Selective elimination of host cells harboring replication-competent human immunodeficiency virus reservoirs: a promising therapeutic strategy for HIV cure / 中华医学杂志(英文版)

Many seminal advances have been made in human immunodeficiency virus (HIV)/AIDS research over the past four decades. Treatment strategies, such as gene therapy and immunotherapy, are yielding promising results to effectively control HIV infection. Despite this, a cure for HIV/AIDS is not envisioned in the near future. A recently published academic study has raised awareness regarding a promising alternative therapeutic option for HIV/AIDS, referred to as "selective elimination of host cells capable of producing HIV" (SECH). Similar to the "shock and kill strategy," the SECH approach requires the simultaneous administration of drugs targeting key mechanisms in specific cells to efficiently eliminate HIV replication-competent cellular reservoirs. Herein, we comprehensively review the specific mechanisms targeted by the SECH strategy. Briefly, the suggested cocktail of drugs should contain (i) latency reversal agents to promote the latency reversal process in replication-competent reservoir cells, (ii) pro-apoptotic and anti-autophagy drugs to induce death of infected cells through various pathways, and finally (iii) drugs that eliminate new cycles of infection by prevention of HIV attachment to host cells, and by HIV integrase inhibitor drugs. Finally, we discuss three major challenges that are likely to restrict the application of the SECH strategy in HIV/AIDS patients.

Effectiveness of glucocorticoid therapy in patients with severe coronavirus disease 2019: protocol of a randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#At the end of 2019, a novel coronavirus outbreak causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The effectiveness of adjunctive glucocorticoid therapy in the management of 2019-nCoV-infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.@*METHODS@#The present study will be conducted as an open-labeled, randomized, controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2 mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at four consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.@*DISCUSSION@#The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in patients with severe coronavirus disease 2019.@*TRIAL REGISTRATION@#ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

Effectiveness of glucocorticoid therapy in patients with severe novel coronavirus pneumonia: protocol of a randomized controlled trial / 中华医学杂志(英文版)

Background@#At the end of 2019, a novel coronavirus outbreak emerged in Wuhan, China, and its causative organism has been subsequently designated the 2019 novel coronavirus (2019-nCoV). The virus has since rapidly spread to all provinces and autonomous regions of China, and to countries outside of China. Patients who become infected with 2019-nCoV may initially develop mild upper respiratory tract symptoms. However, a significant fraction of these patients goes on to subsequently develop serious lower respiratory disease. The effectiveness of adjunctive glucocorticoid therapy uses in the management of 2019-nCoV infected patients with severe lower respiratory tract infections is not clear, and warrants further investigation.@*Methods@#The present study will be conducted as an open-labelled, randomised controlled trial. We will enrol 48 subjects from Chongqing Public Health Medical Center. Each eligible subject will be assigned to an intervention group (methylprednisolone via intravenous injection at a dose of 1-2mg/kg/day for 3 days) or a control group (no glucocorticoid use) randomly, at a 1:1 ratio. Subjects in both groups will be invited for 28 days of follow-up which will be scheduled at 4 consecutive visit points. We will use the clinical improvement rate as our primary endpoint. Secondary endpoints include the timing of clinical improvement after intervention, duration of mechanical ventilation, duration of hospitalization, overall incidence of adverse events, as well as rate of adverse events at each visit, and mortality at 2 and 4 weeks.@*Discussion@#The present coronavirus outbreak is the third serious global coronavirus outbreak in the past two decades. Oral and parenteral glucocorticoids have been used in the management of severe respiratory symptoms in coronavirus-infected patients in the past. However, there remains no definitive evidence in the literature for or against the utilization of systemic glucocorticoids in seriously ill patients with coronavirus-related severe respiratory disease, or indeed in other types of severe respiratory disease. In this study, we hope to discover evidence either supporting or opposing the systemic therapeutic administration of glucocorticoids in severe coronavirus disease 2019 (COVID-19) patients.@*Trial registration@#ClinicalTrials.gov, ChiCTR2000029386, http://www.chictr.org.cn/showproj.aspx?proj=48777.

