Effects of Lianhuaqingwen Capsules in adults with mild-to-moderate coronavirus disease 2019: an international, multicenter, double-blind, randomized controlled trial.

BACKGROUND: In a randomized trial, Lianhuaqingwen (LHQW) capsule was effective for accelerating symptom recovery among patients with coronavirus disease 2019 (COVID-19). However, the lack of blinding and limited sample sizes decreased the level of clinical evidence. OBJECTIVES: To evaluate the efficacy and safety of LHQW capsule in adults with mild-to-moderate COVID-19. METHODS: We conducted a double-blind randomized controlled trial in adults with mild-to-moderate COVID-19 (17 sites from China, Thailand, Philippine and Vietnam). Patients received standard-of-care alone or plus LHQW capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the median time to sustained clinical improvement or resolution of nine major symptoms. RESULTS: The full-analysis set consisted of 410 patients in LHQW capsules and 405 in placebo group. LHQW significantly shortened the primary endpoint in the full-analysis set (4.0 vs. 6.7 days, hazards ratio: 1.63, 95% confidence interval: 1.39-1.90). LHQW capsules shortened the median time to sustained clinical improvement or resolution of stuffy or runny nose (2.8 vs. 3.7 days), sore throat (2.0 vs. 2.6 days), cough (3.2 vs. 4.9 days), feeling hot or feverish (1.0 vs. 1.3 days), low energy or tiredness (1.3 vs. 1.9 days), and myalgia (1.5 vs. 2.0 days). The duration to sustained clinical improvement or resolution of shortness of breath, headache, and chills or shivering did not differ significantly between the two groups. Safety was comparable between the two groups. No serious adverse events were reported. INTERPRETATION: LHQW capsules promote recovery of mild-to-moderate COVID-19 via accelerating symptom resolution and were well tolerated. Trial registration ChiCTR2200056727 .

Clinical findings in 111 cases of influenza A (H7N9) virus infection.

BACKGROUND: During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. METHODS: Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. RESULTS: Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). CONCLUSIONS: During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).

[Highlights of the third edition of Chinese guidelines for AIDS diagnosis and treatment(2015)].

The third edition of Chinese guidelines for AIDS diagnosis and treatment was launched in 2015 by AIDS Professional Group, Society of Infectious Diseases, Chinese Medical Association. New edition emphasizes the importance of timely initiation of anti-retroviral therapy(ART). Like other guidelines, this edition recommends that once the HIV infection is confirmed, the ART should be initiated timely. For patients with HIV and opportunistic infections, once the infections are under control, the ART should be initiated without delay. For AIDS patients complicated with tuberculosis whose CD4 cell counts are less than 200/µL, the ART should start within 2 weeks after the initiation of anti-tuberculosis treatment. In this guideline, the drugs with severe toxicities and poor tolerance are excluded, and new drugs are added such as rilpivrine (RPV) and atazanavir (ATV) because of less toxicity and higher HIV depression effect; and 3TC+TDF+EFV is recommended as the first line regimen. As for children with HIV infection, especially for those less than 5 years, once the infection is confirmed the ART should be initiated immediately. For the prevention of HIV mother to children transmission, new edition recommends that HIV-infected pregnant women start ART early and keep on ART all their lives.

[Proteomic study on effect of tangcao pill on microsome CYP450].

