Addressing the challenges of missed parathyroid glands in ultrasonography for secondary hyperparathyroidism: a retrospective observational study.

Purpose: Preoperative localization plays an important role in secondary hyperparathyroidism (SHPT) surgery. The advantages of neck ultrasound (US) include high availability and low cost. However, the reported sensitivity of US is 54%-76%, and the reason for missed parathyroid glands (PGs) on US has been rarely addressed. Methods: Fifty-four patients who were diagnosed with renal SHPT from September 2020 to March 2022 were included in this retrospective study. Preoperative localization included surgeon-oriented US and technetium 99m-sestamibi single-photon emission CT (SPECT)/CT. Results: A total of 212 PGs were pathologically confirmed, resulting in a success rate of 96.2% (52 of 54). Using echo, 193 PGs (91.0%) were accurately localized, while 19 glands (9.0%) were not identified, including those in ectopic positions (n = 12, at thymus or intrathyroid or others), of small size (<1 cm, n = 6), or overlapping with an ipsilateral PG (n = 1). US accurately detected 4 PGs in 36 (66.7%) patients, while SPECT/CT localized 4 glands in 19 patients (35.2%). Although the number of US-detectable PGs was not associated with success rate, it showed a significant negative correlation with surgical time (rs = -0.459, P = 0.002). Conclusion: US detected 4 glands in 66% of SHPT patients with a sensitivity of 90% for localization. Ectopic position and small size were the most common reasons for the failure to detect PG on US. Complete preoperative echo localization might shorten operating time.

Nitrogen removal strategy for real swine wastewater by combining partial nitrification-denitrification process with anammox.

Anammox process offers reduced operational cost and energy requirement compared to nitrification-denitrification methods due to lower biomass generation and no need for external carbon sources and aeration. High ammonia concetration and low biodegradable anaerobic digester of swaine wastewater provided an advantage for the growth of anammox microorangism. An anoxic/oxic (A/O) SBR and an anammox SBR were implemented parallelly to treat the same swine wastewater with partial nitrification/denitrification and partial nitrification/anammox process, respectively, and to compare their nitrogen removal efficiency. The nitrogen removal rates (NRRs) of the A/O SBR and anammox SBR were 0.054 and 0.26 kg-N/m3/day, respectively. The lower NRR of the A/O SBR could be attributed to insufficient biodegradable organic carbon sources in the denitrification process. The kinetic parameters obtained from the two SBRs were applied to estimate the time required for using the A/O process and partial nitrification/anammox process to treat the same amount of ammonia with the same reaction volume. Results showed that the A/O process required 3.3 times the reaction time of the partial nitrification/anammox process, suggesting that the partial nitrification/anammox process is a more efficient and economic nitrogen removal process for swine wastewater treatment. The next generation sequencing results revealed that Candidatus Brocadia, ranging from 10 to 23%, was the predominant anammox bacteria in the anammox SBR. More than 78.2 % of nitrite in the anammox SBR was removed through the anammox reaction.

Molecular Necklaces Formed Through Zn2+-Templated Binding of Macrocycles with Dynamically Formed Imines as Guest Recognition Sites.

Herein we demonstrate an "in-ring establishing" strategy for assembling interlocked molecules through dynamic imine formation, "establishing" the host recognition sites in situ. Using Zn2+ ions to template the assembly of a pyridine-containing macrocycle with semidumbbell-shaped triazole-containing aldehyde and amine derivatives, we obtained the corresponding [2]rotaxane in high yield (85 %) after subsequent imine reduction (NaBH4) and amine protonation (NH4PF6). We performed the same three steps (assembly, reduction, protonation) to prepare a stable and highly symmetrical [5]molecular necklace ([5]MN) from 12 components (two almost-90°-oriented dialdehydes, two almost-90°-oriented diamines, four macrocycles, four Zn2+ ions) in an overall yield of 69 %.

Performances of full-scale biological nitrogen pre-treatment process for drinking water source: Seasonal variations and microbial community.

