Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV.

Introduction: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals. Methods: A total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis. Results: At 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron. Discussion: This study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges. Clinical trial registration: https://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.

Trends in respiratory diseases before and after the COVID-19 pandemic in China from 2010 to 2021.

BACKGROUND: The ongoing benefits of coronavirus disease 2019 (COVID-19) nonpharmaceutical interventions (NPIs) for respiratory infectious diseases in China are still unclear. We aimed to explore the changes in seven respiratory infectious diseases before, during, and after COVID-19 in China from 2010 to 2021. METHODS: The monthly case numbers of seven respiratory infectious diseases were extracted to construct autoregressive integrated moving average (ARIMA) models. Eight indicators of NPIs were chosen from the COVID-19 Government Response Tracker system. The monthly case numbers of the respiratory diseases and the eight indicators were used to establish the Multivariable generalized linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: Compared with the year 2019, the percentage changes in 2020 and 2021 were all below 100% ranging from 3.81 to 84.71%. Pertussis and Scarlet fever started to increase in 2021 compared with 2020, with a percentage change of 183.46 and 171.49%. The ARIMA model showed a good fit, and the predicted data fitted well with the actual data from 2010 to 2019, but the predicted data was bigger than the actual number in 2020 and 2021. All eight indicators could negatively affect the incidence of respiratory diseases. The seven respiratory diseases were significantly reduced during the COVID-19 pandemic in 2020 and 2021 compared with 2019, with significant estimated IRRs ranging from 0.06 to 0.85. In the GLM using data for the year 2020 and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated the incidence of the seven respiratory diseases decreased rapidly during the COVID-19 pandemic in 2020 and 2021. At the end of 2021, we did see a rising trend for the seven respiratory diseases compared to the year 2020 when the NPIs relaxed in China, but the rising trend was not significant after adjusting for the NPIs indicators. Our study showed that NPIs have an effect on respiratory diseases, but Relaxation of NPIs might lead to the resurgence of respiratory diseases.

A prediction model for COVID-19 liver dysfunction in patients with normal hepatic biochemical parameters.

Coronavirus disease 2019 (COVID-19) patients with liver dysfunction (LD) have a higher chance of developing severe and critical disease. The routine hepatic biochemical parameters ALT, AST, GGT, and TBIL have limitations in reflecting COVID-19-related LD. In this study, we performed proteomic analysis on 397 serum samples from 98 COVID-19 patients to identify new biomarkers for LD. We then established 19 simple machine learning models using proteomic measurements and clinical variables to predict LD in a development cohort of 74 COVID-19 patients with normal hepatic biochemical parameters. The model based on the biomarker ANGL3 and sex (AS) exhibited the best discrimination (time-dependent AUCs: 0.60-0.80), calibration, and net benefit in the development cohort, and the accuracy of this model was 69.0-73.8% in an independent cohort. The AS model exhibits great potential in supporting optimization of therapeutic strategies for COVID-19 patients with a high risk of LD. This model is publicly available at https://xixihospital-liufang.shinyapps.io/DynNomapp/.

[Clinical features of 19 children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 in Hangzhou, China]. / 杭州市19ä¾‹æ–°åž‹å† çŠ¶ç— æ¯’Omicronå˜å¼‚æ ªæ„ŸæŸ“å„¿ç«¥çš„ä¸´åºŠç‰¹å¾.

