Prevalence of HIV Transmitted Drug Resistance in Nanjing from 2018 to 2021.

Background: Transmitted drug resistance (TDR) is a major challenge in the clinical management of acquired immunodeficiency syndrome (AIDS). Therefore, this study aimed to investigate the epidemic characteristics of and risk factors for human immunodeficiency virus (HIV)-1 TDR in Nanjing from 2018 to 2021 to provide support for clinical management. Methods: The HIV-1 Pol gene was amplified by nested reverse transcription polymerase chain reaction from venous blood of 1190 HIV-infected patients who did not receive antiviral therapy, and the amplified product was sequenced using an in-house sequencing method. The sequencing result was compared with the HIV drug resistance database from Stanford University to elucidate the rates of antiviral drug resistance and distribution of drug-resistant mutation sites. Factors associated with TDR were evaluated using a logistic regression model. Results: Detection of drug resistance at the gene level was successful in 1138 of 1190 HIV-1-infected patients (95.6%), and the overall 4-year drug resistance rate was 8.2% (93/1138). The drug resistance rate was higher for non-nucleoside reverse transcriptase inhibitors (NNRTIs; 6.7%) than for nucleoside reverse transcriptase inhibitors (NRTIs; 2.5%) or protease inhibitors (PIs; 0.1%) (χ 2 = 83.907, P<0.0001). The most common NNRTI-related mutation was V179D/E followed by K103N. M184V was the dominant NRTI-associated mutation, and M46L/I was the most prevalent PI-associated mutation. A CD4+ T cell count of <50 cells/µL was significantly associated with an increased risk of TDR (OR=3.62, 95% CI: 1.38-9.51, P=0.009). Conclusion: The prevalence of TDR in the city of Nanjing from 2018 to 2021 was at a moderate epidemic risk according to World Health Organization standards. Continuous monitoring of TDR can inform clinical diagnosis and treatment. Patients with advanced disease and a low CD4+ T lymphocyte count are more likely to have TDR in Nanjing.

Clinicopathologic features and abnormal signaling pathways in plasmablastic lymphoma: a multicenter study in China.

BACKGROUND: Plasmablastic lymphoma (PBL) is a rare but aggressive B-cell lymphoma subtype with poor prognosis. Knowledge about the etiology, clinicopathologic and molecular features, and outcomes of PBL is limited. This study aimed to examine the clinicopathologic characteristics, therapeutic approaches, and clinical outcomes of PBL patients in a Chinese population. METHODS: A total of 102 PBL patients were recruited from three cancer centers. The pathologic features and clinical outcomes of 56 patients with available treatment details and follow-up data were reviewed and analyzed. RNA sequencing was performed in 6 PBL and 11 diffuse large B-cell lymphoma (DLBCL) patients. RESULTS: Most patients in our cohort were male (n = 36, 64.3%), and 35 patients presented with Ann Arbor stage I/II disease at diagnosis. All these patients showed negative findings for human immunodeficiency virus, and the vast majority of patients in our cohort were immunocompetent. Lymph nodes (n = 13, 23.2%) and gastrointestinal tract (n = 10, 17.9%) were the most commonly involved site at presentation. Post-treatment complete remission (CR) was the only prognostic factor affecting overall survival (OS) and progression-free survival (PFS) in the multivariate analysis. RNA-seq demonstrated that B-cell receptor (BCR), T-cell receptor (TCR), P53, calcium signaling, and Wnt signaling pathways were significantly downregulated in PBLs compared with GCB (or non-GCB) DLBCLs. CONCLUSIONS: In this multicenter study in the Chinese population, PBL mainly occurred in immunocompetent individuals and most patients present with early-stage disease at diagnosis. Post-treatment CR was an important prognostic factor affecting OS and PFS. RNA-seq showed that the B-cell receptor (BCR), P53, calcium signaling, cell adhesion molecules, and Wnt signaling pathways significantly differed between PBL and GCB (or non-GCB) DLBCL, which provided theoretical basis for its pathogenesis and future treatment.

Dynamical criticality of spin-shear coupling in van der Waals antiferromagnets.

