The function of lactate dehydrogenase A in retinal neurons: implications to retinal degenerative diseases.

The postmitotic retina is highly metabolic and the photoreceptors depend on aerobic glycolysis for an energy source and cellular anabolic activities. Lactate dehydrogenase A (LDHA) is a key enzyme in aerobic glycolysis, which converts pyruvate to lactate. Here we show that cell-type-specific actively translating mRNA purification by translating ribosome affinity purification shows a predominant expression of LDHA in rods and cones and LDHB in the retinal pigment epithelium and Müller cells. We show that genetic ablation of LDHA in the retina resulted in diminished visual function, loss of structure, and a loss of dorsal-ventral patterning of the cone-opsin gradient. Loss of LDHA in the retina resulted in increased glucose availability, promoted oxidative phosphorylation, and upregulated the expression of glutamine synthetase (GS), a neuron survival factor. However, lacking LDHA in Müller cells does not affect visual function in mice. Glucose shortage is associated with retinal diseases, such as age-related macular degeneration (AMD), and regulating the levels of LDHA may have therapeutic relevance. These data demonstrate the unique and unexplored roles of LDHA in the maintenance of a healthy retina.

Tumor lactic acid: a potential target for cancer therapy.

Tumor development is influenced by circulating metabolites and most tumors are exposed to substantially elevated levels of lactic acid and low levels of nutrients, such as glucose and glutamine. Tumor-derived lactic acid, the major circulating carbon metabolite, regulates energy metabolism and cancer cell signaling pathways, while also acting as an energy source and signaling molecule. Recent studies have yielded new insights into the pro-tumorigenic action of lactic acid and its metabolism. These insights suggest an anti-tumor therapeutic strategy targeting the oncometabolite lactic acid, with the aim of improving the efficacy and clinical safety of tumor metabolism inhibitors. This review describes the current understanding of the multifunctional roles of tumor lactic acid, as well as therapeutic approaches targeting lactic acid metabolism, including lactate dehydrogenase and monocarboxylate transporters, for anti-cancer therapy.

Lactate Production can Function to Increase Human Epithelial Cell Iron Concentration.

Introduction: Under conditions of limited iron availability, plants and microbes have evolved mechanisms to acquire iron. For example, metal deficiency stimulates reprogramming of carbon metabolism, increasing activity of enzymes involved in the Krebs cycle and the glycolytic pathway. Resultant carboxylates/hydroxycarboxylates then function as ligands to complex iron and facilitate solubilization and uptake, reversing the metal deficiency. Similarly, human intestinal epithelial cells may produce lactate, a hydroxycarboxylate, during absolute and functional iron deficiency to import metal to reverse limited availability. Methods: Here we investigate (1) if lactate can increase cell metal import of epithelial cells in vitro, (2) if lactate dehydrogenase (LDH) activity in and lactate production by epithelial cells correspond to metal availability, and (3) if blood concentrations of LDH in a human cohort correlate with indices of iron homeostasis. Results: Results show that exposures of human epithelial cells, Caco-2, to both sodium lactate and ferric ammonium citrate (FAC) increase metal import relative to FAC alone. Similarly, fumaric, isocitric, malic, and succinic acid coincubation with FAC increase iron import relative to FAC alone. Increased iron import following exposures to sodium lactate and FAC elevated both ferritin and metal associated with mitochondria. LDH did not change after exposure to deferoxamine but decreased with 24 h exposure to FAC. Lactate levels revealed decreased levels with FAC incubation. Review of the National Health and Nutrition Examination Survey demonstrated significant negative relationships between LDH concentrations and serum iron in human cohorts. Conclusions: Therefore, we conclude that iron import in human epithelial cells can involve lactate, LDH activity can reflect the availability of this metal, and blood LDH concentrations can correlate with indices of iron homeostasis.

Mutual regulation of lactate dehydrogenase and redox robustness.

The nature of redox is electron transfer; in this way, energy metabolism brings redox stress. Lactate production is associated with NAD regeneration, which is now recognized to play a role in maintaining redox homeostasis. The cellular lactate/pyruvate ratio could be described as a proxy for the cytosolic NADH/NAD ratio, meaning lactate metabolism is the key to redox regulation. Here, we review the role of lactate dehydrogenases in cellular redox regulation, which play the role of the direct regulator of lactate-pyruvate transforming. Lactate dehydrogenases (LDHs) are found in almost all animal tissues; while LDHA catalyzed pyruvate to lactate, LDHB catalyzed the reverse reaction . LDH enzyme activity affects cell oxidative stress with NAD/NADH regulation, especially LDHA recently is also thought as an ROS sensor. We focus on the mutual regulation of LDHA and redox robustness. ROS accumulation regulates the transcription of LDHA. Conversely, diverse post-translational modifications of LDHA, such as phosphorylation and ubiquitination, play important roles in enzyme activity on ROS elimination, emphasizing the potential role of the ROS sensor and regulator of LDHA.

