Background:The aim of this study was to evaluate the clinical value of metagenomic next-generation sequencing (mNGS) of blood samples for identifying Pneumocystis jirovecii pneumonia (PJP) in patients with human immunodeficiency virus (HIV). Methods:A total of 76 people with HIV (PWH) with suspected lung infections were enrolled in the study. The patients were divided into two groups: the PJP group and the non-PJP group.All patients underwent pulmonary computed tomography scans, and blood or respiratory tract specimens were subjected to mNGS and conventional microbiological tests. Patient characteristics were collected from their medical records. Results:Thirty patients were diagnosed with PJP and 46 were confirmed to have non-P jirovecii (Pj) infectious pneumonia. mNGS was conducted on bronchoalveolar lavage fluid samples from 25 patients and on blood samples from 59 patients. Twenty-one of 22 (95.5%) blood samples from the PIP group contained sequences of Pi, with the number of specific reads for circulating Pj sequences ranging from 2 to 2035. In the non-PJP group, 4 blood samples exhibited low Pj sequences, ranging from 1 to 2 reads. The sensitivity and specificity for blood samples were 95.5% (95% confidence interval [CI], 91.2%-98.4%) and 90.0% (95% Cl, 89.5%-100%), respectively. Conclusions:Our study indicates that mNGS of blood samples exhibits high sensitivity and specificity for diagnosing PJP in PWH. Caution should be exercised when interpreting low Pj mNGS read counts in blood samples; the definitive diagnosis of PJP relies on the synthesis of clinical data with Pj mNGS results. Further studies are necessary to validate this finding.

The Acquired Immunodeficiency Syndrome Professional Group of the Society of Infectious Diseases of the Chinese Medical Association formulated the first edition of the Chinese Guidelines for the Diagnosis and Treatment of human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) (referred to as the Guidelines) in 2005. The 2024 edition of the Guidelines has been compiled by updating the 2021 fifth edition, incorporating the latest research advancements in antiviral therapy, comprehensive management, opportunistic infections, concurrent tumors, and the prevention and intervention of HIV infection. The new edition also introduces a new section on "Incomplete immune reconstitution", proposes the concept of "HIV vulnerable populations" for the first time with recommendations for their diagnosis and treatment. This edition of the Guidelines covers 14 sections: epidemiology, pathogenic characteristics, laboratory tests, pathogenesis, clinical presentation and staging, diagnostic criteria, common opportunistic infections, antiretroviral therapy, immune reconstitution inflammatory syndrome, incomplete immune reconstitution, AIDS-related neoplasms, prevention of mother-to-child transmission and conception in serodiscordant couples, pre- and post-exposure prophylaxis, and whole-course management of HIV infection. This edition of the Guidelines aims to assist clinical physicians in making informed decisions in the diagnosis, treatment, and management of HIV/AIDS and will be periodically revised and updated based on domestic and international research progress.

Objective:To explore the dynamic changes of inflammatory cytokines and T lymphocyte activation in the peripheral blood of human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) patients during anti-retroviral therapy (ART).Methods:Two hundred and six HIV/AIDS patients with ART at clinic of the Department of Infectious Diseases in Second Xiangya Hospital, Central-South University between January 2017 and December 2019 were selected as HIV infection group. They were followed up regularly and the blood samples before treatment and at month 6, month 12, month 24 of treatment were collected. Meanwhile, 52 healthy cases were enrolled in the healthy control group and their blood samples were collected. Enzyme-linked immunosorbent assay was used to detect the plasma concentrations of interleukin (IL)-6, hypersensitive C-reactive protein (hsCRP) and tumor necrosis factor (TNF)-α. Flow cytometry was used to detect the CD3 + CD4 + T lymphocytes count and the percentage of CD4 + CD38 + T lymphocytes and CD8 + CD38 + T lymphocytes in the peripheral blood mononuclear cells. Plasma HIV RNA viral load was determined using a quantitative real-time polymerase chain reaction technique. Statistical methods used paired t test and Pearson correlation analysis. Results:The concentrations of IL-6, hsCRP and TNF-α in HIV infection group were (13.42±2.35) pg/mL, (4 012.46±1 012.35) μg/L and (51.78±11.32) μg/L, respectively, which were higher than those in healthy control group ((6.14±0.78) pg/mL, (707.21±305.76) μg/L and (19.01±6.48) μg/L, respectively). The differences were all statistically significant ( t=12.56, 16.79 and 13.45, respectively, all P<0.001). They decreased gradually after initiation of ART in HIV infection group, and returned to normal levels at month 24 of ART. CD3 + CD4 + T cells count was (256.00±65.32)/μL and HIV RNA viral load was (4.467±4.244) lg copies/mL before ART in HIV infection group, which were negatively correlated ( r=-0.625, P=0.041). The percentages of CD8 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in HIV infection group were higher than those in healthy control group. The differences were all statistically significant ( t=3.85, 6.84 and 2.57, respectively, all P<0.050). The percentage of CD8 + CD38 + T lymphocytes was positively correlated with HIV RNA viral load before ART ( r=0.768, P=0.026). The percentages of CD4 + CD38 + T lymphocytes before treatment and at month 12 or month 24 of treatment in the HIV infection group were lower than those in the healthy control group, and the differences were all statistically significant ( t=6.80, 1.10, and 2.11, respectively, all P<0.050). Conclusions:HIV infection could not only cause insufficiency in immune system, but also abnormal activation of immune system, which could get better gradually with ART.

