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Introduction: Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) has been increasingly replaced by bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in the treatment of human immunodeficiency virus (HIV) owing to its more favorable pharmacokinetics and fewer drug–drug interactions. However, the effect of this switch on plasma lipids and lipidomic profiles remains poorly characterized. Methods: HIV infected patients on an E/C/F/TAF regimen were recruited into the study and followed up every 12 weeks. Participants were divided into E/C/F/TAF and B/F/TAF groups depending on whether they were switched to B/F/TAF during follow-up. Clinical information and blood samples were collected at 0, 12, and 24 weeks, and lipidomic analysis was performed using liquid chromatography mass spectrometry. Results: No significant differences were observed between the groups at baseline. At week 24, patients switched to B/F/TAF had lower triglyceride [mmol/L; 1.23 (0.62) versus 2.03 (0.75), P = 0.001] and very low-density lipoprotein cholesterol [mmol/L; 0.64 (0.26) versus 0.84 (0.32), P = 0.037) compared with patients who continued E/C/F/TAF therapy. Small decrease from baseline in Framingham general cardiovascular risk score (FRS) was observed in the B/F/TAF arm [week (W) 0: 2.59 (1.57) versus W24: 2.18 (1.01), P = 0.043]. Lipidomic analysis indicated that E/C/F/TAF treatment increased the levels of several diglycerides (DGs), triacylglycerols (TAGs), and lyso-phosphatidylcholines (LPCs), whereas switching to B/F/TAF led to increased sphingolipids and glycerophospholipids. After adjusting for demographic and clinical parameters, only DG (16:0/18:2), DG (18:2/22:6), DG (18:3/18:2), DG (20:5/18:2), TAG (18:3/18:2/21:5), TAG (20:5/18:2/22:6), and LPC (22:6) were found to be significantly associated with FRS (regression coefficient of 0.17–6.02, P < 0.05). Most of these FRS associate lipid species were significantly elevated in individuals treated with E/C/F/TAF instead of individuals treated with B/F/TAF. Conclusion: E/C/F/TAF promotes the accumulation of lipid species closely associated with cardiovascular disease (CVD) risk among people living with HIV, whereas B/F/TAF has a decreased impact on CVD-related lipid profile and is associated with lower CVD risk. A graphical abstract is available with this article. Trial registration: ClinicalTrials.gov; identifier, NCT06019273. [ABSTRACT FROM AUTHOR]

A new working principle for multimodal excitation of a resonant bidirectional rotary inertial impact piezoelectric motor with a self-clamping structure was developed based on previous research on piezoelectric motors. Unlike previous piezoelectric motors that relied on single harmonic waves for unidirectional rotation, in this motor, we can simply change the driving signal characteristics of the motor without changing the structure of the piezoelectric motor to excite multiple vibration modes, thereby achieving rotation in both directions. Compared with other bidirectional resonant motors, the structure and control signal are simpler. The finite element simulation software COMSOL5.5 was used to simulate the working mode of the motor, and the results were in good agreement with the final experiment. During the experiments, the optimal operating frequency of the motor prototype was 900 Hz. The maximum output speed of the motor prototype was 3.9 rad/s, the maximum output torque was 15 N mm, and the maximum resolution was 0.248° under the conditions of 240 Vp-p voltage, 900 Hz frequency, and 7.8 N mm preload torque. [ABSTRACT FROM AUTHOR]

Background: Patients infected with HIV are at high risk of developing Epstein-Barr Virus (EBV)-related diseases. The genotype and viral biological behavior of EBV infection in patients with human immunodeficiency virus-1 (HIV) in China remain unclear. This study analyzed the characteristics of EBV in patients infected with HIV in southeastern China. Methods: A total of 162 HIV-infected patients and 52 patients without HIV were enrolled in this study. EBV viral load in blood was determined by fluorescence quantitative PCR. EBV typing was performed using saliva according to polymorphisms in the EBNA3C region. EBV LMP-1 carboxy terminus (C-ter) was sequenced, and compared with the epidemic strains in the world. Results: Among HIV infected patients, the EBV strain variant was mainly EBV-1, while EBV-2 had a higher viral load than EBV-1 (P = 0.001) and EBV-1/2 (P = 0.002). HIV infected patients had higher active virus replication. The EBV LMP-1 variants were mainly the China1 variant. HIV-infected patients had different nucleic acid positions of 30-bp deletion (del30) and had a higher incidence of high 33-bp tandem repeats (rep33) copies than non-HIV-infected patients. There was a difference in the mutations of EBV LMP-1 C-ter del30 and ins15 between HIV infected patients and the control group (P < 0.001). Conclusion: In southeastern China, EBV in HIV-infected patients had higher active virus replication; EBV infection was mainly EBV-1, and EBV-2 infection has higher EBV virus load; hotspot mutations of LMP-1 C-ter were different between HIV-infected patients and non-HIV-infected patients. Trial registration: This study was approved by the ethics committee of the First Affiliated Hospital of Zhejiang University School of Medicine (Approval No. 2018764), and registered in Chinese Clinical Trial Registry on 3 June 2019 (ChiCTR, ChiCTR1900023600, http://www.chictr.org.cn/usercenter.aspx). [ABSTRACT FROM AUTHOR]