Lactate dehydrogenases promote glioblastoma growth and invasion via a metabolic symbiosis.

Lactate is a central metabolite in brain physiology but also contributes to tumor development. Glioblastoma (GB) is the most common and malignant primary brain tumor in adults, recognized by angiogenic and invasive growth, in addition to its altered metabolism. We show herein that lactate fuels GB anaplerosis by replenishing the tricarboxylic acid (TCA) cycle in absence of glucose. Lactate dehydrogenases (LDHA and LDHB), which we found spatially expressed in GB tissues, catalyze the interconversion of pyruvate and lactate. However, ablation of both LDH isoforms, but not only one, led to a reduction in tumor growth and an increase in mouse survival. Comparative transcriptomics and metabolomics revealed metabolic rewiring involving high oxidative phosphorylation (OXPHOS) in the LDHA/B KO group which sensitized tumors to cranial irradiation, thus improving mouse survival. When mice were treated with the antiepileptic drug stiripentol, which targets LDH activity, tumor growth decreased. Our findings unveil the complex metabolic network in which both LDHA and LDHB are integrated and show that the combined inhibition of LDHA and LDHB strongly sensitizes GB to therapy.

Discovery of small molecules interacting at lactate dehydrogenases tetrameric interface using a biophysical screening cascade.

Lactate dehydrogenases (LDHs) are tetrameric enzymes of therapeutic relevance for cancer therapy due to their important implications in cancer cell metabolism. LDH active site inhibition suffers from different drawbacks due to several features such as high cellular concentration and a shared active site among the dehydrogenase family. Conversely, targeting the LDH oligomeric state is an exciting strategy that could provide a suitable alternative to active-site inhibition. In the present study, we developed a biophysical screening cascade to probe the LDHs tetrameric interface. Using nanoscale differential fluorimetry (nanoDSF) as a primary screening method, we identified a series of hits that destabilize the tetrameric protein. From this primary screening, we validated selected hits using saturation transfer difference nuclear magnetic resonance (STD NMR) and microscale thermophoresis (MST) as a combination of orthogonal biophysical techniques. Finally, we characterized the validated hits and demonstrated that they specifically interact at the tetrameric interface of LDH-1 and LDH-5 and can inhibit the LDH tetramerization process. Overall, this work provides a convenient method for screening ligands at the LDH tetrameric interface and has identified promising hits suitable for further optimization. We believe that this biophysical screening cascade, especially the use of (nano)DSF, could be extended to other homomeric proteins.

Effect of Karnofsky performance status scale and lactate dehydrogenase as well as their interaction on the therapeutic efficacy of diffuse large B-cell lymphoma / 白血病·淋巴瘤

Objective:To explore the factors influencing complete remission in patients with diffuse large B-cell lymphoma (DLBCL), and to explore the effect of the interaction of Karnofsky performance status scale (KPS) scores and the level of lactate dehydrogenases (LDH) on whether patients with DLBCL are completely relieved.Methods:The clinical data of 373 DLBCL patients admitted to Shanxi Province Cancer Hospital from January 2014 to December 2020 were retrospectively analyzed. SPSS 25.0 logistic regression model and Cox proportional risk regression models were used to explore the factors affecting complete remission in patients with DLBCL and to explore whether there was a multiplicative interaction between the factors. For factors with multiplicative interactions, the Matrix package, epiR package, and survival package in R 4.2.0 software were used to analyze whether there was an additive interaction. The relative excess risk of interaction (RERI), attributable proportion due to interaction (AP), and the synergy index (S) were used to evaluate the presence of additive interactions.Results:Elevated β 2 macroglobulin (β 2-MG), KPS scores below 80, and elevated LDH were risk factors for incomplete remission in patients with DLBCL (all P < 0.05). The risk of incomplete remission in patients with elevated β 2-MG, KPS scores below 80 and LDH was 1.971 times ( OR = 1.971, 95% CI 1.161-3.346), 2.056 times ( OR = 2.056, 95% CI 1.057-4.000) and 3.351 times ( OR = 3.351, 95% CI 1.783-6.300) higher than those in patients with normal β 2-MG, KPS scores above 80 and non-elevated LDH, respectively. There was a negative multiplicative interaction between the two risk factors of KPS scores below 80 and elevated LDH ( OR = 0.317, 95% CI 0.126-0.785). The estimated value of RERI, AP and S was -2.07 (95% CI -4.79-0.64),0.50 (95% CI -1.68-0.32),0.50 (95% CI 0.22-1.13), respectively; and there was no additive interaction among them. Conclusions:Elevated β 2-MG, KPS scores below 80, and elevated LDH are risk factors influencing incomplete remission for patients with DLBCL. The combined effect in patients with the combination of elevated LDH and KPS scores below 80 is lower than the single effect of the multiple of the both. There is a negative multiplicative interaction and no additive interaction in DLBCL patients with KPS scores below 80 and elevated LDH level.

