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Abstract This study aimed to evaluate the efficacy and safety of dolutegravir plus lamivudine (DTG/3TC) in antiretroviral treatment (ART)-experienced people living with HIV (PLWH). A total of 303 PLWH in Shanghai, China, who switched from triple ART to DTG/3TC between January 2019 and June 2022, with a minimum ART duration of 6 months, were retrospectively enrolled. More than 95% of PLWH maintained viral suppression with no significant changes in CD4 counts 12 months after switching. Patients transitioning from non-tenofovir (TDF)-based regimens demonstrated more pronounced improvements in lipid profiles, while those previously on TDF-based regimens showed greater enhancements in bone metabolism.

The migration behavior of nitrate ester-plasticized polyether (NEPE) propellant components significantly impacts safety. Experimentally observing the migration process is challenging and time-consuming. This study employed molecular dynamics (MD) methods to simulate a molecular model of the NEPE propellant/liner interface layer, enabling the prediction of component migration behavior. We visualized the migration process of all propellant components and studied the interface layer components' migration patterns, diffusion coefficients, and concentration gradient distributions. The contents of migrated components of the propellant and liner at different accelerated aging times at 70 °C were determined using high-performance liquid chromatography (HPLC), and the simulation patterns were compared with experimental observations. The results indicate that the migrated components in the propellant mainly consist of nitrate esters (Nitroglycerin, abbreviated as NG, and Butanetriol Trinitrate, abbreviated as BTTN), stabilizers (NMethylnitroaniline, abbreviated as MNA, and 2-Nitrodiphenylamine, abbreviated as 2-NDPA), and solid component (Hexahydro-1,3,5-trinitro-1,3,5-triazine, abbreviated as RDX). The migration process is primarily dominated by the substantial migration of nitrate esters, which is a key factor contributing to the degradation of propellant performance during storage. The migration process can be divided into three stages: swift migration, steady slow migration, and migration equilibrium. The diffusion coefficients are ranked from most significant to most minor as NG > BTTN > RDX > MNA > 2-NDPA. Three migration stages consistent with the simulation process were observed using HPLC, and the migration behavior of nitrate esters aligned with simulation patterns. Our designed full-component model can qualitatively predict component migration behavior. Additionally, a faster diffusion coefficient does not necessarily lead to a greater amount of migration. We employed MD simulations combined with density functional theory (DFT) calculations to explain this phenomenon and found that intermolecular interactions may influence the diffusion coefficient. At the same time, the migration amount is highly correlated with molecular polarity. Therefore, increasing the molecular polarity difference between easily migrating components and liner materials is a beneficial strategy for slowing the migration process and enhancing the storage safety of propellants.

Metal rubber, which has the advantages of low density, strong environmental adaptability, and excellent design flexibility, is widely applied in manufacturing industries such as the aerospace, shipping, and automotive industries. Based on the research object of flexible porous metal rubber (FPMR) structures made of high-temperature elastic alloys, this study established a constitutive model for the quasi-static mechanical properties of FPMR structure under ultra-wide temperature range conditions. Firstly, the forming mechanism and the influencing factors of the static stiffness properties of the FPMR micro-structure were analyzed. Then, the theoretical model of the FPMR micro-element spring was established by applying the cylindrical spiral compression spring stiffness theory, and the theoretical model was corrected based on the large deformation theory and numerical analysis methods. A comparative analysis was carried out through the corrected theoretical model and the test results of different test samples. And the results show that the corrected theoretical model can comprehensively reflect the nonlinear quasi-static stiffness characteristics of the FPMR structure in an ultra-wide temperature range. More importantly, by comparison with the prediction models proposed by other scholars, it is proved that the model proposed in this paper has higher prediction accuracy and the goodness of fit R2 is closer to 1, which provides a theoretical basis for the application of metal rubber in flexible support structures under ultra-high temperature environments.

The study aimed to analyze changes in the clinical and epidemiological aspects of HIV-associated cryptococcal meningitis (CM) patients and to identify factors influencing their prognosis. Clinical data of patients with HIV-associated CM treated in Shanghai, China between 2013 and 2023 were collected. This study included 279 cases, 2.89% of AIDS patients, showing a yearly decrease in CM prevalence among AIDS patients (p < 0.001). Overall mortality was 10.39% with rates declining from a 2013 peak of 15.38% to 0% in 2023 despite no significant temporal pattern (p = 0.265). Diagnosis took an average of 18 ± 1 days post-symptoms, and admission CD4 counts averaged 29.2 ± 2.5 cells/μL, hinting at a non-significant decline. Frequent symptoms included fever (62.4%), headache (61.6%), fatigue (44.1%), and appetite loss (39.8%), with younger patients more likely to initially show signs of meningeal irritation. Logistic regression analysis underscored the prognostic importance of cerebrospinal fluid (CSF) white blood cell (WBC) count and procalcitonin levels. Over the decade spanning from 2013 to 2023, the incidence and mortality rates of CM among AIDS patients exhibited a downward trend. The average duration from the onset of CM to confirmation of diagnosis remained prolonged. CSF WBC count and procalcitonin levels were associated with unfavorable outcomes.

Pancreatic adenocarcinoma (PAAD) is a notably aggressive malignancy with limited treatment options and an unfavorable prognosis for patients. We aimed to investigate molecular mechanisms by which Sam's pointed domain-containing ETS transcription factor (SPDEF) exerts effects on PAAD progression. We analyzed differentially expressed genes (DEGs) and their integration with ETS family members using the The Cancer Genome Atlas (TCGA) database, hence identifying SPDEF as a core gene in PAAD. Kaplan-Meier survival analysis confirmed SPDEF’s prognostic potential. In vitro experiments validated the association with cell proliferation and apoptosis, affecting pancreatic cancer cell dynamics. We detected increased SPDEF expression in PAAD tumor samples. Our in vitro studies revealed that SPDEF regulates mRNA and protein expression levels, and significantly affects cell proliferation. Moreover, SPDEF was associated with reduced apoptosis and enhanced cell migration and invasion. In-depth analysis of SPDEF-targeted genes revealed four crucial genes for advanced prognostic model, among which S100A16 was significantly correlated with SPDEF. Mechanistic analysis showed that SPDEF enhances the transcription of S100A16, which in turn enhances PAAD cell migration, proliferation, and invasion by activating the PI3K/AKT signaling pathway. Our study revealed the critical role of SPDEF in promoting PAAD by upregulating S100A16 transcription and stimulating the PI3K/AKT signaling pathway. This knowledge deepened our understanding of pancreatic cancer's molecular progression and unveiled potential therapeutic strategies targeting SPDEF-driven pathways.