This study investigated the performance of the full-scale unit over a two-year period to enhance nitrification efficiency and provide operational strategies. Results indicated that raw water quality from Donggan River was notably influenced by seasonal variations, particularly during dry and wet seasons, impacting the nitrification efficiency of the biological pretreatment process. Factors such as influent concentrations of ammonia and total Kjeldahl nitrogen were found to have significant effects on nitrification, with temperature and conductivity also showing correlations. The specific rate of ammonia removal was calculated to be approximately 0.1 kg-N/m3/d under the existing operational setup. Moreover, elevating dissolved oxygen levels above 4 mg/L was proposed to potentially boost ammonia oxidation based on findings from experiments conducted in lab-scale bioreactors. In times of increased influent ammonia levels, the elimination of about 1-3 mg-N/L of total nitrogen signified the activation of denitrification processes. This observation was corroborated by results from next-generation sequencing techniques, verifying the existence of denitrifying microorganisms. The real-time PCR analysis results indicated that the abundance of comammox amoA gene was comparable with the abundance of the AOB amoA gene, indicating the presence of comammox Nitrospira and their potential role on nitrification in the system.

Biological treatment of N-methylpyrrolidone, cyclopentanone, and diethylene glycol monobutyl ether distilled residues and their effects on nitrogen removal in a full-scale wastewater treatment plant.

Manufacturing processes in semiconductor and photonics industries involve the use of a significant amount of organic solvents. Recycle and reuse of these solvents produce distillate residues and require treatment before being discharged. This study aimed to evaluate the performance of the biological treatment system in a full-scale wastewater treatment plant that treats wastewater containing distillate residues from the recycling of electronic chemicals. Batch experiments were conducted to investigate the optimal operational conditions for the full-scale wastewater treatment plant. To achieve good nitrogen removal efficiency with effluent ammonia and nitrate concentrations below 20 mg N/L and 50 mg N/L, respectively, it was suggested to control the ammonia concentration and pH of the influent below 500 mg N/L and 8.0, respectively. In addition, the biodegradability of N-methylpyrrolidone, diethylene glycol monobutyl ether, and cyclopentanone distillate residues from the electronic chemicals manufacturing process were evaluated under aerobic, anoxic, and anaerobic conditions. N-methylpyrrolidone and cyclopentanone distillate residues were suggested to be treated under anoxic condition. However, substrate inhibition occurred when using cyclopentanone distillate residue as a carbon source with chemical oxygen demand (COD) levels higher than 866 mg/L and nitrate levels higher than 415 mg N/L. Under aerobic condition, the COD from both N-methylpyrrolidone and cyclopentanone distillate residues could be easily degraded. Nevertheless, a negative effect on nitrification was observed, with a prolonged lag time for ammonia oxidation as the initial COD concentration increased. The specific ammonia oxidation rate and nitrate production rate decreased under high COD concentration contributed by N-methylpyrrolidone and cyclopentanone distillate residues. Furthermore, the biodegradability of diethylene glycol monobutyl ether distillate residue was found to be low under aerobic, anoxic, and anaerobic conditions. With respect to the abundance of nitrogen removal microorganisms in the wastewater treatment plant, results showed that Comammox may have an advantage over ammonia oxidizing bacteria under high pH conditions. In addition, Comammox may have higher resistance to environmental changes. Dominance of Comammox over ammonia oxidizing bacteria under high ammonia condition was first reported in this study.

Preoperative work-up and results of parathyroidectomy plus auto-transplantation for the elderly with secondary hyperparathyroidism.

BACKGROUND: Total parathyroidectomy for secondary hyperparathyroidism has low morbidity and mortality rates and requires a special workup in the preoperative period. METHODS: Neck echography and technetium-99m-sestamibi scintigraphy were performed preoperatively. Cardiac echography, a thallium-201 myocardial perfusion scan, and cardiac catheterization were performed if necessary. During surgery, we removed all the parathyroid glands and the upper thymus and autotransplanted 100 mg of the smallest gland into the subcutaneous tissue of the forearm. RESULTS: The success rate in three months after total parathyroidectomy was 91.7% without mortality. In the elderly (age ≤65 years, n = 35), bone pain, skin itching, general weakness, and insomnia improved three months after surgery, and grip strength increased significantly. One year after parathyroidectomy, the serum levels of Ca, P, alkaline phosphatase, and intact parathyroid hormone were all within the normal ranges. Except for the bone mineral density (BMD) of the radial distal one-third, the BMD of the lumbar spine (L2 to L4), femoral neck, femoral global, and radial global increased significantly. Furthermore, the bone density T-scores of the lumbar spine (L2 to L4), femoral neck, femoral global, radial distal one-third, and radial global improved significantly. CONCLUSIONS: After a meticulous preoperative workup, parathyroidectomy plus autotransplantation can be performed safely for the treatment of symptomatic secondary hyperparathyroidism in the elderly to improve their quality of life and decrease their incidence of bone fractures.

