, there is no evidence or study in the literature to proof this finding. AIM AND OBJECTIVE: This study was designed to evaluate and quantify the skin characters of patients with hyperthyroidism before and after thyroidectomy. MATERIAL AND METHODS: This is a prospective study to include patients with hyperthyroidism who received total thyroidectomy between March 1st, 2018 and February 28th, 2019. The patients received blood test for T4 and TSH analysis and VISIA measurements for skin texture quantification, at the preoperative stage, three, and six months postoperatively. A total of 8 patients were included. Repeated measurement was used to determine the lab data and VISIA measurement changes before and after the operation. Mauchly's sphericity test was performed to determine whether the violation of sphericity occurs, and the Greenhouse-Geisser correction was used when the violation of sphericity occurs. RESULTS: All the patients were female and generally healthy without systemic medical disease except the hyperthyroidism. The T4 and TSH levels were not significantly different before and after the thyroidectomy. In terms of the skin character measurements, the wrinkles, texture, pores, UV spots, and brown spots were not improved after thyroidectomy. A trend of improvement in spots, red area, and porphyrin was noted, although not statistically significant. CONCLUSIONS: Surgical removal of the thyroid gland in patients with hyperthyroidism does not improve the skin quality and texture in examinations via the VISIA system.

Risk factors associated with postoperative complications of free anterolateral thigh flap placement in patients with head and neck cancer: Analysis of propensity score-matched cohorts.

BACKGROUND: From the perspective of a surgeon, knowledge of the operative risk factors that may affect postoperative outcomes is important in free anterolateral thigh (ALT) flap reconstruction for head and neck defects after tumor ablation. Therefore, this study was designed to examine the surgical intervention factors related to postoperative complications in a propensity score matched patient population. PATIENTS AND METHODS: A total of 1,284 head and neck cancer patients who received free ALT flap repair over a 9-year period from March 1, 2008, to February 28, 2017, at a single medical center were selected and divided into two groups (without complications, n = 845 and with complications, n = 439) according to the presence or absence of complications at the recipient site. Complications were defined as the detection of hematoma, surgical site infection, partial flap loss, oral fistula formation, flap partial necrosis, and flap loss. Well-balanced propensity score-matched cohorts with 292 patients each were created using the 1:1 Greedy algorithm, with adjustment for significant baseline patient characteristics. RESULTS: The patients with postoperative complications had a higher proportion of individuals with betel nut chewing (91.8% vs. 86.6%, p = .008), diabetes mellitus (23.0% vs. 17.8%, p = .029), and preoperative chemotherapy (31.7% vs. 25.3%, p = .019), and higher serum creatinine levels (median [Q1-Q3]: 0.92 [0.80-1.07] vs. 0.89 [0.77-1.06], p = .008) and lower serum albumin levels (4.2 [3.9-4.5] vs. 4.3 [4.1-4.5], p < .001) than those without postoperative complications. Individual operator (p < .001), the length of flap (20 [15-23] cm vs. 20 [15-25] cm, p < .001), operative time (6.9 hr [5.7-8.3 hr] vs. 7.3 hr [5.9-8.7 hr], p = .001), operation start time (p = .003), and units of transfused packed red blood cells (0.0 [0.0-0.0] units vs. 0.0 [0.0-2.0] units, p < .001) were the factors significantly associated with the occurrence of postoperative complications. However, in the matched patient cohorts, individual operator (p = .003), flap length (18 [15-22] cm vs. 20 [15-25] cm, p < .001) and length-to-width ratio (2.6 [2.0-3.3] vs. 3.0 [2.5-3.6], p < .001), and operative time (6.9 hr [5.7-8.3 hr] vs. 7.2 hr [5.9-8.7 hr], p = .019) were associated with the occurrence of postoperative complications, but the operation start time (p = .285) and units of transfused packed red blood cells (p = .917) were not. CONCLUSIONS: This study demonstrated in matched patient cohorts that individual operator, flap size, and operative time were associated with postoperative complications of free ALT flap reconstruction in patients with head and neck cancer. To reduce the postoperative complication rate, this study implies the importance of length and length-to-width ratio in harvesting the flap, and meanwhile the surgeon experience in free-flap reconstruction.

