Clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome in underage patients / 中华传染病杂志

Objective:To analyze the clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome (HFRS) in underage patients, and to construct the severe disease risk model.Methods:A total of 170 HFRS patients (<18 years old) from the Second Affiliated Hospital of Air Force Medical University (153 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (17 cases) from January 2009 to December 2021 were included. According to the severity of the disease, the patients were divided into mild and severe groups. Baseline demographic data, symptoms, signs, laboratory examination on admission and prognosis were analyzed between the two groups. Statistical comparisons were performed using the Mann-Whitney U test and chi-square test.Binary logistic regression was used to analyze the independent risk factors of patients with severe disease, and the severe disease risk model was built.The receiver operator characteristic curve was used to analyze the value of the risk model in predicting severity of disease. Results:Among the 170 underage patients, 132 (77.6%) were males, aged (14.9±3.1) years, including 124 cases in mild group and 46 cases in severe group. One hundred and sixty-nine cases (99.4%) had fever, 119 cases (70.0%) had headache, 106 cases (62.4%) had lumbago, 158 cases (92.9%) had skin and mucous congestion, and 101 cases (59.4%) had nausea and vomiting. Renal percussive pain was found in 139(81.8%) patients. The incidence of nausea and vomiting and bleeding of skin and mucosa in the severe group were 71.7%(33/46) and 67.4%(31/46), respectively, which were both higher than those in the mild group (54.8%(68/124) and 44.4%(55/124), respectively), and the differences were statistically significant ( χ2=3.97 and 7.12, respectively, both P<0.05). There were significant differences in platelet count, activated partial thromboplastin time (APTT), serum creatinine (SCr), aspartate aminotransferase, alanine aminotransferase, leukocyte count, total bilirubin and albumin levels between the two groups ( Z=-4.14, -4.04, -4.87, -3.90, -4.07, -2.60, -2.78 and t=2.50, respectively, all P<0.05). Binary logistic regression analysis showed that chemosis (odds ratio ( OR)=8.035, 95% confidence interval (95% CI) 2.946 to 21.916), SCr ( OR=1.010, 95% CI 1.006 to 1.015) and APTT ( OR=1.049, 95% CI 1.003 to 1.098) were the independent risk factors for severe HFRS in the underage patients. The risk model was constructed as: Logit(P)=-10.323+ 2.084×chemosis (no=0, grade Ⅰ=1, grade Ⅱ=2, grade Ⅲ=3)+ 0.010×SCr (μmol/L)+ 0.048×APTT (s). The area under the curve to predict severity of disease in underage HFRS patients was 0.868, with an optimal cut-off value of -4.39, with a sensitivity of 73.90% and a specificity of 91.10%. According to the internal verification of the data of the study based on the severe disease risk model, 34 out of 46 patients with severe disease were severe (sensitivity, 73.91%), 113 out of 124 patients with mild disease were mild (specificity, 91.13%). Conclusions:The clinical manifestations of the underage HFRS patients are not typical.The main manifestations are fever, headache and lumbago, nausea and vomiting, and the incidences of skin and mucous congestion and renal percussive pain are high.Chemosis, SCr and APTT are independent risk factors for severe disease in underage patients with HFRS. The severe disease risk model could effectively predict the severity of disease.

Dynamic changes and predictive values of routine laboratory parameters in patients with hemorrhagic fever with renal syndrome / 中华传染病杂志