Abstract Introduction Cryptococcal meningitis (CM) is a serious and fatal fungal infection that affects individuals infected with human immunodeficiency virus (HIV). Despite treatment, recurrence of symptoms is common and could lead to poor outcomes. Corticosteroids are not always useful in treating symptom recurrence following HIV/CM; thus, alternative therapy is needed. Thalidomide has been reported to be effective in treating symptom recurrence in several patients with HIV/CM. This retrospective study aimed to investigate the efficacy and safety of thalidomide in the treatment of symptom recurrence following HIV/CM. Methods Patients who were treated with thalidomide for symptom recurrence following HIV/CM were retrospectively included. Clinical outcomes and adverse events were recorded and analyzed. Results Sixteen patients admitted between July 2018 and September 2020 were included in the analysis. During a median follow-up period of 295 (166, 419) days, all patients achieved clinical improvement in a median of 7 (4, 20) days. Among them, nine (56%) achieved complete resolution of symptoms at a median of 187 (131, 253) days, including 40% (2/5) of immune reconstitution inflammatory syndrome (IRIS), 50% (3/6) of patients with elevated ICP only, and 80% (4/5) of patients with symptoms only. Seven (43%) patients experienced nine episodes of adverse events, but no severe adverse event attributable to thalidomide was observed. None of the patients withdrew from thalidomide due to adverse events. Conclusion Thalidomide appears to be effective and safe in treating different types of symptom recurrence in HIV/CM. This study provides preliminary evidence supporting future randomized clinical trials to further investigate the efficacy and safety of thalidomide in treating symptom recurrence in this population.

ObjectiveThis study aimed to develop an arbitrary-dimensional nerve root reconstruction magnetic resonance imaging (ANRR-MRI) technique for identifying the leakage orificium of sacral meningeal cysts (SMCs) without spinal nerve root fibres (SNRFs).MethodsThis prospective study enrolled 40 consecutive patients with SMCs without SNRFs between March 2021 and March 2022. Magnetic resonance neural reconstruction sequences were performed for preoperative evaluation. The cyst and the cyst-dura intersection planes were initially identified based on the original thin-slice axial T2-weighted images. Sagittal and coronal images were then reconstructed by setting each intersecting plane as the centre. Then, three-dimensional reconstruction was performed, focusing on the suspected leakage point of the cyst. Based on the identified leakage location and size of the SMC, individual surgical plans were formulated.ResultsThis cohort included 30 females and 10 males, with an average age of 42.6 ± 12.2 years (range, 17–66 years). The leakage orificium was located at the rostral pole of the cyst in 23 patients, at the body region of the cyst in 12 patients, and at the caudal pole in 5 patients. The maximum diameter of the cysts ranged from 2 cm to 11 cm (average, 5.2 ± 1.9 cm). The leakage orificium was clearly identified in all patients and was ligated microscopically through a 4 cm minimally invasive incision. Postoperative imaging showed that the cysts had disappeared.ConclusionANRR-MRI is an accurate and efficient approach for identifying leakage orificium, facilitating the precise diagnosis and surgical treatment of SMCs without SNRFs.

BackgroundThe incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML.MethodsA retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai, China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA.ResultsTwenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL. The estimated probability of survival at six months was 78% (95% confidential intervals [CIs]:0.63-0.85). OIs, low CD4+ T cell count were associated with lower estimated six-month survival (hazard ratio 8.01, 95% CIs: 1.80-35.00, P=0.006 and 5.01, 95% CIs:1.57-16.03, p=0.007). Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p

Carpal tunnel syndrome (CTS) is a common peripheral neuropathy of the hand, mainly manifesting as sensory disturbances, motor dysfunctions, and pain in the fingers and hand. The pathogenesis of the disease is associated with fibrosis of the transverse carpal ligament in the carpal tunnel, which compresses median nerve. In our case, we demonstrate an ultrasound-guided needle knife technique to treat CTS. We guided the patient to a supine position on the examination table. The skin of the wrist area was sterilized for the procedure. After the skin was dry, we positioned sterile drapes, located the median nerve and compression, and marked the compression point. Local anesthesia was administered. An ultrasound-guided needle knife was inserted. The needle knife was advanced under ultrasound guidance. The carpal ligament was incised. A gradual release of pressure on the median nerve was observed on the ultrasound monitor. After treatment, the patient’s finger sensation and motor function can significantly improve, and pain symptoms are markedly reduced, this case demonstrates that small needle-knife treatment can serve as a safe and effective minimally invasive therapeutic method.

IntroductionSacral laminoplasty with titanium mesh and titanium screws can reduce symptomatic sacral extradural spinal meningeal cysts (SESMCs) recurrence and operation complications. However, due to a defect or thinning of the sacrum, the screws cannot be securely anchored and there are also problems with permanent metal implantation for titanium mesh and screws. We propose that sacral laminoplasty with absorbable clamps can provide rigid fixation even for a thinned or defected sacrum without leaving permanent metal implants.MethodsIn the direct microsurgical treatment of symptomatic SESMCs, we performed one-stage sacral laminoplasty with autologous sacral lamina reimplantation fixed by absorbable fixation clamps. Retrospectively, we analyzed intraoperative handling, planarity of the sacral lamina, and stability of the fixation based on clinical and radiological data.ResultsBetween November 2021 to October 2022, we performed sacral laminoplasty with the absorbable craniofix system in 28 consecutive patients with SESMCs. The size of the sacral lamina flaps ranged from 756 to 1,052 mm2 (average 906.21 ± 84.04 mm2). We applied a minimum of two (in four cases) and up to four (in four cases) Craniofix clamps in the operation, with three (in 20 cases) being the most common (82.14%, 20/28) and convenient to handle. Excellent sacral canal reconstruction could be confirmed intraoperatively by the surgeons and postoperatively by CT scans. No intraoperative complications occurred.ConclusionsOne-stage sacral laminoplasty with absorbable fixation clamps is technically feasible, and applying 3 of these can achieve a stable fixation effect and are easy to operate. Restoring the normal structure of the sacral canal could reduce complications and improve surgical efficacy.

Abstract Background Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs. Methods This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death. Results After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P

Due to the lack of flexible interconnection devices, power imbalances between networks cannot be relieved effectively. Meanwhile, increasing the penetration of distributed generators exacerbates the temporal power imbalances caused by large peak-valley load differences. To improve the operational economy lowered by spatiotemporal power imbalances, this paper proposes a two-stage optimization strategy for active distribution networks (ADNs) interconnected by soft open points (SOPs). The SOPs and energy storage system (ESS) are adopted to transfer power spatially and temporally, respectively. In the day-ahead scheduling stage, massive stochastic scenarios against the uncertainty of wind turbine output are generated first. To improve computational efficiency in massive stochastic scenarios, an equivalent model between networks considering sensitivities of node power to node voltage and branch current is established. The introduction of sensitivities prevents violations of voltage and current. Then, the operating ranges (ORs) of the active power of SOPs and the state of charge (SOC) of ESS are obtained from models between networks and within the networks, respectively. In the intraday corrective control stage, based on day-ahead ORs, a receding-horizon model that minimizes the purchase cost of electricity and voltage deviations is established hour by hour. Case studies on two modified ADNs show that the proposed strategy achieves spatiotemporal power balance with lower cost compared with traditional strategies.