Meta-analysis of acupuncture intervening exercise-induced fatigue / 针灸推拿医学（英文版）

Objective: To systematically evaluate the impact of acupuncture on exercise-induced fatigue (EIF). Methods: Scopus, Springer Link, Web of Science, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), and China Biology Medicine Disc (CBM) were systematically searched to identify randomized controlled trials (RCTs) studying acupuncture treatment of EIF from the inception till August 2020. The risk of bias in the included studies was assessed using the Cochrane handbook. RevMan 5.3 was used to conduct statistical analysis on the extracted data. Results: A total of 11 RCTs were included for meta-analysis, involving 531 patients. It was revealed that acupuncture produced more significant effects in alleviating subjective fatigue [standardized mean difference (SMD)=-3.08, 95％ confidence interval (CI) (-4.35, -1.81), P<0.001], increasing the hemoglobin content [weighted mean difference (WMD)=3.89, 95％CI (1.37, 6.42), P=0.003], reducing the lactate dehydrogenase content [WMD=-10.63, 95％CI (-17.67, -3.59), P=0.003], reducing the blood lactic acid content [SMD=-2.65, 95％CI (-4.47, -0.83), P=0.004], and down-regulating the levels of serum creatine kinase [SMD=-0.79, 95％CI (-1.10, -0.48), P<0.001] and blood urea nitrogen [WMD=-1.47, 95％CI (-1.84, -1.11), P<0.001] than the control groups. Conclusion: Based on the existing evidence, acupuncture can be recognized as effective in improving EIF and is worthy of promotion in clinical settings.

Clinical features of Pneumocystis jirovecii pneumonia / 中华检验医学杂志

Objective:The clinical features, laboratory indices, and imaging data of patients with Pneumocystis jirovecii pneumonia (PJP) were described and analyzed, aiming to provide helpful information for the diagnosis and treatment of PJP. Methods:A retrospective study were conducted with data from 154 PJP patients who visited China-Japan Friendship Hospital from May 2017 to August 2020. Their clinical characteristics, laboratory and imaging data, and clinical outcomes were collected for analysis. The patients were further divided into the death group (51 cases) and the survival group(103 cases). The differences between the groups were compared by using t-test, nonparametric test, and chi-square test. Results:Of the 154 PJP patients, there were 89 males and 65 females, with a mean age of (53.7±14.8) years. Among them, 85.7% (132/154) were on immunosuppressive/glucocorticoids agents within the past month. Besides, 27.9% (43/154) and 33.1% (51/154) had kidney diseases and connective tissue diseases, respectively. The major clinical manifestations in these patients involved fever 82.9% (126/154), cough 59.7% (92/154), and dyspnea 52.6% (81/154). For the laboratory data, the lactate dehydrogenase (LDH) was 561.0 (434.3, 749.0) IU/L and the value increased in 91.3% (95/104) of the patients. The CD4+T-cell lymphocytes in 88.0% (95/108) and 57.4% (62/108) of patients were lower than 400/μl and 200/μl, respectively. Furthermore, (1, 3)-β-D glucan (BG) increased in 74.4% (67/90) of PJP patients (≥100.0 ng/L). For the imaging results, chest computed tomography (CT) showed diffuse ground-glass shadows/grid shadows in 90% (117/130) patients. Compared with the survival group, higher LDH [690.5 (528.8, 932.3) IU/L vs 502.5 (381.8, 657.0) IU/L, Z=-3.375, P=0.001], white blood cell count (WBC) [9.8 (5.8, 12.6) ×10 9/L vs 7.3 (5.0, 10.1) ×10 9/L, Z=-2.392, P=0.017], and age [(69.8±14.5) years vs (50.6±14.0) years, t=-3.756, P=0.001] were found in the death group. Lower lymphocyte ratio [5.3 (3.2, 9.3) % vs 9.6 (5.6, 17.2) %, Z=?3.262, P=0.001] and oxygen partial pressure (PaO 2) levels [(73.2±20.5) mmHg vs (64.8±17.7) mmHg (1 mmHg=0.133 kPa), t=2.345, P=0.021] were also observed in the death group. Furthermore, in the death group, the bacterial and fungal infection rate was higher than the rates in the survival group [55.1% (27/51) vs 21.5% (22/103), χ 2=15.372, P=0.001]. Conclusions:Long-term use of immunosuppressive agents or glucocorticoids predispose to PJP. CD4+T-lymphocytes, LDH, and BG might be used as important auxiliary examinations for PJP patients. Age, LDH, WBC, lymphocyte ratio, PaO 2 and possible combinations with bacterial or fungal infections are more closely related to the prognostic of PJP patients.