Tangcao pill is commonly applied in adjuvant and even alternative therapy for patients with AIDS. However, the herb contains complex ingredients, but with unknown effect against anti-HIV drug and unknown function. Because CYP450 emzyme is the main metabolic enzymes of the drug, it is of important significance to study the regulation of CYP450 enzymes before and after the combined administration of Tangcao pill and EFV. Proteomics, due to its high throughout and high sensitivity, has been widely applied in CYP450 enzyme study. In this paper, liver microsomes were separated through differential centrifugation. Their proteins were separated through SDS-PAGE. The three protein bands that CYP450 enzymes were located were cut and identified by liquid chromatography tandem mass spectrometry. Totally 16 CYP450 isoenzymes were identified. Furthermore, in order to make a quantitative analysis on the effect of tang herb on CYP450 emzyme, the multiple reaction monitoring (MRM) technology based on MS was adopted. The CYP2C11 was selected based on the results of the mass spectrum identification of proteins. The characteristic polypeptides were obtained through searching Expasy blast database. The m/z of the fragment ions was less than 800. In the paper, the m/z of ion pairs of CYP2C11 were 711.5/232.1, 711.5/319.2, 711.5/466.2 and 711.5/595.3, and the m/z of ESAT-6 (internal standard, IS) were 735.5/215.3, 735.5/389.3, 735.5/460.3 and 735.5/524.3. The relative peak (analyte/IS) area was adopted for the relative quantitative analysis. Compared with the EFV single administration group, the EFV and Tangcao pill combined administration group showed a 1.6-fold increase in CYP2C11. The results of the paper indicated that Tangcao pill may affect drug metabolism by regulating metabolic enzymes such as CYP2C11, but the specific mechanism still unknown.

Chinese herbal medicine Shufeng Jiedu capsule for mild to moderate COVID-19: a multicenter, randomized, double-blind, placebo-controlled phase II trial.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection. Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up. Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported. Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19. Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

[Epidemiological and clinical features of occult hepatitis B in HIV infection without antiretroviral treatment].

OBJECTIVE: To investigate and analyze the differential prevalence, as well as the risk factors and clinical features, of occult hepatitis B virus (HBV) infection in the human immunodeficiency virus (HIV)-infected population without antiretroviral therapy (ART) as compared to the general (non-HIV-infected) population. METHODS: Two-hundred-and-forty-eight individuals with confirmed HIV infection but ART naive (males: 220, females: 28; 15-82 years old) were enrolled in the study, along with 121 healthy individuals (confirmed HIV antibody-negative; males: 53, females: 68; 20-88 years old). HBV markers (hepatitis B surface antigen (HBsAg); hepatitis B e antigen (HBeAg); anti-HBs, anti-HBe and anti-hepatitis B core (HBc) antibodies) were detected by microparticle enzyme-linked immunosorbent assay (AxSYM immunology analyzer manufactured by Abbott Laboratories); all cases and controls were confirmed negative for hepatitis B surface antigen (HBsAg). Then, the HBV DNA level in serum was detected using nucleic acid amplification assay (COBAS AmpliPrep/COBAS TaqMan HBV test, version 2.0 manufactured by Roche). CD4+ T lymphocytes were measured by flow cytometry, and alanine aminotransferase (ALT, marker of liver function) was measured by enzymatic assay. RESULTS: Twenty-four of the HIV cases (9.7%) and four of the healthy controls (3.3%) tested positive for HBV DNA; the amount of individuals with HBV DNA-positivity was significantly higher in the HIV-infected group (P = 0.035). Among the 24 cases of HBV DNA(+) HIV-infected individuals, the lowest HBV DNA load was < 20 IU/ml and the highest was 3.22 x 10s IU/ml; nine of the individuals (37.5%) had HBV DNA load > 100 IU/ml, four (16.7%) had 20-99 IU/ ml, and 11 (45.8%) had < 20 IU/ml. Among the total HIV-infected cases with HBV DNA-positivity, 7.3% (8/110) were anti-HBc(+)/anti-HBs(+), 20.8% (11/53) were anti-HBc(+)/anti-HBs(-), 14.3% (3/21) were anti-HBc(-)/anti-HBs(+), and 3.1% (2/64) were anti-HBc(-)/anti-HBs(-). The amount of individuals with HBV DNA-positivity in the anti-HBc(+)/anti-HBs(-) group was significantly different from those in the anti-HBc(+)/anti-HBs(+) group (P = 0.018) and the anti-HBc(-)/anti-HBs(-) group (P = 0.003). However, multiple comparison of HBV DNA loads detected between the four groups of HBV marker status revealed no significant difference (P = 0.805). Furthermore, statistical analysis provided no evidence to support that occult hepatitis B infection in HIV-infected individuals had any impact on CD4+ T lymphocytes count (Z = 1.902, P = 0.059) or ALT levels (Z =1.401, P = 0.161). CONCLUSION: HIV-infected individuals who are ART naive and HBsAg(-) have a higher incidence of HBV DNA-positivity than individuals in the general (non-HIV-infected) population. In addition, the highest rate of occult hepatitis B among the HIV-infected cases occurred among individuals who were anti-HBc(+)/anti-HBs(-).