The interplay between a multitude of electronic, spin, and lattice degrees of freedom underlies the complex phase diagrams of quantum materials. Layer stacking in van der Waals (vdW) heterostructures is responsible for exotic electronic and magnetic properties, which inspires stacking control of two-dimensional magnetism. Beyond the interplay between stacking order and interlayer magnetism, we discover a spin-shear coupling mechanism in which a subtle shear of the atomic layers can have a profound effect on the intralayer magnetic order in a family of vdW antiferromagnets. Using time-resolved X-ray diffraction and optical linear dichroism measurements, interlayer shear is identified as the primary structural degree of freedom that couples with magnetic order. The recovery times of both shear and magnetic order upon optical excitation diverge at the magnetic ordering temperature with the same critical exponent. The time-dependent Ginzburg-Landau theory shows that this concurrent critical slowing down arises from a linear coupling of the interlayer shear to the magnetic order, which is dictated by the broken mirror symmetry intrinsic to the monoclinic stacking. Our results highlight the importance of interlayer shear in ultrafast control of magnetic order via spin-mechanical coupling.

A Novel Technique for the Preparation of Iron Carbide and Carbon Concentrate from Blast Furnace Dust.

Blast furnace (BF) dust is a typical refractory iron resource. A novel technology-based utilization of BF dust as iron carbide and carbon concentrate by applying carburization roasting followed by magnetic separation and acid leaching is proposed. Under optimized conditions, an electric arc furnace (EAF) burden assaying 80.79% Fe and 7.63% C with a corresponding iron recovery rate of 87.26% and a carbon concentrate assaying 67.06% C with a corresponding carbon recovery rate of 81.23% were prepared. Furthermore, the carburization behavior and separation mechanism were revealed using X-ray powder diffraction, scanning electron microscopy, and optical microscopy. The results show that the separation efficiency of iron carbide, gangue, and carbon is very low. Na2SO4 is a highly effective additive to strengthen the separation efficiency as it can enhance the carburization index, enlarge the iron carbide particle size, improve the embed embedded relationship of iron carbide and gangue, and promote the gangue leaching efficiency. The study demonstrates that preparation of iron carbide and carbon concentrate from BF dust using the proposed technology is a feasible method.

A novel indicator for defining plain urban river network cyanobacterial blooms: resource use efficiency.

Increasing eutrophication and climate change have led to heavy cyanobacterial blooms in water diversion sources (e.g., lakes, reservoirs), which can potentially cause algae-bearing water to spread to downstream to an urban river network via diversion channels. Defining the extent of cyanobacterial blooms in an urban river network has become a novel concern in urban river management. In this paper, we investigated the physicochemical and algae community characteristics of a small, closed, urban river network, JiangXinZhou (JXZ), in the Lake Taihu basin. We propose a novel indicator, resource use efficiency (RUE), for defining the extent of cyanobacterial blooms in JXZ, whose recreational drinking water comes entirely from outside diversion sources. The results show that the JXZ's aquatic habitat conditions (mean water temperature, total nitrogen concentration, total phosphorus concentration, and nitrogen to phosphorus ratio) are highly suitable for the proliferation of cyanobacterial biomass during the high-water period. The RUE was used for calculation and shows a strong relationship with algae density, which means that it can be used as an index to define the degree of urban river cyanobacterial blooms. The findings indicate that the risk of cyanobacterial bloom is absent when the RUE is less than 46.81; blooms appear in the water bodies when the RUE reaches up to 106.68. This work provides theoretical support for the sustainable use of regional water resources.

Efficacy and Safety of a Simplified Lamivudine Plus Dolutegravir Dual Therapy in HIV-1-Infected Patients: A Multicenter Cohort Study in China.