Reciprocal Regulation of Peroxisome Biogenesis and Myogenic Factors Is Critical for Myogenesis.

Mitochondria (MITO) and peroxisomes (PEXO) are the major organelles involved in the oxidative metabolism of cells, but detailed examination of their dynamics and functional adaptations during skeletal muscle (SKM) development (myogenesis) is still lacking. In this study, we found that during myogenesis, MITO DNA, ROS level, and redox ratio increased in myotubes, but the membrane potential (Δψm) and ATP content reduced, implying that the MITO efficiency might reduce during myogenesis. The PEXO number and density both increased during myogenesis, which probably resulted from the accumulation and increased biogenesis of PEXO. The expression of PEXO biogenesis factors was induced during myogenesis in vitro and in utero, and their promoters were also activated by MyoD. Knockdown of the biogenesis factors Pex3 repressed not only the PEXO density and functions but also the levels of MITO genes and functions, suggesting a close coupling between PEXO biogenesis and MITO functions. Surprisingly, Pex3 knockdown by the CRISPRi system repressed myogenic differentiation, indicating critical involvement of PEXO biogenesis in myogenesis. Taken together, these observations suggest that the dynamics and functions of both MITO and PEXO are coupled with each other and with the metabolic changes that occur during myogenesis, and these metabolic couplings are critical to myogenesis.

Combination of treatments with transoral endoscopic thyroidectomy vestibular approach (TOETVA) for Graves' disease.

Although the success rates of non-surgical treatments for Graves' disease such as antithyroid medication and radioiodine ablation were good, there were still failure of treatments or intolerance for some patients. Traditional thyroid surgery could treat these patients but result in unaesthetic neck scars. Herein, we report the preliminary results of our combination of treatments with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease. A retrospective review of patients who underwent the transoral endoscopic thyroidectomy vestibular approach for the treatment of different sizes of goiters between January 2019 and December 2020 was performed. The demographic and clinical data of patients were collected. All patients were followed up for > 12 months. Each patient's goiter size was determined using four grades-from 0 to 3. In total, 14 female patients receiving the combination treatment with > 1 year of follow-up and a median (range) age of 35 (20-48) years at surgery were included. There were two, three, four, and five patients with grade 0, 1, 2, and 3 goiters, respectively. The median (range) intraoperative blood loss was higher in grade 3 patients (100 [20-850] mL) than in grade 2 patients (20 [10-200] mL) and grade 1 and 0 patients (both < 10 mL) (p = 0.033). All patients had normal-looking necks with a euthyroid or hypothyroid status within 1 year. There were no complications, including re-operation for bleeding, hypoparathyroidism, vocal cord palsy, or infections. The designed combination treatment with the transoral endoscopic thyroidectomy vestibular approach for Graves' disease provides optimal cosmetic results with a high success rate.

Impact of Thyroid Incidentaloma on Liver Transplant: A Study of 1010 Recipients at a Single Center.