OBJECTIVES: To study the clinical features of children infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: The medical data of 19 children who were diagnosed with SARS-CoV-2 Omicron variant infection from January 28 to March 3, 2022 in Hangzhou were retrospectively reviewed. RESULTS: Among the 19 children, there were 7 boys (37%) and 12 girls (63%), and their age ranged from 6 months to 16 years, with a median age of 2 years and 1 month. Most of these children were infants and young children (aged ≤3 years, accounting for 53%). Among these children, 11 (58%) were unvaccinated with SARS-CoV-2 vaccine and 8 (42%) were vaccinated with SARS-CoV-2 vaccine, and 3 children (16%) had a history of underlying diseases. All 19 children had a clear history of close contact with persons infected with SARS-CoV-2, and 10 children (53%) were involved in the cluster outbreak in a maternal and infant care center. In terms of clinical classification, 13 children (68%) had mild coronavirus disease 2019 (COVID-19) and 6 (32%) had common COVID-19, with no severe cases of COVID-19. The most common clinical symptoms were cough (100%) and fever (63%). The children with a normal peripheral white blood cell count accounted for 84%, and those with a normal lymphocyte count accounted for 68%. There were no significant abnormalities in platelet count, procalcitonin, liver function parameters (alanine aminotransferase and aspartate aminotransferase), and renal function parameters (creatinine and urea). Six children (32%) had obvious signs of pneumonia on chest CT. All 19 children were given symptomatic treatment, and 12 children (63%) were given aerosol inhalation of interferon α. All children were cured and discharged. CONCLUSIONS: Children infected with Omicron variant strains are more common in infants and young children, with mild symptoms and good prognosis. Most of the children have a history of close contact with persons infected with SARS-CoV-2, and epidemic prevention and control should be strengthened in places with many infants and children, such as maternal and infant care centers.

Diagnostic of FibroTouch and six serological models in assessing the degree of liver fibrosis among patients with chronic hepatic disease: A single-center retrospective study.

BACKGROUND AND AIMS: The aim of this study was to evaluate the diagnostic value of FibroTouch and serological models on staging hepatic fibrosis in chronic liver diseases. METHODS: We recruited 850 patients undergoing liver biopsy and received FibroTouch test before or after liver biopsy within one week, blood was taken for the routine inspection before the operation within one week. The serological models were calculated by the blood results and routine clinical information. The diagnostic value of FibroTouch and six serological models was analyzed by receiver operating characteristic curve (ROC). RESULTS: Patients with severe liver fibrosis had significantly higher AST, ALT, GGT, RDW, ALP, and FT-LSM. The area under the receiver operating characteristic curve (AUROC) of FT-LSM for the liver diagnosis of S≥2, S≥3 and S = 4 was 0.75(95% confidence interval [CI]:0.72-0.78), 0.83(95% CI: 0.80-0.86), and 0.85 (95% CI: 0.81-0.89), respectively. The optimal cut-off of FT-LSM for diagnosing S≥2, S≥3 and S = 4 was 8.7, 10.7, and 12.3, respectively. CONCLUSIONS: Our study showed the FibroTouch has a higher diagnostic value compared with the non-invasive serological models in staging the fibrosis stage. The cut-off of FibroTouch and five serological models (APRI, FIB-4, S-index, Forns, and PRP) increased with the severe of fibrosis stage.

Mycobacterium tuberculosis bacteremia in a human immunodeficiency virus-negative patient with liver cirrhosis: A case report.

BACKGROUND: With the increasing prevalence of human immunodeficiency virus (HIV), the incidence of Mycobacterium tuberculosis (M. tuberculosis) bacteremia has also increased. As a common affliction of acquired immunodeficiency syndrome patients, M. tuberculosis infection is associated in these patients with severe sepsis and high mortality. In contrast, M. tuberculosis bacteremia is rarely seen in HIV-negative patients, and M. tuberculosis has never been reported from the blood of patients with liver cirrhosis. CASE SUMMARY: We evaluated a 55-year-old Chinese male patient who had been admitted to the hospital with abdominal distension of unknown cause of one-week duration, accompanied by diarrhea, shortness of breath, and occasional fever. Based on these indicators of abnormal inflammation and fever, we suspected the presence of an infection. Although evidence of microbial infection was not found in routine clinical tests and the patient did not show typical clinical symptoms of infection with M. tuberculosis, next-generation sequencing of blood samples nevertheless demonstrated the presence of M. tuberculosis, which was subsequently isolated from blood samples grown in conventional BacT/ALERT FA blood culture bottles. CONCLUSION: Our findings demonstrate that HIV-negative liver cirrhosis patients can also be infected with M. tuberculosis.