Objective:To understand the clinical manifestations and etiological diagnosis characteristics of AIDS patients complicated with tuberculosis, and to explore the method to improve the diagnosis rate of HIV/AIDS patients with tuberculosis.Methods:There were 116 HIV/AIDS patients co-infected with tuberculosis enrolled as the observation group in People's Hospital of Xiangxi Autonomous Prefecture from October 2012 to December 2019, and 59 cases with simple tuberculosis in the same period were enrolled as the control group. The clinical symptoms, extrapulmonary tuberculosis, pulmonary tuberculosis imaging characteristics, PPD tuberculin response, sample mezzanine cup assay acid-fast staining results, tuberculosis infection T cellular immunospot detection (T-SPOT.TB) results, Mycobacterium tuberculosis rpoB gene detection (XPERT) results were collected and compared between the two groups. The positive rates of PPD and respiratory tract sample mezzanine cup acid-fast staining (sputum and bronchial lavage fluid) were further analyzed in the observation group with different CD4 +T cell counts. Results:The main clinical manifestations in the observation group were repeated high fever (82.76%) and weight loss (75.00%) , and the incidence of extrapulmonary tuberculosis (56.89%) was significantly higher than that in the control group ( χ2=10.911, P<0.05) . In the observation group, lung lesions were in 2 and ≥3 lung fields (30.17% and 46.55%) , and millet-like changes were common (21.55%) , which were all significantly higher than those in the control group ( χ2=7.160, 7.310 and 4.709, P<0.05) . The positive rates of routine PPD test, respiratory tract sample mezzanine cup acid stain and the initial T-SPOT.TB in the observation group were 14.66% , 34.48% and 46.67%, which were all significantly lower than 40.68%, 52.54% and 82.35% in the control group ( χ2=14.763, 5.290 and 10.471, P<0.05) . The positive rates of T-SPOT.TB (after review) and XPERT were high in both groups, and there was no significant difference between them ( χ2=1.857 and 0.405, P>0.05) . The positive rate of sample mezzanine cup acid-fast staining from extrapulmonary tissue and puncture fluid in the observation group was 100.00%, which was higher than 66.67% in the control group ( χ2=12.291, P<0.05) . In the observation group, the lower the CD4 +T cell count the lower the positive rates of PPD and sample mezzanine cup acid-fast staining in respiratory tract samples. Conclusions:The clinical manifestations of HIV/AIDS patients co-infected with tuberculosis are atypical, and the positive rate of routine immunological examination is low. The XPERT testing of sputum and extrapulmonary specimens, the modified T-SPOT.TB test of blood, and sample mezzanine cup acid-fast staining of extrapulmonary tissue and puncture fluid are helpful to improve the diagnosis of AIDS patients complicated with tuberculosis.

