Proteomics Investigation of Diverse Serological Patterns in COVID-19

Serum antibodies IgM and IgG are elevated during COVID-19 to defend against viral attack. Atypical results such as negative and abnormally high antibody expression were frequently observed whereas the underlying molecular mechanisms are elusive. In our cohort of 144 COVID-19 patients, 3.5% were both IgM and IgG negative whereas 29.2% remained only IgM negative. The remaining patients exhibited positive IgM and IgG expression, with 9.3% of them exhibiting over 20-fold higher titers of IgM than the others at their plateau. IgG titers in all of them were significantly boosted after vaccination in the second year. To investigate the underlying molecular mechanisms, we classed the patients into four groups with diverse serological patterns and analyzed their two-year clinical indicators. Additionally, we collected 111 serum samples for TMTpro-based longitudinal proteomic profiling and characterized 1494 proteins in total. We found that the continuously negative IgM and IgG expression during COVID-19 were associated with mild inflammatory reactions and high T cell responses. Low levels of serum IgD, inferior complement 1 activation of complement cascades, and insufficient cellular immune responses might collectively lead to compensatory serological responses, causing overexpression of IgM. Serum CD163 was positively correlated with antibody titers during seroconversion. This study suggests that patients with negative serology still developed cellular immunity for viral defense, and that high titers of IgM might not be favorable to COVID-19 recovery.

Proteomic and Metabolomic Investigation of COVID-19 Patients with Elevated Serum Lactate Dehydrogenase

Serum lactate dehydrogenase (LDH) has been established as a prognostic indicator given its differential expression in COVID-19 patients. However, the molecular mechanisms underneath remain poorly understood. In this study, 144 COVID-19 patients were enrolled to monitor the clinical and laboratory parameters over three weeks. Serum lactate dehydrogenase (LDH) was shown elevated in the COVID-19 patients on admission and declined throughout disease course, and its ability to classify patient severity outperformed other biochemical indicators. A threshold of 247 U/L serum LDH on admission was determined for severity prognosis. Next, we classified a subset of 14 patients into high- and low-risk groups based on serum LDH expression and compared their quantitative serum proteomic and metabolomic differences. The results found COVID-19 patients with high serum LDH exhibited differentially expressed blood coagulation and immune responses including acute inflammatory responses, platelet degranulation, complement cascade, as well as multiple different metabolic responses including lipid metabolism, protein ubiquitination and pyruvate fermentation. Specifically, activation of hypoxia responses was highlighted in patients with high LDH expressions. Taken together, our data showed that serum LDH levels are associated COVID-19 severity, and that elevated serum LDH might be consequences of hypoxia and tissue injuries induced by inflammation.

Eleven Routine Clinical Features Predict COVID-19 Severity

Severity prediction of COVID-19 remains one of the major clinical challenges for the ongoing pandemic. Here, we have recruited a 144 COVID-19 patient cohort consisting of training, validation, and internal test sets, longitudinally recorded 124 routine clinical and laboratory parameters, and built a machine learning model to predict the disease progression based on measurements from the first 12 days since the disease onset when no patient became severe. A panel of 11 routine clinical factors, including oxygenation index, basophil counts, aspartate aminotransferase, gender, magnesium, gamma glutamyl transpeptidase, platelet counts, activated partial thromboplastin time, oxygen saturation, body temperature and days after symptom onset, constructed a classifier for COVID-19 severity prediction, achieving accuracy of over 94%. Validation of the model in an independent cohort containing 25 patients achieved accuracy of 80%. The overall sensitivity, specificity, PPV and NPV were 0.70, 0.99, 0.93 and 0.93, respectively. Our model captured predictive dynamics of LDH and CK while their levels were in the normal range. This study presents a practical model for timely severity prediction and surveillance for COVID-19, which is freely available at webserver https://guomics.shinyapps.io/covidAI/.

Serum bilirubin and the risk of rheumatoid arthritis.

BACKGROUND: Oxidative stress and immune imbalance play an important role in the pathogenesis of rheumatoid arthritis (RA). Bilirubin is a powerful antioxidant and also regarded as immunomodulator. Increased evidence shows that bilirubin should be a protective factor for autoimmune disease. However, the relationship between bilirubin and RA remain unclear. METHODS: We analyzed serum bilirubin levels and other laboratory and clinical data in 130 RA patients (35 patients without any complications), 81 osteoarthritis (OA) patients and 96 healthy controls. RESULTS: Binary logistic regression adjusted by age and gender revealed that the levels of serum total, indirect bilirubin were significantly lower in RA patients, when compared with healthy controls (P=.015, OR=0.767, 95% CI=0.619-0.951; P=.010, OR=0.664, 95% CI=0.487-0.906, respectively) or OA patients (P=.000, OR=0.763, 95% CI=0.661-0.882; P=.000, OR=0.656, 95% CI=0.532-0.808, respectively). A reduced trend of levels of bilirubin has been detected along with increased disease activity, despite with no significance (P>.05). Spearman rank test further demonstrated that IgG and ESR were negative associated with total, indirect bilirubin, and albumin, prealbumin, APOA, HDL-C were positively associated with bilirubin. CONCLUSIONS: In conclusion, the levels of serum bilirubins were decreased in RA, and decreased levels could be associated with IgG, albumin and inflammatory marker ESR.