Systemic inflammatory markers and psychophysical olfactory scores in coronavirus disease 2019 patients: is there any correlation?

OBJECTIVE: To analyse the correlations between olfactory psychophysical scores and the serum levels of D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio in coronavirus disease 2019 patients. METHODS: Patients underwent psychophysical olfactory assessment with the Connecticut Chemosensory Clinical Research Center test, and determination of blood serum levels of the inflammatory markers D-dimer, C-reactive protein, ferritin, lactate dehydrogenase, procalcitonin and neutrophil-to-lymphocyte ratio within 10 days of the clinical onset of coronavirus disease 2019 and 60 days after. RESULTS: Seventy-seven patients were included in this study. D-dimer, procalcitonin, ferritin and neutrophil-to-lymphocyte ratio correlated significantly with severe coronavirus disease 2019. No significant correlations were found between baseline and 60-day Connecticut Chemosensory Clinical Research Center test scores and the inflammatory markers assessed. CONCLUSION: Olfactory disturbances appear to have little prognostic value in predicting the severity of coronavirus disease 2019 compared to D-dimer, ferritin, procalcitonin and neutrophil-to-lymphocyte ratio. The lack of correlation between the severity and duration of olfactory disturbances and serum levels of inflammatory markers seems to further suggest that the pathogenetic mechanisms underlying the loss of smell in coronavirus disease 2019 patients are related to local rather than systemic inflammatory factors.

Fully automatic d-lactate assay using a modified commercially available method.

Intestinal infarction is the fast-evolving endpoint of impaired blood perfusion to an intestinal segment which may have fatal outcome. Early diagnosis and treatment within 6 h reduce mortality. Currently, d-lactate is a promising biomarker, however, not available in the acute clinical setting. The aim of this study is implementation of d-lactate analysis in a routine clinical setting. We used a spectrophotometric method, based on enzymatic oxidation of d-lactate by d-lactate dehydrogenase (D-LDH) coupled to the reduction of nicotinamide-adenine dinucleotide (NAD+). The amount of NADH formed in this reaction is equivalent to d-lactate. The primary concern in this method is interfering NADH formed by oxidation of l-lactate by l-lactate dehydrogenase (L-LDH). A commercially available kit for d-lactate measurement was implemented on our existing automated routine laboratory equipment including pH-inactivation of L-LDH. Our setup fulfilled clinical quality goals. We were able to measure d-lactate with an acceptable performance of the analysis and a short turn-around time. The method can be used to distinguish between the expected cut-off for intestinal ischemia around 0.3 mM and the upper reference limit of 0.05 mM. With a turnaround time of just 9 min, the analysis has potential as a readily available detection of circulating d-lactate for early diagnosis of intestinal ischemia.

Discovery of a novel lactate dehydrogenase tetramerization domain using epitope mapping and peptides.