BACKGROUND: Results from both clinical trials and real-world observational studies suggest that lamivudine plus dolutegravir (3TC + DTG) dual therapy has excellent virological efficacy and safety in HIV-1-infected patients. However, there is still no relevant study related to this dual therapy reported in China. METHODS: In this multicenter, retrospective, observational study that included HIV-1-infected patients in China, baseline and follow-up data were collected to analyze the virological suppression rate, immune restoration, and adverse events during follow-up in HIV-1-infected patients who switched to the 3TC + DTG dual therapy. RESULTS: This study recruited 112 HIV-1-infected patients, including 101 men (90.2%), with a median age of 44.0 years (IQR: 33.00-57.75) and median CD4+ T-cell count of 432.13 cells/µL (IQR: 237.75-578.50). The overall virological suppression rate was 94.5% at the 24-week follow-up. However, the virological suppression rates of men who have sex with men patients and patients with CD4+ T-cell count of <350 cells/µL were higher than the baseline value (P < 0.05) at week 24. The results of Cox regression analysis showed that the baseline CD4+ T-cell count was an independent determinant of immune restoration in patients, and patients with baseline CD4+ T-cell count of 350-500 cells/µL outperformed patients with baseline CD4+ T-cell count of <350 cells/µL in immune restoration (hazard ratio: 4.469, 95% confidence interval: 1.801 to 11.091, P = 0.001). Adverse events were reported in 5 patients (incidence rate of 4.5%); among them, 3 patients developed neuropsychiatric symptoms. Results from the laboratory data analysis showed that patients with grade 1 and 2 adverse events had elevated levels of low-density lipoprotein cholesterol and total bilirubin. Furthermore, grade 3 and 4 adverse events were associated with the elevation of blood glucose level in 4 patients. CONCLUSIONS: Thus, the 3TC + DTG dual therapy displayed an excellent virological efficacy against HIV-1 infections and had an acceptable safety profile, with predominantly mild adverse events in HIV-1-infected patients in China.

Tracking virulence genes and their interaction with antibiotic resistome during manure fertilization.

Antibiotic resistance genes, collectively termed as antibiotic resistome, are regarded as emerging contaminants. Antibiotics resistome can be highly variable in different environments, imposing environmental safety concern and public health risk when it is in conjunction with pathogenic bacteria. However, it remains elusive how pathogenic bacteria interact with antibiotic resistome, making it challenging to assess microbial risk. Here, we examined the presence and relative abundance of bacterial virulence genes representing potential pathogens in swine manure, compost, compost-amended soil, and unamended agricultural soil in five suburban areas of Beijing, China. The absolute abundances of virulence genes were marginally significantly (p < 0.100) increased in compost-amended soils than unamended soil, revealing potential health risks in manure fertilization. The composition of potential pathogens differed by sample types and was linked to temperature, antibiotics, and heavy metals. As antibiotics can confer pathogens the resistance to clinic treatment, it was alarming to note that virulence genes tended to co-exist with antibiotic resistance genes, as shown by prevalently positive links among them. Collectively, our results demonstrate that manure fertilization in agriculture might give rise to the development of potentially antibiotic-resistant pathogens, unveiling an environmental health risk that has been frequently overlooked.

C. elegans enteric motor neurons fire synchronized action potentials underlying the defecation motor program.

C. elegans neurons were thought to be non-spiking until our recent discovery of action potentials in the sensory neuron AWA; however, the extent to which the C. elegans nervous system relies on analog or digital coding is unclear. Here we show that the enteric motor neurons AVL and DVB fire synchronous all-or-none calcium-mediated action potentials following the intestinal pacemaker during the rhythmic C. elegans defecation behavior. AVL fires unusual compound action potentials with each depolarizing calcium spike mediated by UNC-2 followed by a hyperpolarizing potassium spike mediated by a repolarization-activated potassium channel EXP-2. Simultaneous behavior tracking and imaging in free-moving animals suggest that action potentials initiated in AVL propagate along its axon to activate precisely timed DVB action potentials through the INX-1 gap junction. This work identifies a novel circuit of spiking neurons in C. elegans that uses digital coding for long-distance communication and temporal synchronization underlying reliable behavioral rhythm.

Facile production of tag-free recombinant human interleukin-11 by transforming into soluble expression in Escherichia coli.

Human interleukin-11 (IL-11) is considered as a difficult-to-express protein in prokaryotic expression systems because of its low expression level and high tendency to form inclusion bodies. The current source of recombinant human IL-11 (rhIL-11) for therapeutic use is mainly obtained from a fusion protein synthesized by Escherichia coli, which requires an additional operation to cleave the fusion tag. Herein, we reported a strategy for the direct expression of tag-free rhIL-11 in E. coli. To explore the soluble expression of rhIL-11 without fusion tags in E. coli, we inserted the rhIL-11 gene into a pBV220 plasmid which is characterized by employing a temperature-sensitive pR/pL promoter to manipulate the transcription and translation of the gene of interest. As a result, the tag free rhIL-11 was efficiently expressed in the soluble form in E. coli. A two-step chromatography method, Capto Butyl-S combined with Capto Q, was developed to efficiently purify the tag-free rhIL-11 from the supernatant of the cell lysate. The resultant rhIL-11 showed a compact and highly ordered structure, as validated by circular dichroism and intrinsic fluorescence emission spectra. Additionally, the biological activity of the purified rhIL-11 was evaluated by TF-1 cell proliferation experiments and the results demonstrated that the E. coli expressed rhIL-11 is biologically active.