Metagenomic Next-Generation Sequencing for the Diagnosis of Suspected Opportunistic Infections in People Living with HIV.

Objective: The diagnosis of suspected opportunistic infections in HIV patients is challenging due to the wide range of potential causes. This study used mNGS to analyse specimens of suspected opportunistic infections in HIV patients from a single centre to explore this method's applicability as a diagnostic tool compared to that of CMTs. Methods: We retrospectively investigated 46 suspected opportunistic infections in people living with HIV(PLWH) Hospitalized at Hangzhou Xixi hospital from January 2020 to August 2021. In total, we collected 49 samples (3 patients provided 2 samples) and sent them out for mNGS. Results: mNGS had a better detection rate for fungi and nontuberculous mycobacteria than that of CMTs. Specifically, the diagnostic detection rate of fungi (11 vs 19, P<0.05) and nontuberculous mycobacteria (1 vs 6, p<0.05) was significantly higher; there was no difference in detection rate for other pathogens (bacteria, Mycobacterium tuberculosis, or viruses). The sensitivity of mNGS was 90.91%, 50%, 0%, 100%, and 100% for detecting fungi, bacteria, Mycobacterium tuberculosis, nontuberculous mycobacteria, and viruses, respectively; the corresponding specificities were 74.29%, 97.73%, 86.36%, 86.67%, and 91.11%. Conclusion: mNGS technology provides an alternative and promising method of identifying suspected opportunistic infections in PLWH. Thus, the best diagnosis strategy may be using a combination of mNGS and CMTs.

Prevalence and antibiotic resistance of Klebsiella pneumoniae in a tertiary hospital in Hangzhou, China, 2006-2020.

OBJECTIVE: This study analyzed the characteristics and tendencies of resistance to common antibiotics for Klebsiella pneumoniae to provide a basis for clinical treatment and prevention. METHODS: A total of 71,743 isolates were collected from hospital clinical specimens following standard procedures from 2006 to 2020. Statistical analyses were conducted on laboratory test results. RESULTS: A total of 3054 isolates of K. pneumoniae were mainly isolated from sputum (53.77%), urine (14.70%), and blood (8.42%). Isolation rates of strains in the AIDS, hepatology, and intensive care wards were 9.72%, 12.52%, and 16.45%, respectively. Resistance rates of imipenem, cefazolin, gentamicin, tobramycin, ciprofloxacin, and ceftazidime respectively increased from 2.33%, 27.91%, 16.28%, 13.95%, 18.60%, and 9.30% to 12.83%, 40.82%, 21.57%, 25.07%, 44.61%, and 17.78%, while piperacillin-tazobactam resistance decreased from 13.95% to 13.70%. Differences in resistance rates to seven antibiotics were significant among specimen types. Detection rates of carbapenem-resistant K. pneumoniae were significantly different among blood, sputum, and urine specimens, and between wards. CONCLUSIONS: The prevalence and drug resistance of K. pneumoniae showed an upward trend over time, and resistance varied according to ward and specimen source. The prevention of nosocomial infections and rational drug use must be emphasized to reduce antimicrobial resistance.

Comparing Noninvasive Predictors of Neurosyphilis Among Syphilis Patients With and Without HIV Co-Infection Based on the Real-World Diagnostic Criteria: A Single-Center, Retrospective Cohort Study in China.