Objective:To investigate the dynamic changes of routine laboratory parameters during the course of hemorrhagic fever with renal syndrome (HFRS) and estimate the predictive value for the severity of the disease.Methods:A retrospective cohort study was conducted, which enrolled 394 HFRS patients admitted to the Second Affiliated Hospital of Air Force Medical University (374 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (20 cases) from January 2019 to January 2022. The patients were divided into mild (mild and moderate) and severe (severe and critical) groups.The basic information, personal history, past history, treatment, complications and other clinical data of patients were collected and the results of the laboratory examinations in the morning at day 1, 2, 3, 4, 5, 7, 10, 15, 20 and 25 of hospitalization and before discharge were recorded. The dynamic changes of the patients′ routine laboratory indicators and the dynamic predictive values of each indicator for severe condition were analyzed. Mann-Whitney U test and chi-square test were used for comparison, and receiver operator characteristic (ROC) curve was used for predictive value evaluation. Results:The age of 212 patients in the mild group was 38(27, 61) years, and that of 182 patients in the severe group was 49(32, 64) years, the difference was statistically significant ( Z=-2.24, P=0.025). The incidences of acute pancreatitis, acute respiratory distress syndrome, multiple organ dysfunction syndrome, the utilization rates of blood purification and mechanical ventilation in the severe group were 6.0%(11/182), 12.6%(23/182), 19.8%(36/182), 89.6%(163/182) and 22.5%(41/182), respectively, and those in the mild group were 0(0/212), 0(0/212), 0(0/212), 15.6%(33/212) and 0.5%(1/212) respectively, and the differences were all statistically significant ( χ2=13.18, 28.45, 46.15, 214.48 and 50.02, respectively, all P<0.05). The levels of white blood cell count, lymphocyte count, monocyte count and neutrophil count were all increased rapidly after onset and peaked at days 4 to 6 of illness, with the counts of 14.2(9.7, 20.7)×10 9/L, 4.2(2.3, 6.2)×10 9/L, 1.5 (0.8, 3.3)×10 9/L and 8.3(4.3, 11.4)×10 9/L, respectively. Aspartate aminotransferase peaked (102(66, 178) U/L) within three days after onset and then decreased rapidly, returned to normal level by day 12. Blood urea nitrogen and creatinine both increased steadily after onset, peaked at day 9 to 10, with the levels of 13.2(7.7, 19.1) mmol/L and 255.4(122.9, 400.9) μmol/L, respectively. Prothrombin time, activated partial thromboplastin time, fibrinogen degradation products and D-dimer levels at day 3 after onset were 12.7(12.0, 13.2) s, 38.7(33.5, 51.9) s, 12.6(6.9, 32.0) mg/L and 4.9(2.2, 13.7) mg/L, respectively.Platelet count at day 4, neutrophil count at day 5, creatinine at day 11 and blood urea nitrogen at day 14 after onset had decent predictive values for estimating severity, of which the area under curve (AUC) values were 0.801(95% confidence interval (95% CI) 0.727 to 0.875), 0.824(95% CI 0.770 to 0.878), 0.862(95% CI 0.805 to 0.919) and 0.810(95% CI 0.722 to 0.897), respectively. Conclusions:Routine blood count, liver function and coagulation are important reference indicators for early warning of severe disease of HFRS, while with the progress of the disease, renal function indicators are effective in differentiating the severity of the disease. The platelet count at day 4, neutrophil count at day 5, creatinine at day 11 and blood urea nitrogen at day 14 after onset have predictive values for severe HFRS.

Clinical epidemiological characteristics and prognostic risk factors in 2 245 patients with hemorrhagic fever with renal syndrome / 中华传染病杂志

Objective:To analyze the clinical epidemiological characteristics and the prognostic risk factors of patients with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 2 245 HFRS patients who were admitted to the Second Affiliated Hospital of Air Force Medical University from September 2008 to December 2021 were enrolled. Clinical epidemiological data (including gender, age, onset season, onset region, case fatality rate, et al) of HFRS patients were analyzed. The clinical epidemiological characteristics of patients with HFRS in the 2008 to 2012, 2013 to 2017, and 2018 to 2021 groups were compared. Statistical comparisons were performed using chi-square test. The Bonferroni adjusted P-value method was used for pairwise comparisons between groups, and logistic regression analysis was used to screen and evaluate the risk factors associated with the prognosis of HFRS patients. Results:The age of 2 245 HFRS patients was (42.3±15.9) years old. Most of them were male (79.24%(1 779/2 245)), and the main incidence area was Xi′an City (69.53%(1 561/2 245)). There were 132 deaths with an overall case fatality rate of 5.88%. There were 1 088 patients (48.46%) from 2008 to 2012, 647 patients (28.82%) from 2013 to 2017, and 510 patients (22.72%) from 2018 to 2021, with a mortality rate of 7.17%(78/1 088), 5.10%(33/647) and 4.12%(21/510), respectively. From 2008 to 2021, both the number of HFRS cases and the case fatality rate had shown a fluctuating downward trend. There were significant differences in case fatality rate, age distribution, onset season, and onset region among patients in the different year groups ( χ2=6.84, 49.22, 83.47 and 19.29, respectively, all P<0.05). The results of pairwise comparisons showed that the proportion of patients aged >60 years in the 2018 to 2021 group (23.33%(119/510)) was higher than those in the 2008 to 2012 group (12.13%(132/1 088)) and the 2013 to 2017 group (12.36%(80/647)), and the differences were statistically significant (both P<0.05). The proportions of patients at large peak (October to December) were 62.35%(318/510) in the 2018 to 2021 group and 56.26%(364/647) in the 2013 to 2017 group, which were both lower than that in the 2008 to 2012 group (75.18%(818/1 088)), and the differences were both statistically significant (both P<0.05). The case fatality rate of patients aged >60 years was 9.67%(32/331), which was higher than those of patients aged <30 years (2.86%(16/559)) and patients aged 30 to 60 years (6.20%(84/1 355)), with statistically significant differences (both P<0.05). Univariate analysis showed that age 30 to 60 years, age >60 years, smoking, complicated with hypertension, hypotensive shock and hypoxemia were significantly correlated with the prognosis of HFRS patients (odds ratio ( OR)=2.243, 3.632, 1.484, 3.532, 79.422 and 143.955, respectively, all P<0.05). The results of multivariate logistic regression analysis indicated that complicated with hypertension ( OR=2.467, P=0.004), hypotensive shock ( OR=11.658, P=0.001), and hypoxemia ( OR=67.767, P<0.001) were the independent risk factors affecting the prognosis of HFRS patients. Conclusions:The prevalence of HFRS has shown new changing characteristics from 2008 to 2021. The numbers of HFRS patients and the case fatality rates show a downward trend, and the proportion of HFRS patients aged >60 years increases. Complicated with hypertension, hypotensive shock and development with hypoxemia are the independent risk factors for the prognosis of HFRS.

