BACKGROUND:Based on China's current HIV-1 testing algorithm, samples with initial positive antibody screening require two additional repeat tests, with infection status confirmed by HIV-1 antibody Western Blot or nucleic acid testing (NAT). In recent years, NAT has gradually become the mainstream supplemental assay due to its shorter window period, holding significant importance in detecting acute HIV-1 infection. Currently, over 800 laboratories in China can perform HIV-1 NAT. However, most NAT kits are designed for viral load (VL) detection, typically used to assess treatment efficacy in confirmed patients. This study aimed to explore the diagnostic efficacy of HIV-1 quantitative NAT at varying medical decision points, as well as the methodological preference for antibody screening, to support better implementation of HIV-1 testing and accurate identification of HIV-1 infections in China. METHODS:Testing records of 11,369 samples with WB-indeterminate or -negative results during 2018-2023 were collected from the central HIV confirmatory laboratory databases of 20 provincial CDCs. Methodological preferences in HIV-1 antibody screening, diagnostic performance of single- or double-reactive results in retesting and quantitative NAT at varying diagnostic thresholds were analyzed. RESULTS:Chemiluminescence immunoassay (CLIA) was the most widely used method for initial screening (42.77%) and the seroconversion rate was significantly higher in cases with double-positive retest results compared to single-positive results (75.95% vs. 27.25% for WB-indeteminate results and 20.31% vs. 7.26% for WB-negative results, respectively). The specificity and positive predictive values of HIV-1 quantitative NAT were 100% at each medical decision points, and the sensitivity and negative predictive value decreased from 99.92% to 99.93% to 94.71% and 95.64%. Two samples with undetectable viral loads were ultimately diagnosed as HIV-1 infections, alerting us to consider individual exposure history when managing antibody screening-reactive but VL-undetectable cases. CONCLUSIONS:Quantitative HIV-1 NAT enables rapid and accurate infection confirmation, earlier identification and timely treatment initiation.

Classical shadow tomography, harnessing randomized informationally complete (IC) measurements, provides an effective avenue for predicting many properties of unknown quantum states with sample-efficient precision. Projections onto $2^n+1$ mutually unbiased bases (MUBs) are widely recognized as minimal and optimal IC measurements for full-state tomography. We study how to use MUBs circuits as the ensemble in classical shadow tomography. For the general observables, the variance to predict their expectation value is shown to be exponential to the number of qubits $n$. However, for a special class termed as appropriate MUBs-average (AMA) observables, the variance decreases to $poly(n)$. Additionally, we find that through biased sampling of MUBs circuits, the variance for non-AMA observables can again be reduced to $poly(n)$ with the MUBs-sparse condition. The performance and complexity of using the MUBs and Clifford circuits as the ensemble in the classical shadow tomography are compared in the end.

Scavenging excessively secreted cytokines from plasma is vital for treating cytokine storm syndrome (CSS). Therefore, appropriate adsorbent materials are highly desired for efficient and selectively capturing the plasma cytokines. For this purpose, injectable porous silicon particles (PSPs) are designed as scavenging adsorbents. The fabricated PSP features high porosity for large pore volume and high specific surface area. Polyethylene glycol is coated on the outer surface of PSP for a longer body circulation time, while antibodies are immobilized on the interior surface of PSP for the specific recognition of targeting biomacromolecules. The resultant injectable scavengers demonstrate satisfactory performance for sequestering tumor necrosis factor (TNF) or TNF receptor (TNFR) in serum and in vivo. The salient biocompatibility of the preparing scavenger is demonstrated through simulative hemoperfusion experiments and in vivo toxicology tests. Importantly, the scavengers are injected into mice like a drug to rapidly remove blood‐circulating endogenous TNFR. These features together with its facile fabrication present the silicon‐based porous particles as candidates in clinical application for relieving the infection‐induced CSS.