Study on correlation between single b-value and multiple b-value DWI and different types of breast lesions / 实用放射学杂志

Objective To investigate the relationship between single b-value and multiple b-value diffusion weighted imaging (DWI)and different types of breast lesions.Methods The data of 92 cases including 8 cases of cyst,11 cases of granulomatous inflammation,33 cases of benign nodules lesions and 40 cases of malignant tumor were analyzed retrospectively,who underwent single b-value DWI and multiple b-value DWI and all patients were confirmed by pathology.The normal side of the mammary gland fiber was taken as the control group.Apparent diffusion coefficient(ADC)were obtained by the monoexponential model.Slow apparent diffusion coefficient(ADCslow),fast apparent diffusion coefficient(ADCfast),the fraction of fast ADC(ffast)were obtained by the biexponential model.ADC,ADCslow,ADCfast,ffastvalues of different breast lesions were analyzed by single factor analysis of variance.The LSD-t test was used to compare the mean values of the parameters of the breast lesions in pairs.Results The ADC and ADCslowvalue of breast lesions were decreased in the order of cyst (2.369 ± 0.380)×10-3mm2/s,(1.294 ± 0.439)×10-3mm2/s,normal gland(1.785 ± 0.298)×10-3mm2/s,(0.946 ± 0.321)×10-3mm2/s,benign tumor(1.647 ± 0.296)×10-3mm2/s,(0.944 ± 0.256)×10-3mm2/s,malignant tumor(1.146 ± 0.191)×10-3mm2/s,(0.584 ± 0.139)×10-3mm2/s and mastitis(1.062 ± 0.231)×10-3mm2/s,(0.567 ± 0.115)×10-3mm2/s.The ADCfastvalue of malignant group(4.445 ± 1.616)×10-3mm2/s was significantly higher than that of other groups,and the difference was statistically significant.The ffastvalue of malignant group 0.364 ± 0.148 was significantly lower than that of benign group,normal gland and cyst.ADCfastvalue in the inflammatory group(3.321 ± 0.660)× 10-3mm2/s was significantly lower than that in the malignant group,and the difference was statistically significant.There was no significant difference in ADC,ADCslowand ffast.Conclusion Compared with the single b-value DWI,the parameters of multiple b-value DWI reflected the pathological features of different breast lesions better.The value of ADCfasthas higher diagnostic value in the identification of mastitis and breast cancer.

Increased TTS expression in patients with rheumatoid arthritis.

Immune system activation is known to be involved in the progression of rheumatoid arthritis (RA). The aim of this work was to study the imbalance expressions of indoleamine 2,3-dioxygenase (IDO) and tryptophanyl-tRNA synthetase (TTS) with RA patients. Forty-nine RA patients and 49 healthy controls were studied. The expressions of IDO and TTS were analyzed by real-time quantitative polymerase chain reaction and flow cytometry in peripheral blood mononuclear cells. The expression of TTS mRNA increased significantly in RA patients when compared with healthy controls and correlated with erythrocyte sedimentation rate (r = 0.424, P < 0.01). In addition, we found TTS increased significantly mainly in CD3(+) T cells in rheumatoid arthritis group. Increased TTS expressions from CD3(+) T cells might link to a pathogenic mechanism involved in increasing survival of autoreactive T cells in RA patients. Determination of expressions of TTS may provide a better understanding of progression of the disease.