BACKGROUND Thyroid incidentalomas are typically nonpalpable thyroid nodules discovered during radiographic evaluation for a non-thyroid issue. Thyroid incidentalomas visualized by computed tomography (CT) and ¹8F-flurodeoxyglucose (FDG) positron emission tomography (PET) before living donor liver transplantation (LDLT) are rare. The aim of the study was to analyze the clinical impact of thyroid incidentalomas discovered prior to transplantation. MATERIAL AND METHODS This retrospective study recruited 1010 patients undergoing LDLT between 2010 and 2019. CT was performed on each patient, whereas PET was performed on randomized patients (n=498). RESULTS The prevalence and malignant risk of thyroid incidentaloma on CT was 2.3% (23/1010) and 13.0% (3/23), respectively. The prevalence of thyroid incidentaloma on PET was 3.0% (15/498). Approximately half of the FDG uptake on PET was diffuse uptake (n=7), whereas the other half was focal uptake (n=8). The malignant risk of PET incidentaloma with focal FDG uptake was 37.5% (3/8). Four asymptomatic thyroid cancers were identified incidentally. After total thyroidectomy followed by LDLT, these patients maintained cancer-free status. CONCLUSIONS Thyroid incidentalomas occurred at a rate of 2-3% in LDLT candidates. The malignant risk was 13.0% on CT incidentaloma, and 37.5% on PET incidentaloma with focal FDG uptake. Curative treatment of incidental thyroid cancer followed by LDLT without delay can achieve a favorable prognosis.

Changes in voice quality, swallowing, and pulmonary function after parathyroidectomy for secondary hyperparathyroidism.

OBJECTIVE: To find changes in voice quality, airway invasion during swallowing, pharyngeal residue after swallowing, acoustic and aerodynamic measurements and pulmonary function tests after total parathyroidectomy plus auto-transplantation for secondary hyperparathyroidism. METHODS: We recruited 38 patients who underwent successful surgery for secondary hyperparathyroidism in this study. Voice quality was evaluated using voice handicap index (VHI-10), eating assessment tool (EAT-10), voice impairment, and the grade, roughness, breathiness, asthenia, strain (GRBAS) scale. Acoustic and aerodynamic measurements included fundamental frequency (F0), maximal phonation time, high pitch, jitter, s/z, shimmer and noise-to-harmonic ratio. Vocal cord mobility, vocal cord closure, premature spillage, the penetration-aspiration scale and the Yale pharyngeal residue severity rating scale (PRSRS) after swallowing were examined using fiber-optic endoscopy. Pulmonary function tests included forced vital capacity, forced expiratory volume in 1 s, bronchodilator test, total lung capacity, diffusion capacity of the lung for carbon monoxide, alveolar volume, and distance and O2 desaturation of the 6 min walking test (6MWT). RESULTS: Four months after successful parathyroidectomy, VHI-10 improved significantly (p < 0.01); incomplete vocal cord closure decreased significantly (p < 0.01); the Yale PRSRS for vallecula and pyriform sinus improved significantly (p = 0.02 and p = 0.02); F0 and high pitch increased significantly (p < 0.01 and p = 0.01); O2 desaturation (<4%) of 6MWT improved significantly (p = 0.04). CONCLUSIONS: Parathyroidectomy for secondary hyperparathyroidism can improve the voice quality, vocal cord closure, the Yale PRSRS for vallecular and pyriform sinus and O2 desaturation of 6MWT, and increase F0 and high pitch.

Preoperative ALBI grade predicts the outcomes in non-B non-C HCC patients undergoing primary curative resection.

BACKGROUND: The albumin-bilirubin (ALBI) grade has been validated as a significant prognostic predictor for hepatocellular carcinoma (HCC). However, there is little information about the ALBI grade in patients with non-B non-C HCC (NBNC-HCC) receiving surgery. AIM: This study aimed to evaluate the prognostic significance of the ALBI grade in patients with NBNC-HCC after primary curative resection. METHOD: From January 2010 to April 2016, 2137 patients with HCC who received hepatectomy were screened for study eligibility. Finally, a total of 168 NBNC-HCC patients who received primary curative resection were analyzed. The impacts of the ALBI grade on disease-free survival (DFS) and overall survival (OS) were analyzed by multivariate analysis. RESULTS: There were 66 (39.3%), 98 (58.3%), and 4 (2.4%) patients with an ALBI grade of I, II, and III, respectively. Patients with an ALBI grade II/III were older (p = 0.002), more likely to have hypoalbuminemia (p < 0.001), and more commonly had Child-Pugh class B (p = 0.009) than patients with an ALBI grade I. After a median follow-up of 76 months, 74 (44%) patients experienced recurrence, and 72 (42.9%) patients died. Multivariate analysis revealed that alpha-fetoprotein (AFP) > 200 ng/mL (p = 0.021), number of tumors (p = 0.001), and tumor stage (p = 0.007) were independent prognostic factors for DFS. Additionally, AFP > 200 ng/mL (p = 0.002), ALBI grade II/III (p = 0.002), and tumor stage (p < 0.001) were independent risk factors for poor OS. CONCLUSION: The preoperative ALBI grade can be used to predict mortality in patients with NBNC-HCC after primary curative resection.