Enhancing adsorption capacity and structural stability of Li1.6Mn1.6O4 adsorbents by anion/cation co-doping.

Modifying the structure of Li1.6Mn1.6O4 (LMO) to enhance its structural stability and adsorption capacity is an effective method to generate materials to recover Li+ ions from mixed solution. Herein, the co-doping of trace non-metal ion (S) and metal ion (Al) into Li1.6Mn1.6O4 (LMO-SAl) is established and shows excellent Li+ adsorption capacity and Mn anti-dissolution properties. The adsorption capacity (when [Li+] is 6 mmol L-1) is increased from 26.1 mg g-1 to 33.7 mg g-1. This is attributed to improved charge density via substitution of S at O sites, which facilitates the adsorption/desorption process. The Mn dissolution is also reduced from 5.4% to 3.0% for LMO-SAl, which may result from the stronger Al-O bonds compared to Li-O bonds that enhance the structural stability of the LMO. The ion-sieving ability of the co-doped material goes by the order of K d (Li+ > Ca2+ > Mg2+ > Na+ > K+), indicating that Li+ can be efficiently separated from Lagoco Salt Lake brine. These results predict that lithium ions are effectively adsorbed from brine by the co-doped LMO material, which manifests the feasibility of lithium recovery and provides basic data for further industrial applications of adsorption.

Unconventional Hysteretic Transition in a Charge Density Wave.

Hysteresis underlies a large number of phase transitions in solids, giving rise to exotic metastable states that are otherwise inaccessible. Here, we report an unconventional hysteretic transition in a quasi-2D material, EuTe_{4}. By combining transport, photoemission, diffraction, and x-ray absorption measurements, we observe that the hysteresis loop has a temperature width of more than 400 K, setting a record among crystalline solids. The transition has an origin distinct from known mechanisms, lying entirely within the incommensurate charge density wave (CDW) phase of EuTe_{4} with no change in the CDW modulation periodicity. We interpret the hysteresis as an unusual switching of the relative CDW phases in different layers, a phenomenon unique to quasi-2D compounds that is not present in either purely 2D or strongly coupled 3D systems. Our findings challenge the established theories on metastable states in density wave systems, pushing the boundary of understanding hysteretic transitions in a broken-symmetry state.

Bacteria are better predictive biomarkers of environmental estrogen transmission than fungi.

The heavy reliance on estrogens in the food industry worldwide greatly contributes to the environmental release of these compounds, begetting serious public concern of their fate. Various microorganisms capable of estrogen degradation, and their catabolic pathways, have been isolated, suggesting that they can eliminate estrogens in both engineered and natural environments. Nonetheless, it remains little understood as to how potential estrogen-degrading microorganisms are distributed within those habitats. An estrogen transmission chain from swine manure to compost, compost-amended soil, and neighboring agricultural soil was investigated in five suburban areas of Beijing, China. The concentrations of major estrogen classes decreased by > 90% from manure to soils, which did not co-vary with environmental antibiotics and heavy metal concentrations. Many bacterial taxa, such as Lactobacillus and Bacteroides, could serve as potential biomarkers of estrogen concentrations, while fungi were only occasionally accurate. To explain this phenomenon, stochasticity was found to be dominant in shaping the fungal communities across all samples, while deterministic selection, arising from biotic interactions, was important for bacterial communities. Metabolic genes involved in oxidizing phenol and catalyzing oxidative ring cleavage of catechol were detected, co-varying with estrogen concentrations. These findings are important as identifying microbial biomarkers of estrogen dynamics, spanning the levels of both taxonomy and functional genes, provides valuable information for assessing estrogen bioavailability and biomarking of estrogen fate in the environment.

Nutrient supply controls the linkage between species abundance and ecological interactions in marine bacterial communities.

