Background:Experience with Dolutegravir/Lamivudine (DTG/3TC) for rapid initiation of antiretroviral therapy (ART) in newly diagnosed people living with HIV (PLWH) remains scarce. We conducted a study to evaluate the effectiveness and safety of DTG/3TC for rapid ART. Methods:This retrospective, real-world study was conducted among treatment-naïve PLWH at three centers in Beijing, Nanjing, and Qingdao. Participants were stratified into the rapid group (≤7 days) and the non-rapid group (>7 days) based on the time from HIV diagnosis to ART initiation. The primary endpoint was the rate of virological suppression (VS) at week 48, which was assessed using both intention-to-treat (ITT) and per-protocol (PP) analyses in accordance with the Food and Drug Administration (FDA) Snapshot algorithm. Results:A total of 145 participants were enrolled between February 2022 and October 2023 (57 in the rapid group and 88 in the non-rapid group). The median time for the two groups to ART initiation was 4.0 (3.0, 5.0) and 17.0 (12.3, 25.5) days, respectively (P < 0.001). No significant baseline differences were observed between the two groups. ITT analysis showed that the 48-week VS rates were 93.0% [95% confidence interval (CI): 86.1%-99.8%] in the rapid group and 90.9% (95% CI: 84.8%-97.0%) in the non-rapid group (P = 0.765). Multivariable logistic regression analysis, adjusted for age, baseline CD4 counts, baseline VL, and treatment initiation pattern, confirmed that rapid ART was not significantly associated with VS at week 48 [adjusted odds ratio (OR) = 1.100, 95% CI: 0.291-4.164, P = 0.888]. Subgroup analyses further demonstrated consistent results: no significant differences in VS rates were detected across subgroups (all P > 0.05). The median increases in CD4 counts from baseline at week 48 were 232 and 243 cells/μL in the rapid and non-rapid groups, respectively (P = 0.951). Throughout the 48-week follow-up period, changes in liver function, renal function, and lipid levels from baseline did not differ significantly between the two groups. Conclusion:Our study provides clinical evidence supporting the effectiveness and safety of DTG/3TC for rapid ART in treatment-naïve PLWH, with outcomes comparable to those of non-rapid initiation.

IntroductionMycoplasma pneumoniae (M. pneumoniae) infections are prevalent among school-age children, and an increasing number of patients are developing resistance to azithromycin (AZM). However, effective biomarkers for diagnosing AZM resistance are currently lacking. This study aimed to identify potential biomarkers for AZM resistance in M. pneumoniae infections by analyzing serum exosomes.MethodsSerum samples were collected from M. pneumoniae-infected patients before and after AZM treatment and were categorized into two groups: responders and non-responders. Serum exosomes were isolated and analyzed using nanoparticle tracking analysis (NTA) and proteomics profiling by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Differential protein expression patterns were compared between AZM-sensitive and resistant patients, and potential biomarkers were identified and validated.ResultsDistinct exosomal protein expression patterns were observed between AZM-sensitive and resistant patients. The HIF-1 and IL-17 signaling pathways were found to be associated with AZM resistance. Four proteins (KCTD12, LTF, TF, and MPO) were identified as potential biomarkers for distinguishing responders from non-responders. These biomarkers demonstrated over 80% sensitivity and 73.33% specificity in differentiating between the two groups.ConclusionThe study successfully identified four potential biomarkers (KCTD12, LTF, TF, and MPO) for AZM resistance in M. pneumoniae infections. These biomarkers may serve as useful diagnostic tools in clinical settings, aiding in the identification of patients who may not respond to AZM treatment. Future research should focus on validating these biomarkers in larger cohorts and exploring their potential applications in clinical practice.