Comparison of the outcomes between free anteromedial thigh flap and anterolateral thigh flap in head and neck cancer reconstruction: Analysis of propensity-score-matched patient cohorts.

BACKGROUND: The anterolateral thigh (ALT) flap is a workhorse flap in head and neck cancer reconstruction. The anteromedial thigh (AMT) flap was developed as a rescue or alternative flap whenever the ALT flap is not available; however, the harvest of AMT flap seems to be more challenging in the sense that perforators have multiple variations. This study was designed to compare the outcome of the AMT and ALT flaps in head and neck cancer reconstruction. METHODS: A total of 1,547 ALT and 57 AMT flaps were used for head and neck cancer reconstruction between March 1, 2008 and February 28, 2017. Differences in patient and operative characteristics were compared between the patients undergoing AMT and ALT flap reconstruction. The primary outcome of the free flap was its survival or failure, while the second outcome was the associated complications. RESULTS: Compared to those who had ALT flap reconstruction, the patients who underwent AMT flap reconstruction had a higher rate of conditions that required reconstruction after previous cancer ablation and recurrence but a lower rate of primary cancer and deeply located cancer. Analysis of the 40 well-balanced pairs of propensity-score-matched patient cohorts revealed that the AMT flaps were associated with a significantly higher failure rate than the ALT flaps (15.0 vs. 0.0%, respectively; p = .026). CONCLUSION: This study revealed that AMT flaps were associated with a significantly higher failure rate than ALT flaps in head and neck cancer reconstruction in the cohort of total patients and the propensity-score-matched cohorts.

The influence of ageing on the incidence and site of trauma femoral fractures: a cross-sectional analysis.

BACKGROUND: This study aimed to determine the influence of ageing on the incidence and site of femoral fractures in trauma patients, by taking the sex, body weight, and trauma mechanisms into account. METHODS: This retrospective study reviewed data from adult trauma patients aged ≥20 years who were admitted into a Level I trauma center, between January 1, 2009 and December 31, 2016. According to the femoral fracture locations, 3859 adult patients with 4011 fracture sites were grouped into five subgroups: proximal type A (n = 1359), proximal type B (n = 1487), proximal type C (n = 59), femoral shaft (n = 640), and distal femur (n = 466) groups. A multivariate logistic regression analysis was applied to identify independent effects of the univariate predictive variables on the occurrence of fracture at a specific site. A two-dimensional plot was presented visually with age and the propensity score accounts for the risk of a fracture at a specific femoral site. RESULTS: This analysis revealed that older age was an independent variable that could positively predict the occurrence of proximal type A (OR [95%CI]: 1.03 [1.03-1.04], p < 0.001) and B fractures (1.02 [1.01-1.02], p < 0.001), and negatively predict the occurrence of proximal type C (0.96 [0.94-0.98], p < 0.001), shaft (0.95 [0.95-0.96], p < 0.001), and distal fractures (0.98 [0.98-0.99], p < 0.001). DISCUSSION: Using the propensity scores which account for the risk of a fracture in a specific femoral site, this study revealed that the older patients were at a higher risk of developing proximal type A and type B fractures, while a lower risk of developing fractures in the shaft and distal femur. This incidence of fracture site can largely be explained by age-related factors, including a decrease in bone strength and falling being the most common mechanism of trauma in older patients. CONCLUSIONS: This study revealed a difference in the involvement of age in the incidence of femoral fracture sites in the trauma patients.

Association between operation- and operator-related factors and surgical complications among patients undergoing free-flap reconstruction for head and neck cancers: A propensity score-matched study of 1,865 free-flap reconstructions.