Biological treatment of volatile organic compounds (VOCs)-containing wastewaters from wet scrubbers in semiconductor industry.

This study investigated biological treatment for two kinds of volatile organic compounds (VOCs)-containing wastewaters collected from wet scrubbers in a semiconductor industry. Batch test results indicated that one wastewater containing highly volatile organic compounds was not suitable for aerated treatment conditions while the other containing much lower volatile organic compounds was suitable for aerobic treatment. Accordingly, two moving bed bioreactors, by adding commercial biocarrier BioNET, were operated under aerobic and anoxic conditions for treating low volatility wastewater (LVW) and high volatility wastewater (HVW), respectively. During 280 days of operation, the aerobic LVW bioreactor attained the highest chemical oxygen demand (COD) removal rate of 98.9 mg-COD/L/h with 81% of COD removal efficiency at hydraulic retention time (HRT) of 1 day. The anoxic HVW bioreactor performed above 80% of COD removal efficiency with the highest COD removal rate of 16.5 mg-COD/L/h at HRT of 2 days after 380 days of operation. The specific COD removal rates at different initial substrate-to-biomass (S0/X0) ratios, using either suspended sludge or microorganisms attached onto BioNET from both bioreactors, followed the Monod-type kinetics, while the half-saturation coefficients were generally higher for the microorganisms onto BioNET due presumably to relatively poor mass transfer efficiency. Based on the results of microbial community analysis using the next generation sequencing technique, the dominant communities of suspended sludge and BioNET, including nitrifiers, denitrifiers, and degraders for polycyclic aromatic hydrocarbons, were similar in the corresponded bioreactors, but microbial community shifts were observed with increased organic loadings.

Can Microscopic Biliary Reconstruction Reduce Biliary Complication Rate in ABO-Incompatible Adult Living Donor Liver Transplantation?

BACKGROUND With the introduction of rituximab, ABO-incompatible (ABOi) living donor liver transplantation (LDLT) has been considered a feasible and safe procedure to overcome the shortage of organ donors. However, higher biliary complication rates remain an unresolved problem in the ABOi group. In our center, biliary anastomosis has been done with microscopic biliary reconstruction (MBR), which effectively reduced the biliary complication rate. The aim of the current study was to investigate whether the microscopic approach reduced anastomotic biliary complications in ABOi LDLT. MATERIAL AND METHODS From March 2006 to December 2018, 30 adult ABOi and 60 ABO-compatible (ABOc) LDLT patients were selected from over 1300 recipients through 1: 2 propensity score-matched cohorts. All patients received MBR during the transplantation. Biliary complications included bile leakage and biliary stricture. Patients with diffuse intrahepatic biliary stricture were excluded from analysis. RESULTS Patient characteristics were similar in the 2 groups. There was no in-hospital mortality in the ABOi LDLT. The long-term survival rates of the ABOi patients were comparable to those of the patients that underwent ABOc LDLT (87.1% vs 87.4%, P=0.964). Those in the ABOi group with anastomotic biliary complications were about 40%, which was higher than in the ABOc patients (40% vs 15%, P=0.01). CONCLUSIONS Microscopic biliary reconstruction does not help to reduce the high biliary complication rate in ABOi LDLT. Further investigation and identification regarding other risk factors and precautionary measures involving immunologic and adaptation mechanisms are needed.

Reduced Expression of Metallothionein-I/II in Renal Proximal Tubules Is Associated with Advanced Chronic Kidney Disease.