Does every Staphylococcus aureus infection require anti-MRSA drugs? Three case reports of a Staphylococcus aureus infection.

Staphylococcus aureus is a common clinical pathogen. Does every S. aureus infection require anti-MRSA drugs? Reported here are three cases of a community-acquired infection with S. aureus. The first case involveds a 45-year-old male who was admitted due to right ankle pain for 1 month; he was diagnosed with chronic suppurative osteomyelitis and an acute soft tissue infection of the ankle. S.aureus was cultured from the pus and was resistant to penicillin and sensitive to oxacillin and vancomycin. After receiving oxacillin, he was cured and discharged 45 days after admission. The second case involved a 44-year-old male who was admitted due to lumbar pain with right lower limb numbness for more than 1 month and fever for 1 day. S. aureus was cultured from blood specimens and was resistant to penicillin and sensitive to oxacillin and vancomycin. After receiving oxacillin, he as cured. The third case involved a 7-day-old newborn who was admitted due to skin jaundice for 6 days. S. aureus was cultured from skin secretions specimens and was resistant to penicillin and sensitive to oxacillin, erythromycin, and vancomycin. The newborn was treated with oxacillin for 4 days, and she was cured and discharged. Not all cases a suspected S. aureus infection require anti-MRSA drugs; instead, previous S. aureus susceptibility results in the area and hospital, as well as the patient's clinical profile, need to be taken into account.

Deep learning-based lung sound analysis for intelligent stethoscope.

Auscultation is crucial for the diagnosis of respiratory system diseases. However, traditional stethoscopes have inherent limitations, such as inter-listener variability and subjectivity, and they cannot record respiratory sounds for offline/retrospective diagnosis or remote prescriptions in telemedicine. The emergence of digital stethoscopes has overcome these limitations by allowing physicians to store and share respiratory sounds for consultation and education. On this basis, machine learning, particularly deep learning, enables the fully-automatic analysis of lung sounds that may pave the way for intelligent stethoscopes. This review thus aims to provide a comprehensive overview of deep learning algorithms used for lung sound analysis to emphasize the significance of artificial intelligence (AI) in this field. We focus on each component of deep learning-based lung sound analysis systems, including the task categories, public datasets, denoising methods, and, most importantly, existing deep learning methods, i.e., the state-of-the-art approaches to convert lung sounds into two-dimensional (2D) spectrograms and use convolutional neural networks for the end-to-end recognition of respiratory diseases or abnormal lung sounds. Additionally, this review highlights current challenges in this field, including the variety of devices, noise sensitivity, and poor interpretability of deep models. To address the poor reproducibility and variety of deep learning in this field, this review also provides a scalable and flexible open-source framework that aims to standardize the algorithmic workflow and provide a solid basis for replication and future extension: https://github.com/contactless-healthcare/Deep-Learning-for-Lung-Sound-Analysis .

Efficacy and safety of Lianhua Qingwen capsules combined with standard of care in the treatment of adult patients with mild to moderate COVID-19 (FLOSAN): protocol for a randomized, double-blind, international multicenter clinical trial.