Nutrient scarcity is pervasive for natural microbial communities, affecting species reproduction and co-existence. However, it remains unclear whether there are general rules of how microbial species abundances are shaped by biotic and abiotic factors. Here we show that the ribosomal RNA gene operon (rrn) copy number, a genomic trait related to bacterial growth rate and nutrient demand, decreases from the abundant to the rare biosphere in the nutrient-rich coastal sediment but exhibits the opposite pattern in the nutrient-scarce pelagic zone of the global ocean. Both patterns are underlain by positive correlations between community-level rrn copy number and nutrients. Furthermore, inter-species co-exclusion inferred by negative network associations is observed more in coastal sediment than in ocean water samples. Nutrient manipulation experiments yield effects of nutrient availability on rrn copy numbers and network associations that are consistent with our field observations. Based on these results, we propose a "hunger games" hypothesis to define microbial species abundance rules using the rrn copy number, ecological interaction, and nutrient availability.

A retrospective clinical study of dolutegravir- versus efavirenz-based regimen in treatment-naïve patients with advanced HIV infection in Nanjing, China.

Currently, there are limited data related to the efficacy and safety of ART regimens, as well as factors influencing immune recovery in antiretroviral therapy (ART)-naïve patients with advanced HIV infection, especially in China. We designed a single-center, retrospective cohort study from March 1, 2019, to May 31, 2022, at The Second Hospital of Nanjing, China. ART-naïve adults with advanced HIV infection (CD4+ T-cell count < 200 cells/µL) who met the study criteria were included. The plasma viral load (VL), CD4+ T-cell count, CD4/CD8 ratio, treatment discontinuation, and immune reconstitution inflammatory syndrome (IRIS) events were collected to compare the efficacy and safety of the dolutegravir (DTG) and the efavirenz (EFV) regimens. Factors of immune recovery were analyzed using the Cox regression model. Study enrolled 285 ART-naïve adults with advanced HIV-1 infection, of which 95 (33.3%) started regimens including DTG and 190 (66.7%) were treated with EFV. After ART initiation, the proportion of patients with HIV-1 RNA < 50 copies/mL was higher (22.5% versus 6.5%, P < 0.001) in those on DTG-based regimens at month 1, but no significant difference at other follow-up points. Compared to the baseline, the median CD4+ T-cell count and CD4/CD8 ratio increased significantly during follow-up both in the EFV and the DTG groups. However, the CD4+ T-cell count increased greater in patients on DTG-based regimens at months 6, 12, 24, and 36 (P < 0.05). A total of 52 (18.2%) patients discontinued treatment, with no significant difference between ART regimens in treatment discontinuation rates. Only 7 patients reported IRIS, without significant difference between ART regimens (P=0.224). Overall, 34.0% (97/285) achieved a CD4+ T-cell count ≥ 350 cells/µL during follow-up. Age (P < 0.001), baseline CD4+ T-cell count (P < 0.001), baseline VL (P < 0.001) and ART regimens (P = 0.019) were associated with the CD4+ T-cell count ≥ 350 cells/µL after adjusting for potential confounders. Among ART-naïve adults with advanced HIV infection, it appeared that DTG-based regimens were better options for initial therapy compared to regimens including EFV; in addition, ART regimens, age, baseline VL and CD4+ T-cell count were associated with immune recovery.

Characteristics of Germline Non-BRCA Mutation Status of High-Risk Breast Cancer Patients in China and Correlation with High-Risk Factors and Multigene Testing Suggestions.