Diagnosis of neurosyphilis is currently based on the cerebrospinal fluid (CSF) assessments and CSF-Venereal Disease Research Laboratory (CSF-VDRL) is the traditional "gold standard." In the real world, CSF assessments and CSF-VDRL are not always available. This study aimed to identify noninvasive predictors of neurosyphilis based on real-world clinical parameters and diagnostic criteria in populations with different HIV status. In this retrospective cohort study, syphilis patients with different HIV statuses hospitalized for neurosyphilis screening were retrospectively recruited at an infectious disease hospital. Neurosyphilis was defined by real-world diagnostic criteria. Logistic regression and receiver operating characteristic curve analysis were used to investigate and evaluate predictors of neurosyphilis. In total, 528 patients were enrolled, including 143 syphilis patients without HIV infection and 385 HIV/syphilis-co-infected patients. One hundred twelve and 304 neurosyphilis patients were identified in the HIV-negative and HIV-positive groups, respectively. A high serum toluidine red unheated serum test (TRUST) titer was a robust predictor of neurosyphilis in all participants. An age ≥50 years old [adjusted odds ratio (aOR) = 5.062, 95% confidence interval (CI), 1.449-17.680] in the HIV-negative group and CD4+ T cell count <330/µL (<300 as reference, aOR = 0.552, 95% CI, 0.315-0.966) in the HIV-positive group were predictors of asymptomatic neurosyphilis. In real-world situations, for asymptomatic syphilis patients, relatively old age and a high serum TRUST titer in HIV-negative populations, and CD4+ T cells <330/µL and/or serum TRUST titer >1:64 in HIV-positive populations might predict neurosyphilis.

Case Report: Tropheryma whipplei Hide in an AIDS Patient With Pneumocystis Pneumonia.

Introduction:Pneumocystis pneumonia (PCP) is one of the most common opportunistic infections in HIV-infected patients. However, coinfection with Tropheryma whipplei is infrequent in AIDS patients with PCP. Case Presentation: We report a 28-year-old male AIDS patient coinfected with T. whipplei and Pneumocystis jirovecii diagnosed in the bronchoalveolar lavage. After sulfamethoxazole-trimethoprim and meropenem treatment, the patient showed clinical improvement in 2 weeks. Conclusion: Clinicians need to be alert to the occurrence of T. whipplei infection in AIDS patients with PCP and timely diagnosis and antibacterial treatments are essential. This case may help clinicians for timely diagnosis of the coinfection of T. whipplei and P. jirovecii in AIDS patients.

Corylin sensitizes breast cancer cells to overcome tamoxifen resistance by regulating OAS1/miR-22-3p/SIRT1 axis.

Breast cancer (BCa) is one of the leading causes of cancer-related death among women worldwide. At present, the clinical treatment with tamoxifen (TAM) is challenged by the development of drug resistance. To investigate the effect of corylin on TAM resistance in BCa cells, this study investigated the molecular mechanisms involving miRNA-mRNA targets modulated by corylin. The TAM-resistant MCF-7TR and T47DTR cell lines were generated, and it was found that corylin treatment reduced the cell viability of these cells significantly. Furthermore, OAS1 was validated to be highly expressed in TAM-resistant cells, while OAS1 knockdown sensitized MCF-7TR and T47DTR cells to TAM treatment. Meanwhile, OAS1 was also repressed by corylin treatment, indicating that OAS1 was a key regulator of corylin function. Through bioinformatic analysis, the tumor suppressive miRNA miR-22-3p was identified to directly target and inhibit OAS1. Moreover, corylin treatment up-regulated miR-22-3p expression, which thus down-regulated the OAS1 expression. Interestingly, OAS1 itself functioned as a miR-22-3p sponge to repress miR-22-3p expression. Further, SIRT1 was identified to be up-regulated in TAM-resistant cells and participated in the OAS1/miR-22-3p regulatory axis via the miR-22-3p direct target. In conclusion, corylin sensitized TAM-resistant cells to TAM treatment by inhibiting OAS1 expression and modulating the OAS1/miR-22-3p/SIRT1 axis.

Sequential [3+2] annulation reaction of prop-2-ynylsulfonium salts and hydrazonyl chlorides: synthesis of pyrazoles containing functional motifs.

A novel sequential [3+2] annulation reaction has been developed using prop-2-ynylsulfonium salts and hydrazonyl chlorides, affording a series of pyrazoles with functional motifs that can be post modified in the preparation of various drugs or drug candidates. Further transformation and gram-scale operations could also be achieved efficiently.

