ABSTRACT
Infectious diseases are one of the major threats to global public health. Inconvenience of diagnosis and treatment frequently causes misdiagnosis, missing diagnosis or overtreatment, resulting in serious clinical outcomes. As an important branch of artificial intelligence, machine learning has been widely used in multiple fields. Predictive models created based on patients’ clinical characteristics, laboratory tests, and imaging examinations are effective for prediction and evaluation of clinical diagnosis, therapeutic efficacy and prognosis, as well as detection of outbreaks. Machine learning modeling has the advantages of high efficiency, high accuracy and interpretability as compared to traditional modeling approaches, which provides a new tool for diagnosis and treatment of infectious diseases. This review summarizes the advances of applications of machine learning in clinical predictive models for infectious diseases.
ABSTRACT
ObjectivesComorbidities have significant indications for the disease outcome of COVID-19, however which underlying diseases that contribute the most to aggravate the conditions of COVID-19 patients is still largely unknown. SARS-CoV-2 viral clearance is a golden standard for defining the recovery of COVID-19 infections. To dissect the underlying diseases that could impact on viral clearance, we enrolled 106 COVID-19 patients who were hospitalized in the Zhongnan Hospital of Wuhan University, Wuhan, China between Jan 5 and Feb 25, 2020. MethodologyWe comprehensively analyzed demographic, clinical and laboratory data, as well as patient treatment records. Survival analyses with Kaplan-Meier and Cox regression modelling were employed to identify factors influencing the viral clearance negatively. ResultsWe found that increasing age, male gender, and angiotensin-converting enzyme 2 (ACE2) associated factors (including hypertension, diabetes, and cardiovascular diseases) adversely affected the viral clearance. Furthermore, analysis by a random forest survival model pointed out hypertension, cortisone treatment, gender, and age as the four most important variables. ConclusionsWe conclude that patients at old age, males, and/or having diseases associated with high expression of ACE2 will have worse prognosis during a COVID-19 infections.
ABSTRACT
BackgroundViral clearance is one important indicator for the recovery of SARS-CoV-2 infected patients. Previous studies have pointed out that suboptimal T and B cell responses can delay viral clearance in MERS-CoV and SARS-CoV infected patients. The role of leukomonocytes in viral clearance of COVID-19 patients is not yet well defined. MethodsFrom January 26 to February 28, 2020, an observational study was launched at the Department of Infectious Diseases, Zhongnan Hospital of Wuhan University, Wuhan, China. We enrolled 25 laboratory-confirmed COVID-19 patients, whose throat-swab specimens were tested positive for SARS-CoV-2 infection by qRT-PCR. To investigate the factors that contribute to the viral clearance, we comprehensively analyzed clinical records, counts of lymphocyte subsets including CD3+, CD4+, CD8+ T cells, B cells and NK cells in the patients who successfully cleared SARS-CoV-2, and compared to those that failed to, after a standardized treatment of 8-14 days. FindingsIn 25 enrolled COVID-19 patients, lymphopenia was a common feature. After the treatment, 14 out of the 25 enrolled patients were tested negative for SARS-CoV-2. The patients that cleared the infection had restored the numbers of CD3+, CD4+, CD8+ T cells and B cells as compared to the still viral RNA positive patients, while the recovered patients had a higher count of leukomonocytes. ConclusionsBy comparison of leukomonocytes counts in COVID-19 patients at different stages of the disease, we found that CD3+, CD4+, CD8+ T cells and B cells appear to play important roles in viral clearance. The restoration of leukomonocytes counts from peripheral blood can be used as prognosis for the recovery of an COVID-19 infection. We propose that restoration of leukomonocytes counts can be added to the COVID-19 diagnostic guidance as a criterion for releasing and discharging patients.