Investigation of the peripheral blood mononuclear cells expressing HLA-G of patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the expression of HLA-G in lymphocytes,CD3+ T cells,and CD14+ monocytes from patients with rheumatoid arthritis (RA) and their associations with disease activity,disease duration,medication used and clinical parameters.Methods We studied 68 RA patients as well as 63 healthy controls.HLA-G expression was analyzed by flow cytometry in peripheral blood mononuclear cells (PBMCs).Mann Whitney U tests and Spearman rank correlation coefficient test were used for statistical analysis.Results We found that lymphocytes as well as CD3+ T cells,and CD14+ monocytes in RA patients showed a diminished expression of HLA-G compared with healthy controls [1.98％(1.17％-3.66％) vs 2.93％ (1.70％-5.40％),U=1624.5,P＜0.05; 1.35％(0.57％-2.79％) vs 2.16％(1.15％-4.45％),U=1387,P=0.000; 22.65％ (10.59％-36.81％) vs 32.76％ (20.73％-44.62％),U=1526,P＜0.01].Spearman analysis showed that the levels of HLA-G+ lymphocytes as well as CD3+ HLA-G+ T cells was negatively associated with DAS28 score(r=-0.288,P=0.017; r=-0.373,P=0.001),but no significant correlation was detected between the levels of CD14+HLA-G+monocytes and DAS 28 score (P＞0.05).In addition,the levels of expression of HLA-G was not correlated to disease duration,medication used,ESR,CRP,RF,anti-CCP and ANA (P＞0.05).Conclusion Decreased expression of HLA-G are detected in lymphocytes,CD3+ T cells,and CD14+ monocytes from pa-tients with RA,and the abnormality of HLA-G may play an important role in the development of RA.

Effects of Vertebral Basilar Artery Bloodstream about CSA Treated by Small Needle Knife Combining with Massage Manipulation in Clinical Practice / 世界科学技术-中医药现代化

This study was aimed to explore the action mechanism of massage treatment in combination with small needle knife to cervical spondylotic vertebral arteriopathy (CSA). A total of 400 CSA patients were randomly divided into four groups, which included group A (medicine treatment group), group B (small needle knife therapy group), group C(massage treatment group) and group D (small needle knife combined with massage treatment group). The observation was given on the average blood flow velocity (Vm), pulsatility index (PI) and treatment efficiency of ver-tebral artery(VA) and basilar artery (BA) before and after treatment among 400 cases using transcranial doppler (TCD). The results showed that TCD detection of Vm of VA and BA in group B, C and D were obviously improved after treatment; and the PI of them was close to normal. The total effective rate of group A was 66.0%, 78.6% in group B, 80.2% in group C, and 96.0% in group D. It was concluded that the treatment by massage in combination with small needle knife therapy of vertebral artery type of cervical spondylosis had a clear effect. Its mechanism may be related to the improvement of Vm and PI of vertebral basilar artery.

Study on intestinal probiotics for the prevention of recurrent liver cirrhosis spontaneous bacterial peritonitis / 中国综合临床

Objective To explore the risk factors and the recurrence of spontaneous bacterial peritonitis after taking intestinal probiotics.Methods Fifty-six patients with spontaneous bacterial peritonitis were randomly divided into control group and probiotics group,and each group were 28 cases.Patients in control group were treated by regular hepatoprotective drug,while in probiotics group were administrated with Jinshuangqi orally,every time 0.5 g × 4 tablets,2 times a day besides regular hepatoprotective drug.The course of the treatment was for 3 months.The symptoms and other risk factors,and the relief time were recorded.Results Incidence of spontaneous bacterial peritonitis in probiotics group and control group were 21.4％ and46.4％ respectively(x2 =3.784,P ＜ 0.05).Rate of gastric ulcer were 17.9％ and 42.9％ respectively and the difference was significant(x2 =4.139,P ＜ 0.05).The relief time of fever in probiotics group was (2.52 ± 0.78) d,lower than that of control group ((4.21 ± 1.34) d,t =2.029,P ＜ 0.05).Meanwhile the relief time of abdominal tenderness was (4.02 ± 0.96) d in probiotics group,and (6.34 ± 1.27) d in control group (t =2.433,P ＜ 0.05).Conclusion Intestinal probiotics treatment can significantly reduce the recurrence rate of spontaneous bacterial peritonitis,shorten the relief time of each symptom and reduce the incidence of other risk factors.

Retention enema with rhubarb for the treatment of severe acute pancreatitis with intestine paralysis / 中华胰腺病杂志

ObjectiveTo investigate the efficacy of retention enema with rhubarb for severe acute pancreatitis (SAP) with intestine paralysis.MethodsTotally 60 patients with SAP since last five years were included,and then they were randomly divided into control group and treatment group with 30 patients in each group.Patients in control group received routine treatment of SAP,including fasting,gastrointestinal decompression,antibiotics,inhibition of pancreatic secretion,inhibition of SIRS and organ support.Patients in treatment group received additional retention-enema with rhubarb (200mL soak solution by 100g rhubarb),once daily until the recovery of bowel function.The bladder pressure ( the 1,2,5 and 6 days after admission)was evaluated,and APACHE Ⅱ score was determined.The recovery of bowel function ( the bowel sounds,the flatus and defecation of intestinal tract),SIRS recovery time,hospital stay,and the mortality were observed.ResultsAt the 5 and 6 days after admission,the bladder pressure and APACHE Ⅱ score in treatment group were significantly lower than those in control group [ (21.9 ±9.0)cmH2O vs (25.3 ±9.5)cmH2O,( 16.5 ±7.5)cmH2O vs (20.6 ±7.7)cmH2O,1 cmH2O =0.098 kPa; (9.8 ±3.8) vs (12.5 ±3.6),(9.2 ±2.4)vs ( 11.2 ± 2.5 ),P ＜ 0.05 ) ].The recovery time of bowel function and SIRS recovery time,hospital stay,and the mortality in treatment group were ( 126.8 ± 28.2 ) h,( 131.2 ± 29.6) h,( 25.6 ± 6.2) d and 16.7 ％,and the recovery time of bowel function and SIRS recovery time,hospital stay were significantly lower than those in control group [ ( 169.9 ± 53.4 ) h,( 160.4 ± 30.4) h,( 33.2 ± 6.4) d,P ＜ 0.05 ).The mortality was reduced,but the difference between the two groups was not statistically significant ( 26.7％,P ＞ 0.05 ).ConclusionsThe retention-enema with rhubarb can accelerate the recovery time of bowel function of SAP patients and reduce the hospital stay.