Severity-associated markers and assessment model for predicting the severity of COVID-19: a retrospective study in Hangzhou, China.

BACKGROUND: The severity of COVID-19 associates with the clinical decision making and the prognosis of COVID-19 patients, therefore, early identification of patients who are likely to develop severe or critical COVID-19 is critical in clinical practice. The aim of this study was to screen severity-associated markers and construct an assessment model for predicting the severity of COVID-19. METHODS: 172 confirmed COVID-19 patients were enrolled from two designated hospitals in Hangzhou, China. Ordinal logistic regression was used to screen severity-associated markers. Least Absolute Shrinkage and Selection Operator (LASSO) regression was performed for further feature selection. Assessment models were constructed using logistic regression, ridge regression, support vector machine and random forest. The area under the receiver operator characteristic curve (AUROC) was used to evaluate the performance of different models. Internal validation was performed by using bootstrap with 500 re-sampling in the training set, and external validation was performed in the validation set for the four models, respectively. RESULTS: Age, comorbidity, fever, and 18 laboratory markers were associated with the severity of COVID-19 (all P values < 0.05). By LASSO regression, eight markers were included for the assessment model construction. The ridge regression model had the best performance with AUROCs of 0.930 (95% CI, 0.914-0.943) and 0.827 (95% CI, 0.716-0.921) in the internal and external validations, respectively. A risk score, established based on the ridge regression model, had good discrimination in all patients with an AUROC of 0.897 (95% CI 0.845-0.940), and a well-fitted calibration curve. Using the optimal cutoff value of 71, the sensitivity and specificity were 87.1% and 78.1%, respectively. A web-based assessment system was developed based on the risk score. CONCLUSIONS: Eight clinical markers of lactate dehydrogenase, C-reactive protein, albumin, comorbidity, electrolyte disturbance, coagulation function, eosinophil and lymphocyte counts were associated with the severity of COVID-19. An assessment model constructed with these eight markers would help the clinician to evaluate the likelihood of developing severity of COVID-19 at admission and early take measures on clinical treatment.

Regulation of Mitochondrial Function by Natural Products for the Treatment of Metabolic Associated Fatty Liver Disease.

Metabolic associated fatty liver disease (MAFLD) is a multifactorial systemic disorder that occurs in the absence of excessive alcohol consumption. The disease is characterized by fatty degeneration and fat accumulation in liver parenchymal cells, the incidence of which is increasing annually, particularly in younger adults. MAFLD is caused by genetic and metabolism related disorders, of which mitochondrial dysfunction is the major contributor. Natural products can relieve MAFLD through restoring mitochondrial function. In this article, we describe the relationship between mitochondria and MAFLD and discuss the beneficial effects of natural products as a future anti-MAFLD strategy. Significance Statement. We herein propose that the development of mitochondrial regulators/nutrients from natural products can remedy mitochondrial dysfunction which represents an attractive strategy for the treatment of MAFLD. Furthermore, the mitochondrial regulation of natural products can provide new insight into the underlying mechanisms of action of natural products used for future MAFLD therapeutics.

The Chinese Society of Hepatology position statement on the redefinition of fatty liver disease.

Fatty liver disease associated with metabolic dysfunction is of increasing concern in mainland China, the world's most populous country. The incidence of fatty liver disease is highest in China, surpassing the incidence in European countries and the USA. An international consensus panel recently published an influential report recommending a novel definition of fatty liver disease associated with metabolic dysfunction. This recommendation includes a switch in name from non-alcoholic fatty liver disease (NAFLD) to metabolic (dysfunction)-associated fatty liver disease (MAFLD) and adoption of a set of positive criteria for disease diagnosis that are independent of alcohol intake or other liver diseases. Given the unique importance of this proposal, the Chinese Society of Hepatology (CSH) invited leading hepatologists and gastroenterologists representing their respective provinces and cities to reach consensus on alternative definitions for fatty liver disease from a national perspective. The CSH endorses the proposed change from NAFLD to MAFLD (supported by 95.45% of participants). We expect that the new definition will result in substantial improvements in health care for patients and advance disease awareness, public health policy, and political, scientific and funding outcomes for MAFLD in China.