BackgroundChemotherapy induced nausea and vomitting (CINV) is associated with significant deterioration in quality of life. The standard antiemetic therapy for highly emetogenic chemotherapy are combination therapies, and dexamethasone is a necessary component. However, dexamethasone has diverse side effects and it may not be an appropriate antiemetic for use in immunotherapy. Guidelines recommend using olanzapine (10mg) in preventing CINV, but excessive sedation was reported. A trail reported that lower dose olanzapine (5mg) was effective in control of CINV and had less serious sedation events. We initiated this trial to validate whether olanzapine (5mg) could be a non-inferiority alternative of dexamethasone in the triplet antiemetic combination therapy.MethodsThe predicted sample size in this trial (NCT04437017) is 548 (power=80%, α=0.05, non-inferiority margin=10%). Eligible patients are randomized in a 1: 1 ratio into two groups to receive olanzapine or dexamethasone plus a 5-HT3 receptor antagonist (5-HT3 RA) and a NK-1 receptor antagonist (NK-1 RA). The primary endpoint is 0–120 h complete response (CR) rate, and the secondary endpoints are 25–120 h CR rate and 0–120 h no nausea rate. The endpoints and side effects will be recorded after the initiation of chemotherapy for 5 days.ResultsPatients in the olanzapine group achieved a 0–120 h CR rate (83.6% v.s. 84.9%, difference [one-sided 95% CI]: 1.2% [-∞, 6.4%], Pnoninferiority = 0.003), 25–120 h CR rate (85.5% v.s. 85.6%, difference [one-sided 95% CI]: 0.1% [-∞, 5.1%], Pnoninferiority = 0.024) and 0–120 h no nausea rate (38.7% v.s. 39.9%, difference [one-sided 95% CI]: 1.2% [-∞, 8.1%], Pnoninferiority = 0.001) non-inferior to that in patients in the olanzapine group. Moreover, side effects such as constipation (P = 0.045), hiccups (P < 0.001) as well as insomnia (P < 0.001) were more frequent in patients receiving dexamethasone than in those receiving olanzapine.ConclusionsOlanzapine (5mg) could be a non-inferiority alternative of dexamethasone in the triplet combination anti-emetic therapy and has less side effects than dexamethasone.Legal entity responsible for the studyThe Fifth Affiliated Hospital of Sun Yat-sen University.FundingBeijing Xisike Clinical Oncology Research Foundation and the Investigator-Initiated Clinical Trial foundation of the Fifth Affiliated hospital of Sun Yat-sen University.DisclosureAll authors have declared no conflicts of interest. BackgroundChemotherapy induced nausea and vomitting (CINV) is associated with significant deterioration in quality of life. The standard antiemetic therapy for highly emetogenic chemotherapy are combination therapies, and dexamethasone is a necessary component. However, dexamethasone has diverse side effects and it may not be an appropriate antiemetic for use in immunotherapy. Guidelines recommend using olanzapine (10mg) in preventing CINV, but excessive sedation was reported. A trail reported that lower dose olanzapine (5mg) was effective in control of CINV and had less serious sedation events. We initiated this trial to validate whether olanzapine (5mg) could be a non-inferiority alternative of dexamethasone in the triplet antiemetic combination therapy. Chemotherapy induced nausea and vomitting (CINV) is associated with significant deterioration in quality of life. The standard antiemetic therapy for highly emetogenic chemotherapy are combination therapies, and dexamethasone is a necessary component. However, dexamethasone has diverse side effects and it may not be an appropriate antiemetic for use in immunotherapy. Guidelines recommend using olanzapine (10mg) in preventing CINV, but excessive sedation was reported. A trail reported that lower dose olanzapine (5mg) was effective in control of CINV and had less serious sedation events. We initiated this trial to validate whether olanzapine (5mg) could be a non-inferiority alternative of dexamethasone in the triplet antiemetic combination therapy. MethodsThe predicted sample size in this trial (NCT04437017) is 548 (power=80%, α=0.05, non-inferiority margin=10%). Eligible patients are randomized in a 1: 1 ratio into two groups to receive olanzapine or dexamethasone plus a 5-HT3 receptor antagonist (5-HT3 RA) and a NK-1 receptor antagonist (NK-1 RA). The primary endpoint is 0–120 h complete response (CR) rate, and the secondary endpoints are 25–120 h CR rate and 0–120 h no nausea rate. The endpoints and side effects will be recorded after the initiation of chemotherapy for 5 days. The predicted sample size in this trial (NCT04437017) is 548 (power=80%, α=0.05, non-inferiority margin=10%). Eligible patients are randomized in a 1: 1 ratio into two groups to receive olanzapine or dexamethasone plus a 5-HT3 receptor antagonist (5-HT3 RA) and a NK-1 receptor antagonist (NK-1 RA). The primary endpoint is 0–120 h complete response (CR) rate, and the secondary endpoints are 25–120 h CR rate and 0–120 h no nausea rate. The endpoints and side effects will be recorded after the initiation of chemotherapy for 5 days. ResultsPatients in the olanzapine group achieved a 0–120 h CR rate (83.6% v.s. 84.9%, difference [one-sided 95% CI]: 1.2% [-∞, 6.4%], Pnoninferiority = 0.003), 25–120 h CR rate (85.5% v.s. 85.6%, difference [one-sided 95% CI]: 0.1% [-∞, 5.1%], Pnoninferiority = 0.024) and 0–120 h no nausea rate (38.7% v.s. 39.9%, difference [one-sided 95% CI]: 1.2% [-∞, 8.1%], Pnoninferiority = 0.001) non-inferior to that in patients in the olanzapine group. Moreover, side effects such as constipation (P = 0.045), hiccups (P < 0.001) as well as insomnia (P < 0.001) were more frequent in patients receiving dexamethasone than in those receiving olanzapine. Patients in the olanzapine group achieved a 0–120 h CR rate (83.6% v.s. 84.9%, difference [one-sided 95% CI]: 1.2% [-∞, 6.4%], Pnoninferiority = 0.003), 25–120 h CR rate (85.5% v.s. 85.6%, difference [one-sided 95% CI]: 0.1% [-∞, 5.1%], Pnoninferiority = 0.024) and 0–120 h no nausea rate (38.7% v.s. 39.9%, difference [one-sided 95% CI]: 1.2% [-∞, 8.1%], Pnoninferiority = 0.001) non-inferior to that in patients in the olanzapine group. Moreover, side effects such as constipation (P = 0.045), hiccups (P < 0.001) as well as insomnia (P < 0.001) were more frequent in patients receiving dexamethasone than in those receiving olanzapine. ConclusionsOlanzapine (5mg) could be a non-inferiority alternative of dexamethasone in the triplet combination anti-emetic therapy and has less side effects than dexamethasone. Olanzapine (5mg) could be a non-inferiority alternative of dexamethasone in the triplet combination anti-emetic therapy and has less side effects than dexamethasone.