Context The mechanism of tetrandrine (TET) in hepatocellular carcinoma (HCC) progression and sorafenib (Sora) chemosensitivity deserves investigation. Objective Using network pharmacology approaches to elucidate the mechanisms of TET in HCC. Materials and methods CCK-8, colony formation, and flow cytometry assays were used to measure cell phenotypes. BALB/c nude mice were divided into Control, Sora (10 mg/kg), TET (50 mg/kg), and TET + Sora (10 mg/kg Sora plus 50 mg/kg TET) groups to evaluate the antitumor effects of TET for 21 days. Sora and TET were given by intraperitoneal injection or oral gavage. Results For SMMC7721 (IC50 = 22.5 μM) and PLC8024 (IC50 = 18.4 μM), TET (10, 20 μM) reduced colony number (0.68 ± 0.04- and 0.50 ± 0.04-fold, 0.56 ± 0.04- and 0.42 ± 0.02-fold), induced cell cycle arrest at G0/G1 stage (1.22 ± 0.03- and 1.39 ± 0.07-fold, 1.37 ± 0.06- and 1.55 ± 0.05-fold), promoted apoptosis (2.49 ± 0.26- and 3.63 ± 0.33-fold, 2.74 ± 0.42- and 3.73 ± 0.61-fold), and inactivated PI3K/AKT/mTOR signalling. Sora (10 μM) decreased cell proliferation, enhanced apoptosis, and inhibited PI3K/AKT/mTOR signalling, and these effects were further aggravated in the combination group. Activating PI3K/AKT/mTOR reversed the effects of TET on cell proliferation and Sora sensitivity. In the combination group, tumour volumes and weights were decreased to 202.3 ± 17.4 mm3 and 151.5 ± 25.8 mg compared with Sora (510.6 ± 48.2 mm3 and 396.7 ± 33.5 mg). Discussion and conclusions TET enhances Sora sensitivity by inactivating PI3K/AKT/mTOR, suggesting the potential of TET as a chemosensitizer in HCC.

The massive growth of online commercial data has raised the request for an automatic recommender system to benefit both users and merchants. One of the most frequently used recommendation methods is collaborative filtering, but its accuracy is limited by the sparsity of the rating dataset. Most existing collaborative filtering methods consider all features when calculating user/item similarity and ignore much local information. In collaborative filtering, selecting neighbors and determining users’ similarities are the most important parts. For the selection of better neighbors, this study proposes a novel biclustering method based on modified fuzzy adaptive resonance theory. To reflect the similarity between users, a new measure that considers the effect of the number of users’ common items is proposed. Specifically, the proposed novel biclustering method is first adopted to obtain local similarity and local prediction. Second, item-based collaborative filtering is used to generate global predictions. Finally, the two resultant predictions are fused to obtain a final one. Experiment results demonstrate that the proposed method outperforms state-of-the-art models in terms of several aspects on three benchmark datasets.

Trends in and risk factors for drug resistance in Mycobacterium tuberculosis (M. tuberculosis) in human immunodeficiency virus (HIV)-infected patients with active tuberculosis were analyzed. The clinical data of M. tuberculosis and HIV-coinfected patients treated at the Shanghai Public Health Clinical Center between 2010 and 2022 were collected. The diagnosis of tuberculosis was confirmed by solid or liquid culture. The phenotypic drug susceptibility test was carried out via the proportional method, and the resistance to first-line and second-line drugs was analyzed. Logistic regression analysis was performed to identify associated risk factors for drug resistance in M. tuberculosis. Of the 304 patients with a M. tuberculosis-positive culture and first-line drug susceptibility test results, 114 (37.5%) were resistant to at least one first-line anti-tuberculosis drug. Of the 93 patients with first-line and second-line drug susceptibility test results, 40 (43%) were resistant to at least one anti-tuberculosis drug, and 20 (21.5%), 27 (29.0%), 19 (20.4%), 16 (17.2%), and 14 (15.1%) were resistant to rifampicin, streptomycin, ofloxacin, levofloxacin, and moxifloxacin, respectively; 17 patients (18.3%) had multidrug-resistant tuberculosis (MDR-TB). Between 2010 and 2021, the rate of resistance to streptomycin and rifampicin ranged from 14.3% to 40.0% and from 8.0% to 26.3%, respectively, showing an increasing trend year by year. From 2016 to 2021, the rate of resistance to quinolones fluctuated between 7.7% and 27.8%, exhibiting an overall upward trend. Logistic regression analysis showed that being aged p = 0.023; RR 7.734, p = 0.047; RR 3.733, p = 0.009). Retreatment tuberculosis was a risk factor for resistance to rifampicin, ofloxacin, of levofloxacin (RR 2.984, p = 0.047; RR 4.517, p = 0.038; RR 6.277, p = 0.014). The drug resistance rates of M. tuberculosis to rifampicin and to quinolones in HIV/AIDS patients were high and have been increasing year by year. Age and a history of previous anti-tuberculosis treatment were the main factors associated with the development of drug resistance in HIV/AIDS patients with tuberculosis.

Abstract The optimal texture shape considering surface roughness is determined by solving the average Reynolds equation, selecting Jakobsson–Floberg–Olsson boundary conditions, and using a genetic algorithm. The effects of surface roughness as indicated by the combined root-mean-square (RMS), surface pattern parameter, and operating parameters on the friction coefficient, area ratio, and depth of the optimal self-defined shape and optimal dimple were studied. Results show that the friction coefficient will be significantly reduced during the shape optimization considering the effect of surface roughness. The variation laws of the optimal dimple area ratio with the combined RMS, surface pattern parameter, minimum film thickness, sliding speed and the variation law of the optimal depth of the optimal self-defined shape with surface roughness and working parameters are obtained. Finally, this study concludes that the influence of roughness parameters on the optimal dimple shape is greater than that on the optimal self-defined shape under different sliding speeds.

Abstract Background We summarize 5 cases of primary gliosarcoma with widespread extracranial metastases including our case. The glial components are eliminated due to the needs of the living environment in the process of parasitism and survival of brain glioma-sarcoma cells in lung metastasis. Methods A PubMed search using the keywords “gliosarcoma” and “extracranial metastases” was performed followed by a review of cited literature. Our case was a 50-year-old female presented with headache and dizziness. MRI examination showed that there was a cystic solid tumor in the right temporal lobe. The tumor was removed totally. Seven months after the operation, the patient suffered recurrent intermittent headache. The resection for the recurrent tumor was performed. Postoperative pathology confirmed the recurrent gliosarcoma. A needle biopsy was performed for the nodular on the right lung. The lung tumor pathology suggested a sarcoma structure. Results There was a female patient in five cases. The age range is 47 to 69 years old. The tumor recurred within a year. A combination of treatment modalities may extend survival; however, the prognosis remains poor. Conclusion Primary gliosarcoma with extracranial metastases is extremely rare. Some findings uncovered an unexpected spatiotemporal morphological variation in the different foci of the same malignancy.