The Presence of Secondary Evans Syndrome in AIDS Patients with Talaromyces marneffei Infection.

OBJECTIVE: Talaromyces marneffei (T.M) is a common opportunistic fungus in human immunodeficiency virus (HIV) infection individual. Secondary Evans syndrome in AIDS patients with Talaromyces marneffei infection has not been reported before. Here, we described cases related to this comorbidity. METHODS: AIDS patients diagnosed with Talaromyces marneffei infection from 2016 to 2020 at Xixi Hospital of Hangzhou were included in this retrospective study. RESULTS: Total 76 AIDS patients with T.M infection were enrolled. The most common symptoms were fever and cough (70/76; 55/76, respectively). 53/76 (69.74%) patients got positive results of direct antiglobulin test. 14/76 AIDS-T.M patients combined with secondary Hemophagocytic lymphohistiocytosis (HLH). Five patients were diagnosed with AIDS-T.M associated Evans syndrome. There were severe inflammatory reaction, liver dysfunction, coagulation dysfunction and immunodeficiency status in AIDS-T.M patients with secondary Evans syndrome. All patients received antifungal therapy and three patients received corticosteroids for Evans syndrome treatment. One patient died due to sepsis. CONCLUSION: AIDS-T.M patients with secondary Evans syndrome is extremely rare and we need to be alert to the occurrence of secondary Evans syndrome in AIDS-T.M patients. Clinicians should timely start effective antifungal treatments with suspicious T.M infection in AIDS patients.

Oridonin interferes with simple steatosis of liver cells by regulating autophagy.

Oridonin has significant liver-protective effects, but its effect on liver steatosis has not been reported. We investigated the effects of oridonin on liver steatosis by cell cultures. The optimal experimental concentration of oridonin was determined through cytotoxicity experiments. A simple steatosis liver cell model was induced using free fatty acids (FFA). After adding oridonin to the FFA-induced cell model for 24 h, the lipid droplets and triglyceride (TG) content in the cells were measured by Oil Red O staining and TG kits. The expressions of autophagy-related markers (cyclin dependent kinases inhibitor 1a (p21), Beclin-1, microtubule-associated protein light chain 3 (LC3)-I and LC3-II, protein kinase B (AKT), phosphorylated-AKT (p-AKT), AMP-activated protein kinase (AMPK), and phosphorylated-AMPK (p-AMPK)) were detected by Western blot. Based on the results, the cell model was further treated by autophagy inhibitor 3-methyladenine (3-MA) to determine the degree of steatosis and the expressions of autophagy-related factors. Oridonin at a concentration higher than 10 µmol/L caused cytotoxicity to the cells. Adding 10 µmol/L oridonin to the FFA-induced cell model effectively reduced lipid droplets and TG content in the cells. Oridonin up-regulated p21, Beclin-1 and LC3-II expressions, but down-regulated those of p62 and LC3-I. Also, oridonin increased the ratios of LC3-II/LC3-I and p-AMPK/AMPK, but reduced that of p-AKT/AKT. With the addition of 3-MA, the effect of oridonin on reducing steatosis was partially reversed, and the autophagy was inhibited. This study found that oridonin can activate autophagy, thereby preventing simple steatosis of liver cells.

Corylin suppresses metastasis of breast cancer cells by modulating miR-34c/LINC00963 target.