OBJECTIVE: Efforts have been devoted to clarify the possible factors related to postoperative complications in free-flap reconstruction. While patient-related factors have been widely discussed, studies regarding the operation/operator-related factors are rather limited in the literature. This study was designed to investigate the relationship between operation/operator-related factors and the surgical complications in free-flap reconstruction following head and neck cancer resection. METHODS: Data of 1,841 patients with a total of 1,865 free-flap reconstructions (24 double free-flap reconstructions) between March 2008 and February 2017 were retrieved from the registered microsurgery database of the hospital. The association of operation/operator-related factors (including flap length and length-width ratio, flap types, use of vein graft, opposite side microanastomosis, number of microanastomoses, operators, operator experience, and operation time) with surgical complications was assessed by 1:1 propensity score-matched study groups. RESULTS: After propensity score matching of the patient-related factors, the rate of vein grafting was significantly higher (0.6% vs. 2.2%, p = .038) and the operation time was longer (7.0 [5.8-8.5] vs. 7.4 [6.1-8.8] hr, p = .006) in the complication group. In addition, flap length and length-width ratio, flap types, opposite side microanastomosis, number of microanastomoses, operators, and operator experience were not associated with surgical complications. CONCLUSIONS: In a hospital that consisted of surgeons with high-volume or very-high-volume experience, the operators or operation experience were not significantly associated with the surgical complications. Only a longer operation time was associated with surgical complications in the patients who underwent free-flap reconstruction for head and neck cancer.

Comparison of contraction-type and noncontraction-type lymphatic vessels in lymphaticovenous anastomosis for cancer-related unilateral lower limb lymphedema: a retrospective cohort propensity-score-matched outcome analysis.

BACKGROUND: Contraction-type lymphatic vessels (LV) are considered suboptimal for lymphaticovenous anastomosis (LVA). However, despite these pathological changes, their functionality and link to outcomes have not been fully elucidated. The aim of this study was to determine the impact on outcomes when contraction-type LVs were used for LVA compared to the noncontraction-type (normal + ectatic) counterpart for treating lower limb lymphedema. STUDY DESIGN: Eighty-three patients with gynecologic cancer-related unilateral lower-limb lymphedema who underwent LVA as their primary treatment were enrolled in this study. The study group included 20 patients who used only contraction-type LVs. An additional 63 patients (control group) received noncontraction-type LVs only. Patients with a history of LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, functional parameters, and pre-LVA and post-LVA volume changes were recorded and matched using propensity scores. The primary endpoint was the volume change at 6/12 months after LVA. RESULTS: After matching, 20 patients were included in each group. All parameters were matched, except that the study group still had a significantly inferior indocyanine green (ICG)-positive ratio, lymph flow-positive ratio, and washout-positive ratios ( P <0.001, P =0.003, and P <0.001, respectively) when compared to the control group after matching. However, at 1-year follow-up, the postoperative percentage volume reduction was comparable between the groups ( P= 0.619). CONCLUSION: The use of contraction-type LVs for LVA is encouraged when no other LVs are available.

Exploring the Regulatory Role of XIST-microRNAs/mRNA Network in Circulating CD4+ T Cells of Hepatocellular Carcinoma Patients.

Hepatocellular carcinoma (HCC) is one of the most common cancers and the main cause of cancer-related death globally. Immune dysregulation of CD4+ T cells has been identified to play a role in the development of HCC. Nevertheless, the underlying molecular pathways of CD4+ T cells in HCC are not completely known. Thus, a better understanding of the dysregulation of the lncRNA-miRNA/mRNA network may yield novel insights into the etiology or progression of HCC. In this study, circulating CD4+ T cells were isolated from the whole blood of 10 healthy controls and 10 HCC patients for the next-generation sequencing of the expression of lncRNAs, miRNAs, and mRNAs. Our data showed that there were different expressions of 34 transcripts (2 lncRNAs, XISTs, and MIR222HGs; 29 mRNAs; and 3 other types of RNA) and 13 miRNAs in the circulating CD4+ T cells of HCC patients. The expression of lncRNA-XIST-related miRNAs and their target mRNAs was confirmed using real-time quantitative polymerase chain reaction (qPCR) on samples from 100 healthy controls and 60 HCC patients. The lncRNA-miRNA/mRNA regulation network was created using interaction data generated from ENCORI and revealed there are positive correlations in the infiltration of total CD4+ T cells, particularly resting memory CD4+ T cells, and negative correlations in the infiltration of Th1 CD4+ T cells.

Deciphering the Divergent Gene Expression Landscapes of m6A/m5C/m1A Methylation Regulators in Hepatocellular Carcinoma Through Single-Cell and Bulk RNA Transcriptomic Analysis.