The outbreak of coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pandemic. SARS-CoV-2 vaccination is currently being actively promoted worldwide as a promising measure to combat the pandemic. However, human immunodeficiency virus (HIV)-infected individuals who manifest varying degrees of immunodeficiency and chronic inflammation may require special consideration with regards to vaccine types and the timing of immunization depending on specific clinical situations. The present recommendation provides a reference for SARS-CoV-2 vaccination in HIV-infected patients.

OBJECTIVE To explore the clinical application effect of noninvasive mechanical ventilation for patients with acquired immune deficiency syndrome (AIDS) complicated with pneumonia. METHODS A prospective study was conducted on 86 patients with AIDS complicated with pneumocystis pneumonia. The patients were randomly divided into a control group and an experimental group, both of which were treated with conventional drugs. The control group was supplemented with oxygen via a mask, and the experimental group was additionally treated with noninvasive ventilator ventilation. The changes of arterial oxygen partial pressure, oxygenation index, respiratory frequency, pulse rate, serum albumin and other indicators between the two groups before and after treatment were observed. The patient's hospitalization time, overall improvement and mortality rate were compared. RESULTS Compared with those before treatment, the arterial oxygen partial pressure, oxygenation index, respiratory frequency, and pulse rate of the two groups of patients were significantly improved after treatment (P<0.05). The improvement of the experimental group after treatment was more significant than that of the control group, and the difference was statistically significant (P<0.001). After treatment, the proportion of recovery rate of serum albumin in the experimental group was 81.40%, which was significantly higher than that in the control group (53.49%), and the difference was statistically significant (P<0.05). Compared with the control group, hospitalization time, treatment improvement and mortality rate in the experimental group had significant advantages and statistical significance (P<0.05). CONCLUSION For AIDS patients complicated with pneumonia, noninvasive mechanical ventilation had obvious treatment effects, which could significantly improve respiratory function, reduce mortality rate, and increase recovery rate. It can be considered as a therapeutic method to be included in routine treatment protocols.

COVID-19 is an emerging infectious disease caused by the new coronavirus (SARS-CoV-2) that can be transmitted between humans and animals, and poses a serious threat for the people’s lives. The early diagnosis of suspected cases, effective treatments of confirmed cases, and prevention measures against infectious links are essential to prevent and control COVID-19. The current progresses of COVID-19 about diagnosis and treatment are reviewed in this article, with a view to providing reference for the control of COVID-19.

Introduction Nasopharyngeal carcinoma (NPC) is a common malignancy in China and known prognostic factors are limited. In this study, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune inflammation index (SII), and systemic inflammation response index (SIRI) were evaluated as prognostic factors in locally advanced NPC patients. Materials and Methods NPC patients who received curative radiation or chemoradiation between January 2012 and December 2015 at the Second Xiangya Hospital were retrospectively reviewed, and a total of 516 patients were shortlisted. After propensity score matching (PSM), 417 patients were eventually enrolled. Laboratory and clinical data were collected from the patients' records. Receiver operating characteristic curve analysis was used to determine the optimal cut-off value. Survival curves were analyzed using the Kaplan-Meier method. The Cox proportional hazard model was used to identify prognostic variables. Results After PSM, all basic characteristics between patients in the high SIRI group and low SIRI group were balanced except for sex (p=0.001) and clinical stage (p=0.036). Univariate analysis showed that NLR (p=0.001), PLR (p=0.008), SII (p=0.001), and SIRI (p<0.001) were prognostic factors for progression-free survival (PFS) and overall survival (OS). However, further multivariate Cox regression analysis showed that only SIRI was an independent predictor of PFS and OS (hazard ratio (HR):2.83; 95% confidence interval (CI): 1.561-5.131; p=0.001, HR: 5.19; 95% CI: 2.588-10.406; p<0.001), respectively. Conclusion Our findings indicate that SIRI might be a promising predictive indicator of locally advanced NPC patients.