Despite being initially regarded as a metabolic waste product, lactate is now considered to serve as a primary fuel for the tricarboxylic acid cycle in cancer cells. At the core of lactate metabolism, lactate dehydrogenases (LDHs) catalyze the interconversion of lactate to pyruvate and as such represent promising targets in cancer therapy. However, direct inhibition of the LDH active site is challenging from physicochemical and selectivity standpoints. However, LDHs are obligate tetramers. Thus, targeting the LDH tetrameric interface has emerged as an appealing strategy. In this work, we examine a dimeric construct of truncated human LDH to search for new druggable sites. We report the identification and characterization of a new cluster of interactions in the LDH tetrameric interface. Using nanoscale differential scanning fluorimetry, chemical denaturation, and mass photometry, we identified several residues (E62, D65, L71, and F72) essential for LDH tetrameric stability. Moreover, we report a family of peptide ligands based on this cluster of interactions. We next demonstrated these ligands to destabilize tetrameric LDHs through binding to this new tetrameric interface using nanoscale differential scanning fluorimetry, NMR water-ligand observed via gradient spectroscopy, and microscale thermophoresis. Altogether, this work provides new insights on the LDH tetrameric interface as well as valuable pharmacological tools for the development of LDH tetramer disruptors.

l-Lactate Dehydrogenase Identified as a Protein Tyrosine Phosphatase 1B Substrate by Using K-BIPS.

Kinases and phosphatases are major players in a variety of cellular events, including cell signaling. Aberrant activity or mutations in kinases and phosphatases can lead to diseases such as cancer, diabetes, and Alzheimer's. Compared to kinases, phosphatases are understudied; this is partly a result of the limited methods for identifying substrates. As a solution, we developed a proteomics-based method called kinase-catalyzed biotinylation to identify phosphatase substrates (K-BIPS) that previously identified substrates of Ser/Thr phosphatases using small molecule inhibitors. Here, for the first time, K-BIPS was applied to identify substrates of a tyrosine phosphatase, protein tyrosine phosphatase 1B (PTP1B), under siRNA knockdown conditions. Eight possible substrates of PTP1B were discovered in HEK293 cells, including the known substrate pyruvate kinase. In addition, l-lactate dehydrogenase (LDHA) was validated as a novel PTP1B substrate. With the ability to use knockdown conditions with Ser/Thr or Tyr phosphatases, K-BIPS represents a general discovery tool to explore phosphatases biology by identifying unanticipated substrates.

The diagnostic performance of current tumour markers in surveillance for recurrent testicular cancer: A diagnostic test accuracy systematic review.

In this diagnostic test accuracy systematic review we summarise the evidence on the diagnostic accuracy of blood α-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) in surveillance for testicular cancer recurrence in adults. We searched four electronic databases for studies that reported the diagnostic accuracy of HCG, AFP, and/or LDH in sufficient detail for sensitivity and specificity to be calculated by extracting a 2 × 2 table comparing biomarker positivity with testicular cancer recurrence. Screening, data extraction and QUADAS-2 quality assessment were completed by two independent reviewers. From 2406 studies, nine met our inclusion criteria. Eight reported data at the per-patient level. Sample sizes were small (range 5 to 449 patients) and clinical heterogeneity precluded meta-analysis. In most studies the specificity for recurrence with AFP and HCG was high (90-100%) but sensitivity was often relatively low, suggesting that many recurrences would not be detected by tumour markers alone. The diagnostic performance of LDH appears poorer. Studies were methodologically weak, with probable selection, incorporation and partial verification bias, and many studies were excluded for not reporting on recurrence-free patients. Limitations including small sample sizes, high heterogeneity, and inconsistent and incomplete reporting mean these results must be interpreted with caution. Despite inclusion of biomarkers in international surveillance guidance, there remains a lack of high quality evidence about their accuracy, optimal thresholds, and the most effective surveillance strategy in relation to contemporary investigative modalities. Higher quality research using data from modern-day follow-up cohorts is necessary to identify opportunities to reduce unnecessary testing.

Plasma fibrinogen level as possible prognostic biomarker in diffuse large B-cell lymphoma.

OBJECTIVES: Although many studies have assessed numerous molecular and immunohistochemical prognostic markers for diffuse large Bcell lymphoma (DLBCL), there is always a need for simple widely available markers. This study was planned to illustrate the clinical significance of baseline plasma fibrinogen levels in DLBCL patients. METHODS: We prospectively investigated 76 DLBCL patients treated with rituximab plus cyclophosphamide, vincristine, doxorubicin and hostacortine between August 2015 and February 2018. Baseline plasma fibrinogen level was measured and correlated with patients' clinical features, laboratory parameters, response to therapy, progression-free survival and overall survival. RESULTS: Significant association between fibrinogen level and clinical features such as the presence of B symptoms (P < .001) and clinical stage (P < .001) was observed while no association with age, gender, number of involved extranodal sites, performance status and international prognostic index (IPI) was found. Baseline fibrinogen level was significantly related to laboratory parameters including red cell distribution width (RDW) (P < .001), platelet count (P = .02), serum lactate dehydrogenase (LDH) (P = .009) and B2-microglobulin (P = .008). No statistically significant correlations were detected between baseline fibrinogen levels; and response to therapy, progression-free survival and overall survival. CONCLUSION: Baseline plasma fibrinogen level did not show prognostic significance for DLBCL patients, although it was associated with patients' clinical features and laboratory parameters. Being simple, cheap and widely available laboratory test, its use should be encouraged routinely in clinical practice to precisely clarify its predictive merit.