Introduction: RNA modifications mediated by the m6A, m1A, and m5C regulatory genes are crucial for the progression of malignancy. This study aimed to explore the expression of regulator genes for m6A/m5C/m1A methylation at the single-cell level and to validate their expression in cancerous and adjacent para-cancerous liver tissues of adult patients with HCC who underwent tumor resection. Methods: The bulk sequencing from The Cancer Genome Atlas (TCGA) database and the single-cell RNA sequencing (scRNA-seq) data obtained from the Gene Expression Omnibus (GEO) database were used to identify the dysregulated m6A/m5C/m1A genes for hepatocellular carcinoma (HCC). A real-time polymerase chain reaction (real-time PCR) was used to measure the expression of dysregulated m6A/m5C/m1A genes in collected human HCC tissues and compared with adjacent para-cancerous liver tissues. Immune cell infiltration with these significantly expressed methylation-related genes was evaluated using Timer2.0. Results: A discrepancy in m6A/m5C/m1A gene expression was observed between bulk sequencing and scRNA-seq. The clustered heatmap of the scRNA-seq-identified dysregulated m6A/m5C/m1A genes in TCGA cohort revealed heterogeneous expression of these methylation regulators within the cancer, whereas their expression in the adjacent liver tissues was more homogeneous. The real-time PCR validated the significant overexpression of DNMT1, NSUN5, TRMT6, IGF2BP1, and IGFBP3, which were identified using scRNA-seq, and IGFBP2, which was identified using bulk sequencing. These dysregulated methylation genes are mainly correlated with the infiltration of natural killer cells. Discussion: This study suggests that cellular diversity inside tumors contributes to the discrepancy in the expression of methylation regulator genes between traditional bulk sequencing and scRNA-seq. This study identified five regulatory genes that will be the focus of further studies regarding the function of m6A/m5C/m1A in HCC.

Using Second Measurement of De Ritis Ratio to Improve Mortality Prediction in Adult Trauma Patients in Intensive Care Unit.

The De Ritis ratio (DRR), the ratio of serum levels of aspartate aminotransferase/alanine aminotransferase, has been reported to be a valuable biomarker in risk stratification for many liver and non-liver diseases. This study aimed to explore whether the inclusion of DRR at the date of intensive care unit (ICU) admission or days after ICU admission improves the predictive performance of various prognosis prediction models. This study reviewed 888 adult trauma patients (74 deaths and 814 survivors) in the trauma registered database between 1 January 2009, and 31 December 2020. Medical information with AST and ALT levels and derived DRR at the date of ICU admission (1st DRR) and 3-7 day after ICU admission (2nd DRR) was retrieved. Logistic regression was used to build new probability models for mortality prediction using additional DRR variables in various mortality prediction models. There was no significant difference in the 1st DRR between the death and survival patients; however, there was a significantly higher 2nd DRR in the death patients than the survival patients. This study showed that the inclusion of the additional DRR variable, measured 3-7 days after ICU admission, significantly increased the prediction performance in all studied prognosis prediction models.

Impact of retrograde anastomosis during supermicrosurgical lymphaticovenous anastomosis for cancer-related lower limb lymphedema: A retrospective cohort propensity-score-matched outcome analysis.

BACKGROUND: In addition to antegrade anastomosis, retrograde anastomosis has been thought to offer further improvements after lymphaticovenous anastomosis (LVA) by bypassing the retrograde lymphatic flow. However, this concept has yet to be validated. The aim of this study was to determine the impacts on outcomes of performing both retrograde and antegrade anastomosis, as compared to antegrade-only anastomosis for treating lower limb lymphedema. STUDY DESIGN: This was a retrospective cohort propensity score-matched study. Eighty-seven patients with gynecologic cancer-related lower limb lymphedema were enrolled, including 58 patients who had received both antegrade and retrograde anastomoses (Group I) and 29 patients who had received antegrade-only anastomoses (Group II) as the control group. LVA was the primary treatment. Patients who had previous LVA, liposuction, or excisional therapy were excluded. Patient characteristics, intraoperative findings, and functional parameters including the ratio of indocyanine green-enhanced and flow-positive lymphatic vessels were recorded. Magnetic resonance volumetry was used for outcome assessments. The primary endpoint was the volume change at 6 months after LVA. RESULTS: After matching, a total of 26 patients have remained in each group. All parameters were matched except that Group I still had significantly more median LVA performed compared to Group II (8 [IQR: 5.3-10.0] vs. 5.5 [4.3-6.0], p = 0.001, respectively). Group II showed more post-LVA improvements at six-month and one-year follow-up compared to Group I but without statistically significant differences. CONCLUSION: The use of supplementary retrograde anastomoses is discouraged since it may lead to inferior post-LVA outcome compared to antegrade-only anastomoses.