Efficacy and safety of the 12-week sofosbuvir-coblopasvir regimen in treatment of chronic hepatitis C / 临床肝胆病杂志

Objective To investigate the efficacy and safety of the 12-week regimen with sofosbuvir and coblopasvir hydrochloride in the treatment of chronic hepatitis C (CHC) in northwest China. Methods This study enrolled 101 patients with CHC of any genotype who received sofosbuvir (400 mg) combined with coblopasvir hydrochloride (60 mg) for 12 weeks in The First Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Air Force Medical University, The Second Affiliated Hospital of Xi'an Jiaotong University, and Baoji Central Hospital from July 1 to December 31, 2021, among whom 13 had liver cirrhosis and 88 did not have live cirrhosis. Other antiviral drugs such as ribavirin were not added regardless of the presence or absence of liver cirrhosis or the genotype of CHC. Related clinical data ere extracted, including HCV RNA quantification and liver biochemical parameters at baseline, at week 12 of treatment, and at 12 weeks after drug withdrawal. The primary endpoints were sustained virologic response at 12 weeks after the end of treatment (SVR12) and safety at week 12 of treatment, and the secondary endpoint was the effect of the 12-week treatment on liver biochemical parameters. The non-normally distributed continuous data were expressed as M ( P 25 - P 75 ), and the Mann-Whitney U test was used for comparison between groups. Results A total of 101 patients were included in the analysis, among whom there were 55 male patients (54.5%) and 46 female patients, and the median age was 53 years. Among these patients, 12.8% had liver cirrhosis, 1.0% had liver cancer, 3.0% were treatment-experienced patients, and 3.0% had type 2 diabetes. As for genotype distribution, 8% had CHC genotype 1, 60% had CHC genotype 2, 19% had CHC genotype 3, and 6% had CHC genotype 6, and genotype was not tested for 7% of the patients. After 12 weeks of treatment, all 101 patients had a HCV RNA level of below the lower limit of detection and an SVR12 rate of 100%, with a significant reduction in the serum level of alanine aminotransferase (ALT) from baseline to week 12 of treatment ( P < 0.05). Among these patients, 22.7% had concomitant medications such as atorvastatin calcium, aspirin, metformin, nifedipine, bicyclol, and compound glycyrrhizin. The incidence rate of adverse events was 16.8%, and fatigue (12.9%) was the most common adverse event. Conclusion The 12-week treatment with sofosbuvir and coblopasvir hydrochloride can obtain high SVR12 in CHC patients in northwest China and has good antiviral safety, with a significant improvement in abnormal serum ALT at week 12 of treatment.

Clinical features of patients with malignant tumor-related pyogenic liver abscess / 临床肝胆病杂志