ABSTRACT
Objective To study the characteristics of lamivudine-resistant mutation associated chronic severe hepatitis B during lamivudine treatment.Methods Twenty-seven patients with lamivudine-resistant mutation associated chronic severe hepatitis B during lamivudine treatment were analyzed retrospectively.YMDD motif mutation was detected by gene chips or DNA sequencing.The pathological features of liver tissues from 8 patients undergoing liver transplantation were analyzed.The X2 test were used to perform the stafistical analysis.Results The YMDD motif mutations of 27 lamivudine-resistant patients were 5 cases of YVDD mutation,2 of YVDD+L180M,13 of YIDD mutation,4 of YIDD+L180M,1 of YVDD+YIDD mutations,2 of YVDD+YIDD+L180M,and there was no single L180 M mutation among patients.Twenty-seven patients were divided into cirrhotic group and noncirrhotic group according to whether they were diagnosed with cirrhosis before treatment.Compared to cirrhotic group,incidence of severe hepatitis was lower,prognosis was better,the age of patients was younger and hepatitis Be antigen(HBeAg)positive rate was higher in noncirrhotic group.There were two types of pathological features of liver tissues from 8 patients,which were active hepatic cirrhosis and massive or submassive hepatic necrosis with liver shrinking significantly.Conclusions Hepatic cirrhosis is a risk factor of lamivudine-resistant mutation associated chronic severe hepatitis B.There may be two mechanisms in lamivudine-resistant mutation associated chronic severe hepatitis B.
ABSTRACT
Objective To investigate the distribution of genotypes in chronic HBV infection (CHB) and acute HBV infection (AHB) patients in Shanghai. Methods Sixty-two patients with AHB and 73 patients with CHB admitted to ('hanghai Hospital of Shanghai between 2003 and 2007 were studied. Viral genotypes of all the patients were determined by direct gene sequencing.Meanwhile, epidemiological, clinical and biochemical parameters of all patients were collected. Mean values of different groups were compared by t test while frequency was compared by chi square test. Results The major prevalent genotypes in both AHB and CHB patients were genotype B and C (48.4% vs 51.6% in AHB patients and 26.0% vs 74.0% in CHB patients). The proportion of genotype B was higher in AHB patients compared to CHB patients (P= 0.02). Epidemiological factors and clinical outcomes were not statistically different among patients with different viral genotypes. The proportion of genotype C was much higher in CHB patients compared to AHB patients (P=0.006). The main transmission route of AHB was heterosexual interaction which was 18 out of 62 (29.0%), but in CHB patients, it was prenatal transmission which was 38 out of 73 (52.1%). Conclusions In shanghai, the main HBV genotypes in both AHB and CHB patients are genotype B and C. The proportion of genotype B is relatively high in AHB patients while proportion of genotype C is more common in CHB patients. There is no significant relationship between genotypes and the clinical outcomes of AI-IB patients.
ABSTRACT
Objective To analyze clinical courses and rescue therapies of adefovir-resistant chronic hepatitis B patients who had lamivudine resistance before and then changed to take adefovir dipivoxil. Methods 15 patients resistant to lamivudine were retrospectively analyzed, who had virological breakthrough after adefovir dipivoxil monotherapy and were treated with rescue therapy.Adefovir-resistant mutations were detected by direct sequencing of the HBV polymerase gene. Results 15 patients with former lamivudine resistance were treated with adefovir dipivoxil monotherapy for a median of 16 months, and 14 patients were found adefovir-resistant mutations at rtA181T/V and(or) rtN236T, only 1 patient was found multi-mutations at rtM204I + rtL180M + rtA181T. Rescue therapies were given to all the 15 patients after drug resistance. Among the 7 patients treated with lamivudine in combination with adefovir for 3 months,whose HBV DNA levels decreased (2.2±0.6)lg copy/mL on average, 5 patients achieved HBV DNA undetectable after 6 months combinative therapy. The HBV DNA levels of the 3 patients treated with entecavir decreased 2.8～3.5 lg copy/mL within 6 months treatment. Conclusion These preliminary data suggest the combination of lamivudine and adeforvir dipivoxil may be an effective rescue therapy for adefovir-resistant patients who have former lamivudine resistance.
ABSTRACT
Objective: To obtain polycystin-1 intracellular region. Methods: cDNA of polycystin-1 intracellular region was generated by PCR and then cloned into pProEX Hta, which was prokaryotic expression vector. After verified by sequencing, the recombinant was transformed into E.coli host to express and purify the fusion protein by affinity chromatography. Results: 660 bp cDNA of polycystin-1 intracellular region and 2.6×104 fusion protein were obtained. Conclusion: The fusion protein containing polycystin-1 intracellular region is obtained and is helpful for preparing anti-polycystin-1 monoclonal antibody.