Background: Expert consensus on BRCA1/2 genetic testing and clinical application in Chinese breast cancer patients recommends that BRCA1/2 testing should be performed in those with clinical risk factors, such as an early onset, triple-negative breast cancer (TNBC) or family history of cancer. With the increasing application of multigene panels, testing for genes beyond BRCA1/2 has become more prevalent. However, the non-BRCA mutation status of Chinese high-risk breast cancer patients has not been fully explored. Methods: A total of 230 high-risk breast cancer patients from Fudan University Shanghai Cancer Center who had undergone peripheral blood germline 72 genes next-generation sequencing (NGS) from June 2018 to June 2020 were enrolled for retrospective analysis. The 72 genes include common hereditary breast cancer genes, such as homologous recombination repair (HRR) genes and other DNA damage repair genes. High-risk factors included: 1) TNBC; 2) male breast cancer; 3) primary bilateral breast cancer; 4) diagnosed with breast cancer at age less than or equal to 40 years; or 5) at least one first- and/or second-degree relative with BRCA-related cancer (breast or ovarian or prostate or pancreatic cancer). Results: The germline pathogenic or likely pathogenic mutation rate was 29.6% (68/230) in high-risk breast cancer patients. Among them, 44 (19.1%, 44/230) were identified as harboring BRCA1/2 mutation, and 28 (12.2%, 28/230) patients carried non-BRCA germline variants. Variants were detected in 16 non-BRCA genes, including PALB2 (5, 2.2%), ATM (4, 1.7%), RAD51D (3, 1.3%), TP53 (3, 1.3%), CHEK2 (2, 0.9%), FANCA (2, 0.9%) and ATR, BARD1, BRIP1, ERCC3, HOXB13, MLH1, MRE11, PMS2, RAD51C, RAD54L (1, 0.4%). Besides, 22 (9.6%, 22/230) patients were non-BRCA HRR gene mutation (including ATM, ATR, BARD1, BRIP1, CHEK2, FANCA, MRE11, PALB2, RAD51C RAD51D and RAD54L) carriers. Among high-risk factors, family history showed a correlation with both BRCA (p = 0.005) and non-BRCA HRR gene mutation status (p = 0.036). In addition, TNBC showed a correlation with BRCA1 gene mutation status (p = 0.038). However, other high-risk factors have not shown significantly related to BRCA1/2, non-BRCA genes and non-BRCA HRR gene mutations (p > 0.05). In addition, 312 unique variants of uncertain significance (VUS) were identified among 175 (76.1%, 175/230) patients and 65 different genes. Conclusions: Non-BRCA gene mutations are frequently identified in breast cancer patients with high risk factors. Family history showed a correlation with both BRCA (p = 0.005) and non-BRCA HRR gene mutation status (p = 0.036), so we strongly suggest that breast cancer patients with a BRCA-related family history receive comprehensive gene mutation testing in China, especially HRR genes, which are not only related to high risk of breast cancer, but also potentially related to poly ADP ribose polymerase inhibitor (PARPi) targeted therapy. The exact relationship of rare gene mutations to breast cancer predisposition and the pathogenicity of VUS need to be further investigated.

Role of Equilibrium Fluctuations in Light-Induced Order.

Engineering novel states of matter with light is at the forefront of materials research. An intensely studied direction is to realize broken-symmetry phases that are "hidden" under equilibrium conditions but can be unleashed by an ultrashort laser pulse. Despite a plethora of experimental discoveries, the nature of these orders and how they transiently appear remain unclear. To this end, we investigate a nonequilibrium charge density wave (CDW) in rare-earth tritellurides, which is suppressed in equilibrium but emerges after photoexcitation. Using a pump-pump-probe protocol implemented in ultrafast electron diffraction, we demonstrate that the light-induced CDW consists solely of order parameter fluctuations, which bear striking similarities to critical fluctuations in equilibrium despite differences in the length scale. By calculating the dynamics of CDW fluctuations in a nonperturbative model, we further show that the strength of the light-induced order is governed by the amplitude of equilibrium fluctuations. These findings highlight photoinduced fluctuations as an important ingredient for the emergence of transient orders out of equilibrium. Our results further suggest that materials with strong fluctuations in equilibrium are promising platforms to host hidden orders after laser excitation.

Universal extracellular vesicles and PD-L1+ extracellular vesicles detected by single molecule array technology as circulating biomarkers for diffuse large B cell lymphoma.

Plasma extracellular vesicles (EVs) have been reported to be a promising source of diagnostic and prognostic biomarkers in various cancers. However, further research in this area is needed due to the limitations of circulating extracellular vesicles detection methods. Using the Single Molecule array (SiMoa) technology, we developed two extracellular vesicle detection assays, CD9-CD63 and PD-L1-CD63, to determine circulating universal EVs and PD-L1 positive EVs, respectively. A total of 164 diffuse large B-cell lymphoma (DLBCL) patients were retrospectively included in this study. Compared with healthy volunteers (n = 25), elevated CD9-CD63 and PD-L1-CD63 signals were detected in the plasma of DLBCL patients (n = 164). High CD9-CD63 signals was associated with molecular subtype, extranodal site and treatment response in DLBCL. A high PD-L1-CD63 signal was also associated with certain clinical features, including extranodal site and treatment response. CD9-CD63 and PD-L1-CD63 signals were found to be important prognostic factors for both progression-free and overall survival. Furthermore, PD-L1-positive EVs were found in all patients, though PD-L1 protein expression was positive in only 35.4% (17/48) of tumor biopsies. No correlation was found between circulating PD-L1+ EVs and soluble PD-L1 (sPD-L1) levels. Our results show that plasma universal EV and PD-L1-positive EV levels are significantly elevated in DLBCL and might serve as biomarkers for predicting survival outcomes in DLBCL patients.