Classical shadow tomography, harnessing randomized informationally complete (IC) measurements, provides an effective avenue for predicting many properties of unknown quantum states with sample-efficient precision. Projections onto $2^n+1$ mutually unbiased bases (MUBs) are widely recognized as minimal and optimal measurements for tomography. We aim to establish a theoretical framework for conducting classical shadow tomography with MUBs. This approach may offer several advantages over random Clifford measurements [Nat. Phys. 16, 1050 (2020)]. Firstly, it simplifies the random measurement process since $2^n+1$ MUBs circuits are a subset of all $O(2^{n^2})$ Clifford circuits, and significantly reducing the number of all possible classical snapshots. Secondly, MUBs share the same reconstruction channel as Cliffords but with a lower shadow norm square ($< 2\mathrm{tr}(O_0^2)$), enabling equivalent property predictions with reduced sampling complexity (two-thirds). Thirdly, MUBs exhibit a uniform circuit structure, enhancing coherence with a consistent gate sequence like $-CZ-P-H-$, which is simpler than that of the Clifford circuits.

Objective:We aim to investigate the protective effect and underlying mechanisms of BMSCs-exo on human endometrial stromal cells (HESCs) induced by mifepristone in this study.Methods:BMSCs-exo were extracted and then identified by transmission electron microscopy and western-blot assay. RT-PCR assay was used to determine the level of miR-941. MiR-941 mimics or inhibitor were transfected into BMSCs and the exosomes were extracted. Then, Cell activity, apoptosis rate, cell migration and invasion, as well as the expression of angiogenic proteins were determined in HESCs stimulated by mifepristone and BMSCs-exo. Next, Dual-luciferase reporting assay was used to verify the targeted binding of miR-941 to TLR3, and the TLR3 expression in HESCs was detected by RT-PCR and western-blot. Finally, TLR3 was overexpressed to evaluate the effects of miR-941 from BMSCs-exo on cell apoptosis, cell invasion and angiogenesis in HESCs induced by mifepristone.Results:miR-941 was highly expressed in BMSCs-exo. Exosome miR-941 in BMSCs-exo inhibited the cell apoptosis, and promoted cell activity, cell migration, invasion as well as angiogenesis were also improved in HESCs induced by mifepristone. TLR3 was a target of miR-941, which was up-regulated in mifepristonetreated HESCs. We further found that miR-941 derived from BMSCs-exo down-regulated the expression of TLR3 in HESCs treated by mifepristone. In addition, TLR3 overexpression blocked the inhibition of miR-941 on mifepristone-induced cell apoptosis, as well as cell migration and angiogenesis in HESCs.Conclusions:Thus, we concluded that BMSCs-exo has protective effect on mifepristone-induced cell damage by delivering miR-941 which targeted TLR3 and regulated cell activity, migration, and angiogenesis in HESCs.

AbstractBackground:This study surveyed the prevalence of hepatitis B surface antigen (HBsAg）and hepatitis C virus（HCV）antibody (anti-HCV) among inpatients with HIV infection and analyzed the correlated factors.Methods:We conducted a retrospective data collection of the HIV-infected inpatients in our hospital from January 2010 to December 2020. We utilized multivariate logistic regression to find the correlated factors.Results:The proportion of patients screened for HBsAg were 81.8% , which increased from 66.7% in 2010 to 85.7% in 2020. The proportion of patients with anti-HCV screening were 73.9%, which increased from 58.3% in 2010 to 86.7% in 2020. The prevalence of HBsAg-positive was 10.9%, which decreased from 15.0% in the period of 2010-2015 to 9.0% for HBsAg during 2016-2020. There were 4.1% cases with positive anti-HCV. Compared to 4.8% at the period of 2010-2015, there was a similar prevalence of 3.1% for anti-HCV during 2016-2020. Among HBsAg-positive cases, HBV DNA was screened in 70.8% cases. Among anti-HCV positive cases, HCV RNA were screened in 90% cases. The ALB <30 g/L, thrombocytopenia, AST >40 U/L were associated with HBsAg-positive. The AST >40 U/L and higher CD4+ T counts were associated with HIV/HCV coinfection.Conclusions:The routine screening for both HBV and HCV among HIV-positive inpatients has been greatly improved in the past decade. However, the screening of the complete HBV serological markers in HIV-positive inpatients, and HCV genotyping among HCVRNA-positive cases leaves much to be desired. A concerted effort should be taken for improving HBV vaccine compliance in the HIV-positive population and providing direct-acting antiviral therapies to HCVRNA-positive patients.