IntroductionBenign paroxysmal positional vertigo (BPPV), the most common cause of dizziness, especially for older adults, exposes patients to the lethal risk of falling. However, the diagnosis of BPPV in this population can be more elusive as they present few characteristic symptoms. Therefore, we explored the application of a subtype-determining questionnaire in BPPV diagnosis among the geriatric population.MethodsPatients were assigned to the aware and unaware groups. In the aware group, the technician would directly test the suspected canal indicated by the questionnaire, whereas, in the unaware group, the technician performed the regular positional test. The diagnostic parameters of the questionnaire were examined.ResultsThe accuracy, sensitivity, and specificity of questions 1–3 for diagnosing BPPV were 75.8, 77.6, and 74.7%, respectively. Question 4 demonstrated an accuracy of 75.6% in ascertaining the BPPV subtype, question 5 showed an accuracy of 75.6% in determining the affected side, and question 6 yielded an accuracy of 87.5% in distinguishing canalithiasis or cupulolithiasis. Examination time was shorter in the aware group than that in the unaware group (P < 0.05). No difference was found between the two groups for treatment time (P = 0.153).ConclusionThis subtype-determining questionnaire is practical in daily use and capable of providing instructive information for an efficient diagnosis in geriatric patients with BPPV.

BackgroundParaganglioma in the sellar region is an extremely rare entity, with a limited number of cases reported in the literature. Due to the paucity of clinical evidence, the diagnosis and treatment of paragangliomas in the sellar region remain challenging. Herein, we reported a case of sellar paraganglioma with parasellar and suprasellar extension. Particularly, the dynamic evolution of this benign tumor within a 7-year longitudinal observation was presented. Additionally, the relevant literature regarding sellar paraganglioma was comprehensively reviewed.Case descriptionA 70-year-old woman presented with progressive visual deterioration and headache. Brain magnetic resonance imaging demonstrated a mass in the sellar region with parasellar and suprasellar extension. The patient refused surgical treatment. Seven years later, brain magnetic resonance imaging showed the lesion significantly progressed. Neurological examination revealed bilateral tubular contraction of visual fields. Laboratory examinations showed endocrine hormone levels were normal. Surgical decompression was performed via a subfrontal approach, and subtotal resection was achieved. Histopathological examination confirmed a diagnosis of paraganglioma. Postoperatively, she developed hydrocephalus, and ventriculoperitoneal shunting was performed. Eight months later, cranial CT showed no recurrence of the residual tumor, and the hydrocephalus had been relieved.ConclusionParaganglioma occurring in the sellar region is rare, and the preoperative differential diagnosis is difficult. Owing to the infiltration to the cavernous sinus and internal carotid, complete surgical resection is usually impracticable. There has been no consensus regarding postoperative adjuvant radiochemotherapy for the tumor residue. In-situ recurrence and metastasis have been reported in the literature, and close follow-up is warranted.

Abstract Introduction Individual variability of rivaroxaban was observed in clinical application. This study aimed to identify genetic variants associated with the variability of pharmacodynamics and bleeding risk of rivaroxbaban in patients with nonvalvular atrial fibrillation (NVAF). Materials and Methods From June 2017, and July 2019, this study enrolled 257 patients with NVAF receiving rivaroxaban. Pharmacodynamics was assessed by determining anti‐Factor Xa (anti‐FXa) level 3 h after rivaroxaban administration as peak concentration. Whole‐exome sequencing was performed to detected single nucleotide polymorphisms (SNPs). This study was registered (NCT03161496). Results The bleeding events within 12 months were significantly related to the peak anti‐FXa level (p = .027). SUSD3 rs76292544 was associated with 12‐month bleeding events (odds ratio [OR]: 4.20, 95% confidence interval [CI]: 2.17–8.14, p = 6.43×10−5). Five SNPs including NCMAP rs4553122 (p = 2.29×10−5), PRF1 rs885821 (p = 7.02×10−5), PRKAG2 rs12703159 (p = 7.97×10−5), PRKAG2 rs13224758 (p = 8.70×10−5), and POU2F3 rs2298579 (p = 8.24×10−5) were associated with peak anti‐FXa level. Genetic variants of 52 SNPs from 36 genes including GOT2 rs14221 and MMP13 rs640198 were potentially related to 12‐month bleeding events caused by rivaroxaban's efficacy. Conclusions Peak anti‐FXa level was associated with risk of bleeding events in patients with NVAF receiving rivaroxaban. SUSD3 rs76292544 was suggestively associated with 12‐month bleeding events and five SNPs (NCMAP rs4553122, PRF1 rs885821, PRKAG2 rs12703159, rs13224758 and POU2F3 rs2298579) were suggestively associated with peak anti‐FXa level.

Objectives: Cross-reactivity with nontuberculous mycobacteria (NTM) species might limit the use of urine lipoarabinomannan (LAM) test to diagnose tuberculosis (TB) in people living with HIV (PLWH). This study aimed to investigate the utility of the LAM test among hospitalized HIV-positive patients. Methods: This prospective study enrolled HIV-positive inpatients with any TB symptom or seriously ill patients with advanced immunodeficiency. Urine samples were tested using the Alere Determine LAM Ag, and participants were categorized as confirmed TB, confirmed NTM infection, unclassified mycobacteria infection, and no mycobacteria infection based on microbiologic reference standards. Results: A total of 382 participants were included. The prevalence of confirmed TB and NTM infection was 5.24% (20 of 382) and 4.45% (17 of 382), respectively. The sensitivity and specificity of the urine LAM for TB diagnosis were 65.00% (95% confidence interval [CI] 40.78-84.61) and 89.36% (95% CI 85.68-92.36), respectively. The LAM test for NTM yielded a sensitivity of 58.82% (95% CI 32.92-81.56) and specificity of 88.61% (95% CI 84.87-91.70). Notably, the negative predictive values of the urine LAM for TB and NTM were 97.85% (95% CI 95.63-99.13) and 97.85% (95% CI 95.63-99.13), respectively. Conclusions: Cross-reactivity with NTM cause high false-positive LAM for TB diagnosis in PLWH. The correct identification of mycobacteria species is crucial for deciding treatment strategies.

Background: Rifamycins are the cornerstone of anti-tuberculosis therapy while they are potent inducers of drug metabolizing enzymes. For the first time, we evaluated the effect of rifampicin (RIF) and rifabutin (RBT) on the pharmacokinetics (PK) of dolutegravir (DTG) in patients with HIV and tuberculosis (TB)/ mycobacterium avium complex (MAC) co-infection. Methods: Both HIV/TB (or MAC) co-infected patients and HIV infected patients without TB/MAC were enrolled. Patients in the RIF group received DTG 50 mg twice daily together with 600mg of RIF, while patients in the RBT group received DTG 50 mg once daily together with 300 mg of RBT. The DTG pharmacokinetic profiles in different groups were assessed. Results: A total of 13 subjects in the RIF group, 12 subjects in the RBT group, and 10 subjects in non-TB/MAC group were enrolled. The geometric mean ratio (GMR) of the trough concentration (Ctr) of DTG in the RIF group to non-TB/MAC group was 1.33 [90% confidence interval (CI):0.97 to 1.81], while the GMR of the maximum concentration (Cmax) of DTG was 1.29 (90% CI: 1.23 to 1.36). The GMR of the Ctr of DTG in the RBT group to non-TB/MAC group was 0.41 (90% CI: 0.30 to 0.57), while the GMR of the Cmax of DTG was 0.55 (90% CI: 0.52 to 0.57). Conclusions: Due to the relatively low trough concentrations of DTG with RBT, DTG 50mg once daily together with RBT could only serve as an alternative option for HIV/TB (or MAC) co-infected patients.