Asymptomatic cryptococcal antigenemia in HIV-infected patients: a review of recent studies / 中华医学杂志(英文版)

The prevalence of asymptomatic cryptococcal antigenemia (ACA) in human immunodeficiency virus (HIV) infected individuals has been observed to be elevated. The prevalence of ACA ranges from 1.3% to 13%, with different rates of prevalence in various regions of the world. We reviewed studies conducted internationally, and also referred to two established expert consensus guideline documents published in China, and we have concluded that Chinese HIV-infected patients should undergo cryptococcal antigen screening when CD4 T-cell counts fall below 200 cells/μL and that the recommended treatment regimen for these patients follow current World Health Organization guidelines, although it is likely that this recommendation may change in the future. Early screening and optimized preemptive treatment for ACA is likely to help decrease the incidence of cryptococcosis, and is lifesaving. Further studies are warranted to explore issues related to the optimal management of ACA.

Clinical Study on TCM Foot bath in Adjuvant Treatment for Type 2 Diabetes Lower-extremity Peripheral Arterial Disease / 中国中医药信息杂志

Objective To observe the clinical efficacy of TCM foot bath in adjuvant treatment for early diabetic lower-extremity peripheral arterial disease (LEPAD). Methods Totally 90 cases with early diabetic LEPAD were divided into treatment group and control group by random number table method, with 45 cases in each group. Control group was given routine treatment, including health education, diet control, proper exercise, control of blood sugar, blood pressure and blood lipids, nutritional nerves, dilation of blood vessels. On the basis of control group, the treatment group was given TCM foot bath, soaking the lower limbs for 30 minutes each time, once a day, for 12 weeks. The clinical efficacy of the two groups was evaluated. The TCM syndrome score, maximum painless walking distance, temperature of the toe skin, diameter of the lower extremity arterial blood vessels, lower extremity arterial blood flow, ankle brachial index (ABI), blood pressure (BP), FBG, HbA1c, serum adiponectin, IL-6 and TNF-α were detected. The blood routine, liver and kidney function were detected and adverse reactions were recorded. Results The total effective rate was 82.22% (37/45) in the treatment group and 68.89% (31/45) in the control group. The treatment group was significantly better than the control group (Z=-2.099, P=0.036). Compared with before treatment, the levels of TCM syndromes, BP, FBG, HbA1c, serum IL-6 and TNF-α were significantly lower in both groups after treatment (P<0.05); serum adiponectin level increased after treatment (P<0.05); the maximum painless walking distance, the temperature of the toe skin, the diameter of the lower extremity arterial blood vessels, the lower extremity arterial blood flow and ABI were significantly improved. Compared with the control group, the scores of TCM syndromes in the treatment group were significantly lower (P<0.05); the levels of IL-6 and TNF-α in the treatment group were significantly lower than those in the control group (P<0.05); the maximum painless walking distance, the temperature of the toe skin, the diameter of the lower extremity arterial vessels, the lower extremity arterial blood flow and ABI, serum adiponectin level in the treatment group were significantly higher than those of the control group (P<0.05). Conclusion TCM foot bath in adjuvant treatment for early diabetic LEPAD is with obvious efficacy, and the mechanism may be related to improving the level of serum inflammatory cytokines to inhibit the inflammatory injury of blood vessels.

Human umbilical cord blood-derived mononuclear cells repopulate injured mouse liver / 生物工程学报