Breast cancer is one of the cancers leading to most death cases among women and metastasis is the major cause of breast cancer mortality. In this study, Corylin, the flavonoid compound which is extracted and purified from Psoralea corylifolia L., the effect on breast cancer metastasis was investigated. Corylin showed inhibitory effect on migration and invasion abilities of breast cancer cells. Meanwhile, the epithelial-mesenchymal transition was also regulated by corylin. The long non-coding RNA LINC00963 was found to have a significantly high expression level in breast cancer while it can be down-regulated by corylin. In addition, both wound-healing assay and transwell assay showed that LINC00963 induced breast cancer cells metastasis. MiR-34c was increased by corylin treatment depending on p53, and it was firstly identified that the LINC00963 was a direct target of miR-34c. Corylin was verified here that it prohibited MCF-7 migration and invasion depending on miR-34c/LINC00963 target. In conclusion, corylin suppresses metastasis of breast cancer cells via increasing miR-34c expression, which was dependent on p53. LINC00963 was a direct target of miR-34c and the target axis was necessary for corylin function. Therefore, corylin is a promising drug candidate and LINC00963 can be seen as a promising target in breast cancer treatment.

Preparation, evaluation, and in vitro cytotoxicity studies of artesunate-loaded glycyrrhetinic acid decorated PEG-PLGA nanoparticles.

OBJECTIVE: The objective of this study was to prepare the liver targeting drug delivery system (TDDS) of artesunate (ART)-loaded polyethylene glycol (PEG)-poly(d,l-lactic-co-glycolic) acid (PLGA) nanoparticles (NPs) modified by glycyrrhetinic acid (GA), and evaluate its in vitro cytotoxicity. SIGNIFICANCE: The GA-PEG-PLGA-ART NPs enhanced the in vitro cytotoxicity on HCC cell lines. The development of GA-PEG-PLGA NPs will greatly push the clinical applications of ART as a novel anticancer drug. METHODS: The NPs were prepared using solvent evaporation method, and the formulation was optimized through an orthogonal design. In addition, physical properties were determined, including particle size, polydispersity index (PDI), zeta potential (ZP), morphology, drug loading capacity (LC) and encapsulation efficiency (EE), and in vitro drug release. Moreover, the in vitro cytotoxicity of NPs with three human cancer cell lines viz. HepG2, Hep3B, and SMCC-7721 was conducted using the SRB assay. Additionally, lyophilization was conducted to improve the long-term physical stability. RESULTS: The GA-PEG-PLGA-ART NPs have spherical shape, small particle size (around 88 nm) with a narrow size distribution (PDI < 0.3), high drug LC (up to 59.3 ± 1.65%), and high EE (up to 73.13 ± 5.17%). In vitro drug release behavior showed that drugs were released from NPs in a sustained and controlled release pattern. Cytotoxicity study indicated the NPs achieved lower cancer cell survival fraction. The GA-PEG-PLGA NPs freeze-dried with 3% (w/v) of mannitol showed better effect on long-term physical stability. CONCLUSION: The GA-PEG-PLGA-ART NPs appear as a potential liver targeted intracellular delivery platform for ART.

Pathogenic microorganism detection in AIDS patients using bronchoalveolar lavage fluid.

This study aimed to investigate the use of fiberoptic bronchoscopy and bronchoalveolar lavage in the diagnosis of pulmonary pathogenic microorganism infection in AIDS patients. We retrospectively analyzed the clinical data, fiberoptic bronchoscopy and bronchoalveolar lavage fluid laboratory examinations of 209 AIDS patients with pulmonary infection. Among 209 patients, we found 42 cases of mycobacterial infection, 3 cases of bacterial infection, 58 cases of pneumocystis carinii pneumonia (PCP), 27 cases that were fungal positive, 99 cases of CMV, and 103 cases positive for GM test of which 83 cases were considered Aspergillus positive. BALF pathogen distribution was related to CD4+ T lymphocyte count. The primary pathogens of pulmonary infection in AIDS patients were cytomegalovirus, Mycobacterium tuberculosis, fungi, and Pneumocystis carinii. Fiberoptic bronchoscopy and bronchoalveolar lavage are important in the diagnosis of pathogenic microorganisms in lung infections of AIDS patients.