Background: In this study, we surveyed the prevalence of hepatitis B virus (HBV) surface antigen (HBsAg) and hepatitis C virus (HCV) antibody (anti-HCV) among inpatients with human immunodeficiency virus (HIV) infection and analyzed the correlated factors. Methods: We conducted a retrospective data collection of the HIV-infected inpatients in our hospital from January 2010 to December 2020. We utilized multivariate logistic regression to identify the correlated factors. Results: The proportion of patients screened for HBsAg was 81.8%, which increased from 66.7% in 2010 to 85.7% in 2020. The proportion of patients with anti-HCV screening was 73.9%, which increased from 58.3% in 2010 to 86.7% in 2020. The prevalence of HBsAg positivity was 10.9%, which decreased from 15.0% in the period of 2010–2015 to 9.0% during 2016–2020. Positive anti-HCV was identified in 4.1% of cases. Compared to 4.8% in the period of 2010–2015, there was a similar prevalence of anti-HCV at 3.1% during 2016–2020. Among the HBsAg-positive cases, HBV deoxyribonucleic acid was screened in 70.8% of cases. Among the anti-HCV positive cases, HCV ribonucleic acid (RNA) was screened in 90% of cases. Albumin < 30 g/L, thrombocytopenia and aspartate aminotransferase (AST) > 40 U/L were associated with HBsAg positivity. AST > 40 U/L and higher CD4-positive T lymphocyte counts were associated with HIV/HCV coinfection. Conclusions: The routine screening for both HBV and HCV among HIV-positive inpatients has been greatly improved in the past decade. However, screening for the complete HBV serological markers in HIV-positive inpatients and HCV genotyping among HCV RNA-positive cases leaves much to be desired. A concerted effort should be made to improve HBV vaccine compliance in the HIV-positive population and provide direct-acting antiviral therapies to HCV RNA-positive patients.

Splenic infarction is extremely rare in human immunodeficiency virus-infected populations. We report a rare case of splenic infarction involving Mycobacterium avium complex infection in a patient with acquired immune deficiency syndrome with immune reconstitution failure. A young man was initially admitted with cryptococcus meningitis and found to be infected with human immunodeficiency virus. He had anti-cryptococcosis treatment performed in combination with placement of an Ommaya capsule because of persistent intracranial hypertension, and first-line therapy followed by second-line anti-retroviral therapy were performed. Although there was an absence of immune reconstitution, the patient refused to take prophylactic sulfamethoxazole/trimethoprim, isoniazid, and clarithromycin continuously because of gastrointestinal intolerance. Pneumocystis pneumonia then developed. Finally, the patient developed a fever again accompanied by abdominal pain and splenic infarction. M. avium complex infection was verified by a metagenomic next-generation sequencing test using a whole blood sample. M. avium complex infection should be considered as an etiology of splenic infarction in human immunodeficiency virus-infected patients with an extremely low CD 4 + T-cell count.

Background:This study investigated the factors correlated with severe liver damage among HIV-infected inpatients.Methods:We retrospectively collected the first hospitalized HIV-infected patients in the Department of Infectious Disease of the First Affiliated Hospital of China Medical University from January 1, 2010, to December 31, 2019. We used multivariate logistic regression to identify the factors associated with severe liver damage.Results:A total of 493 patients with abnormal liver tests were recruited. Among 63 cases (12.8%) with severe liver injury, drug-induced liver injury (DILI) identified by the updated Roussel Uclaf Causality Assessment Method (RUCAM) score as the direct cause was found in 43 cases. Anti-tuberculosis drug (ATD) exposure [adjusted odds ratio (aOR) = 1.835, 95% confidence interval (CI): 1.031–3.268], cotrimoxazole exposure (aOR = 2.775, 95% CI: 1.511–5.096), comorbidity of viral hepatitis (aOR = 2.340, 95% CI: 1.161–4.716), alcohol consumption history (aOR = 2.392, 95% CI: 1.199–4.769), and thrombocytopenia (aOR = 2.583, 95% CI:1.127–5.917) were associated with severe liver injury (all P < 0.05).Conclusions:DILI was the predominant cause of severe liver damage, followed by hepatitis virus co-infection. For patients with alcohol consumption and thrombocytopenia, frequent monitoring of liver function tests should be considered.