Regular Exercise and Weight-Control Behavior Are Protective Factors against Osteoporosis for General Population: A Propensity Score-Matched Analysis from Taiwan Biobank Participants.

The rising prevalence of osteoporosis, which can lead to osteoporotic fractures, increases morbidity, mortality, and socioeconomic burden. Multiple factors influencing bone mass have already been identified. The aim of this study was to investigate whether exercise habits and weight-control behaviors can lower the incidence of osteoporosis in the general population. This retrospective study recruited all participants aged 35-70 years who underwent dual-energy X-ray absorptiometry (DXA) from Taiwan Biobank (TWB). The final analysis consisted of 3320 eligible participants divided into two groups; demographic characteristics, prevalence of clinical symptoms, comorbidities, and daily behavior were collected using a self-reported questionnaire. After propensity score matching with a 1:1 ratio, 1107 out of 2214 individuals were classified into the osteoporosis group. Age, body fat rate, body shape, diabetes mellitus, and social status were found to affect the incidence of osteoporosis. Subjects with a habit of regular exercise and weight-control behavior showed decreased odds of osteoporosis. (odds ratio: 0.709 and 0.753, 95% confidence interval: 0.599-0.839 and 0.636-0.890). In the general population, regular exercise or weight-control behavior lowers the incidence of osteoporosis.

The Network of miRNA-mRNA Interactions in Circulating T Cells of Patients Following Major Trauma - A Pilot Study.

Purpose: Following major trauma, genes involved in adaptive immunity are downregulated, which accompanies the upregulation of genes involved in systemic inflammatory responses. This study investigated microRNA (miRNA)-mRNA interactome dysregulation in circulating T cells of patients with major trauma. Patients and Methods: This study included adult trauma patients who had an injury severity score ≥16 and required ventilator support for more than 48 h in the intensive care unit. Next-generation sequencing was used to profile the miRNAs and mRNAs expressed in CD3+ T cells isolated from patient blood samples collected during the injury and recovery stages. Results: In the 26 studied patients, 9 miRNAs (hsa-miR-16-2-3p, hsa-miR-16-5p, hsa-miR-185-5p, hsa-miR-192-5p, hsa-miR-197-3p, hsa-miR-23a-3p, hsa-miR-26b-5p, hsa-miR-223-3p, and hsa-miR-485-5p) were significantly upregulated, while 58 mRNAs were significantly downregulated in T cells following major trauma. A network consisting of 8 miRNAs and 22 mRNAs interactions was revealed by miRWalk, with three miRNAs (hsa-miR-185-5p, hsa-miR-197-3p, and hsa-miR-485-5p) acting as hub genes that regulate the network. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis suggested that "chemokine signaling pathway" was the predominant pathway. Conclusion: The study revealed a miRNA-mRNA interactome consisting of 8 miRNAs and 22 mRNAs that are predominantly involved in chemokine signaling in circulating T cells of patients following major trauma.

Effect of Lymphaticovenous Anastomosis on Muscle Edema, Limb, and Subfascial Volume in Lower Limb Lymphedema: MRI Studies.