<p><b>AIM</b>To repopulate the liver of mice with acute liver injury and to make mouse models with chimeric liver by using human umbilical cord blood (hUCB)-derived mononuclear cells.</p><p><b>METHODS</b>Fifteen acute liver injury mouse models were induced by carbon tetrachloride intraperitoneal injection followed by two-thirds hepatectomy and all mice were divided into three groups: cell transplantation group (n = 7), negative control group (n = 3) and blank control group (n = 5). HUCB cell preparations were transplanted into mouse spleens of cell transplantation group and phosphate bufferd saline (PBS) was injected into spleens of negative controls. Neither cell suspension nor PBS was given to the blank controls. Pathological changes were observed 7, 14 and 21 days after cell transplantation. Human albumin (ALB) and cytokeratin 19 (CK19) were also detected in the mouse sera and liver tissues.</p><p><b>RESULTS</b>All mice showed histological features of acute liver injury. Positive expression of human ALB and CK19 were observed in liver tissues of cell transplantation group 7, 14 and 21 days after cell transplantation. Human ALB could be detected from the sera and liver homogenates of cell-transplanted mice. No positive expression of human ALB and CK19 were observed in liver tissues and no human ALB was detected in sera of negative control group.</p><p><b>CONCLUSIONS</b>HUCB-derived mononuclear cells can differentiate into functional human hepatocytes and biliary cells in large quantity in mouse models with acute liver injury, thus a great progress were made in establishing mouse models with chimeric liver.</p>

A double-blind, randomized, lamivudine-controlled clinical trial of DAIDING (adefovir dipivoxil) for lamivudine-resistant patients with chronic hepatitis B / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To investigate the efficacy and safety of adefovir dipivoxil (ADV, DAIDING) for Chinese chronic hepatitis B patients with lamivudine (LAM) resistance.</p><p><b>METHODS</b>This study was a multicenter, double-blind clinical trial. 209 chronic hepatitis B patients with LAM resistance were randomly put in an ADV, DAIDING or a LAM group. After 24 and 48-weeks of treatment, serum HBV DNA levels were measured by quantitative PCR and liver function tests; HBV serology and safety assessments were also conducted.</p><p><b>RESULTS</b>The mean reduction of HBV DNA from baseline at 24 and 48 weeks was significantly greater in the ADV group compared with that in the LAM group (2.40 log10 vs 0.94 log10, P < 0.01; 2.71 log10 vs 1.07 log10, P < 0.01). In the ADV group, the virological response and ALT normalization at 24 and 48 weeks were significantly higher than those in the LAM group. There was no significant difference between the two groups in the portion of HBeAg reduction, HBeAg seroconversion and incidence of adverse events. There was no severe adverse event related to the investigational product, DAIDING, in this trial.</p><p><b>CONCLUSION</b>DAIDING (ADV) is effective and safe for the treatment of chronic hepatitis B patients with LAM resistance.</p>

Lemological Teaching must be Reformed to Accommodate New Situations / 中华医学教育探索杂志

The following measures have been taken with improved teaching effects in our recent practice of lemological teaching Firstly,we adjusted our teaching scope from classical communicable diseases to infectious diseases and brought the newest progress into our contents.Secondly,we adopted rich and colorful teaching methods to boost the students' learning interest.Thirdly,the students' clinical capabilities have been emphasized in our lemological examination.And lastly,multimedia has been employed to display our contents more actively.

Isolation, culture and intraspleenic transplantation of rat hepatic oval cells / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To observe the evolution and differentiation of hepatic oval cells after transplanted into the spleens of homogenous rats, providing experimental data for treating hepatic failure with hepatic stem cells.</p><p><b>METHODS</b>A two-step perfusion procedure was used to separate hepatic parenchymal cells from nonparenchymal cells. Then the suspension of nonparenchymal cells was centrifuged in Percoll gradients. The isolated cells were cultured, identified, and then transplanted into the spleens of homogenous rats undergone 2/3 hepatectomy.</p><p><b>RESULTS</b>The obtained cells were various in size with ovoid nuclei and inadequate cytoplasm. After 12 hours' culture, they revealed the characteristics of epithelial cells. Both the freshly isolated and cultured cells showed positive staining for cytokeratin 19 (CK19), OV6, alpha fetal protein (AFP), but negative for leucocyte common antigen (LCA). After intraspleenic transplantation into homogenous rats undergone partial hepatectomy, hepatic oval cells were differentiated into liver tissue-like structure including hepatocyte cords and bile ducts, and formed hepaticized spleen. But this kind of structure was not observed in the controls.</p><p><b>CONCLUSION</b>The isolated rat hepatic oval cells show the biological characteristics of hepatic stem cells and can differentiate into hepatocytes and biliary epithelial cells under appropriate circumstances.</p>