Transient increase in lactate dehydrogenase after granulocyte colony-stimulating factor administration during chemotherapy in a patient with advanced seminoma.

INTRODUCTION: Granulocyte colony-stimulating factor is often reported to induce increases in lactate dehydrogenase, complicating the evaluation of treatment effects on germ cell tumors. CASE PRESENTATION: A 30-year-old patient was diagnosed with left testicular seminoma showing enlarged para-aortic lymph nodes and a retroperitoneal tumor. Serum levels of lactate dehydrogenase were elevated. Three cycles of bleomycin, etoposide, and cisplatin were administered. After chemotherapy, computed tomography showed marked reduction in the metastatic sites. However, serum lactate dehydrogenase levels increased transiently at the end of each course of chemotherapy. In consideration of the residual tumors, one cycle of another chemotherapy was added. Five months after final chemotherapy, lactate dehydrogenase remained within normal limits with no evidence of tumor recurrence. CONCLUSION: In our case, transient elevation of lactate dehydrogenase was considered relevant to granulocyte colony-stimulating factor use. Examination of lactate dehydrogenase isoenzymes may be helpful to estimate the cause of serum lactate dehydrogenase elevation.

Diagnosing malignant pleural effusion using clinical and analytical parameters.

BACKGROUND: Malignant pleural effusion (MPE) is common and diagnosis is often problematic. A cancer ratio (serum lactate dehydrogenases: pleural adenosine deaminase ratio) has been proposed for diagnosing MPE. However, the usefulness of this "cancer ratio" and the clinical-radiological criteria for diagnosing MPE has not been clearly determined to date. The aim of this study was to assess the performance of those parameters in the diagnosis of MPE. METHODS: We analyzed 240 patients including 120 with MPE and 120 with non-MPE (93 tuberculous and 27 parapneumonic). Patients were divided into two groups: MPE and non-MPE (eg, tuberculous and parapneumonic). We constructed two predictive models to assess the probability of MPE: (a) clinical-radiological data only and (b) a combination of clinical-radiological data, the cancer ratio, and the carcinoembryonic antigen (CEA). The performances of the predictive models were assessed using receiver operating characteristic (ROC) curves and by examining the calibration. RESULTS: The area under the ROC curves for model 1 and model 2 were excellent, 0.936 and 0.998, respectively. The overall diagnostic accuracies for model 1 and model 2 were 87.5% and 98.8%, respectively. CONCLUSION: The results confirm that both models achieved a high diagnostic accuracy for MPE; however, model 2 was superior with the addition of its simplicity of use in daily practice. This model should be applied to determine which patients with a pleural effusion of unknown origin would not benefit from further invasive procedures.

Clinical value of differential diagnosis of matrix metalloproteinase-3 in benign and malignant hydrothorax and ascites / 中华检验医学杂志