Abstract Background Few data are available regarding the long-term case-fatality rate (CFR) among people living with HIV (PLWH) with nontuberculous mycobacteria (NTM) disease. The aim of this study is to analyze the long-term CFR in patients with NTM disease and to identify risk factors for their death. Methods A retrospective cohort study of 379 cases of microbiologically confirmed NTM disease in PLWH was conducted from January 1, 2012, to December 31, 2020, in Shanghai, China. We used Kaplan–Meier survival analysis and the log-rank test to compare the long-term CFR in patients with disseminated NTM (DNTM) and localized NTM disease. Univariate Cox proportional hazards regression analysis and a stepwise Cox proportional hazards regression model were used to estimate the predictors of long-term CFR. Results The cohort was followed up for a median of 26 months. The total CFR was 15.7% by one year and increased to 22.6% at 5 years after the diagnosis of NTM disease. The 5-year CFR of PLWH with DNTM was significantly higher than that of PLWH with localized NTM (26.7% vs 19.6% for DNTM and localized NTM disease, respectively). Older age [hazard ratio (HR) = 1.04, 95% confidence interval (CI): 1.02–1.06, P

Current genetic studies (e.g. gene knockout) have suggested that EsxA and EsxB function as secreted virulence factors that are essential for Mycobaterium tuberculosis (Mtb) intracellular survival, specifically in mediating phagosome rupture and translocation of Mtb to the cytosol of host cells, which further facilitates Mtb intracellular replicating and cell-to-cell spreading. The EsxA-mediated intracellular survival is presumably achieved by its pH-dependent membrane-permeabilizing activity (MPA). However, the data from other studies have generated a discrepancy regarding the role of EsxA MPA in mycobacterial intracellular survival, which has raised a concern that genetic manipulations, such as deletion of esxB-esxA operon or RD-1 locus, may affect other codependently secreted factors that could be also directly involved cytosolic translocation, or stimulate extended disturbance on other genes’ expression. To avoid the drawbacks of gene knockout, we first engineered a Mycobacterium marinum (Mm) strain, in which a DAS4+ tag was fused to the C-terminus of EsxB to allow inducible knockdown of EsxB (also EsxA) at the post-translational level. We also engineered an Mm strain by fusing a SpyTag (ST) to the C-terminus of EsxA, which allowed inhibition of EsxA-ST MPA at the post-secretional level through a covalent linkage to SpyCatcher-GFP. Both post-translational knockdown and functional inhibition of EsxA resulted in attenuation of Mm intracellular survival in lung epithelial cells or macrophages, which unambiguously confirms the direct role of EsxA MPA in mycobacterial intracellular survival.

Background: The COVID-19 pandemic is a serious challenge to human medicines. Modern medicine (MM) has been excellent in identifying the virus, sequencing its mutants, and monitoring the pandemic progress. However, due to lack of effective antivirals in the first two years of the pandemic, MM treated COVID-19 mainly by conventional supportive care with limited efficacy. In China, traditional Chinese medicine (TCM) has been actively participating the control of COVID-19, and the combination of TCM and conventional supportive care has shown better efficacies than the conventional care alone. Purpose: Clinical studies have shown that TCM treats COVID-19 through a holistic action, such as repairing organ injuries, anti-inflammation, immunoregulation and antiviral activities, etc. However, it is not clear how TCM is able to achieve these effects, and the scientific interpretation of TCM theories is lacking. This review aims to elucidate the scientific basis underlying TCM theories in the context of host-pathogen interaction and provide a working model for TCM in treating infectious diseases. Procedure: This review focuses on the essential components of host-pathogen interaction and performs an in-depth analysis of current literatures, including TCM theories and clinical studies as well as the most recent findings of tolerance (self-healing) mechanism in biomedical sciences. Conclusion: TCM treats COVID-19 through a holistic regulation of host responses, particularly by promoting patients’ self-healing power and balancing immune responses. Compared to the pathogen-centered MM, the host-centered TCM doesn't require specific antivirals and has less side-effects and drug resistance. This review provides a scientific insight into the mechanism of TCM and sheds a light on the prospective integration of TCM and MM for future challenges.

Abstract Introduction To identify the potential factors responsible for the individual variability of dabigatran, we investigated the genetic variations associated with clinical outcomes and pharmacodynamics (PD) in Chinese patients with nonvalvular atrial fibrillation (NVAF). Materials and methods Chinese patients with NVAF taking dabigatran etexilate with therapeutic doses were enrolled. The primary (bleeding events) and secondary (thromboembolic and major adverse cardiac events) outcomes for a 2‐year follow‐up were evaluated. Peak and trough PD parameters (anti‐FIIa activity, activated partial thromboplastin time and prothrombin time) were detected. Whole‐exome sequencing, genome‐wide sequencing and candidate gene association analyses were performed. Results There were 170 patients with NVAF treated with dabigatran (110 mg twice daily) who were finally included. Two single‐nucleotide polymorphisms (SNPs) were significantly related with bleeding, which include UBASH3B rs2276408 (odds ratio [OR] = 8.79, 95% confidence interval [CI]: 2.99–25.83, p = 7.77 × 10−5 at sixth month visit) and FBN2 rs3805625 (OR = 8.29, 95% CI: 2.87–23.89, p = 9.08 × 10−5 at 12th month visit), as well as with increased trends at other visits (p

Abstract Recent studies have shown that ANXA2 is important in the development of many cancers, while its role in glioma-related immune response remains unclear. We aimed to comprehensively investigate its biological characteristics and clinical value in glioma. We analyzed 699 glioma samples from The Cancer Genome Atlas as training cohort and 325 samples from the Chinese Glioma Genome Atlas as validation cohort. All the statistical analyses and figures were generated with R. ANXA2 was overexpressed significantly in high-grade glioma, isocitrate dehydrogenase wild-type and mesenchymal-subtype glioma. ANXA2 was a special indicator of mesenchymal subtype. The survival analysis showed that highly-expressed ANXA2 was related to worse survival status as an independent factor of poor prognosis. Further gene ontology analysis showed that ANXA2 was mainly involved in immune response and inflammatory activities of glioma. Subsequent correlation analysis showed that ANXA2 was positively correlated with HCK, LCK, MHC II, STAT1 and interferon but negatively with IgG. Meanwhile, ANXA2 was positively related to the infiltration of tumor-related macrophages, regulatory T cells and myeloid-derived suppressor cells. Our study revealed that ANXA2 is a biomarker closely related to the malignant phenotype and poor prognosis of glioma, and plays an important role in immune response, inflammatory activity and immunosuppression.