BackgroundThe purpose of this study is to examine the diagnostic and therapeutic value of CXCL13 (CSF-CXCL13), CXCL10 (CSF-CXCL10), and CXCL8 (CSF-CXCXCL8) in NS patients in a systematic manner.MethodThe study will include individuals who are the first to undergo neurosyphilis (NS) screening from August 2023 to October 2024, and will gather demographic, clinical, and laboratory data, as well as cerebrospinal fluid (CSF) and blood samples. Enzyme-linked immunosorbent assay (ELISA) was used to quantitatively detect the concentrations of CXCL13, CXCL10, and CXCL8 in CSF and blood samples. Use receiver operating characteristic (ROC) curves to evaluate the ability of cytokines to distinguish between NS and non-NS individuals, and further evaluate in different populations, including the total population, People Living with HIV(PLWH), Non-People Living with HIV(Non-PLWH) population. Develop an NS diagnostic model using logistic regression analysis results, and ensure the model is valid by conducting 5-fold cross-validation, calibration curve, and clinical decision curve (DCA). Use a Nomogram to visualize the model.ResultA total of 233 participants were included in the study. ROC shows that the area under the curve (AUC) of CSF-CXCL13 in distinguishing NS from Non-NS,#x3001; NS from CNS infections is 0.812 and 0.839, respectively. In contrast, the AUC of CSF-CXCL10 and CSF-CXCL8 in distinguishing NS from Non-NS were 0.568 and 0.638, respectively. The AUC in distinguishing NS from other CNS infections were 0.604 and 0.556, respectively. To enhance the effectiveness of differential diagnosis, we employed logistic regression analysis to screen variables and developed a predictive model MODEL1. The results showed that the AUC value of MODEL1 was 0.888, and the calibration curve and DCA curve demonstrated good accuracy and clinical benefits of the model, demonstrating good predictive performance. After NS treatment, the levels of CSF-CXCL13, CSF-CXCL10, and CSF-CXCL8 slightly decreased.ConclusionCSF-CXCL13 has good differential value in distinguishing NS from Non-NS, NS from CNS infections, while CSF-CXCL10 and CSF-CXCL8 have lower differential sensitivity. The diagnostic performance of the NS diagnostic model (Model 1) based on CSF-CXCL13 has been improved.

Daily oral medication is currently the most common antiretroviral therapy (ART) for people living with human immunodeficiency virus (PLWH). As the first complete long-acting (LA) ART regimen, cabotegravir (CAB) and rilpivirine (RPV), offer a novel treatment approach with less frequent administration, via bimonthly infusion. Due to the upcoming availability of this regimen in China, the study aimed to analyze the willingness and reasons of PLWH to switch to CAB+RPV therapy. A questionnaire survey among PLWH receiving oral ART was carried out between March 25 and April 8, 2023, in the Second Hospital of Nanjing, China. Participants were asked about their willingness to switch to the CAB+RPV LA regimen and provided reasons for their decision. We analyzed the reasons for switching, and the factors affecting their willingness were analyzed by multinomial logistic regression. Among 693 participants, 56.7% expressed willingness to switch to the CAB+RPV regimen, 32.6% were uncertain, and 10.7% were unwilling. The primary reason for switching to CAB+RPV therapy was not being concerned about daily adherence to ART (22.6%). Uncertainty about switching was mainly associated with participants' concerns in terms of price (31.6%) and safety (31.1%) of the novel drugs. Unwillingness was mainly due to participants' satisfaction with their current treatment regimen (20.3%). In multivariate analysis, higher education (odds ratio [OR]: 2.990; 95% confidence interval [CI]: 1.171-7.636) was positively associated with willingness to switch, whereas the age of ≥60 (OR: 0.142; 95% CI: 0.036-0.554) was negatively associated. Our survey demonstrated that the majority of PLWH were willing to switch to CAB+RPV therapy, mainly due to its improved convenience and reduced risk of disease exposure. However, their concerns regarding price, efficacy, and safety could be the key challenges for the clinical implementation of the CAB+RPV LA regimen in the future.