Objective To investigate the clinical features of malignant tumor-related pyogenic liver abscess (PLA), and to provide a basis for early judgment of disease progression and timely and effective treatment. Methods A retrospective analysis was performed for the clinical data of 371 patients with PLA who were admitted to the Second Affiliated of Air Force Medical University, from March 2005 to July 2018, among whom 34 patients with malignant tumor-related PLA were enrolled as tumor group, and after matching for time and at a ratio of 1∶2, 70 patients without malignant tumor-related PLA were enrolled as non-tumor group. Clinical features were compared between the two groups. The group t -test was used for comparison of normally distributed continuous data between groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results In the tumor group, there were 22 patients with hepatobiliary tumor (64.7%), 7 patients with gastrointestinal tumor (20.6%), and 5 patients with non-gastrointestinal tumor (14.7%). Compared with the non-tumor group, the tumor group had a significantly higher proportion of patients with a history of abdominal surgery (44.1% vs 7.1%, χ 2 =20.142, P 16 (44.1% vs 15.7%, χ 2 =9.846, P =0.002). Compared with the non-tumor group in terms of laboratory examination, the tumor group had a significantly lower level of albumin [(27.2±5.2) g/L vs (30.8±2.6) g/L, t =-3.131, P =0.002] and a significantly higher level of total bilirubin [54(13~313) μmol/L vs 33(7~96) μmol/L, U =1 816.0, P < 0.001]. Escherichia coli was the main pathogen in the tumor group (23.5%), while Klebsiella pneumonia was the main pathogen in the non-tumor group (23.5%), and compared with the non-tumor group, the tumor group had a significantly higher proportion of patients infected with more than two types of bacteria (11.8% vs 2.8%). Radiological examination showed that the tumor group had a significantly higher proportion of patients with multiple abscesses than the non-tumor group (47.1% vs 24.3%, χ 2 =5.479, P =0.019). Compared with the non-tumor group, the tumor group had a significantly longer mean length of hospital stay ( U =1 728.5, P < 0.001) and a significantly higher treatment failure rate ( P =0.005). Conclusion Patients with malignant tumor-related PLA often have hepatobiliary tumor, with Escherichia coli as the main pathogen. Abscesses at multiple sites are common, and patients tend to have a poor prognosis. Appropriate antibiotics combined with percutaneous drainage should be used in clinical practice, and for the high-risk population, the threshold for surgical intervention can be lowered to reduce mortality.

Role and mechanism of interleukin-35 in hepatitis B virus-related diseases / 临床肝胆病杂志

Interleukin-35 (IL-35) is an immunosuppressive cytokine mainly secreted by regulatory T cells and regulatory B cells and is involved in the pathogenesis of infectious diseases, tumors, and autoimmune diseases. This article summarizes the immunoregulatory role and mechanism of IL-35 in hepatitis B, liver cirrhosis, liver failure, and hepatocellular carcinoma caused by hepatitis B virus (HBV) infection. The analysis shows that IL-35 is a "double-edged sword" in HBV-related diseases, and it can not only promote the chronicity of infection and the progression of hepatocellular carcinoma, but also alleviate liver inflammation and inhibit liver fibrosis.

Clinical characteristics of patients with hemorrhagic fever with renal syndrome during pregnancy: a multicenter clinical study / 中华传染病杂志

Objective:To analyze the clinical characteristics and prognosis of pregnant women with hemorrhagic fever with renal syndrome (HFRS).Methods:A total of 11 pregnant women with HFRS admitted to The Second Affiliated Hospital of Xi′an Jiaotong University (four cases), The Second Affiliated Hospital of Air Force Medical University (four cases), The First Affiliated Hospital of Xi′an Jiaotong University (one case) and Central Hospital of Xianyang City (two cases) between November 2009 and February 2019 were included as the study group, and 24 age-matched non-pregnant women with HFRS were selected as the control group. The age, complications, clinical classification and laboratory indexes of the two groups were analyzed retrospectively, and the clinical outcomes of pregnant women and their fetuses in the study group were followed up. The data between two groups were compared using Mann-Whitney U test or chi-square test. Results:Patients in the study and control groups were 29 (22, 33) and 32 (24, 37) years old, respectively. Seven of 11 patients in study group were severe and critical cases, which was significantly higher than that in the control group (16.7%(4/24), χ2=7.722, P=0.015). In the study group, 10 patients had hypervolemic syndrome, 10 patients had pulmonary edema and six patients had overlapping hypotension shock phase and oliguria phase, which were all higher than those in the control group ((2/24, 8.3%), (2/24, 8.3%) and (2/24, 8.3%), respectively; χ2=22.828, 22.828 and 9.135, respectively, all P<0.01). Compared with the control group, the pregnant patients in study group had a higher urea nitrogen maximum and serum creatinine maximum, and the differences were both statistically significant ( Z=-2.453 and -2.336, respectively, both P<0.05), while they had a lower serum albumin minimum, hemoglobin maximum and hemoglobin minimum, and the differences were all statistically significant ( Z=-3.742, -3.350 and -4.034, respectively, all P<0.01). All pregnant women with HFRS recovered. Nine pregnant women gave birth to nine healthy infants. All of them received breastfeeding and the feeding duration were more than six months. No abnormal growth and development were found during an average follow-up of three years. Conclusions:Pregnancy can aggravate the severity of HFRS, and pregnant women have higher risk of the multiple stages overlap and the complications such as hypervolemic syndrome and acute pulmonary edema. After recovery from HFRS, mother may carry to full-term pregnancy.