Objective To investigate the effect of high active antiretroviral therapy ( HAART) on growth and development of infants born to pregnant women infected with human immunodeficiency virus (HIV) and the effect on blocking mother to children transmission.Methods Totally 165 pregnant women diagnosed with HIV infection from May 2006 to May 2017 and their 169 infants, including four pairs of twins were enrolled, and 82 infants born to HIV negative pregnant women in the same period were enrolled as control .All of the pregnant women in the experimental group were administrated with HAART when HIV antibody test was positive.The delivery intervention and artificial feeding were carried out as well.The weight, height, hemoglobin (Hb), serum iron and serum calcium level of infants at birth , 12 months and six years old were monitored and compared between the two groups.Apgar scores of newborns and intelligence tests at six-year-old were also recorded.Statistical analysis was performed by t test.Results Pregnant women were generally in good conditions and well tolerated to the drugs.There were no significant differences in neonatal Apgar scores , body weight, body length, Hb, serum iron, serum calcium and CD4+T lymphocyte count between HIV positive experimental group and control group (t ＝-1.27,-1.12,-3.41,-5.62,-0.89,-3.02 and-0.74, respectively, all P＞0.05).At the age of 12 months, there were no significant differences in body weight , length, Hb, serum iron, serum calcium and CD4+T lymphocyte count between the two groups ( t ＝1.02, 1.41, 1.32, 1.03, 0.89 and 1.06, respectively, all P ＞0.05).At the age of six years, there were no significant differences in all indexes between the two groups (t＝1.02, 0.87, 1.58, 1.03, 0.92 and 2.07, respectively, all P ＞0.05).Intelligence assessment was performed in 78 children of the experimental group and 45 children of the control group at the age of six years , and there was no significant difference between the two groups ((89.7 ±12.5) score vs (91.2 ±13.7) score, t＝1.67, P＝0.43).All the children in the experimental group were positive for HIV antibody at birth , and six cases were positive for HIV RNA who were diagnosed with neonatal HIV infection.HAART was initiated for the six cases , while HIV antibody tests were still positive until the age of 18 months after HAART.The rest of the children′s HIV antibody tests became negative with the mother to children tramsission rate of 3.55%(6／169).Conclusion HAART could not only block mother to children tramsission of HIV , but also has no effect on growth and intellectual development of children during the observation period.

Objective To analyze the impact of secondary infection on prognosis of liver failure. Methods A total of 384 hospitalized patients who were diagnosed with liver failure from January 2015 to Decembet 2017 in the Department of Infectious Diseases of the Second Xiangya Hospital of Central South University were retrospectively analyzed.The patients were divided into infected group and non-infected group according to whether they were complicated with infection during hospitalization .The cause of liver failure, the area and source of infection were recorded.The infected group was divided into bacterial group and fungal group.The liver and kidney function , international normalized ratio ( INR).The model for end-stage liver disease ( MELD ) score, hospitalization days , medical expenditure , and mortality were calculated and evaluated.T test was used for normally distributed continuous variables , and chi-square test was used for classified variables.Results A total of 384 hospitalized patients with liver failure were enrolled , including 321 males and 63 females with age of (45.5 ±13.4) years.There were 240 patients (62.5%, infected group) who had secondary infection during the whole course , and 144 patients (37.5%, non-infected group ) were not infected.Among the 384 patients, 328 patients (85.4%) were infected with hepatitis B virus, 8(2.1%) with hepatitis C virus, and 10(2.6%) with alcoholic hepatitis.As for the clinical types of liver failure , 187 patients (48.7%) were diagnosed with acute-on-chronic (subacute) liver failure and 158 (41.1%) with chronic liver failure.Among the 240 patients in the infected group, 122 patients (50.8%) had abdominal infection, 84 (35%) had pulmonary infection, 8(3.3%) had urinary tract infection, 13(5.4%) had biliary tract infection , and 11 ( 4.6%) had bloodstream infection.The levels of total bilirubin , creatinine, MELD scores, hospitalization days and medical expenditure in the infected group and non -infected group were statistically significant (all P＜0.01) after 30 days in hospital.In the infected group, 362 various samples from 240 patients were submitted for bacterial culture , among which 87 samples were positive, including Candida in 15 samples, Aspergillus in 8 samples, Acinetobacter baumannii in 13 samples, Staphylococcus in 10 samples, Escherichia coli in 11 samples, Klebsiella pneumoniae in 14 samples, Bacillus faecalis in 4 samples, Bacillus pallid in 4 samples, Stenotrophomonas maltophilia in 4 samples and Aeromonas hydrophila in 4 samples.Among the 240 patients in the infected group , 182 patients were diagnosed with bacterial infection and 58 with fungal infection. There were significant differences in total bilirubin , serum creatinine, INR, MELD scores and mortality rate between the two groups ( all P＜0.05).Conclusions The rate of secondary infection in patients with liver failure is not related with age.The development of secondary infection , especially fungal infection , worsens the prognosis of patients with liver failure.