Background: Effective anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) drugs are not only the next defense after vaccines but also the key part of establishing a multi-tiered coronavirus disease 2019 (COVID-19) prevention and control system. Previous studies had indicated that Lianhua Qingwen (LHQW) capsules could be an efficacious Chinese patent drug for treating mild to moderate COVID-19. However, pharmacoeconomic evaluations are lacking, and few trials have been conducted in other countries or regions to evaluate the efficacy and safety of LHQW treatment. So, this study aims to explore the clinical efficacy, safety, and economy of LHQW for treating adult patients with mild to moderate COVID-19. Methods: This is a randomized, double-blind, placebo-controlled, international multicenter clinical trial protocol. A total of 860 eligible subjects are randomized at a 1:1 ratio into the LHQW or placebo group to receive two-week treatment and follow-up visits on days 0, 3, 7, 10, and 14. Clinical symptoms, patient compliance, adverse effects, cost scale, and other indicators are recorded. The primary outcomes will be the measured median time to sustained improvement or resolution of the nine major symptoms during the 14-day observation period. Secondary outcomes regarding clinical efficacy will be evaluated in detail on the basis of clinical symptoms (especially body temperature, gastrointestinal symptoms, smell loss, and taste loss), viral nucleic acid, imaging (CT/chest X-ray), the incidence of severe/critical illness, mortality, and inflammatory factors. Moreover, we will assess health care cost, health utility, and incremental cost-effectiveness ratio (ICER) for economic evaluation. Discussion: This is the first international multicenter randomized controlled trial (RCT) of Chinese patent medicine for the treatment of early COVID-19 in accordance with WHO guidelines on COVID-19 management. This study will help clarify the potential efficacy and cost-effectiveness of LHQW in the treatment of mild to moderate COVID-19, facilitating decision-making by healthcare workers. Registration: This study is registered at the Chinese Clinical Trial Registry, with registration number: ChiCTR2200056727 (date of first registration: 11/02/2022).

Clinical features of the initial cases of 2009 pandemic influenza A (H1N1) virus infection in China.

BACKGROUND: The first case of 2009 pandemic influenza A (H1N1) virus infection in China was documented on May 10. Subsequently, persons with suspected cases of infection and contacts of those with suspected infection were tested. Persons in whom infection was confirmed were hospitalized and quarantined, and some of them were closely observed for the purpose of investigating the nature and duration of the disease. METHODS: During May and June 2009, we observed 426 persons infected with the 2009 pandemic influenza A (H1N1) virus who were quarantined in 61 hospitals in 20 provinces. Real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) testing was used to confirm infection, the clinical features of the disease were closely monitored, and 254 patients were treated with oseltamivir within 48 hours after the onset of disease. RESULTS: The mean age of the 426 patients was 23.4 years, and 53.8% were male. The diagnosis was made at ports of entry (in 32.9% of the patients), during quarantine (20.2%), and in the hospital (46.9%). The median incubation period of the virus was 2 days (range, 1 to 7). The most common symptoms were fever (in 67.4% of the patients) and cough (69.5%). The incidence of diarrhea was 2.8%, and the incidence of nausea and vomiting was 1.9%. Lymphopenia, which was common in both adults (68.1%) and children (92.3%), typically occurred on day 2 (range, 1 to 3) and resolved by day 7 (range, 6 to 9). Hypokalemia was observed in 25.4% of the patients. Duration of fever was typically 3 days (range, 1 to 11). The median length of time during which patients had positive real-time RT-PCR test results was 6 days (range, 1 to 17). Independent risk factors for prolonged real-time RT-PCR positivity included an age of less than 14 years, male sex, and a delay from the onset of symptoms to treatment with oseltamivir of more than 48 hours. CONCLUSIONS: Surveillance of the 2009 H1N1 virus in China shows that the majority of those infected have a mild illness. The typical period during which the virus can be detected with the use of real-time RT-PCR is 6 days (whether or not fever is present). The duration of infection may be shortened if oseltamivir is administered.

Brain abscess due to Aggregatibacter aphrophilus in association with atrial septal defect：Case report and literature review.