Abstract Increasing evidence has indicated that senescent cells are associated with the glioma development. Thus, we aimed to explore the relationship between the cellular senescence gene profile and the clinical prognosis of diffuse glioma. In total, 699 gliomas from The Cancer Genome Atlas (TCGA) dataset were used as the training cohort and 693 gliomas from the Chinese Glioma Genome Atlas (CGGA) dataset were used as the validation cohort. Bioinformatics statistical methods are used to develop the risk signature and to study the prognostic value of the risk signature. We identified a 14-gene risk signature and its risk score was an independent prognostic factor (P

Objectives: To evaluate the clinical utility of metagenomic next-generation sequencing (mNGS) for the diagnosis of central nervous system (CNS) infection in people living with human immunodeficiency virus (PLWH) in a real-world situation. Methods: Cerebrospinal fluid (CSF) was sent for mNGS for PLWH who tested negative on all conventional tests but were still suspected to have CNS infection. A retrospective analysis was undertaken of the results and the clinical effect of mNGS on this cohort. The final diagnosis was adjudicated by a panel discussion following hospital discharge when the results of all tests and patients’ responses to the empiric therapy were available. Results: Eighty-eight eligible PLWH, including 51 (58%) patients suspected of encephalitis and 34 (46.7%) patients suspected of meningitis, were included in the analysis. Sixty-eight (77.3%) patients were diagnosed with CNS infection, of which 50 were based on the pathogens identified by mNGS. The most common disease missed by mNGS was clinically suspected tuberculous meningitis, followed by clinically suspected non-tuberculous mycobacterial meningitis. The results from mNGS led to modification of treatment in 21 (23.9%) patients, and increased confidence in continuation of original therapy in 30 (34.1%) patients. During hospitalization, two (2.3%) patients died and 66 (75%) patients improved. Conclusions: mNGS of CSF is a useful tool for the diagnosis of CNS infection among PLWH. Further investigations are warranted to improve its sensitivity.

Abstract Background Talaromyces marneffei (TM) bloodstream infection is common in Acquired Immunodeficiency Syndrome (AIDS) patients with extreme immunodeficiency in Southeast Asia and South China, however, clinical case study on TM bloodstream infection is scarce. We retrospectively analyzed the clinical characteristics of TM bloodstream infection in hospitalized AIDS patients and determined the outcomes of hospitalization after diagnosis in our hospital over the past 5 years. Methods From January 2015 to July 2020, 87 cases of TM detected by blood culture in patients admitted to our center were collected. The admission complaints, blood cells, biochemistry, CD4 and CD8 cell counts and 1,3-β-D-glucan (BDG), procalcitonin (PCT), CRP level on the day of blood culture test, and outcomes during hospitalization were analyzed. Logistic regression analysis was performed for the risk factors for poor prognosis (60 cases). Spearman correlation analysis was used to analyze the correlation between peripheral blood cells, albumin and the time required for TM turnaround in blood culture. The difference was statistically significant when the P value was 200/μl (p = 0.04), and those with BDG 100 pg/mL (p = 0.01). Conclusions TM bloodstream infection is becoming more common in advanced AIDS patients in endemic areas. For those patients with extremely low CD4 and CD8 cell counts below 200/μl is with an increased risk of poor prognosis.

Abstract This paper investigates the impact of economic policy uncertainty (EPU) on the crash risk of US stock market during the COVID-19 pandemic. To this end, we use the GARCH-S (GARCH with skewness) model to estimate daily skewness as a proxy for the stock market crash risk. The empirical results show the significantly negative correlation between EPU and stock market crash risk, indicating the aggravation of EPU increase the crash risk. Moreover, the negative correlation gets stronger after the global COVID-19 outbreak, which shows the crash risk of the US stock market will be more affected by EPU during the epidemic.

Clubroot disease is a common soilborne disease caused by Plasmodiophora brassicas Wor. and widely occurs in Chinese cabbage. Soil microorganisms play vital roles in the occurrence and development of plant diseases. The changes in the soil bacterial community could indicate the severity of plant disease and provide the basis for its control. This study focused on the bacterial community of the clubroot disease-infected soil–root system with different severity aiming to reveal the composition and structure of soil bacteria and identified potential biomarker bacteria of the clubroot disease. In the clubroot disease-infected soil, the bacterial community is mainly composed of Actinobacteria, Gammaproteobacteria, Alphaproteobacteria, Bacilli, Thermolrophilia, Bacteroidia, Gemmatimonadetes, Subgroup_6, Deltaproteobacteria, KD4-96, and some other classes, while the major bacterial classes in the infected roots were Oxyphotobacteria, Gammaproteobacteria, Alphaproteobacteria, Actinobacteria, Bacilli, Bacteroidia, Saccharimonadia, Thermoleophilia, Clostridia, Chloroflexia, and some other classes. The severe clubroot disease soil–root system was found to possess a poorer bacterial richness, evenness, and better coverage. Additionally, a significant difference was observed in the structure of the bacterial community between the high-severity (HR) and healthy (LR) soil–root system. Bacillus asahii and Noccaea caerulescens were identified as the differential bacteria between the LR and HR soil and roots, respectively. pH was demonstrated as a vital factor that was significantly associated with the abundance of B. asahii and N. caerulescens. This study provides novel insight into the relationship between soil bacteria and the pathogen of clubroot disease in Chinese cabbage. The identification of resistant species provides candidates for the monitoring and biocontrol of the clubroot disease.

Abstract Background Tuberculosis (Tb) is the most frequent opportunistic infection among people living with HIV infection. The impact of Tb co-infection in the establishment and maintenance of the HIV reservoir is unclear. Method We enrolled 13 HIV-infected patients with microbiologically confirmed Tb and 10 matched mono-HIV infected controls. Total HIV DNA in peripheral blood mononuclear cells (PBMCs), plasma interleukin-7 (IL-7) concentrations and the activities of indoleamine 2,3-dioxygenase (IDO) were measured for all the participants prior to therapy and after antiretroviral therapy (ART). Results After a duration of 16 (12, 22) months’ ART, patients co-infected with Tb who were cured of Tb maintained higher levels of HIV DNA compared with mono-HIV infected patients [2.89 (2.65- 3.05) log10 copies/106 cells vs. 2.30 (2.11–2.84) log10 copies/106 cells, P = 0.008]. The levels of on-ART HIV DNA were positively correlated with the baseline viral load (r = 0.64, P = 0.02) in Tb co-infected group. However, neither plasma IL-7 concentration nor plasma IDO activity was correlated with the level of on-ART HIV DNA. Conclusions Tb co-infection was associated with the increased surrogate marker of the HIV reservoir, while its mechanism warrants further examination.

In this research, a model is proposed using piecewise fractal theory that considers abrasive and adhesive wear. The model demonstrated improved wear computation accuracy of a contact mechanical seal end face. The validity of the model was established by comparing the simulation results with experimental data and the conventional MB and Archard models. The loading effect and surface morphology parameters involved in wear were also investigated. Results show that severe wear occurs with increasing load ratio, large fractal dimensions, and a higher scale coefficient of the surface morphology. The findings offer a novel method for precisely calculating and projecting the amount of wear of a contact mechanical seal and predicting its wear behavior.