aDepartment of Infectious Diseases bPathology Department, The First Hospital of China Medical University, Shenyang, Liaoning Province, China. Correspondence to Ying Wen, Department of Infectious Diseases, The First Hospital of China Medical University, 155 Nanjing North Street, Shenyang 110001, Liaoning Province, China. Tel: +86 15840210638; e-mail: [email protected] Received 23 October, 2020 Accepted 27 October, 2020

Manipulation of ions and molecules by external control at the nanoscale is highly relevant to biomedical applications. We report a biocompatible electrode-embedded nanofluidic channel membrane designed for electrofluidic applications such as ionic field-effect transistors for implantable drug-delivery systems. Our nanofluidic membrane includes a polysilicon electrode electrically isolated by amorphous silicon carbide (a-SiC). The nanochannel gating performance was experimentally investigated based on the current-voltage (I-V) characteristics, leakage current, and power consumption in potassium chloride (KCl) electrolyte. We observed significant modulation of ionic diffusive transport of both positively and negatively charged ions under physical confinement of nanochannels, with low power consumption. To study the physical mechanism associated with the gating performance, we performed electrochemical impedance spectroscopy. The results showed that the flat band voltage and density of states were significantly low. In light of its remarkable performance in terms of ionic modulation and low power consumption, this new biocompatible nanofluidic membrane could lead to a new class of silicon implantable nanofluidic systems for tunable drug delivery and personalized medicine.

Background: Acquired immune deficiency syndrome (AIDS), caused by human immunodeficiency virus (HIV) infection, is a serious public health issue. This study investigated the correlated factors and possible changing trend of in-hospital death in patients diagnosed with HIV in the past decade in our hospital. Methods: We retrospectively collected data of firstly hospitalized patients with HIV in the Department of Infectious Disease in the First Affiliated Hospital of China Medical University from January 1, 2010 to December 31, 2019, and compared various factors that correlated with in-hospital death, including age, sex, opportunistic infections, and antiretroviral therapy (ART) status. Cox regression analysis was used to identify the risk factors for death. Results: In total, 711 patients were recruited for this study, and 62 patients died in the hospital. The in-hospital mortality rate was 8.72%. Tuberculosis (TB), malignancies, and thrombocytopenia were associated with mortality. Antiviral treatment before admission was found to be a protective factor. There was a declining trend in in-hospital mortality from 19.2% in 2010 to 6.3% in 2019 (linear-by-linear association test, p < 0.001), partly due to intensified medical care strategy. Conclusions: Till date, AIDS-defining illnesses remain the major cause of hospital admission and in-hospital mortality. TB and malignancies were correlated risk factors for in-hospital mortality. ART before admission was found to be beneficial, and considering the decreasing rate of in-hospital mortality, the implementation of intensified medical care strategy requires further effort.

Patient-centered therapeutic management for chronic medical conditions is a desired but unmet need, largely attributable to the lack of adequate technologies for tailored drug administration. While triggered devices that control the delivery of therapeutics exist, they often rely on impractical continuous external activation. As such, next generation continuously tunable drug delivery systems independent of sustained external activation remain an elusive goal. Here we present the development and demonstration of a silicon carbide (SiC)-coated nanofluidic membrane that achieves reproducible and tunable control of drug release via electrostatic gating. By applying a low-intensity voltage to a buried electrode, we showed repeatable and reproducible in vitro release modulation of three model analytes. A small fluorophore (Alexa Fluor 647), a large polymer poly(sodium 4-styrenesulfonate) and a medically relevant agent (DNA), were selected as representatives of small molecule therapeutics, polymeric drug carriers, and biological therapeutics, respectively. Unlike other drug delivery systems, our technology performed consistently over numerous cycles of voltage modulation, for over 11 days. Importantly, low power consumption and minimal leakage currents were achieved during the study. Further, the SiC coating maintained integrity and chemical inertness, shielding the membrane from degradation under simulated physiological and accelerated conditions for over 4 months. Through leveraging the flexibility offered by electrostatic gating control, our technology provides a valuable strategy for tunable delivery, setting the foundation for the next generation of drug delivery systems.