Background The pathogens causing unexplained pneumonia in both HIV-infected or HIV-unfected patients are likely to be complex. This retrospective study aimed to characterize the etiology of pneumonia in HIV-infected and HIV-uninfected patients using bronchoalveolar lavage fluid (BALF) analysis with metagenomic next-generation sequencing (mNGS) and X-pert MTB/RIF. Methods Between January 2022 and May2024, 141 HIV-infected and 104 HIV-uninfected patients admitted to Nanjing Second Hospital with pneumonia were included. BALF samples were collected and analyzed using mNGS to detect bacteria, fungi, viruses, tuberculosis (TB) and non-tuberculous mycobacteria (NTM), and X-pert for TB detection. Clinical data including CD4 T-cell counts, comorbidities, and ART status were collected and analyzed. Results HIV-uninfected patients were found to be older and exhibited a higher prevalence of comorbidities compared to HIV-infected patients. Despite higher median CD4 T-cell counts in HIV-uninfected individuals (412 cells/μL vs. 31 cells/μL in HIV-infected), TB detection rates using X-pert and mNGS were lower than anticipated, particularly in HIV-infected patients. Mixed-pathogen infections were significantly more prevalent in HIV-infected patients, especially those with lower CD4 T-cell counts. ART use showed variable impacts on pathogen diversity, with longer treatment durations associated with reduced infection complexity but persistent immunodeficiency in some cases.In patients with pneumonia, whether HIV-infected or HIV-uninfected, pathogens often exhibit complexity, underscoring the critical role of timely mNGS and X-pert analysis of BALF for early pathogen detection.

Despite advancements in antiretroviral therapy (ART) suppressing HIV-1 replication, existing antiviral drugs pose limitations, including lifelong medication, frequent administration, side effects and viral resistance, necessitating novel HIV-1 treatment approaches. CD4, pivotal for HIV-1 entry, poses challenges for drug development due to neutralization and cytotoxicity concerns. Nevertheless, Ibalizumab, the sole approved CD4-specific antibody for HIV-1 treatment, reignites interest in exploring alternative anti-HIV targets, emphasizing CD4’s potential value for effective drug development. Here, we explore anti-CD4 nanobodies, particularly Nb457 from a CD4-immunized alpaca. Nb457 displays high potency and broad-spectrum activity against HIV-1, surpassing Ibalizumab’s efficacy. Strikingly, engineered trimeric Nb457 nanobodies achieve complete inhibition against live HIV-1, outperforming Ibalizumab and parental Nb457. Structural analysis unveils Nb457-induced CD4 conformational changes impeding viral entry. Notably, Nb457 demonstrates therapeutic efficacy in humanized female mouse models. Our findings highlight anti-CD4 nanobodies as promising HIV-1 therapeutics, with potential implications for advancing clinical treatment against this global health challenge. In this study, Zhu et al. report Nb457, an alpaca-derived nanobody with broad-spectrum anti-HIV1 activity and show that Nb457 induces conformational changes in CD4, blocking viral entry and completely inhibiting HIV-1 in its trimeric form.

OBJECTIVES:This study aimed to explore the effects of bone morphogenetic protein 2 (BMP-2) encapsula-ted in poly(lactic-co-glycolic acid) (PLGA) microcapsules with different molecular weights on the osteogenic ability of osteoblasts. METHODS:PLGA microcapsules with different molecular weights (12 000, 30 000) encapsulating BMP-2, were prepared using a dual-channel microinjection pump. The morphology and structure of the microcapsules were characterized by optical microscopy and scanning electron microscopy. The sustained-release performance of the microcapsules was characterized by phosphate buffered saline immersion method. The cell compatibility of the microcapsules was detected by the Calcein-AM/PI staining and CCK-8 method. The chemotactic effect of BMP-2-encapsulated microcapsules on MC3T3-E1 cells after 48 h of treatment was detected by the Transwell assay. The alkaline phosphatase activity assay and Alizarin Red S staining were used to characterize the effect of microcapsules on the osteogenic ability of MC3T3-E1 cells. RESULTS:Both types of microcapsules with different molecular weights exhibited smooth surfaces, as well as uniform and good cell compatibility. The chemotactic effect of the 12 000 microcapsules was outstanding. The 30 000 microcapsules had a longer sustained-release time, and the initial burst release was reduced by approximately 25% compared with the 12 000 microcapsules. In addition, 30 000 microcapsules performed better in long-term osteogenesis induction than 12 000 microcapsules. CONCLUSIONS:In this study, the release of BMP-2 is regulated by adjusting the molecular weight of PLGA, and the results indicate that 30 000 microcapsules can better induce the long-term osteogenic ability of MC3T3-E1 cells.