BACKGROUND: Although satisfactory volume reduction in secondary unilateral lower limb lymphedema after lymphaticovenous anastomosis (LVA) in the affected limb has been well reported, alleviation of muscle edema and the impact of LVA on the contralateral limb have not been investigated. STUDY DESIGN: This retrospective cohort study enrolled patients who underwent supermicrosurgical LVA between November 2015 and January 2017. Pre- and post-LVA muscle edema were assessed using fractional anisotropy (FA) and apparent diffusion coefficient (ADC). The primary endpoint was changes in limb/subfascial volume assessed with magnetic resonance volumetry at least 6 months after LVA. RESULTS: Twenty-one patients were enrolled in this study. Significant percentage reductions in post-LVA muscle edema were found in the affected thigh (83.6% [interquartile range = range of Q1 to Q3; 29.8-137.1] [FA], 53.3% [27.0-78.4] [ADC]) as well as limb (21.7% [4.4-26.5]) and subfascial (18.7% [10.7-39.1]) volumes. Similar findings were noted in the affected lower leg: 71.8% [44.0-100.1] (FA), 59.1% [45.8-91.2] (ADC), 21.2% [6.8-38.2], and 28.2% [8.5-44.8], respectively (all p < 0.001). Significant alleviation of muscle edema was also evident in the contralateral limbs (thigh: 25.1% [20.4-57.5] [FA]; 10.7% [6.6-17.7] [ADC]; lower leg: 47.1% [35.0-62.8] [FA]; 14.6% [6.5-22.1] [ADC]; both p < 0.001), despite no statistically significant difference in limb and subfascial volumes. CONCLUSIONS: Our study found significant reductions in muscle edema and limb/subfascial volumes in the affected limb after LVA. Our findings regarding edema in the contralateral limb were consistent with possible lymphedema-associated systemic influence on the unaffected limb, which could be surgically relieved.

Lymphaticovenous Anastomosis for Treating Secondary Lower Limb Lymphedema in Older Patients-A Retrospective Cohort Study.

Despite an increased incidence of secondary lower limb lymphedema (LLL) and severity of comorbidities with age, the impact of age on the effectiveness of lymphaticovenous anastomosis (LVA) in the older patients remains unclear. Methods: This retrospective cohort study enrolled older patients (age > 65 years) with secondary unilateral LLL. All patients underwent supermicrosurgical LVA. Demographic data and intraoperative findings including lymphatic vessel (LV) diameter, LV functionality (indocyanine green-enhanced and Flow positivity), and lymphosclerosis classification were recorded. Magnetic resonance volumetry was used for measuring preoperative and postoperative volume changes at 6 months and one year after LVA as primary and secondary endpoints. Results: Thirty-two patients (29 females/3 males) with a median age of 71.0 years [range, 68.0 to 76.3] were enrolled. The median duration of lymphedema was 6.4 [1.0 to 11.7] years. The median LV diameter was 0.7 [0.5 to 0.8] mm. The percentage of ICG-enhanced and Flow-positive LVs were 89.5% and 85.8%, respectively. The total percentage of suitable LVs (s0 and s1) for LVA based on lymphosclerosis classification was 75.9%. There were significant six-month and one-year post-LVA percentage volume reductions compared to pre-LVA volume (both p < 0.001). A significant reduction in cellulitis incidence was also noted after LVA (p < 0.001). No surgical or postoperative complications were found. Conclusion: Relief of secondary LLL was achievable through LVA in older patients who still possessed favorable LV characteristics, including larger LV diameters as well as a high proportion of functional LVs with a low grade of lymphosclerosis.

Recovery of Dysregulated Genes in Cancer-Related Lower Limb Lymphedema After Supermicrosurgical Lymphaticovenous Anastomosis - A Prospective Longitudinal Cohort Study.

PURPOSE: This study aims at profiling the expression of dysregulated genes in circulating monocytes of patients with cancer-related lower limb lymphedema before and after treatment with supermicrosurgical lymphaticovenous anastomosis (LVA). MATERIALS AND METHODS: This prospective longitudinal cohort study enrolled 51 women with post-treatment gynecological cancer, including those with unilateral lymphedema (study group, n = 25) and those without (control group, n = 26). Venous blood samples obtained from the study group before and after LVA and those from the controls were sent for next-generation sequencing, which was validated by real-time PCR. Dysregulated gene expression in the study group, relative to expression in the controls, was recorded before LVA. After one month, postoperative changes in the expression of the identified genes were evaluated. Protein-protein interaction (PPI) was used to investigate dysregulated genes whose expression returned to baseline levels after LVA. RESULTS: Of the 148 preoperative dysregulated genes, which comprised 108 up- and 40 down-regulated genes, 78 genes, consisting of 69 up- and 9 down-regulated genes, showed post-LVA recovery to baseline levels. Through PPI analysis, five functional modules involving immunity, lipid metabolism, oxidative stress, transcriptional regulators, and tumor suppression, as well as six hub genes (CCL2, LPL, PDK4, FOXO3, EGR1, and DUSP5), were identified. Cross-linking and co-regulated genes between modules were also identified. CONCLUSION: Localized lymphedema leads to dysregulated gene expression in circulating monocytes. The current study is the first to identify the hub genes related to lymphedema and demonstrate the recovery of some dysregulated genes after LVA.