Individualized long-term management of chronic pathologies remains an elusive goal despite recent progress in drug formulation and implantable devices. The lack of advanced systems for therapeutic administration that can be controlled and tailored based on patient needs precludes optimal management of pathologies, such as diabetes, hypertension, rheumatoid arthritis. Several triggered systems for drug delivery have been demonstrated. However, they mostly rely on continuous external stimuli, which hinder their application for long-term treatments. In this work, we investigated a silicon nanofluidic technology that incorporates a gate electrode and examined its ability to achieve reproducible control of drug release. Silicon carbide (SiC) was used to coat the membrane surface, including nanochannels, ensuring biocompatibility and chemical inertness for long-term stability for in vivo deployment. With the application of a small voltage (≤ 3 V DC) to the buried polysilicon electrode, we showed in vitro repeatable modulation of membrane permeability of two model analytes—methotrexate and quantum dots. Methotrexate is a first-line therapeutic approach for rheumatoid arthritis; quantum dots represent multi-functional nanoparticles with broad applicability from bio-labeling to targeted drug delivery. Importantly, SiC coating demonstrated optimal properties as a gate dielectric, which rendered our membrane relevant for multiple applications beyond drug delivery, such as lab on a chip and micro total analysis systems (µTAS).

PurposeMounting evidence demonstrates that combining radiation therapy (RT) with immunotherapy can reduce tumor burden in a subset of patients. However, conventional systemic delivery of immunotherapeutics is often associated with significant adverse effects, which force treatment cessation. The aim of this study was to investigate a minimally invasive therapeutics delivery approach to improve clinical response while attenuating toxicity.Methods and MaterialsWe used a nanofluidic drug-eluting seed (NDES) for sustained intratumoral delivery of combinational antibodies CD40 and PDL1. To enhance immune and tumor response, we combined the NDES intratumoral platform with RT to treat the 4T1 murine model of advanced triple negative breast cancer. We compared the efficacy of NDES against intraperitoneal administration, which mimics conventional systemic treatment. Tumor growth was recorded, and local and systemic immune responses were assessed via imaging mass cytometry and flow cytometry. Livers and lungs were histologically analyzed for evaluation of toxicity and metastasis, respectively.ResultsThe combination of RT and sustained intratumoral immunotherapy delivery of CD40 and PDL1 via NDES (NDES CD40/PDL1) showed an increase in both local and systemic immune response. In combination with RT, NDES CD40/PDL1 achieved significant tumor burden reduction and liver inflammation mitigation compared with systemic treatment. Importantly, our treatment strategy boosted the abscopal effect toward attenuating lung metastatic burden.ConclusionsOverall, our study demonstrated superior efficacy of combination treatment with RT and sustained intratumoral immunotherapy via NDES, offering promise for improving therapeutic index and clinical response.

Malignant syphilis is considered a rare disease, more commonly affecting individuals with poor immunity. We report a case of acquired immune deficiency syndrome (AIDS) with repeated crusted ulcerations. Our report shows the typical skin lesions of malignant syphilis and a reinfection with the same rashes. A 22-year-old homosexual male was admitted to hospital for fever and ulcerations with overlying brown-black rupioid crusts. Then he was confirmed human immunodeficiency virus infection. Malignant syphilis was diagnosed by positive markers and biopsy pathology. After application of benzathine penicillin for 3 weeks, the symptoms improved and rapid plasma regain (RPR) decreased from 1:64 to 1:4 in 8 months. But the patient appeared with rashes that was accurately the same with rashes before 13 months later, and RPR rose to 1:128, which was likely to be reinfection after frequent sexual activity. And he responded well to doxycycline treatment. Although the clinical manifestations of malignant syphilis are severe, the response to the therapy of penicillin and doxycycline are excellent, even with repeated infection.