A resonant inertial impact rotary piezoelectric motor based on a self-clamping structure is designed, assembled, and tested. The designed piezoelectric motor mainly includes a rotor (two vibrators, preload mechanism, and intermediate connection mechanism), a clamping mechanism, and another auxiliary mechanism. The piezoelectric ceramic sheet on the rotor drives the vibrator to swing under the excitation of a single harmonic wave. Because there is a clamping mechanism formed by the combination of clamp baffle and fixed clamp ring, thus the half-cycle resonant rotation of the rotor can be effectively completed, and repeated harmonic excitation can realize the unidirectional continuous rotation and swing of the rotor. The whole excitation process of the motor is in a resonance state, which has significant advantages, such as low friction and simple structure, compared with the traditional quasi-static piezoelectric motor. The structure of the piezoelectric motor is designed and analyzed using COMSOL5.5 software and then the motor performance is tested and analyzed by building an experimental platform to verify the feasibility of the motor design. The final experimental results show that the optimal working frequency of the piezoelectric motor is 150 Hz, which is consistent with the characteristic frequency of the simulation. When the motor prototype is under the conditions of optimal operating frequency 150 Hz, voltage 240 Vp-p, and preload torque 7.8 N.mm, the maximum angular speed can reach 2.4 rad/s, the maximum load can reach 27.8 N mm and the maximum resolution of the movement angle can reach 0.941°. [ABSTRACT FROM AUTHOR]

Background: Patients with human immunodeficiency virus-associated cryptococcal meningitis (HIV-CM) have persistent intracranial inflammation despite negative cerebrospinal fluid (CSF) fungal cultures after optimal treatment for CM, which could be devastating for the central nervous system. However, a definitive treatment strategy for persistent intracranial inflammation despite optimal antifungal therapies is undefined. Methods: We identified 14 HIV-CM patients with persistent intracranial inflammation and conducted a 24-week, prospective, interventional study. All participants received lenalidomide (25 mg, p.o.) on days 1 to 21 of a 28-day cycle. Follow-up lasted for 24 weeks with visits at baseline and weeks 4, 8, 12, and 24. The primary endpoint was the change in clinical manifestations, routine CSF parameters, and MRI findings after lenalidomide treatment. An exploratory analysis was made on changes in cytokine levels in CSF. Safety and efficacy analyses were undertaken in patients who received at least one dose of lenalidomide. Results: Of 14 participants, 11 patients completed the 24 weeks of follow-up. Rapid clinical remission following lenalidomide therapy was observed. Clinical manifestations (fever, headache, altered mentation) were reversed fully by week-4 and remained stable during follow-up. A significant reduction in white blood cell (WBC) count in CSF was noted occurred at week-4 (P = 0.009). The median protein concentration in CSF decreased from 1.4 (0.7–3.2) g/L at baseline to 0.9 (0.6–1.4) at week-4 (P = 0.004). The median albumin concentration in CSF decreased from 79.2 (48.4–149.8) mg/L at baseline to 55.3 (38.3–89.0) mg/L at week-4 (P = 0.011). The WBC count, protein level, and albumin level in CSF remained stable and approached a normal range through week-24. There was no significant change in immunoglobulin-G, intracranial pressure (ICP), or chloride-ion concentration at each visit. Brain MRI demonstrated multiple lesions to be absorbed post-therapy. Levels of tumor necrosis factor-α granulocyte colony stimulating factor, interleukin (IL)-6, and IL-17A decreased significantly during 24-week follow-up. Two (14.3%) patients had mild skin rash, which resolved spontaneously. Lenalidomide-related serious adverse events were not observed. Conclusion: Lenalidomide could improve persistent intracranial inflammation in HIV-CM patients significantly and was well tolerated without serious adverse events observed. And the additional randomized controlled study is required to further validate the finding. [ABSTRACT FROM AUTHOR]

With the increase in the number of cases of autoimmune encephalitis (AE), the cerebrospinal fluid (CSF) of people living with HIV (PLWH) showing abnormal behavior, cognitive impairment or abnormal movements should be actively screened for the antibody panel of AE. Early recognition and treatment can prevent severe seizures or coma and markedly improve the prognosis of patients. The first-line immunotherapy for AE includes intravenous methylprednisolone and immunoglobulin. However, whether long-time immunosuppressive maintenance therapy is needed is debated. For PLWH, immunosuppressive therapy and even steroids could be more challenging. Here, we review and summarize the clinical characteristics often reported cases and report one case from our center to improve the diagnosis and treatment of anti-N-methyl-d-aspartate receptor encephalitis in PLWH. [ABSTRACT FROM AUTHOR]