Clinical features of culture-negative liver abscess / 临床肝胆病杂志

ObjectiveTo investigate the clinical features and prognosis of culture-negative liver abscess (CNLA) versus culture-positive liver abscess (CPLA), and to provide a reference for early diagnosis and effective treatment. MethodsA retrospective analysis was performed for the clinical data of 371 patients with liver abscess who were admitted to The Second Affiliated Hospital of Air Force Medical University from 2005 to 2018, among whom 145 (39.1%) had positive results of pathogen test (CPLA group) and 226 (60.9%) had negative results (CNLA group). The two groups were compared in terms of clinical features, laboratory examination, imaging data, and prognosis. The t-test was used for comparison of normally distributed or approximately normally distributed continuous data between two groups, and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups; the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsCompared with the CNLA group, the CPLA group had a significantly older age (t=-3.464, P=0.001) and a significantly higher proportion of patients with diabetes (χ2=17.362, P＜0.001) or cardiovascular disease (χ2=10.827, P=0.001), and compared with the CPLA group, the CNLA group had a significantly higher proportion of patients with AIDS (χ2=4.354, P=0.037). Compared with the CNLA group, the CPLA group had significantly greater increases in leukocyte count, percentage of neutrophils, alkaline phosphatase, gamma-glutamyl transpeptidase, and total bilirubin (U=20393, 19711, 18586, 19349, and 18496, all P＜0.05), a significantly greater reduction in albumin (t=3.348, P=0.001), and a significantly higher proportion of patients with a baseline APACHE Ⅱ score of ≥16 (χ2=9.550, P=0.002). Compared with the CNLA group, the CPLA group had a significantly higher proportion of tumors with a diameter of ＞5 cm (χ2=53.61, P＜0.001). In the CNLA group, 19.9% of the patients were treated with anti-infective therapy alone, while for both groups, anti-infective therapy combined with ultrasound- or CT-guided percutaneous drainage was the main treatment method. There were no significant differences in the length of hospital stay, recurrence rate, and mortality rate between the two groups (all P＞0.05). ConclusionCompared with CPLA patients, CNLA patients tend to have a younger age and are less likely to develop severe inflammatory response and liver insufficiency, with a smaller diameter of abscess which is less likely to be treated by percutaneous drainage, while there is no significant difference in prognosis between CPLA patients and CNLA patients.

Mechanism of gamma-chain cytokines in regulating the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 in CD8+ T cells of chronic hepatitis B patients / 临床肝胆病杂志

ObjectiveTo investigate the mechanism of gamma-chain (γC) cytokines in regulating the expression of T-cell immunoglobulin and mucin domain-containing molecule 3 (TIM-3) in CD8+ T cells of chronic hepatitis B (CHB) patients. MethodsA total of 23 CHB patients who attended Tangdu Hospital, Fourth Military Medical University, from January to May, 2017, were enrolled. Peripheral blood was collected from all patients, and Ficoll density gradient centrifugation was used to isolate peripheral blood mononuclear cells (PBMCs). PBMCs were stimulated with interleukin-7 (IL-7), interleukin-15 (IL-15), and interleukin-21, respectively, and then anti-γC antibody and/or anti-IL-7Rα, anti-IL-2Rβ, and anti-IL-21R were added to the culture solution. After 96 hours of culture, flow cytometry was used to measure the expression of TIM-3, interleukin-2 (IL-2), interleukin-10 (IL-10), and interferon-γ (IFNγ) and the phosphorylation level of signal transducer and activator of transcription (STAT) in CD8+ T cells. A one-way analysis of variance and the least significant difference t-test were used for comparison of continuous data. ResultsThe CD8+ T cells stimulated by IL-7 and IL-15 had a significantly higher percentage of TIM-3-positive CD8+ T cells than those without stimulation (t=9.966 and 9074, P＜0.05), as well as significantly higher expression levels of IL-2, IL-10, and IFN-γ and phosphorylation levels of STAT-5 and STAT-1 (all P＜0.05). Stimulation with anti-IL-7Rα and anti-γC antibody significantly reduced the elevated expression levels of TIM-3, IL-2, and IL-10 in the IL-7 stimulation group (t=5.537, 6.224, and 4.500, P＜0.05). Stimulation with anti-IL-2Rβ alone or in combination with anti-γC antibody significantly reduced the expression levels of TIM-3 and IL-2 and the phosphorylation level of STAT-1 in the IL-15 stimulation group (P ＜0.05). ConclusionIL-7 and IL-15 can upregulate the expression of TIM-3 in CD8+ T cells of CHB patients, possibly via the γC receptor-mediated STAT-cytokine signaling pathway.