Calibration of aerial mapping camera has an important influence on the applications of earth observation. However, the traditional aerial mapping cameras calibrations depend on large-scale calibration target or collimated light, moreover, it is difficult to build the large-scale calibration targets and the collimated light method requires an accurate turntable and a high-precision goniometer, which is a kind of expensive instrument. To solve this problem, this paper proposes a novel high-precision calibration method which is not restricted by the rigorous conditions, such as small aperture, unevenly energy distribution and expensive equipment. Specifically, a collimator and an elaborately designed multiple pinhole mask are firstly used to generate the collimated light of a large aperture with known directions to simulate the calibration targets at infinity. Then, the camera takes pictures for the aperture of the multiple pinhole collimator at multiple angles to ensure that the image points cover the entire detector. Thirdly, the final calibrated results are obtained by solving the data acquired from multiple angles. Finally, the proposed method is verified by Monte-Carlo simulation and real experimental data, whose results indicate that our method can reach the same accuracy performance as the existing methods at lower cost and faster speed, and thus is practical for engineering application.

ABSTRACTReduced doses of antiretroviral (ARV) drugs may lower toxicity while preserving efficacy. We aimed to evaluate the efficacy of reduced doses of both tenofovir disoproxil fumarate (TDF) and efavirenz for the treatment of HIV-1 infection. In this open-label, non-inferiority trial, HIV-1-infected antiretroviral-naive adults were randomly assigned to receive either a lower dose anti-retroviral regimen comprised of TDF (200 mg), efavirenz (400 mg), and standard dose lamivudine (300 mg) or the standard dose regimen. The primary endpoint was the proportion of participants with HIV-1 RNA≤ 50 copies/mL at week 48 using a non-inferiority margin of –10%. At week 48, 79 of 92 (85.9%) participants in the lower dose regimen group and 78 of 92 (84.8%) in the standard dose regimen group achieved HIV-1 RNA≤ 50 copies/mL (treatment difference 1.1%, 95% CI −9.1 to 11.3) in the intention-to-treat analysis. Drug-related adverse events occurred more frequently in the participants receiving the standard dose regimen compared with the lower dose one (63.0% vs 80.4%). Changes in estimated glomerular filtration rate and bone mineral density were comparable between the two groups. The non-inferior efficacy and better safety profile of the lower dose ARV regimen support its use as alternative initial therapy for HIV-1 infected patients.

Abstract Objective Increased translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor (PBR), in glial cells of the brain has been used as a neuroinflammation marker in the early and middle stages of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB). In this study, we investigated the changes in TSPO density with respect to late stage AD and DLB. Methods TSPO density was measured in multiple regions of postmortem human brains in 20 different cases: seven late stage AD cases (Braak amyloid average: C; Braak tangle average: VI; Aged 74–88, mean: 83 ± 5 years), five DLB cases (Braak amyloid average: C; Braak tangle average: V; Aged 79–91, mean: 84 ± 4 years), and eight age‐matched normal control cases (3 males, 5 females: aged 77–92 years; mean: 87 ± 6 years). Measurements were taken by quantitative autoradiography using [3H]PK11195 and [3H]PBR28. Results No significant changes were found in TSPO density of the frontal cortex, striatum, thalamus, or red nucleus of the AD and DLB brains. A significant reduction in TSPO density was found in the substantia nigra (SN) of the AD and DLB brains compared to that of age‐matched healthy controls. Interpretation This distinct pattern of TSPO density change in late stage AD and DLB cases may imply the occurrence of microglia dystrophy in late stage neurodegeneration. Furthermore, TSPO may not only be a microglia activation marker in early stage AD and DLB, but TSPO may also be used to monitor microglia dysfunction in the late stage of these diseases.

Under the condition of convergence, a textured non-parallel 2D slider bearing model was established, and the tribological properties of textured surface under the convergence gap were numerically studied with the load-carrying capacity as an indicator. Firstly, whether the convergence ratio parameter can accurately characterize the joint effects of film thickness difference and oil film thickness on the surface tribological properties was verified, and the effects of film thickness difference and oil film thickness on the load-carrying capacity of textured and non-textured surface were studied, respectively. The results show that the efficiency of improving the load-carrying capacity of the surface structure first increases and then decreases with the increase of the oil film thickness. In the case of large film thickness difference, the surface texture will reduce the efficiency of improving the load-carrying capacity. In addition, the effects of texture depth, texture width, and sliding velocity on the load-carrying capacity under the convergence gap are also studied. In particular, an optimal texture width to maximize the load-carrying capacity exists.

Pore-forming toxins (PFTs) have been discovered in a wide range of organisms. Their functions are essential to the survival or virulence of many species. PFTs often interact with lipid membranes. Large unilamellar vesicles (LUV), also known as liposomes, have been commonly used as reliable membrane models for testing PFTs activity. Liposomes have great adaptability in size, lipid composition, and loading cargo. Incorporating the fluorescent dye/quencher pair, 8-Aminonaphthalene-1,3,6-Trisulfonic Acid (ANTS) and p-Xylene-Bis-Pyridinium Bromide (DPX), in liposomes is an effective approach for measuring membrane leakage. When ANTS and DPX are encapsulated in a liposome, the fluorescence of ANTS is quenched by DPX. However, disruption of liposome integrity and subsequent leakage result in measurable fluorescence emitted by ANTS. Here, we report our protocol for optimal liposome preparation for measuring liposome leakage by fluorescence dequenching.

The CCF4-AM Förster resonance energy transfer (FRET) assay is a sensitive approach to measure bacterial cytosolic translocation in live cells. The FRET pair hydroxycoumarin (donor) and fluorescein (acceptor) are linked by a CCF4-AM β-lactam ring, the substrate of β-lactamase. The exogenously added, neutral charged-FRET reagent can diffuse across the membrane and stay in the cytosol only once it is charged in the cytosol. When bacteria translocate from subcellular organelles (e.g., phagosomes) to the cytosol, the bacteria-associated β-lactamase cleaves the β-lactam ring, resulting in loss of FRET signal. Here we describe the fluorometer-based approach optimized for direct measurement of cytosolic translocation as a result of the EsxAB complex of Mycobacterium marinum in RAW264.7 cells.

This paper investigates the reliability of welded metal bellows used in mechanical seals under specified working conditions. Firstly, considering the working environment of mechanical seals and the structural characteristics of welded metal bellows, a stress relaxation test bench was developed to obtain projectile loss data of welded metal bellows under different compression loads at elevated temperatures. The creep constants for a stress relaxation simulation were derived from the experimental data, and a stress relaxation finite element analysis (FEA) of the bellows was conducted using Workbench under different compression loads. We found that the stress relaxation simulation of welded metal bellows can accurately simulate the relaxation characteristics of welded metal bellows. The reliability of the welded metal bellows was calculated using Six Sigma response surface reliability by taking the material properties and compression load as variable parameters and the residual elasticity of the bellows as the objective function. We concluded that the reliability calculation method of welded metal bellows promotes reliability research into welded metal bellows for mechanical seals.