The Effect of Post-Graduate Year Training on the Self-Efficacy and Emotional Traits of Physicians Facing the COVID-19 Pandemic.

Background: Taiwan implemented the post-graduate year (PGY) training to reform the medical education system to provide holistic medical care after severe acute respiratory syndrome in 2003. In late 2019, COVID-19 quickly spread across the globe and became a pandemic crisis. This study aimed to investigate whether the establishment of the PGY training had positive effects on the self-efficacy and emotional traits of medical workers. Methods: One hundred and ten physicians, including PGY, residents, and visiting staff, were investigated using the General Self-Efficacy Scale (GSES) and Emotional Trait and State Scale (ETSS), and their feedback and suggestions were collected. An exploratory factor analysis was done to reduce the factor dimensions using the varimax rotation method, which was reduced to four factors: "the ability to cope with ease", "proactive ability", "negative emotion", and "positive emotion". A comparison with and without PGY training when facing the COVID-19 pandemic was conducted. Results: Those who had received PGY training (n = 77) were younger, had a lower grade of seniority, and had less practical experience than those who had not received PGY (n = 33). Those who had received PGY training had significantly higher scores for the factors "ability to cope with ease", "proactive ability", and "positive emotion" than those who had not received PGY training. Conclusion: The study revealed that PGY training may have had positive effects on the personal self-efficacy and emotional traits of physicians coping with the COVID-19 pandemic.

Disparity of Hepatocellular Carcinoma in Tumor Microenvironment-Related Genes and Infiltrating Immune Cells between Asian and Non-Asian Populations.

Hepatocellular carcinoma (HCC) is the most common cause of primary liver cancer deaths worldwide. The major risk factors for liver cancer development are cirrhosis, hepatitis B virus (HBV), hepatitis C virus (HCV) infection, and chronic alcohol abuse. HCC displays heterogeneity in terms of biology, etiology, and epidemiology. In Southeast Asia and Africa, chronic HBV infection is a major risk factor for HCC, whereas chronic HCV infection is a risk factor for HCC in western countries and Japan. Environmental and genetic conditions also play a role in the regional and temporal variations in the incidence of HCC. In this study, we used the ESTIMATE (ESTIMATE, Estimation of stromal and immune cells in malignant tumor tissues using expression data) algorithm and the CIBERSOFT tool to analyze gene expression profiles and infiltrating immune cells in HCC between Asian and non-Asian patients. The results showed that stromal and immune scores were dependent on overall survival (OS) in non-Asian patients but not in Asian patients. Kaplan-Meier survival analysis revealed four differentially expressed genes (DEGs) that were significantly associated with OS in non-Asian patients only. CIBERSORT (CIBERSORT, Cell type identification by estimating relative subsets of known RNA transcripts) analysis indicated that the composition of infiltrating immune cells was significantly different between Asian and non-Asian patients. By parsing the subclasses of HCC, the ability to predict prognosis and guide therapeutic targets for potentially actionable HCC may be improved.

Comparison of the surgical outcomes of free flap reconstruction for primary and recurrent head and neck cancers: a case-controlled propensity score-matched study of 1,791 free flap reconstructions.

This study was designed to compare the outcome and analyze the operation-related risk factors in free flap reconstruction for patients with primary and recurrent head and neck cancers. A 1:1 propensity score-matched analysis of the microsurgery registry database of the hospital. The primary outcome of the free flap reconstruction had a higher failure rate in the recurrent group than the primary group (5.1% vs. 3.1%, p = 0.037). Among the 345 pairs in the matched study population, there were no significant differences between the primary and recurrent groups regarding the rate of total flap loss (3.5% vs. 5.5%, p = 0.27) and secondary outcomes. This study revealed that free flap reconstruction had a higher failure rate in the recurrent group than the primary group, but such a difference may be attributed by the different patient characteristics.