Experiences in construction of infection disease outpatient service / 中华临床感染病杂志

The infectious disease outpatient service as a frontier is an important fulcrum of public health service. Its standardized construction is an important support for ensuring medical safety, reducing nosocomial infections, and controlling the epidemic of infectious diseases. The sub-specialty outpatient service of infection diseases includes fever outpatient service, intestinal outpatient service, tuberculosis outpatient service, AIDS outpatient service, liver disease outpatient service, etc. According to the characteristics of each subspecialty outpatient service and combining with clinical practice, we elaborated the setting norms of subspecialty outpatient service for common infectious diseases from the perspective of planning and design, building layout, equipment and facilities configuration, staffing, daily management and demonstration.

Clinical features of Klebsiella pneumoniae liver abscess versus Escherichia coli liver abscess / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of the two most common types of pyogenic liver abscess in clinical practice, Klebsiella pneumoniae liver abscess (KPLA) and Escherichia coli liver abscess (ECLA), and to provide a reference for early diagnosis and effective treatment. MethodsA retrospective analysis was performed for the clinical data of 371 patients with liver abscess who were admitted to The Second Affiliated Hospital of Air Force Medical University from March 2005 to July 2018, among whom 145 patients tested positive for pathogen. KPLA patients and ECLA patients were compared in terms of clinical features, laboratory examination, radiological examination, and prognosis. The t-test or the Mann-Whitney U test was used for comparison of continuous data between two groups, and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A multivariate logistic regression analysis was used to determine the influencing factors for prognosis. ResultsAmong the 145 patients that tested positive for pathogen, 66 tested positive for Klebsiella pneumonia and 42 tested positive for Escherichia coli. Compared with the KPLA patients, the ECLA patients tended to have an older age (t=-2.25, P=0.027), biliary diseases (χ2=10.019, P=0.002), a history of abdominal surgery (χ2=27.481, P＜0.001), tumor (χ2=17.745, P＜0.001), and a significantly higher proportion of individuals with recurrent liver abscess (χ2=13745, P＜0.001). KPLA was often observed in patients with diabetes (χ2=17.505, P＜0.001). As for laboratory examination, compared with the KPLA patients, the ECLA patients had a significant increase in total bilirubin (U=880.000, P=0.001) and significant reductions in albumin (t=-2.625, P=0.010) and platelet count (U=1719.000, P=0.036). Radiological examination showed that there was a higher proportion of patients with multiple liver abscess in ECLA (χ2=23.372, P＜0.001), while KPLA often had an abscess diameter of ＞5 cm (χ2=7.637, P=0.006). As for complications, the ECLA patients were more likely to develop pulmonary infection (χ2=18857, P＜0.001) and emphysema (P=0.013). ECLA patients were more likely to have multidrug-resistant organisms, and most patients were treated with antibiotics combined with ultrasound-guided percutaneous drainage in both groups. The multivariate logistic regression analysis showed that Acute Physiology and Chronic Health Evaluation Ⅱ score on admission (odds ratio=0.049, 95% confidence interval: 0.026-0.266, P＜0.001) was an influencing factor for prognosis. ConclusionECLA is commonly seen in elderly patients with biliary diseases, with easy recurrence, multiple abscesses on radiological examination, and a high proportion of pulmonary infection and emphysema. There is a high positive rate of extended-spectrum beta-lactamases produced by ECLA, and therefore, antibiotics should be used reasonably in the early stage.

Research advances in the clinical effect of tenofovir alafenamide in treatment of chronic hepatitis B / 临床肝胆病杂志

Tenofovir alafenamide (TAF) is a novel nucleoside reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus (HIV) infection and chronic hepatitis B virus (HBV) infection. Compared with tenofovir disoproxil fumarate, TAF has better plasma stability and stronger liver-targeting ability and can significantly reduce the adverse events of renal injury and reduced bone mineral density. This article summarizes the research advances in the pharmacological characteristics, metabolic pathways, drug interactions, drug resistance, and renal safety of TAF and its role in patients with chronic HBV infection.

Application of metagenomic next generation sequencing in infectious diseases / 中华临床感染病杂志

Almost all pathogens have DNA or RNA genomes.Theoretically, genomes of pathogens can be effectively detected by sequencing technology , it would be of value for etiological diagnosis of infectious diseases.The next generation sequencing ( NGS) emerged in 2005, the advantages of low cost , high efficiency and high accuracy make it a favorable technical platform for clinical identification of microorganisms.As a new sequencing technique , metagenomic next generation sequencing ( mNGS) has great potential in improving the accuracy and efficiency of pathogenic diagnosis , especially in the areas where conventional diagnostic methods have limitations.This article introduces the common platforms and principle of the high throughput sequencing , reviews the clinical applications and the advantages of mNGS in identification of different pathogenic microorganisms , and reflects on its limitations and seeks possible solutions.