Objectives: The purpose of this study was to investigate the clinical features and related laboratory indicators of cytomegalovirus retinitis in HIV infected patients in order to find a suitable laboratory reference guide to aid in the early diagnosis of CMVR, which should improve the prognosis of the severe retinitis.Methods: PLHIVs who were admitted to our hospital from January 2010 to December 2016 were included. The diagnosis of AIDS follows the AIDS Treatment Guidelines. Levels of CMV IgG and IgM were measured by ELISA in order to detect the CMV infection status of the patient. CMV-DNA levels were assessed by a quantitative PCR method, and CD4+ T lymphocytes were detected by flow cytometry. Logistical regression was used to analyze the risk factors for CMV retinitis in HIV-infected patients.Results: There were 93 patients with HIV that were also diagnosed with CMV retinitis. After ART, the intraocular pressure, visual acuity, cotton plaque incidence, and CD4+ T lymphocyte count were significantly improved, and the yellow-white retinal lesions gradually disappeared. In patients with HIV infections, the CD4+ T lymphocyte count, and peripheral blood quantitative CMV-DNA levels were found to be independent risk factors for CMV retinitis (P < 0.05). Patients with HIV infection who had CMV-DNA levels >6,390 copies/mL were associated with more severe ophthalmolgic conditions related to CMV retinitis.Conclusion: Patients with HIV infections with quantitative CMV-DNA levels >6,390 copies/mL have a higher probability of having a diagnosis of CMV retinitis and a worse prognosis than those whose CMV-DNA level is

The NR5A-family nuclear receptors are highly conserved and function within the somatic follicle cells of the ovary to regulate folliculogenesis and ovulation in mammals; however, their roles in Drosophila ovaries are largely unknown. Here, we discover that Ftz-f1, one of the NR5A nuclear receptors in Drosophila, is transiently induced in follicle cells in late stages of oogenesis via ecdysteroid signaling. Genetic disruption of Ftz-f1 expression prevents follicle cell differentiation into the final maturation stage, which leads to anovulation. In addition, we demonstrate that the bHLH/PAS transcription factor Single-minded (Sim) acts as a direct target of Ftz-f1 to promote follicle cell differentiation/maturation and that Ftz-f1’s role in regulating Sim expression and follicle cell differentiation can be replaced by its mouse homolog steroidogenic factor 1 (mSF-1). Our work provides new insight into the regulation of follicle maturation in Drosophila and the conserved role of NR5A nuclear receptors in regulating folliculogenesis and ovulation.

Ground source heat pumps (GSHPs), a high-efficiency and energy-saving air-conditioning technology that utilizes shallow geothermal resources for both heating and cooling, are a vital green energy system for residential and commercial buildings. Improving the performance of such a system was the focus of the current research. As soil temperature and thermal radius are two important aspects that affect the performance of ground source heat pump systems, we conducted a new numerical simulation to capture the changes in sensitive factors and propose the optimized paths. The numerical simulation analyzed the thermal characteristics of a borefield under different pre-cooling times and soil types. The results indicated the following: (1) The rate of the ground temperature change with pre-cooling during the discharging period had a faster rise than in the case without pre-cooling. The longer the precooling time was, the smaller the thermal radius became. In particular, when the precooling time was longer than 14 days, the decrease in the thermal radius rate percentages was less than 4%. (2) Among the three kinds of soils compared, the soils with lower thermal conductivity and thermal diffusivity best suppressed the thermal interference effects. (3) Using a multivariate nonlinear function regression model, a simulation formula was proposed to predict- the thermal radius, which considered the factors of thermal diffusivity, precooling time, and discharging time. The prediction deviation was within 14.8%.

It is well known that the dimple area density is a key parameter for the design of mechanical seal with dimples. In the present paper, the integrated influence of sliding velocity, outlet pressure, and seal clearance on optimum dimple area density, represented by dimple number along the dimple column taken from the seal surface, are conducted theoretically by solving Reynolds equation, where the Floberg-Jakobsson-Olsson cavitation theory is implemented using a mass-conservative algorithm to accurately predict the behavior of cavitation. The results show that the optimum dimple area density is closely related to the operation parameters and the influence of each operation parameter can be divided into three regions. Moreover, for each operation parameter, both of the range of the divided regions and the corresponding values of the optimum dimple area density are strongly associated with the other two operation parameters. In addition, the influences of operation parameters on optimum dimple area density can be investigated by their effects on the maximum pressure caused by dimples.

An output feedback finite-time control strategy for five degree of freedoms (DOF) upper-limb exoskeleton is investigated in this paper. First, a multivariable second-order sliding mode control is proposed to improve the response speed and stability of the exoskeleton system with parameter uncertainties and external disturbances. Furthermore, for the sake of high control precision with limited information, a finite-time linear extended state observer is constructed to estimate both the unmeasured states and the lumped perturbations. Finally, by utilizing the 5-DOF upper-limb model, simulation results are presented to demonstrate the effectiveness of the control strategy.

In order to reduce the influence of the optical window on the image quality of a hypersonic visible light optical remote sensor, we propose a method of adding a double-layer semicircular honeycomb core microstructure with flexible support of a high temperature elastic alloy between a window glass and a frame to reduce the influence of complex thermal stress on the surface accuracy of the optical window. An equivalent model of a semicircular honeycomb structure was established, the elastic parameters of the semicircular honeycomb sandwich microstructure were derived by an analytical method, and a numerical verification and finite element simulation were carried out. The results show that the equivalent model is in good agreement with the detailed model. The optical-mechanical-thermal integrated simulation analysis of the optical window assembly with flexible supporting microstructure proves that the semicircular honeycomb sandwich flexible supporting structure has a positive effect on stress attenuation of the window glass and ensures the wave aberration accuracy of the transmitted optical path difference of the optical window (PV < 0.665 λ, RMS < 0.156 λ, λ = 632.8 nm). Combined with the actual optical system, the optical performance of the window assembly under the flexible support structure is verified. The simulation results show that the spatial frequency of the modulation transfer function (MTF) of the optical system after focusing is not less than 0.58 in the range of 0–63 cycle/mm and the relative decline of MTF is not more than 0.01, which meet the imaging requirements of a remote sensor. The study results show that the proposed metal-based double-layer semicircular honeycomb sandwich flexible support microstructure ensures the imaging quality of the optical window under ultra-high temperature conditions.

In this study, a spiral groove liquid film vaporization model based on the viscosity–temperature equation, fluid internal friction, saturation temperature, and pressure relationship equation was established. Using a multiphase flow model based on the finite volume method, the influence of the change in the mass transfer coefficient on the vaporization of the liquid film was studied. Moreover, the influence law of structural parameter changes in liquid film vaporization characteristics and sealing performance was analyzed. The results indicate that, with an increase in the mass transfer coefficient, the average vapor phase volume fraction first increases and then gradually stabilizes. When calculating the average vapor phase volume fraction, it is necessary to consider the influence of the mass transfer coefficient, whereas its effect on the opening force and leakage can usually be neglected. Under the optimal mass transfer coefficient conditions, the average vapor phase volume fraction increases with an increase in the helix angle, groove-weir ratio, and groove depth. By comparison, with an increase in the groove-diameter ratio, the average vapor phase volume fraction first increases and then decreases. The opening force decreases with an increase in the helix angle, groove-to-weir ratio, and groove depth. On the other hand, it first decreases and then increases with an increase in the groove-diameter ratio. The leakage rate increases first and then stabilizes with an increase in the helix angle. Moreover, it increases continuously with an increase in the groove-diameter ratio, groove-weir ratio, and groove depth.