Objective: To investigate the optimal duration of pegylated-alpha interferon (Peg-INFα) combined with ribavirin (RBV) in treating chronic hepatitis C infection in human immunodeficiency virus (HIV)-infected patients. Methods: A multicenter prospective study was conducted. The study subjects were divided into two groups; HIV/HCV co-infections (Group A, n = 158) and control with HCV-monoinfections (Group B, n = 60). All recruited patients received standard Peg-INFα plus RBV therapy. Group A was divided into 3 subgroups according to CD4(+) cell counts: A1 subgroup, 79 cases, CD4(+) counts > 350 cells /μl, who received anti-HCV before combination antiretroviral therapy(cART); A2 subgroup, 45 cases, CD4(+) counts between 200 and 350 cells/μl, who did not start anti-HCV until they could tolerate cART well; A3 subgroup, 34 cases, CD4(+) counts < 200 cells /μl, cART was administered first, and anti-HCV therapy was started when CD4(+) counts > 200 cells/μl. The anti-HCV efficacy of two groups and 3 subgroups were compared. Statistical analysis for normal distribution and homogeneity of variance data was calculated by t-test and the counting data was analyzed by χ (2) test. The Mann-Whitney U test was used for non-normal data. A one-way analysis of variance (ANOVA) was used for the comparison of multiple groups, followed by SNK method. Multiple independent samples were used for non-parametric tests. Results: There was no significant difference in age and baseline HCV RNA levels between groups and subgroups (P > 0.05). By an intent-to-treat (ITT) analysis, in Group A, the ratio of complete early virological response (cEVR) rate was 75.3% (119/158), the ratio of end of treatment virological response (eTVR) rate was 68.4% (108/158), and the ratio of sustained virological response (SVR) rate was 48.7% (77/158); in Group B, the ratio of cEVR rate was 93.3% (56/60), the ratio of eTVR rate was 90.0% (54/60), and the ratio of SVR rate was 71.7% (43/60); The therapeutic index of Group A were lower than those of Group B (P≤0.05). By per-protocol (PP) analysis, the ratio of cEVR rate in Group A [75.2% (88/112)] was still lower than that in Group B [93.3% (56/60)], but no significant differences were found in the ratio of eTVR rate and SVR rate between 2 groups (P > 0.05). Comparing the efficacy of subgroups (A1, A2 and A3) by ITT analysis, the ratios of cEVR rate were respectively 78.5% (62/79), 75.6% (34/45) and 67.6% (23/34); the ratios of eTVR rate were respectively 68.4%(54/79), 80.0%(36/45)and 52.9%(18/34); and the ratios of SVR rate were respectively 41.8%(33/79), 64.4%(29/45)and 44.1%(15/34). The ratio of eTVR in subgroup A2 was obviously higher than that in subgroup A3 and the ratio of SVR in subgroup A2 was statistically higher than that of subgroup A1(P≤0.05). However, by PP analysis, no significant differences of the therapeutic indexes were found among the respective subgroups (P > 0.05). Conclusion: HIV-HCV co-infected patients would have better anti-HCV efficacy with Peg-INFα-2a plus RBV than HCV- monoinfected patients. The best time for initiating anti-HCV therapy in HIV-HCV co-infected patients is when CD4(+) counts 200 cells/ μl.

Increasing evidence has indicated that long noncoding RNAs (lncRNAs) are a class of significant regulators in various tumorigenesis processes. The lncRNA homeobox transcript antisense RNA (HOTAIR) has been reported to act as a functional lncRNA in cervical cancer development. The present study investigated the underlying mechanism of HOTAIR and miR-17-5p in cervical cancer tumorigenesis. The results showed that HOTAIR expression was significantly upregulated in both cervical cancer tissues and cell lines. Loss-of-function experiments showed that HOTAIR knockdown inhibited the proliferation, migration, and invasion of cervical cells. In addition, miR-17-5p expression was downregulated in cervical cancer tissues and cell lines. Pearsons correlation analysis indicated that miR-17-5p expression was negatively correlated to that of HOTAIR. Luciferase reporter assay revealed that miR-17-5p directly targeted HOTAIR 3-UTR. Rescue experiments showed that miR-17-5p knockdown could reverse the tumor-suppressing effect caused by si-HOTAIR transfection. In summary, our results reveal the tumor-promoting role of HOTAIR in cervical cancer via sponging miR-17-5p, providing a novel therapeutic target for future treatment of cervical cancer.