CD4+ T cells are the central element of the adaptive immune responses and protect the body from a variety of pathogens. Starting from naive cells, CD4+ T cells can differentiate into various effector cell subsets with specialized functions including T helper (Th) 1, Th2, Th17, regulatory T (Treg) and T follicular helper (Tfh) cells. Among them, Tregs and Th17 cells show a strong plasticity allowing the functional adaptation to various physiological and pathological environments during immune responses. Although they are derived from the same precursor cells and their differentiation pathways are interrelated, the terminally differentiated cells have totally opposite functions. Studies have shown that Tregs and Th17 cells have rather complex interplays in viral infection: Th17 cells may contribute to immune activation and disease progression while Tregs may inhibit this process and play a key role in the maintenance of immune homoeostasis, possibly at the cost of compromised viral control. In this review, we take respiratory syncytial virus (RSV), hepatitis B virus (HBV)/hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections as examples to discuss these interplays and their impacts on disease progression in viral infection. [ABSTRACT FROM AUTHOR]

Based on our previous research, this article adds new research content and further refines the previous research on bionic motors. It is in the form of note as a complementary improvement to the previous article. This article proposes a novel approach to achieving reversal motion in such motors driven by a single harmonic signal, specifically the multimode mode of the vibrator. In contrast to the conventional inertial impact piezoelectric motor, we propose a bidirectional piezoelectric motor that can achieve bidirectional motion only by altering the driving signal characteristics. Compared to other bidirectional piezoelectric motors, this motor features a simpler structure and more convenient control. The COMSOL6.0 finite element analysis software was utilized to optimize the working mode of the piezoelectric motor, and an experimental platform was constructed for testing and verifying the performance of the designed prototype. The final experimental data demonstrate that, with an excitation voltage of 300 Vp-p, a preload of 2 N, and an excitation frequency of 781 Hz, the motor prototype achieves a maximum no-load speed of 12.15 mm/s, a maximum resolution of 15.27 μm, and a maximum load of 14 g. These results confirm the validity of the new working mode. [ABSTRACT FROM AUTHOR]

Robotic rectal cancer resection with natural orifice extraction is a recently developed minimally invasive surgery used in the treatment of patients with rectal cancer. However, its safety and feasibility remain undiscussed and controversial. This study reported the clinical outcomes and prognostic factors pertaining to traditional robotic assisted rectal cancer resection alone against that of robotic rectal cancer resection with natural orifice extraction to provide a discussion on this issue. 49 patients who underwent robotic rectal cancer resection with natural orifice extraction and 49 matched patients who underwent conventional robotic assisted rectal cancer resection were systematically analyzed in this study. Regarding the baseline characteristics, after matching, no significant differences were observed between the natural orifice specimen extraction (NOSE) group and the robotic assisted rectal cancer resection (RARC) group. Patients in the NOSE group had a reduced visual analog scale (p < 0.001), passed flatus more quickly (p = 0.002) and suffered less surgical stress than those in the RARC group. Moreover, 4 complications were observed in the NOSE group and 7 complications in the RARC group with no significant difference (p = 0.337) in terms of complications. The two groups had a similar survival outcomes, where the 3-year overall survival (p = 0.738) and 3-year progression-free survival (p = 0.986) were all comparable between the two groups. Histological differentiation and T stage could be regarded as independent prognostic factors for 3-year overall survival and 3-year progression-free survival. Robotic rectal cancer resection with natural orifice extraction is a safe and feasible minimally invasive surgery for patients suffering from rectal cancer as it encompasses considerable several advantages. Histological differentiation and T stage may serve as independent prognostic factors for 3-year overall survival and 3-year progression-free survival. [ABSTRACT FROM AUTHOR]

In this study, a resonant single-wing bionic piezoelectric motor based on a biasing self-clamping mechanism inspired by dragonfly flight was designed, assembled, and tested. The main mechanism of the designed piezoelectric motor includes a mover (including a vibrator, clamping foot, bionic pedestal, etc.), a stator, and other auxiliary components. The clamping foot of the mover contacts the side of the stator to form a biasing self-clamping mechanism, which can achieve a clamping effect within half a cycle of the vibrator's resonant vibration. The piezoelectric plate on the vibrator receives a single harmonic excitation from the signal generator, causing the base plate to bend and distort. The base plate drives the clamping foot to move regularly, causing the mover to perform a linear motion. Moreover, repeated single harmonic excitations can realize the continuous movement of the mover. The structure of the piezoelectric motor was optimized using COMSOL6.0, which is a finite element analysis software. The first-order bending vibration of the vibrator was chosen as the working mode through finite element simulation, and an experimental platform was built. The performance of the prototype piezoelectric motor was tested and verified on the experimental platform. The final experimental data show that under the conditions of 300 Vp–p excitation voltage and 109 Hz driving frequency, the maximum no-load speed of the prototype reaches 6.184 mm/s, and the maximum load of the motor is 4 g. [ABSTRACT FROM AUTHOR]