Objective@#To investigate the levels of matrix metalloproteinases-3 (MMP-3), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) in the hydrothorax and ascites, and to approach the diagnostic value of three combined indexes in benign and malignant hydrothorax and ascites.@*Methods@#Case-control study. A total of 278 patients with hydrothorax and ascites were enrolled in this study who were hospitalized in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2018 to July 2019 to detect the levels of MMP-3, ADA and LDH in the hydrothorax and ascites. The benign group (208 patients) and malignant group (70 patients) were compared with MMP-3, ADA, LDH, receiver operating characteristic (ROC) curve, sensitivity and specificity in the hydrothorax and ascites, and the results were compared comprehensively.@*Results@#(1)The MMP-3 level in the benign hydrothorax group was 89.21±61.93 ng/mL, the ADA level was (9.08±8.89) U/L, the LDH level was (143.34±68.63) U/L, and the MMP-3 level in the malignant hydrothorax group was (205.63±98.16) ng/mL, he ADA level was (10.96±5.04) U/L, the LDH level was (243.44±131.20) U/L. The MMP-3 level in the benign ascites group was (84.91±73.48) ng/mL, the ADA level was (3.48±2.80) U/L, the LDH level was (99.48±69.53) U/L, and the MMP-3 level in the malignant ascites group was (174.89±82.48) ng/mL, the ADA level was (6.31±4.42) U/L, the LDH level was (191.86±94.52) U/L. The levels of MMP-3, ADA and LDH in the hydrothorax and ascites of the malignant group were higher than those in the benign group, and the difference was statistically significant (Z1 values were 5.215, 2.549, 3.212, respectively, and Z2 values were 6.188, 4.524, 6.38, respectively, P1 and P2 were <0.05). (2)The area under the curve (AUC) of MMP-3 for diagnosis of hydrothorax, liver cancer ascites and gastric cancer ascites was 0.853, 0.826, and 0.763, respectively. The sensitivity was 76%, 96.9%, and 92.3%, respectively, and the specificity was 80%, 64.5%, 61.6%. The diagnostic efficacy of MMP-3 in lung cancer hydrothorax and liver cancer ascites was higher than ADA (AUC were 0.672, 0.691,respectively) and LDH (AUC were 0.717, 0.804, respectively), and the diagnostic efficacy of gastric cancer ascites was lower than ADA (AUC is 0.808) and LDH (AUC is 0.849), and LDH was the best. (3)The AUC of MMP-3, ADA and LDH combined diagnosis of lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites were 0.861, 0.842, and 0.879, respectively. The sensitivities were 64%, 96.9%, and 84.6%, respectively, and the specificities were 92.9%, 63.8%, and 80.4%, respectively. In the lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites, the combined efficacy of the three combined tests was better than the combined detection of MMP-3 and LDH (AUC were 0.86, 0.839, 0.872, respectively), combined detection of MMP-3 and ADA (AUC were 0.845, 0.831, 0.855, respectively), LDH and ADA combined detection (AUC were 0.713, 0.791, 0.846, respectively).@*Conclusions@#MMP-3 is important for the differential diagnosis of benign and malignant hydrothorax and ascites, and may be one of the important indicators for the differential diagnosis of benign and malignant hydrothorax and ascites. The diagnostic efficacy of MMP-3 combined with ADA and LDH and three combined detection is better than single index, which has certain clinical value for differential diagnosis of benign and malignant hydrothorax and ascites.

Clinical significance and prognostic value of cellular immunity, inflammatory factors and myocardial enzymes in septic shock / 中国基层医药

Objective@#To investigate the clinical significance of cellular immune function, inflammatory factors and myocardial enzyme detection in evaluation of prognosis of septic shock, so as to provide a reference for clinical diagnosis and treatment of septic shock.@*Methods@#From June 2015 to June 2018, 73 patients with septic shock treated in the First People's Hospital of Yongkang were selected as the research subjects.According to the 28d prognosis after the patients entered the ICU, the patients were divided into the death group and the survival group.Another 67 cases of health examination from June 2015 to June 2018 were selected as control group.The changes of T lymphocyte subsets includingCD3, CD4 and CD8 were measured by BD FACSCanto I I flow cytometry, the content of procalcitonin(PCT) was determined by immunoluminescence assay, the content of C-reactive protein(CRP) was determined by immunoturbidimetry, and the content of creatine kinase MB(CK-MB), cardiac troponin I(cTnI) and lactate dehydrogenase(LDH) was determined by enzymatic kinetics.@*Results@#The APACHE Ⅱ score and MODS score of the survival group and the death group were higher than those of the control group [(2.20±0.61)points and (4.86±1.29)points]. The APACHE Ⅱ score and MODS score of death group [(16.45±4.28)points and (27.63±4.97)points] were higher than those of survival group [(9.84±2.45)points and (19.84±3.28)points](all P<0.05). The CD3+, CD4+ and CD4+/CD8+ in the survival group and the death group were significantly lower than those in the control group[(71.32±6.96)%, (42.63±4.26)%, (1.67±0.31)%](all P<0.05). The contents of PCT and CRP in the survival group and the death group were higher than those in the control group [(0.19±0.03)ng/mL and (2.19±0.76)mg/L], and the contents of PCT [(15.93±3.26)ng/mL] and CRP [(184.32±29.80)mg/L] in the death group were higher than those in the survival group [(6.87±1.94)ng/mL and (69.49±17.42)mg/L] (all P<0.05). The CK-MB content in the survival group and the death group of septic shock was lower than that in the control group [(1.97±0.21)μg/L], and the cTnI and LDH contents were higher than that in the control group [(0.03±0.01)μg/L and (168.93±16.52)U/L], the content of CK-MB [(0.68±0.10)μg/L] in the death group was lower than that in the survival group [(1.27±0.13)μg/L], while the contents of cTnI [(0.39±0.06)μg/L] and LDH [(384.52±39.89)U/L] in the death group were lower than those in the survival group [(0.17±0.04)μg/L and (257.18±25.47)U/L] (P<0.05).@*Conclusion@#The immune function of the patients with septic shock is obviously reduced, there are obvious inflammatory reactions and abnormal myocardial enzymes, and the detection of cellular immune function, inflammatory factors and myocardial enzymes can be used as an effective index to judge the shock of septic shock.