Effect of low dose low molecular weight heparin on acute pancreatitis / 中华胰腺病杂志

Objective To investigate the effect of low dose low molecular weight heparin (LMWH) on acute pancreatitis (AP). Methods 98 AP patients who were admitted in our hospital from 2002 to 2008 were randomly divided into anticoagulant therapy group (n = 40) and control group (n = 58). Anticoagulant therapy group consisted of 15 cases of severe acute pancreatitis (SAP) and 25 cases of mild acute pancreatitis (MAP) ; while there were 19 cases of SAP and 39 cases of MAP in control group. The patients of control group received conventional treatment, and conventional therapy together with 3 000 U LMWH subcutaneous injection every 12 hours were used in anticoagulant therapy group for two weeks. The changes of APACHE II score, complication rate, mortality and length of hospital stay were observed and the coagulation changes before and after anticoagulant therapy were documented. Results 7 days later, the APACHE II score, complication rate, mortality and length of hospital stay of SAP patients in the anticoagulant therapy group were 9. 9 ±4. 9, 20% , 13.3% , (20.6 ±10.4)d, respectively; while they were 12. 2 ±4.8, 42. 1%, 47.4%, (28. 2 ± 12. 5) d, respectively, in the control group, and the difference was statistically significant (P < 0. 05). The corresponding values were not statistically significantly different among MAP patients in the two groups. The coagulation after treatment in anticoagulant therapy group was not statistically different with that before treatment. Conclusions Low dose LMWH could reduce the rate of complication rate, mortality and decrease the length of hospital stay, without complication of hemorrhage, which should be recommended in the early phase of SAP.

CT and MRI manifestations of aggressive fibromatosis / 中华放射学杂志

Objective To discuss CT and MRI features of aggressive fibromatosis (AF), especially the characteristic signs of MRI, and to evaluate the value of MRI in diagnosing the disease. Methods The CT and MRI studies in 9 cases with pathologically proven AF were retrospectively analyzed. Results Among 9 cases with AF, one cases could not be discovered by CT and all cases could be discovered by MRI. Appearances of lesion were infiltrating in 7 cases and mass-like in 2 cases. All cases were without calcification and lipo-tissue in the lesion and without edema on adjacent muscle structures. A homogeneous density and high density was seen on CT plain scans and high density on contrast enhanced scans. On MRI scans, variable signal intensity was demonstrated on T 1WI, and high signal intensity on T 2WI, as well as increased signal intensity after contrast enhancement. The signal characteristics primarily reflected the underlying histologic composition of the lesions. Conclusion MRI is more excellent than CT in delineating the site, shape, and extent of these lesions. MRI is valuable in detecting and differentiating AF.

Determination of Taurine in Mactra Veneriformis by Pre-column Derivatization RP-HPLC / 中药新药与临床药理

Objective To determine the content of taurine in Mactra veneriformis by pre-column derivation HPLC.Methods Ultrasound method was used for the extraction of taurine from Mactra veneriformis.In alkaline condition,amino acids reacted with phenyl isothiocyanate and resulted in the derivatives of benzene isothiocyanate-amino acid complex.Kromasil C18 column(4.6 mm ?250 mm,5 ?m) was used and the absorbance at 254 nm was measured.The mobile phase consisted of sodium acetate solution,water and methanol.Results Corresponding chromatographic peaks of taurine were obtained in extract sample and the control.The linear range of taurine was from 10.04 ?g?mL-1 to 50.20 ?g?mL-1,and the recovery was 97.95 %(RSD=1.41%,n=9).Conclusion This method is simple,accurate and reproducible.The seasonal variation range of taurine level is from 10.56 mg/g to 20.91 mg/g,and the taurine level arrived to the peak in June.