Role of Kupffer cells in hepatitis B virus infection / 中华临床感染病杂志

Hepatitis B virus(HBV)infection is the main cause of chronic liver diseases in China. The clearance of HBV is important for patients with chronic hepatitis B.Current antiviral therapy includes interferon and nucleotide analogues.The adverse reactions of interferon are common which restrict its application.Nucleotide analogues need long-term maintenance treatment.Kupffer cells (KCs) are the main innate immune cells in the liver.Studies have shown that KCs play an important role in hepatitis B virus infection.It can inhibit virus replication effectively , but may also result in immune dysfunction , causing HBV persistence.Understanding the mechanism related to the role of KCs in hepatitis B virus infection may lead to a new approach of antiviral therapy.

Improving understanding of liver immune function and enhancing research on cell therapy for liver diseases / 临床肝胆病杂志

As an important immune organ,the liver has a unique immune microenvironment,and is one of the important places for innate immunity and adaptive immunity.The liver is closely connected with the immune system through the gut-liver axis and is also the target or-gan of immune injury.However,the defensive role of the liver for Hepadnaviridae remains unclear.Cell therapy for liver diseases includes input of liver cells or stem cells for functional replacement,therapy by immune cells for antiviral and antitumor purposes,and genetic therapy for hereditary hepatopathy with cells as the carrier.The features of mesenchymal stem cells,multi-directional differentiation potential and immunomodulatory property,become the hot spots of cell therapy for liver diseases,and efficient in vitro amplification of cells makes it possi-ble for the use of NK cells in the treatment of hepatocellular carcinoma.

Persistent hepatitis virus infection and immune homeostasis / 临床肝胆病杂志

Homeostasis between the host and viruses is naturally maintained.On the one hand,the immune system activates the immune re-sponse to kill or eliminate viruses;on the other hand,the immune system controls the immune response to maintain immune homeostasis. The cause of persistent infections with hepatitis viruses such as HBV and HCV is that viral molecules damage the immune system of the host and their variants escape immune clearance.Long-term coexistence of the host and viruses is the process involving various immune cells and molecules and is the result of homeostasis maintenance in antiviral immune response.The immune homeostasis maintained during persis-tent infections with hepatitis viruses is analyzed by the cellular and molecular mechanisms.

Practice of training for postgraduates in infectious diseases and its reflection / 中华医学教育探索杂志

Clinical medicine is a comprehensive discipline integrating natural science and hu-manities and social science. Lemology is closely related with basic medicine and medical microbiology and medical immunology are the basis of lemology. Therefore, in the process of cultivating postgradu-ates of lemology, we should not only should attach importance to the cultivation of basic medical knowl-edge and clinical professional quality, but also pay more attention to the development of the intelligence factors and non-intelligence factors. Meanwhile education on humanity, social sciences and relevant laws and regulations should be enhanced to cultivate doctors' professional quality. Reverse thinking and lateral thinking in the clinical diagnosis should be strengthened to achieve the training objectives of cultivating international medical talents.

Detection of circulating Toll-like receptor 2 and 4 and CD4 + CD25 + regulatory T cells in patients with HBV-related liver cirrhosis / 中华微生物学和免疫学杂志

Objective To detect circulating CD4 + CD25 + regulatory T cells (Treg) and Toll-like receptor(TLR)2 and TLR4 expression on the peripheral blood mononuclear cells (PBMCs) of patients with HBV-related liver cirrhosis (LC), and to explore the correlation between them. Methods PBMCs isolated from 30 LC patients, 21 chronic hepatitis B (CHB) patients and 16 normal controls(NC) were stained with fluorescent labeling anti-TLR2-PE, anti-TLR4-APC, anti-CD14-FITC monoclonal antibodies and anti-CD4-PerCP, anti-CD25-FITC, anti-CD127-PE. Samples were detected by flow cytometry. Statistic analysis be-tween groups was performed by Kruskal-Wallis H test. Spearman rank correlation was used to analyze the correlation of Treg and TLR2, TLR4. Results The expression of TLR2 and TLR4 were significantly up-reg-ulated in patients with LC than those in the controls (TLR2 : 200.3 ± 96.8 vs 94.1 ± 17.6, P < 0.05 ; TLR4:32.1 ±7.2 vs 17.8 ±3.9, P<0.05). The expression of TLR4 was significantly increased in pa-tients with LC than those in patients with CHB (TLR4 : 32. 1 ± 7.2 vs 25.2 ± 8.3, P < 0.05), but there were no differences of TLR2 expression between LC and CHB(200.3 ± 96.8 vs 214.0 ± 72.6, P > 0.05). Treg/CD4+ T cells were 5.07% ±1.43%, 5.88% ±1.66%, 4.21% ±1.24% in patients with LC, CHB and NC, respectively. Treg/CD4+ T cells were significantly increased in patients with CHB than those in pa-tients with NC(P<0. 05) and LC(P <0.05), but there were no differences between LC and NC(P > 0.05). TLR4 expression and Treg were positive correlation (r = 0. 469, P = 0. 032) and TLB2 expression were negative correlation in patients with LC (r = -0.428, P = 0.021). Conclusion The expression of TLR2 and TLR4 were up-regulated on PBMCs in patients with LC. It seems to be expression of TLR2 and TLR4 in-volved in the pathogenesis of LC.