BACKGROUND: Aggregatibacter aphrophilus（A. aphrophilus）is one of the organisms of the HACEK group. Previously reported cases of brain abscesses caused by A. aphrophilus infection have occurred in children with a basis for congenital heart disease, or in adults with a basis for dental disease. Rare cases of brain abscess caused by A. aphrophilus have been reported in adults with congenital heart disease or in patients without dental disease history. Herein we present a rare case of brain abscess caused by A. aphrophilus, who was in association with atrial septal defect for more than 20 years, and had no dental disease and did not develop infective endocarditis. CASE PRESENTATION: A 51-year-old female was admitted due to progressively worsening headache and left limb weakness for more than 10 days. She denied the history of chronic diseases such as hypertension and diabetes, and no periodontal disease. While she had a history of atrial septal defect, a form of congenital heart disease with severe pulmonary hypertension for more than 20 years. After admission, echocardiographic illustrated congenital heart disease with severe pulmonary hypertension. CT and MRI showed brain abscess. Cerebrospinal fluid (CSF) results also confirmed the presence of intracranial infection. Empirical therapy with vancomycin 1.0 g i.v q12h and meropenem 2.0 g i.v q8h was initiated from the day of admission. On the fourth day after admission, brain abscess resection and decompressive craniectomy were performed, and the pus drained on operation were cultured and Gram-negative bacilli grew, which was identified as A.aphrophilus. Vancomycin was discontinued and meropenem was continued（2.0 g i.v q8h）for 5 weeks, followed by oral levofloxacin 0.5 qd for 4 weeks of out-patient antibiotics. The patient recovered fully within 9 weeks of treatment. CONCLUSIONS: This is the first case of A. aphrophilus to cause brain abscess in adult with a history of congenital heart disease for more than 20 years, who had no dental disease and did not develop infective endocarditis. We also highlight the value of bacterial 16 S rDNA PCR amplification and sequencing in identifying bacteria in abscesses which are culture-negative, and prompt surgical treatment，choosing effective antibiotics and appropriate course of treatment will get better clinical effect.

[Markers of endothelial injury and plasma adipocytokine in antiretroviral-naive HIV patients].

OBJECTIVES: To investigate the markers of endothelial injury, adipocytokine and thrombotic activity and explore whether there are cardiovascular disease risk factors in antiretroviral-naive HIV patients. METHODS: Clinical data and venous blood samples were collected from 43 anti-retroviral naive HIV-infected patients during February-October 2009 in our center, and compared with 17 healthy subjects. Plasma leptin, adiponectin, soluble intercellular adhesion molecule-1 (sICAM-1), D-dimer were measured by ELISA. Four markers and cholesterol, triglyceride, fasting plasma glucose were compared between the two groups. The CD(4)(+)T cells and percentages of CD(38), HLA-DR on CD(8)(+)T were determined by flow cytometry and plasma HIV copies were detected with bDNA analyzer among HIV-infected participants. Spearman correlations between the significant markers and CD(4)(+) T cells, CD(8)(+) CD(38)(+)/CD(8)(+), CD(8)(+) HLA-DR(+)/CD(8)(+), HIV viral load were examined among HIV-infected participants. Analyses were conducted by using Stata version 7. RESULTS: Thirty-eight of the 43 patients were sexually infected by HIV and the median absolute CD(4)(+)T cell count was (133 ± 82) cells/µl, HIV RNA was (4.42 ± 0.66) lg copies/ml. HIV-infected patients, compared with healthy subjects, had lower leptin [11.41(7.91, 14.53) µg/L vs 55.31 (16.49, 229.65) µg/L, P = 0.0005], adiponectin [1.79 (1.40, 4.00) mg/L vs 3.36 (2.92, 4.18) mg/L, P = 0.003] and higher sICAM-1 [1.71(1.11, 2.40) mg/L vs 0.69 (0.57, 0.80) mg/L, P = 0.0000]. No significant differences exist in cholesterol, triglyceride, fasting plasma glucose. For HIV-infected participants, sICAM-1 tended to correlate with CD(8)(+)CD(38)(+)/CD(8)(+) and HIV viral load (r = 0.3378, P = 0.0267; r = 0.3904, P = 0.0096). CONCLUSION: Patients with untreated HIV infection have lower leptin, adiponectin and higher sICAM-1 levels and the relationship of these markers to HIV-mediated atherosclerotic risk requires further study.

Early predicting indicators of conversion from mild to moderate in overseas-imported COVID-19 cases.