Background: We report a rare case of AIDS patient with crusted ulcerations.Case presentation: A 22-year-old homosexual male was admitted to hospital for fever and ulcerations with overlying brown–black crusts. Then he was confirmed human immunodeficiency virus infection . Secondary syphilis was diagnosed by positive Markers and biopsy pathology. After application of benzathine penicillin for 3 weeks, the symptoms improved. Conclusions: Malignant syphilis is a rare form of secondary syphilis, but tends to occur in AIDS patients because of low immune function. It is usually treated well after regular treatment.

Exosomes are membrane-enclosed extracellular vesicles which have been indicated as important biomarkers of cancerous cell functionality, such as multiple drug resistance (MDR). Nanoparticles based chemotherapy is a promising strategy to overcome MDR by interfering the production and composition of exosomes. Therefore, tumor-derived exosomes post-treatment by nanotherapy are implied to play critical roles of biomarkers on cancer MDR analysis. However, the efficient isolation of such exosomes from extracellular environment for their therapeutic response analysis remains challenging. In this study, we presented a microfluidic device featured exosome specific anti-CD63 immobilized ciliated micropillars, which were capable to isolate cancer-derived exosomes from cell culture medium. The captured exosomes can be recovered intact by dissolving the cilia on the micropillars using PBS soaking. Owing to the immobilized antibody in the microfluidic device, nearly 70% of exosome from the biofluid could be isolated. So the secreted exosomes of the MDR and ordinary human breast cancer cells pre-treated by free drug or nanotherapy could be isolated with high purity. The drug contents of the isolated exosomes were measured to analysis of the exosomal pathway response of MDR cells to different chemotherapeutic formulations. Such analyses and further definition of the biomarkers of these exosomes could benefit the future investigations of accurately and reliably determine design principle, functional activity, and mechanisms of nanotherapy for MDR overcoming.

Surfaces with tunable topological features enable important applications, such as optical devices, precision metrology, adhesion, and wetting. In this study, we demonstrate a facile method to fabricate and control the surface morphologies by combining thin film wrinkling and thermal expansion. This approach utilizes self-assembled surface wrinkling induced by shape recovery of shape memory polymers (SMPs) and localized thermal expansion caused by Joule heating. Recovering the prestrain in the SMP substrate induces global wrinkling of the thin film on the substrate. Joule heating in the SMP by a heating wire embedded in the substrate induces thermal expansion of the substrate in a localized area, which leads to the disappearance of the wrinkling pattern. This effect is reversed when heating is stopped, leading to reversible and repeatable tuning of the surface morphology in a controllable localized surface region. With metal coating, the SMP surface can be switched from specular to diffuse reflectance in response to external Joule heating. Finally, we demonstrate a smart micromirror device with its diffuse reflectance tunable between 13.5% and 81.9% in the visible light region. This approach provides a method to modulate surface diffusivity by controlling its surface morphologies, with potential applications in optical display and optical microelectromechanical systems devices.

Highly organized hierarchical surface morphologies possess various intriguing properties that could find important potential applications. In this paper, we demonstrate a facile approach to simultaneously form multiscale hierarchical surface morphologies through sequential wrinkling. This method combines surface wrinkling induced by thermal expansion and mechanical strain on a three-layer structure composed of an aluminum film, a hard Polydimethylsiloxane (PDMS) film, and a soft PDMS substrate. Deposition of the aluminum film on hard PDMS induces biaxial wrinkling due to thermal expansion mismatch, and recovering the prestrain in the soft PDMS substrate leads to wrinkling of the hard PDMS film. In total, three orders of wrinkling patterns form in this process, with wavelength and amplitude spanning 3 orders of magnitude in length scale. By increasing the prestrain in the soft PDMS substrate, a hierarchical wrinkling-folding structure was also obtained. This approach can be easily extended to other thin films for fabrication of multiscale hierarchical surface morphologies with potential applications in different areas.