Observation of chimeric hepatitis C virus In infected Huh7.5 cell through transmission electron microscopy / 中华微生物学和免疫学杂志

Objective To observe the morphological characteristics of HCV particles and intracel-lular ultrastructure changes in Huh7. 5 cells which was infected with chimeric HCV via transmission electron microscopy. Methods Plasmid J6/JFH encoding the full length HCV chimeric genome was transcribed to HCV RNA in vitro and the RNA was transfected into Huh7.5 cells by electroporation. Quantitative real-time PCR(qRT-PCR) was used to assay HCV copies of the supernatant of transfected cells. Indirect immunofluo-rescence was used to detect the expression of HCV proteins. The cell culture superoatant were used to infect narve Huh7.5 cells, transmission electron microscopy was used to observe morphological characteristics of vi-rus particles and intracellular ultrastructure changes in infected Huh7. 5 cells. Results qRT-PCR showed high level virus copies in supernatant of transfected cells collected in different times, indirect immuno-fluo-rescencc proved high expression of HCV NS5A proteins in the transfected cells. Large numbers of enveloped or unenveloped virus-like particles (VLPs) were observed in infected Huh7. 5 cells via transmission electronmicroscopy. We also found hyperplasia of some membrane-enclosed organelles in the cytoplasm. Several fea-tures characterizing flavivirus infected cells and a cytoplasmic inclusion of unknown origin were observed. Conclusion The chimeric HCV from in vitro cell culture system is proved to be intact virus particles which can efficiently infect Huh7.5 cells.

Toll-like receptor-4 siRNA protects mice from acute liver injury induced by lipopolysaccharide and D-galactosamine / 中华传染病杂志

Objective To observe the protective effects of Toll-like receptor(TLR)-4 siRNA against acute liver injury in mice induced by lipopolysaccharide(LPS)and D-galactosamine(D-GalN).Methods One hundred and fifty C57BL/6 male mice were divided into 5 groups: phosphate buffered solution(PBS)pretreatment group,negative control plasmid pretreatment group,TS4 pretreatment group,TS6 pretreatment group and TS7 pretreatment group.Acute liver injury was induced in mice by intraperitoneal coinjection of LPS(10 ng/g)and D-GalN(1 mg/g).In vivo delivery of siRNA was performed via the tail vein by hydrodynamic injections(50 μg siRNA dissolved in 1 mL PBS)24 h and 48 h before coinjection of LPS and D-GalN. Expression of TLR-4 in liver tissues was measured by immunohistochemistry.The changes of TLR-4,tumor necrosis factor(TNF)-α and macrophage nflammatory protein(MIP)-2 mRNA levels in liver tissues were determined by reverse transcriptasepolymerase chain reaction(RT-PCR)analysis.MIP-2 and TNF-α concentrations in the sera of mice were determined by enzyme-linked immunosorbent assay(ELISA). Levels of alanine transaminase (ALT) and aspartate transaminase(AST) in serum were measured by standard autoanalyzer techniques. Liver pathological changes were observed by haematoxylin-eosin staining, while cell apoptosis levels in liver were determined by terminal deoxynucleotidyl-mediated-dUTP nick end labeling (TUNEL)assay. The difference of survival rates in 5 groups was analyzed by Fisher's exact probability test.ResultsPretreatment with TLR-4 siRNA down-regulated the TLR-4 mRNA and protein expressions,and significantly decreased the mortality and liver injury caused by coinjection of LPS and D-GalN in C57BL/6 mice.TLR-4 siRNA significantly down-regulated the TNF-α and MIP-2 mRNA expression and cytokine levels as determined by RT-PCR and ELISA,respectively. TLR-4 siRNA abrogated hepatocyte necrosis and inflammatory infiltration and also remarkably reduced serum concentrations of transaminases. The percentage of TUNEL-positive hepatocytes was significantly reduced in TLR-4 siRNA pretreatment group(TS4 pretreatment group: 0.065±0.015 vs PBS pretreatment group; 0.346±0.062,P＜0.05).ConclusionIt suggest that inhibition of TLR-4 expression by TLR-4 siRNA may provide potential application value for preventing liver injury.