BACKGROUND: Due to the ongoing pandemic of coronavirus disease 2019 (COVID-19) in foreign countries and regions, many overseas people arrive in China by air. Currently, most of the new cases of COVID-19 were imported from overseas. Here, we evaluated the predictive effect of the level of blood albumin (ALB) and serum prealbumin (PA) level in overseas-imported cases on the conversion of mild COVID-19 to moderate and its value in guiding nutritional support for these travelers. METHODS: We retrospectively analyzed serum levels of ALB and PA of 193 patients with imported COVID-19 admitted to the Shanghai Public Health Clinical Center at the time of admission on April 8, 2020. RESULTS: Since the first overseas-imported case was admitted to Shanghai on March 5, 2020, 195 overseas-imported cases have been treated in the Shanghai Public Health Clinical Center. The disease was mild or moderate. A total of 193 patients (111 males and 82 females) entered our analysis and the disease was moderate in 108 patients and mild in 85 patients. Patients were aged 6 to 66 years (mean: 28 years). There was a strong negative correlation between the proportion of moderate type and ALB (P=0.0073); thus, patients with a lower level of ALB were more likely to be diagnosed with moderate type. The correlation coefficient was close to 0 in the scatter plot, indicating that there was no linear correlation between PA and the diagnosis of moderate type (P>0.05). There was a strong negative correlation between age and ALB level (P<0.001), while length of hospital stay did not show a linear correlation with ALB or PB levels (both P>0.05). Therefore, older patients had lower levels of ALB and were more likely to develop moderate COVID-19. CONCLUSIONS: The serum ALB level can be an early predictive indicator for the conversion of mild COVID-19 to moderate in cases imported overseas and may guide nutritional support.

Effect of albumin and CYP2B6 polymorphisms on exposure of efavirenz: A population pharmacokinetic analysis in Chinese HIV-infected adults.

BACKGROUND: Efavirenz is a vital component used to treat HIV-1 infection. Nevertheless, it shows large between-subject variability, which affects both its therapeutic response and adverse effects. OBJECTIVE: To investigate the impact of gene polymorphisms and non-genetic factors on the variability of efavirenz pharmacokinetics and to propose the optimal dose regimens. METHODS: A total of 769 plasma samples from 376 HIV-infected Han Chinese outpatients were collected to develop a population pharmacokinetic model using NONMEM software. The impact of patient demographics, laboratory tests, concomitant medication, and genetic polymorphisms of CYP2B6 and ABCB1 on efavirenz pharmacokinetics were explored. According to the final model, the model-informed dose optimization was conducted. RESULTS: The pharmacokinetics of efavirenz was characterized by a one-compartment model with first-order absorption and elimination. The typical values of the estimated apparent oral clearance, volume of distribution, and absorption rate constant in the final model were 9.44 L/h, 200 L, and 0.727 h - 1, respectively. Efavirenz clearance was significantly influenced by CYP2B6 variants, including rs2099361, rs3745274, and rs2279343, along with albumin and weight. The volume of distribution was affected by albumin and weight. Based on the CYP2B6 polymorphisms of patients, the recommended daily doses of efavirenz were 100 mg for CYP2B6 slow metabolizers, 400 or 600 mg for intermediate metabolizers, and 800 or 1000 mg for extensive metabolizers. CONCLUSIONS: Polymorphisms of CYP2B6, along with albumin and weight, resulted as the predictors of efavirenz pharmacokinetic variability, which could be used in prescribing optimal efavirenz doses.

Dynamic anti-spike protein antibody profiles in COVID-19 patients.

OBJECTIVES: This study intended to investigate the dynamics of anti-spike (S) IgG and IgM antibodies in COVID-19 patients. METHODS: Anti-S IgG/IgM was determined by a semi-quantitative fluorescence immunoassay in the plasma of COVID-19 patients at the manifestation and rehabilitation stages. The immunoreactivity to full-length S proteins, C-terminal domain (CTD), and N-terminal domain (NTD) of S1 fragments were determined by an ELISA assay. Clinical properties at admission and discharge were collected simultaneously. RESULTS: The positive rates of anti-S IgG/IgM in COVID-19 patients were elevated after rehabilitation compared to the in-patients. Anti-S IgG and IgM were not apparent until day 14 and day ten, respectively, according to Simple Moving Average analysis with five days' slide window deduction. More than 90% of the rehabilitation patients exhibited IgG and IgM responses targeting CTD-S1 fragments. Decreased total peripheral lymphocytes, CD4+ and CD8+ T cell counts were seen in COVID-19 patients at admission and recovered after the rehabilitation. CONCLUSIONS: Anti-S IgG and IgM do not appear at the onset with the decrease in T cells, making early serological screening less significant. However, the presence of high IgG and IgM to S1-CTD in the recovered patients highlights humoral responses after SARS-CoV-2 infection, which might be associated with efficient immune protection in COVID-19 patients.