ABSTRACT
Objective To analyze the clinical features and mutation patterns of HBV polymerase gene in patients with chronic hepatitis B(CHB) after the emergence of drug-resistance during Lamivudine(LAM) therapy.Methods LAM-resistant mutations were detected by direct sequencing of the HBV polymerase gene in hospitalized patients and outpatients of CHB with LAM-resistance in Changhai Hospital from Dec.2005 to Dec.2007.Clinical features after the emergence of LAM-resistant mutations were retrospectively analyzed.Results Two hundred and fifteen patients with CHB were diagnosed as LAM-resistant.Among them 192 patients were found to have LAM-resistant-associated mutations in the HBV polymerase gene.The mean value of serum HBV DNA was 6.25?1.31(log10copies/ml),the mean value of alanine aminotransferase(ALT) was 75U/L(ranged 19-821 U/L).ALT elevation and hepatitis recrudescence were found in 139 among 192(72.4%) patients.99.0%(190/192) patients had YMDD mutations.Four major mutation patterns of LAM-resistant HBV were identified as rtM204I(33.9%),rtL180M+rtM204V(26.0%),rtL180M+rtM204I(21.9%) and rtV173L+rtL180M+rtM204V(11.5%).The rtM204V mutation was accompanied more frequently by the rtL180M mutation compared with the rtM204I mutation(P0.05).Conclusions YMDD is the major mutation pattern of HBV polymerase gene after emergence of LAM-resistance.The mutation patterns of HBV polymerase gene are possibly not related to the clinical severity of CHB patients during LAM therapy.
ABSTRACT
Objective: To prepare the monoclonal antibodies against polycystin 1 intracellular region and to study the distribution and expression of polycystin 1 in kidney tissues. Methods: Using the recombinant fusion protein containing polycystin 1 intracellular region as antigen, the hybrid cells secreting the monoclonal antibodies against polycystin 1 intracellular region were established by hybridoma technique. The distribution and expression of polycystin 1 in polycystic kidney, fetal kidney and adult kidney were investigated by immunohistochemical methods(standard EnVision method) with the monoclonal antibodies. Results: Four cell lines of hybrids steadily secreting the monoclonal antibodies against polycystin 1 intracellular region were established. The antibody titers were 1∶10 6. The 50th generation of these cell lines of hybrids still can secret the monoclonal antibodies and the titers remain similar. Polycystin 1 was weakly expressed in tubules and collecting ducts of normal kidney, the strong staining was seen at tubules of fetal kidney, and very strong staining of cyst lining epithelium of polycystic kidney was observed. Conclusion: The monoclonal antibodies against polycystin 1 intracellular region will be a useful tool in the studies of polycystin 1 structure and function.
ABSTRACT
Objective To study the expression of extracellular matrix and polycystin-1 in ADPKD and their relation to cyst formation. Methods The expression of polycystin-1, fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen were analysed in the normal kidney, fetal kidney and polycystic renal tissue by using immunohistochemical technique. Results The expression Of fibronectin, laminin, type Ⅰ collagen, and type Ⅳ collagen increased in polycystic renal tissue compared with normal kidney. The basement membrane lining cysts was markedly thickened. Type Ⅰ collagen was detected in the interstitium between cysts. Laminin, fibronectin and type Ⅳ collagen were localized in cyst basement membrane. The expression of polycystin-1 increased in polycystic renal tissue. The expression of extracellular matrix had significant correlation with the expression of polycystin-1. Conclusion The abnormal expressions of extracellular matrix and polycystin-1 exist in ADPKD. Abnormal expression of polycystin-1 may result in the alterations of extracellular matrix that is related to cyst formation.
ABSTRACT
Objective To evaluate the efficacy and safety of adefovir dipivoxil(ADV) monotherapy and ADV lamivudine(LAM) combined therapy for patients with LAM-resistant chronic hepatitis B.Methods 124 chronic hepatitis B patients with LAM-resistant mutations were enrolled in the present study.74 patients were treated with ADV combined with LAM therapy,and other 50 patients subjected to ADV monotherapy.There were no differences between the two groups in patients' baseline characteristics.Sequencing of the HBV polymerase gene was performed to determine LAM and ADV mutations occurred at baseline or during therapy.All patients were monitored with clinical examinations and routine laboratory tests during the therapy.Results The reduced logarithmic values of serum HBV DNA after 12-week and 24-week treatment were 1.99?0.64 and 2.61?0.80 in ADV group,obviously lower compared with those in ADV+LAM group(2.55?0.74 and 3.19?0.82,respectively,P