Three patients of coronavirus disease (COVID-19) showed the symptoms of olfactory dysfunction. Clinical characteristics and treatment were retrospective analyzed. Olfactory disorders are uncommon symptoms of COVID-19. Early diagnosis and intervention are key to the recovery of olfactory disorders. Particular attention should be devoted to rare symptoms of COVID-19.

Background Some children hospitalized due to severe community-acquired pneumonia (CAP) require to the pediatric intensive care unit (PICU) because of severe complications. The purpose of this study was to identify the risk factors for mortality in this patient population. Methods This study evaluated the medical records of 113 hospitalized children with severe CAP, who were transferred to the PICU within 48 h of admission at the Guangzhou Women and Children's Medical Center between 2013 and 2017. Results The study group consisted of 87 boys (77%) and 26 girls (33%), aged between 1 month and 9 years; 72.6% (82/113) of patients were aged <12 months. The mortality rate was 12.3% (14/113). The most common viral and bacterial pathogens isolated were adenovirus (17.7%, 20/113) and Haemophilus influenzae (8.8%, 10/113). Wheezing, cyanosis, oxygen saturation <90%, Pediatric Early Warning Score (PEWS) >3 on admission, not receiving corticosteroid therapy prior to admission, the need for mechanical ventilation, septic shock, multi-organ dysfunction (MODS), and acute renal failure (ARF) occurring prior to transfer to the PICU, increased alanine aminotransferase (ALT) and aspartate transaminase (AST) levels, and decreased hemoglobin and albumin (ALB) levels were associated with mortality (P < 0.05). Non-survivors were more likely to have an oxygen saturation <90% on admission and lower levels of ALB prior to transfer to the PICU than survivors (P < 0.05). Conclusions Our results showed that hospitalized children with severe CAP who were transferred to the PICU within 48 h of hospital admission were mainly aged <1 year. Additionally, an oxygen saturation <90% and decreased ALB levels were early prognostic variables independently associated with death.

Objective To study the correlation between fractional exhaled nitric oxide (FeNO) and lung function in young children for acute attack of wheezing,and to compare the FeNO in different stages in order to explore the best suitable time for the experiment of FeNO in young children by the method of on-line tidal breathing.Methods Recurrent wheezing children aged 1-5 year old were selected who were underwent the test at lung function laboratory from January 2016 to March 2018,at Guangzhou Women and Children's Medical Center.The children aged less than 5 years old were detected for FeNO in both stages of acute exacerbation and 2 weeks after treatment,and the children aged less than 3 years were also detected for the tidal lung function in the acute exacerbation stage.According to time ratio of reaching tidal peak flow to total expiratory time(TPTEF/TE) and ratio of volume at tidal peak flow to total tidal volume (VPEF/VE),the children aged less than 3 years were divided into 4 groups (normal group,mild group,moderate group and severe group).Results The FeNO of the normal group [9.85 (5.17,19.62) ppb] and mild group[13.00 (7.00,23.30) ppb] were significantly higher than that of the severe group [3.10 (2.20,5.25)ppb],and the differences were statistically significant (all P ＜ 0.05).And there was a positive correlation between TPTEF/TE and FeNO(r =0.304,P ＜ 0.05),VPEF/VE and FeNO(r =0.320,P ＜ 0.05),tidal volume per kilogram (VT/kG) and FeNO(r =0.293,P ＜ 0.05)and a negative correlation between respiration rate(RR) and FeNO (r =-0.449,P ＜ 0.05).The FeNO in the stage of acute exacerbation was significantly lower than that in the stage of 2 weeks after treatment[(10.49± 8.49) ppb vs.(20.41 ± 9.13) ppb],and there was a significant difference among them(t =-5.79,P ＜ 0.01).Conclusions If researchers want to use the method of on-line breathing to test FeNO in young children with wheezing,they should choose the time of 2 weeks after treatment,and analyze the results combined with the lung function.