[Molecular mechanisms of fluconazole resistance in clinical isolates of Candida glabrata].

OBJECTIVE: To determine if changes in the levels of expression of ERG11, CDR1 and CDR2 genes could be associated with resistance phenotype in clinical isolates of Candida glabrata (C. glabrata). METHODS: We used quantitative RT-PCR analysis to evaluate the expression of the ERG11, CDR1 and CDR2 genes in clinical isolates including 9 fluconazole-resistant, 9 fluconazole-susceptible dose dependent (S-DD) and 10 fluconazole-sensitive C. glabrata isolates. RESULTS: In the fluconazole-resistant isolates, the S-DD isolates and the fluconazole-sensitive isolates, the levels of expression of ERG11 gene were 121.4 +/- 96.8, 102.9 +/- 78.8, 51.2 +/- 20.7, respectively; the levels of expression of CDR1 gene were 3.1 +/- 1.4, 1.9 +/- 0.7, 1.1 +/- 0.4, respectively; the levels of expression of CDR2 gene were 3.7 +/- 2.2, 3.4 +/- 2.4, 1.9 +/- 0.9, respectively. Quantitative RT-PCR analyses revealed that the fluconazole-resistant isolates expressed ERG11 at higher levels than fluconazole-sensitive isolates (P = 0.041). CDR1 expression was significantly higher in the fluconazole-resistant isolates as compared with that in the fluconazole-sensitive isolates (P < 0.001) and the expression was also significantly higher in the S-DD isolates as compared with that in the fluconazole-sensitive isolates (P = 0.009). CDR2 upregulation was observed in the fluconazole-resistant isolates as compared with the susceptible isolates (P = 0.018). With the decrease of susceptibility to fluconazole, the levels of expression of ERG11, CDR1 and CDR2 genes in the isolates appeared to be increased. CONCLUSIONS: These results provide evidence that the overexpression of ERG11, CDR1 and CDR2 genes is associated with the increase of fluconazole resistance in clinical isolates of C. glabrata. ERG11, CDR1 and CDR2 upregulation is a major molecular mechanism of fluconazole resistance in clinical isolates of C. glabrata.

[LC-MS/MS method for simultaneous quantification of lopinavir and ritonavir in human plasma].

A liquid chromatographic-tandem mass spectrometric (LC-MS/MS) method was developed for the determination of lopinavir and ritonavir in human plasma. Analytes were separated from plasma by a combination of alkalinized protein precipitation and liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Agilent ZORBAX Eclipse XDB-C18 column with the mobile phase consisted of methanol-0.1% formic acid in water (80:20). A tandem mass spectrometer equipped with electrospray ionization source was used as detector and operated in the positive ion mode. Quantification was performed using multiple reaction monitoring (MRM) of the transitions m/z 629.6 --> 155.2, m/z 721.4 --> 268.2, and m/z 515.2 --> 276.2 for lopinavir, ritonavir and telmisartan (internal standard), respectively. The method showed a good linearity in a concentration range of 62.5 - 10000 ng mL(-1) for lopinavir, and 12.5 - 2000 ng mL(-1) for ritonavir. The lower limits of quantification were 15 pg mL(-1) and 8 pg mL(-1) for lopinavir and ritonavir, respectively. The intra- and inter-day precision was less than 15% and the absolute recovery was above 75%. This method was selective and rapid, sensitive for investigating blood drug concentrations in clinics.

[Rhodococcus equi pneumonia among patients with AIDS clinical features and treatment].