Clinical value of differential diagnosis of matrix metalloproteinase-3 in benign and malignant hydrothorax and ascites / 中华检验医学杂志

Objective To investigate the levels of matrix metalloproteinases-3 (MMP-3), adenosine deaminase (ADA) and lactate dehydrogenase (LDH) in the hydrothorax and ascites, and to approach the diagnostic value of three combined indexes in benign and malignant hydrothorax and ascites. Methods Case-control study. A total of 278 patients with hydrothorax and ascites were enrolled in this study who were hospitalized in the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from August 2018 to July 2019 to detect the levels of MMP-3, ADA and LDH in the hydrothorax and ascites. The benign group (208 patients) and malignant group (70 patients) were compared with MMP-3, ADA, LDH, receiver operating characteristic (ROC) curve, sensitivity and specificity in the hydrothorax and ascites, and the results were compared comprehensively. Results (1)The MMP-3 level in the benign hydrothorax group was 89.21±61.93 ng/mL, the ADA level was (9.08±8.89) U/L, the LDH level was (143.34± 68.63) U/L, and the MMP-3 level in the malignant hydrothorax group was (205.63 ± 98.16) ng/mL, he ADA level was (10.96±5.04) U/L, the LDH level was (243.44±131.20) U/L. The MMP-3 level in the benign ascites group was (84.91±73.48) ng/mL, the ADA level was (3.48±2.80) U/L, the LDH level was (99.48±69.53) U/L, and the MMP-3 level in the malignant ascites group was (174.89 ± 82.48) ng/mL, the ADA level was (6.31 ± 4.42) U/L, the LDH level was (191.86±94.52) U/L. The levels of MMP-3, ADA and LDH in the hydrothorax and ascites of the malignant group were higher than those in the benign group, and the difference was statistically significant (Z1 values were 5.215, 2.549, 3.212, respectively, and Z2 values were 6.188, 4.524, 6.38, respectively, P1 and P2 were <0.05). (2)The area under the curve (AUC) of MMP-3 for diagnosis of hydrothorax, liver cancer ascites and gastric cancer ascites was 0.853, 0.826, and 0.763, respectively. The sensitivity was 76％, 96.9％, and 92.3％, respectively, and the specificity was 80％, 64.5％, 61.6％. The diagnostic efficacy of MMP-3 in lung cancer hydrothorax and liver cancer ascites was higher than ADA (AUC were 0.672, 0.691, respectively) and LDH (AUC were 0.717, 0.804, respectively), and the diagnostic efficacy of gastric cancer ascites was lower than ADA (AUC is 0.808) and LDH (AUC is 0.849), and LDH was the best. (3)The AUC of MMP-3, ADA and LDH combined diagnosis of lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites were 0.861, 0.842, and 0.879, respectively. The sensitivities were 64％, 96.9％, and 84.6％, respectively, and the specificities were 92.9％, 63.8％, and 80.4％, respectively. In the lung cancer hydrothorax, liver cancer ascites and gastric cancer ascites, the combined efficacy of the three combined tests was better than the combined detection of MMP-3 and LDH (AUC were 0.86, 0.839, 0.872, respectively), combined detection of MMP-3 and ADA (AUC were 0.845, 0.831, 0.855, respectively), LDH and ADA combined detection (AUC were 0.713, 0.791, 0.846, respectively). Conclusions MMP-3 is important for the differential diagnosis of benign and malignant hydrothorax and ascites, and may be one of the important indicators for the differential diagnosis of benign and malignant hydrothorax and ascites. The diagnostic efficacy of MMP-3 combined with ADA and LDH and three combined detection is better than single index, which has certain clinical value for differential diagnosis of benign and malignant hydrothorax and ascites.