Chronic kidney disease (CKD) is a commonly occurring complex renal syndrome that causes overall mortality in many diseases. The clinical manifestations of CKD include renal tubulointerstitial fibrosis and loss of renal function. Metallothionein-I/II (MT-I/II) is potentially expressed in the liver and kidney, and possesses antioxidant and metal detoxification properties. However, whether MT-I/II expression is associated with the prognosis of nephropathy remains unknown. In this study, we investigated the MT-I/II level in human CKD, using immunohistochemistry. MT-I/II is located on the proximal tubules and is notably reduced in patients with CKD. MT-I/II expression was significantly correlated with the functional and histological grades of CKD. In an aristolochic acid (AAI)-induced nephropathy mouse model, MT-I/II was abundantly increased after AAI injection for 7 days, but decreased subsequently compared to that induced in the acute phase when injected with AAI for 28 days. Furthermore, we found that ammonium pyrrolidinedithiocarbamate (PDTC) restored AAI-induced MT-I/II reduction in HK2 cells. The injection of PDTC ameliorated AAI-induced renal tubulointerstitial fibrosis and reduced the concentrations of blood urea nitrogen and creatinine in mouse sera. Taken together, our results indicate that MT-I/II reduction is associated with advanced CKD, and the retention of renal MT-I/II is a potential therapeutic strategy for CKD.

The Role of Protease-Activated Receptor 2 in Hepatocellular Carcinoma after Hepatectomy.

Background and Objectives: Protease activated receptor-2 (PAR2) is elevated in a variety of cancers and has been promoted as a potential therapeutic target. However, the clinical and prognostic values of PAR2 in hepatocellular carcinoma (HCC) are poorly characterized. This study aimed to evaluate the expression of PAR2 in HCC tissues and examine the prognostic value of PAR2 after resection in HCC. Materials and Methods: Two hundred and eight resected specimens were collected from HCC patients at Kaohsiung Chang Gung Memorial Hospital. PAR2 protein expression was assessed by western blotting in HCC tissues and matched normal tissues. The correlation between PAR2 expression and clinicopathological parameters was analyzed. Disease-free survival (DFS) and overall survival (OS) were compared using the log-rank test. A Cox regression model was used to identify independent prognostic factors. Results: PAR2 was expressed at higher levels in HCC tissues than the paired adjacent nontumor tissues. High expression of PAR2 was associated with advanced tumor, node, metastasis (TNM )stage and histological grade. Kaplan-Meier analysis indicated high PAR2 expression was associated with poorer DFS and OS compared to low PAR2 expression. Multivariate analyses indicated high PAR2 expression [hazard ratio (HR), 1.779, p = 0.006), α-fetoprotein (AFP) (HR, 1.696, p = 0.003), liver cirrhosis (HR, 1.735, p = 0.002), and advanced TNM stage (HR, 2.061, p < 0.001) were prognostic factors for DFS, and advanced TNM stage (HR, 2.741, p < 0.001) and histological grade (HR, 2.675, p = 0.002) and high PAR2 expression (HR, 1.832, p = 0.012) were significant risk factors for OS. In subgroup analyses, the combination of PAR2 expression and serum AFP provided improved prognostic ability for OS and DFS. Conclusion: Combination PAR2 and AFP predict HCC outcomes after resection. PAR2 represents a potentially clinically relevant biomarker for HCC.

Scarless Completion Thyroidectomy After Initial Transoral Approach for Differentiated Thyroid Cancer: How and When to Start?