Objective To observe the expression of apoptosis related protein c-inhibitor of apoptosis protein (IAP)2 by RNA interference of human immunodeficiency virus-1 (HIV-1)vpr gene and analyze the apoptosis of Jurkat cells.Methods Vector (NC),HIV-1vpr (vpr),vpr+ pRNAT-U6.1/Neo-vpr-56 (Si56) and vpr+ pRNAT-U6.1/Neo-vpr-160 (Si160) were transfected to Jurkat cells and cultured for 48 hours.The total RNA and protein were extracted.Expression of vpr gene was detected by reverse transcription (RT)-polymerase chain reaction (PCR) to confirm the success of transfection.Expression of c IAP2 was detected by RT-PCR and Western Blot.The apoptosis of Jurkat cells was observed by flow cytometry.Results Expression of vpr gene was detected in vpr,Si56 and Si160 groups.The mRNA expression levels in Si56 and Si160 groups were significantly lower than that in vpr group,which declined 87.2％ and 82.2％,respectively (P＜0.05).The levels of c IAP2 mRNA expression in vpr,Si56 and Si160 groups were increased by 3.75,2.49 and 2.65 folds,respectively,compared to that in NC group.However,the c-IAP2 mRNA expressions in Si56 and Si160 groups were lower than that in vpr group,which declined 33.7％ and 29.5％,respectively (P ＜ 0.05).The c-IAP2 protein expression was consistent with mRNA by immunoblotting,and those in Si56 and Si160 groups were declined 42.2％ and 46.8％,respectively,compared to that in vpr group (P＜0.05).The apoptosis of J urkat cells was detected in all groups.Compared to NC group,the apoptotic rate in vpr group was increased by 1.76 folds.However,the differences of apoptosis rate among NC,Si56 and Si160 groups were not statistically significant (all P＞0.05).Compared to vpr group,the apoptotic rates in Si56 and Si160 were significantly decreased by 19.26％ and 18.05％,respectively (P＜0.05).Conclusions The expression of c-IAP2 could be downregulated by knockdown of HIV-1 vpr gene in transcription and protein levels,and the apoptosis of Jurkat cells is inhibited.

OBJECTIVE:Tongue squamous cell carcinoma (TSCC) is significantly more malignant than other type of oral squamous cell carcinoma (OSCC). In this study, we aimed to identify specific global gene expression signatures of TSCC to investigate the more invasive behavior of the deeply infiltrating cancer.METHODS:Using RNA-seq technology, we detected gene expression of 20 TSCCs, 20 matched paratumor tissues, and 10 healthy normal mucosa tissues. Enrichment analysis of gene ontology (GO) and pathway was conducted using online tools DAVID for the dysregulated genes. Additionally, we performed the quantitative real-time RT-PCR (qRT-PCR) to validate the findings of RNA-Seq in 10 samples of TSCC, matched paratumor, and normal mucosa, respectively.RESULTS:We detected 252 differentially expressed genes (DEGs) between TSCC and matched paratumor tissue, including 117 up-regulated and 135 down-regulated genes. For comparison between TSCC and normal mucosa, 234 DEGS were identified, consisting of 67 up-regulated and 167 down-regulated genes. For both two comparisons, GO categories of muscle contraction (GO: 0006936), epidermis development (GO: 0008544), epithelial cell differentiation (GO: 0030855), and keratinization (GO: 0031424) were commonly enriched. Altered gene expression affected some cancer-related pathways, such as tight junction. The qRT-PCR validation showed that gene expression patterns of FOLR1, NKX3-1, TFF3, PIGR, NEFL, MMP13, and HMGA2 were fully in concordance with RNA-Seq results.CONCLUSION:Findings in this study demonstrated the genetic and molecular alterations associated with TSCC, providing new clues for understanding the molecular mechanisms of TSCC pathogenesis.

BACKGROUND:Cytokines have been widely demonstrated to involve in the pathogenesis of AIDS and the mechanisms of antiretroviral therapy. Interleukin 27 (IL-27) is a new member of the IL-12 cytokine family and has been shown to interfere HIV-1 virus replication with controversial findings. This study is to investigate the dynamic changes in plasma IL-27 level and cell surface IL-27 receptor expression in HIV/AIDS patients who underwent HAART.METHODS:Whole blood was collected from 34 HIV-positive/AIDS patients 0, 6, and 12 months after initiation of HAART and 27 healthy subjects. Plasma IL-27, IFN-γ, and IL-4 were measured by enzyme-linked immunosorbent assay, while peripheral blood CD3+CD4+ T cells count and the gp130 expressed CD3+CD4+cell were measured by flow cytometry.RESULTS:The plasma IL-27 concentration, IFN-γ concentration, and percentage of positive gp130 CD4 cells were significantly decreased in previously treatment-naive HIV/AIDS patients compared to healthy controls, but gradually increased 6 and 12 months after initiation of HAART. Conversely, IL-4 levels were significantly increased in treatment-naive HIV/AIDS patients compared to healthy controls, but gradually decreased 6 and 12 months after HAART. The concentrations of plasma IL-27 were positively correlated with the percentage of gp130 positive CD4 cells (r=0.438, p=0.016). Both plasma IL-27 concentration and gp130 positive cell percentage were positively associated with peripheral blood CD3+CD4+ T cell count (P<0.05 or P<0.01), but negatively associated with plasma HIV viral load (P<0.05 or P<0.01).CONCLUSION:IL-27 signaling (IL-27 and its receptor) may be involved in the pathogenesis of HIV infection and immune reconstitution in HIV/AIDS patients who underwent HAART. IL-27 may exert effects through regulating Th1 / Th2 ratio.