Acupuncture Combined with Three-Step Analgesic Drug Therapy for Treatment of Cancer Pain: A Systematic Review and Meta-Analysis of Randomised Clinical Trials.

OBJECTIVE: The purpose of this study was to systematically evaluate the efficacy and safety of acupuncture combined with the WHO three-step analgesic drug ladder for cancer pain. METHODS: The Cochrane Library, PubMed, and CNKI Database of Systematic Reviews were searched. Using the Cochrane Register for Randomized Controlled Trials, the quality of the included literature was evaluated, and the meta-analysis was carried out with RevMan 5.3 software. RESULTS: Compared with three-step analgesia alone, acupuncture combined with three-step analgesia for cancer pain increased pain relief response rates (RR = 1.12, 95% CI: 1.08∼1.17, P < 0.00001), reduced NRS score (SMD = -1.10, 95% CI: -1.86∼-0.35, P=0.004), reduced the rate of side effects (RR = 0.45, 95% CI: 0.38∼0.53, P < 0.00001), including nausea (P < 0.00001), vomiting (P=0.008), constipation (P < 0.00001), and dizziness (P=0.010), reduced the burst pain rate (SMD = -1.38; 95% CI: -2.44∼-0.32, P=0.01), shortened analgesia effect onset time (P=0.004), and extended the duration of response (P < 0.0001). CONCLUSION: For the treatment of cancer pain, acupuncture combined with three-step analgesic drugs is better than using only three-step analgesic drugs.

Fast whole-body motor neuron calcium imaging of freely moving Caenorhabditis elegans without coverslip pressed.

Caenorhabditis elegans (C. elegans) is an ideal model organism for studying neuronal functions at the system level. This article develops a customized system for whole-body motor neuron calcium imaging of freely moving C. elegans without the coverslip pressed. Firstly, we proposed a fast centerline localization algorithm that could deal with most topology-variant cases costing only 6 ms for one frame, not only benefits for real-time localization but also for post-analysis. Secondly, we implemented a full-time two-axis synchronized motion strategy by adaptively adjusting the motion parameters of two motors in every short-term motion step (~50 ms). Following the above motion tracking configuration, the tracking performance of our system has been demonstrated to completely support the high spatiotemporal resolution calcium imaging on whole-body motor neurons of wild-type (N2) worms as well as two mutants (unc-2, unc-9), even the instantaneous speed of worm moving without coverslip pressed was extremely up to 400 µm/s.

Based on BATMAN-TCM to Explore the Molecular Mechanism of Xihuang Pill Regulating Immune Function to Treat Breast Precancerous Lesions.

OBJECTIVE: The specific mechanism of Xihuang Pill in the treatment of breast precancerous lesions and breast cancer has not yet been elucidated. METHODS: In our study, BATMAN-TCM (a Bioinformatics Analysis Tool for Molecular mechanisms of Traditional Chinese Medicine) was used to forecast the relationship among chemical components, immune targets, and diseases of each herb in Xihuang Pill and constructed a component-target-disease network. Taking breast precancerous lesion model rats as the research object, the molecular mechanism of Xihuang Pill regulating immunity was analyzed. RESULTS: BATMAN-TCM prediction showed that 309 genes were enriched in the biological process of "immune system response", which was the target of Xihuang Pill to regulate the immune system. The target of breast cancer disease and the genes related to Xihuang Pill's immune system response were crossed, and 88 cross genes were obtained. According to the enrichment results of GO/KEGG pathway, T cell activation was found to be the most relevant. We select Th1 cells (IL-2, IFN-γ) and Th2 cells (IL-4, IL-10) among them for animal experiment verification. The results show that Xihuang Pill can upregulate the serum IFN-γ and IL-2 levels, reduce the IL-4 and IL-10 levels, and regulate the balance of Th1/Th2 cells in the peripheral blood of rats with breast precancerous lesions. CONCLUSION: Xihuang Pill targets a variety of immune-related molecules related to breast precancerous lesions and is a traditional Chinese medicine formula that effectively regulates immune function.