BACKGROUND: With growing literature, the feasibility of transoral endoscopic thyroidectomy vestibular approach (TOETVA) has been confirmed as a valid method for managing differentiated thyroid cancer. Completion thyroidectomy (CT) is recommended in patients who have been diagnosed with differentiated thyroid cancer after unilateral lobectomy by TOETVA. In this retrospective study, the authors addressed the critical questions of how and when to do the second operation of CT to avoid a neck scar. MATERIALS AND METHODS: The authors retrospectively reviewed our patients who had received TOETVA in our hospital from August 2016 to December 2019. Those who received CT after initial TOETVA as cTOETVA were further separated according to the approaching methods. Demographic data, operative variables, and postoperative variables were collected and analyzed. RESULTS: A total of 97 patients were enrolled using TOETVA. Malignancies were present in 42 patients (43.3%) using TOETVA. There were 3 approaching methods of cTOETVA and separated into reopen transcervical approach (re-TCA), retransoral TOETVA (re-TOETVA), and transaxillary approach (TAA) groups. There were no significant complications among patients for cTOETVA. Of the 8 patients for the cTOETVA, 3 received re-TCA, 3 re-TOETVA, and 2 TAA. CONCLUSIONS: The outcomes are encouraging and demonstrate the feasibility of scarless completion thyroidectomy after initial TOETVA. The re-TOETVA procedure should be completed within 14 days after the initial TOETVA procedure, TAA beyond 14 days, and re-TCA may be completed at any time. The cTOETVA techniques using re-TOETVA or TAA have better cosmetic results than re-TCA in oncological equivalency.

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients.

BACKGROUND: Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. METHODS: We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. RESULTS: During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.

The Perioperatively Altered Neutrophil-to-Lymphocyte Ratio Associates with Impaired DNA Damage Response in Liver Transplantation Recipients with Hepatocellular Carcinoma.

Increasing evidence has suggested that elevated systemic inflammation with a high neutrophil-lymphocyte ratio (NLR) is associated with poor prognosis after liver transplantation (LT). The ongoing molecular events involved in poor survival remain unclear. This retrospective study evaluated LT recipients whose data was collected at Kaohsiung Chang Gung Memorial Hospital between 2005 and 2014. Clinical records of 347 patients with hepatocellular carcinoma from seven days before LT to 30 days after LT illustrated that longitudinal values of lymphocytes, RBC, and hemoglobin were persistently low in patients with peritransplant high NLR (PTH-NLR, pre-LT ≥ 4 and post-LT ≥ 5), which indicated a significantly worse survival rate in association with increased RDW-CV and pancytopenia when compared to other patients (p = 0.008). We further found that PTH-NLR patients had decreased DNA damage response (DDR) genes and detoxifying enzymes of ADH and ALDH families, and increased mitochondrial stress response genes in their liver tissues. Reduced lineage markers of liver progenitor cells were also observed in PTH-NLR patients signifying the presence of unresolved impairments after LT. Our results demonstrate the association between hematopoietic deficiencies and lack of protection against DDR with PTH-NLR in LDLT recipients with HCC and may imply abnormal hematological and organismal defects in those patients.

Aerobic degradation of high tetramethylammonium hydroxide (TMAH) and its impacts on nitrification and microbial community.

Tetramethylammonium hydroxide (TMAH) was often used as developer in the high-tech industries. Information regarding biological treatment of high TMAH-containing wastewater is limited. This study investigated aerobic degradation of high TMAH, its impacts on nitrification, and microbial community in a sequencing batch reactor (SBR). The initial TMAH concentrations of SBR gradually increased from 200 to 4666 mg L-1 (equivalent to 31 to 718 mg-N L-1) to enrich microbial community for aerobic TMAH degradation and nitrification. The results indicated that the aerobic specific TMAH degradation rates followed the Monod-type kinetics with a maximum specific TMAH degradation rate of 2.184 mg N hour-1 g volatile suspended solid (VSS)-1 and the half-saturation coefficient of 175.1 mg N L-1. After TMAH degradation and ammonia release, the lag time for the onset of nitrification highly correlated with initial TMAH fed for the SBR. According to the microbial community analysis using next generation sequencing (NGS), potential aerobic TMAH-degraders including Mycobacterium sp. and Hypomicrobium sp. were enriched in the aerobic SBR. The results of real-time quantitative polymerase chain reaction (qPCR) and reverse transcript (RT)-qPCR indicated that Hyphomicrobium sp. may be able to utilize both TMAH and its degradation intermediates such as trimethylamine (TMA), while Thiobacillus sp. can only utilize TMAH. The qPCR and RT-qPCR results suggested that TMAH may inhibit nitrification by inactive expression of amoA gene and the intermediates of TMAH degradation may compete ammonia monooxygenase (AMO) enzyme with ammonia for nitrification inhibition.