Bone fractures are very common, and above 5% of the fractures are impaired, leading to nonunions and severe disablilities.The traditional Chinese medicine Bushen Huoxue decoction (BHD) has been used to treat fracture in China.Our previous report has found that BHD promotes migration of rat mesenchymal stem cells (rMSCs) by activating Wnt5a signaling pathway.However, whether and how miRNAs are involved in modulating rMSCs migration induced by BHD has not been explored.In the present study, miRNA microarray analysis and further validation by real-time quantitative RT-PCR revealed that miR-539-5p was down-regulated in BHD-induced rMSCs.Transfection of miR-539-5p mimics suppressed rMSCs migration while the miR-539-5p inhibitor promoted rMSCs migration.Our results suggested that miR-539-5p was a negative regulator of migration of rMSCs induced by BHD.Target prediction analysis tools and Dual-luciferase reporter gene assay identified Wnt5a as a direct target of miR-539-5p.MiR-539-5p inhibited the expression of the Wnt5a and its downstream signaling molecules including JNK, PKC and CaMKII, which played a critical role in regulating migration of rMSCs.Taken together, our results demonstrate that miR-539-5p negatively regulates migration of rMSCs induced by BHD through targeting Wnt5a.These findings provide evidence that miR-539-5p should be considered as an important candidate target for the development of preventive or therapeutic approaches against bone nonunions.

Sanger sequencing technologies have revolutionized clinical and research as soon as it came out as first generation sequencing .The first human genetic map was finished after 13 years of the effort and cooperation of countries which reflects sequencing technologies have expanded the width and depth of scientific study .More throughput ,lower cost and more precise sequencing technologies have been applicated in laboratory with the advance of science and technology .This review is to introduce the technologies and application in respiratory infection .

Objective To analyze the clinical manifestations and results of etiological examinations of 17 elderly patients with influenza A (H1N1) viral pneumonia, and to understand the clinical features of pneumonia and molecular characteristics of influenza A (H1N1) virus infection in the elderly. Methods The elderly patients with pneumonia who were hospitalized in the Department of Respiratory Diseases of Nanjing First Hospital from January 2018 to March were enrolled. The cases were confirmed by nucleic acid examination for influenza virus and the clinical data were collected. After the amplification of the whole genome of influenza virus, the high throughput sequencing and bioinformatics analysis were performed. Results The mean age of the 17 enrolled patients was 73. 8 ± 10. 8. All of them had at least 1 underlying disease, and 7 cases had co-infection. Respiratory symptoms and fever were the most prominent clinical manifestations. Lesions in both lungs were found in 76. 5％ of the patients. The result of high throughput sequencing showed that all the viruses were highly homologous to the vaccine strain, and the HA gene belonged to the 6B. 1 subgroup. Furthermore, three variations of antigenic locus (H138Y, S74R and S164T in HA) and a drug-resistant variation (H275Y in NA) were detected in the circulating strains. Conclusions Elderly patients with influenza A (H1N1) virus pneumonia often have underlying diseases and are prone to have co-infection. The molecular characteristics of the virus and the variation of key amino acid loci should be closely monitored in order to provide evidence for epidemic prevention and clinical antiviral treatment.