OBJECTIVE: To summarize the characteristics of clinical manifestation, chest radiology and microbiology of Rhodococcus equi pneumonia among patients with AIDS. METHODS: Total 1908 AIDS patients who have therapy in Longtan hospital of Guang Xi province since May 2007 to Nov 2009, 15 patients (0.79%) who were co-infected with Rhodococcus equi, and average age was 35 +/- 13 years, we retrospectively reviewed clinical manifestations, chest radiology and microbiology of nine HIV-infected patients complicated with Rhodococcus equi pneumonia. RESULTS: 14 patients presented with pneumonia or lung abscess, the clinical manifestations included fever (100%), cough and expectoration (93.3%), bellyache (26.7%), etc. And 5 patients Hb lower than 60 g/L, CD(4)(+)T cell count was between (1 - 51) x 10(6)/L, average was (20 +/- 16) x 10(6)/L, Patients presented with consolidation of lung. X-ray, or CT of lung showed large patchy consolidation image, inanition, atelectasis in the lung. Rhodococcus equi could be cultured from sputum, blood, tissue obtained through lung puncture, broncho-alveolar lavage fluid, etc. Though susceptible antibiotics were used, the focus in the lung was absorbed slowly, All of 15 patients begin with HAART, after 33 day to 2 years follow up 4 patients die and alive patients have perfect immune-rebuilt. CONCLUSIONS: Rhodococcus equi infection, an unusual disease, can be seen in AIDS patients and can be cured only with long-term effective antibiotic.

[Clinical features and prognosis of the mild cases of pandemic influenza H1N1 virus infection].

OBJECTIVE: Analyze the clinical characteristics of the mild cases of pandemic influenza H1N1 virus infection, as well as the relationship of clinical characteristics and patient genders. METHODS: A total of 245 influenza A (H1N1) patients confirmed by viral nucleic acid detection were included in the study. The patients' personal information, signs and symptoms, lab and iconography data, disease course, negative seroconversion duration of new influenza A (H1N1) viral nucleic acid after antiviral treatment and hospitalization stay were analyzed. Measurement data were analyzed using one-way analysis of variance (ANOVA) by software SPSS 11.5. P < 0.05 was defined as statistically significant. RESULTS: (1) Among the 245 patients, 130 were males and 115 were females, yielding a sex ratio of 1.13:1. Almost 52.0% (127/245) of the patients came from Australia, and 64.5% (158/245) were between 18 and 40 years old. (2) Clinical manifestations included fever (98.4%, 241/245), cough (80.8%, 198/245) and throat congestion (95.9%, 235/245), and lab findings were characterized by elevated C-reaction protein (CRP, 71.0%, 174/245) and neutrophil (52.2%, 128/245). (3) Female patients had significantly lower serum Prealbumin (pre-A) levels than male patients [(245.04 ± 75.3) vs (273.34 ± 92.18) mg/L, F = 5.55, P = 0.019]. (4) The patients' serum CRF levels significantly decreased after the treatment [(4.06 ± 3.47) vs (14.54 ± 14.68) mg/L, F = 6.18, P = 0.016], while the levels of CD3, CD4 and CD8 were significantly increased after treatment [(1451.23 ± 443.97) vs (819.97 ± 375.75) cell/µl, F = 32.61, P = 0.000; (771.33 ± 251.92) vs (435.36 ± 215.35) cell/µl, F = 44.43, P = 0.000; (593.16 ± 237.19) vs (342.47 ± 180.12) cell/µl, F = 28.518, P = 0.000, respectively]. (5) Approximately 30.6% (75/245) of the patients had abnormal signs on chest CT iconography, and 22.0% (54/245) had obvious signs indicating pneumonia. The average disease course was (3.9 ± 1.2) days, the average hospitalization stay was (5.0 ± 1.4) days, and the negative seroconversion duration of the mRNA after antiviral treatment was (3.8 ± 1.4) days. CONCLUSION: The influenza A (H1N1) virus was characterized by fever, cough and throat congestion, with elevated CRP and neutrophil being the most significant lab findings. The influenza A (H1N1) strain was able to affect multiple organs, including being able to affect hepatic synthesis of pre-A as well as immune functioning. The influenza A (H1N1) influenza virus strain was mild clinically, with short disease course and good prognosis.