Macrophages are resistant to cell death and are one of HIV reservoirs. HIV viral protein Vpr has the potential to promote infection of and survival of macrophages, which could be a highly significant factor in the development and/or maintenance of macrophage viral reservoirs. However, the impact of vpr on macrophages resistance to apoptosis is yet to be comprehended. Autophagy is a cell survival mechanism under stress state. In this study, we investigated whether autophagy is involved in macrophages resistant to vpr-induced apoptosis. Using the THP1 macrophages, we studied the interconnection between macrophages resistance to apoptosis and autophagy. We found that vpr is able to trigger autophagy in transfected THP-1 macrophages confirmed by electron microscopy (EM) and western blot analysis, and inhibition of autophagy with 3MA increased vpr-induced apoptosis. The results indicate that autophagy may be responsible for maintenance of macrophage HIV reservoirs.

Background: Problem/case-based learning (PCBL) is one of the most commonly used educational methods in medical schools.Aim: To further improve PCBL in clinical course of severe infection by introducing competition mode.Methods: Two classes of medical students were divided into two groups by class-based simple randomization and were taught the course of severe infection by PCBL. A team-based competition was introduced in the study group (n = 35) while not in the control group (n = 36). After the course, four closely associated references were recommended. All the students were notified about a group consultation on a similar case. In the final examination, a case with severe infection complicated with infectious shock was presented for the students to analyze and resolve listed questions. Their performances were qualitatively evaluated to justify the effectiveness of the competition-based PCBL.Results: The students in the study group were more active and initiative in case discussion and interaction, in referring to case-related articles and attending clinical group-consultation. They had better performance in the case analysis in the final examination. The typical case analysis test easily figured out more excellent students in the study group.Conclusions: The PCBL with competition mode introduced in is an effective approach to guide students to fully understand the clinical diagnoses and treatment of severe infection. It also prompts medical students' initiative in referring to case-related articles and attending group-consultation, both of which are essential to equip medical students with sufficient competency for clinical practice.

Cisplatin (DDP) -based chemotherapy is a standard strategy for cervical cancer, while chemoresistance remains a challenge. Recent evidence highlights the crucial regulatory roles of long non-coding RNAs (lncRNA) in tumor biology. However, the roles and regulatory mechanisms of the novel lncRNA, cancer susceptibility candidate 2 (CASC2), in cervical cancer tumorigenesis and chemoresistance are poorly understood. In this study, CASC2 expression was down-regulated in cervical cancer tissues, and was related to a shorter survival time and poorer clinicopathologic features. Exogenous CACS2 alone was sufficient to inhibit cervical cancer cell proliferation and amplified DDP-induced repression of cell proliferation. A lower expression of CACS2 was observed in the DDP-resistant cervical cancer tissues, compared to DDP-sensitive cancer tissues; CACS2 overexpression could sensitize DDP-resistant cervical cancer cell (HeLa/DDP and CaSki/DDP) to DDP. Further functional experiments indicate that CASC2 upregulated PTEN expression by direct inhibiting miR-21 in the DDP-resistant cancer cells, leading to the down-regulation of p-AKT protein. In DDP-resistant cervical cancer tissues, miR-21 was up-regulated while PTEN was down-regulated. Taken together, these observations suggest CASC2 up-regulates PTEN as a ceRNA of miR-21 and plays an important role in cervical cancer sensitivity to DDP and may serve as a potential target for cancer diagnosis and treatment.

Objective To understand the therapeutic effect of clindamycin combined with compound sulfamethoxazole tablets on pneumocystis pneumonia(PCP)associated with acquired immunodeficiency syndrome (AIDS).Methods 97 AIDS patients with PCP in a hospital from January 2014 to March 2015 were randomly divided into control group (n=49,received compound sulfamethoxazole )and trial group(n=48,received clindamycin on the basis of com-pound sulfamethoxazole ),levels of partial pressure of oxygen in arterial blood (PaO2 ),arterial blood oxygen satu-ration(SaO2 ),serum albumin(ALB),and lactic dehydrogenase (LDH)in two groups of patients before and after treatment were recorded.Results Levels of PaO2 ,SaO2 ,ALB,and LDH between two groups of patients before treatment was not significantly different(all P >0.05).After treatment,PaO2 in control group and trial group were (73.01 ±4.62)mmHg and(84.92 ±5.34)mmHg respectively,SaO2 were (75.81 ±4.28)% and(90.86 ±5.94)%respectively,ALB were (32.62±4.41 )g/L and(43.95 ±5.03)g/L respectively,LDH were(416.53 ±30.77)U/L&nbsp;and(331 .58±20.86)U/L respectively,levels of PaO2 and SaO2 in trial group were both higher than control group , difference in ALB and LDH between two groups of patients after treatment were both statistically significant(both P <0.05).The total effective rate of trial group was 89.58% (n=43),which was higher than 69.39%(n=34)in control group (χ2 =6.04,P =0.014).Conclusion Clindamycin combined with compound sulfamethoxazole tablets has good therapeutic effect on AIDS and PCP,which is worthy of clinical popularization and application.