The profile of HIV-1 drug resistance in Shanghai, China: a retrospective study from 2017 to 2021.

BACKGROUND: HIV-1 drug resistance is a huge challenge in the era of ART. OBJECTIVES: To investigate the prevalence and characteristics of acquired HIV-1 drug resistance (ADR) in Shanghai, China. METHODS: An epidemiological study was performed among people living with human immunodeficiency virus (PLWH) receiving ART in Shanghai from January 2017 to December 2021. A total of 8669 PLWH were tested for drug resistance by genotypic resistance testing. Drug resistance mutations (DRMs) were identified using the Stanford University HIV Drug Resistance Database program. RESULTS: Ten HIV-1 subtypes/circulating recombinant forms (CRFs) were identified, mainly including CRF01_AE (46.8%), CRF07_BC (35.7%), B (6.4%), CRF55_01B (2.8%) and CRF08_BC (2.4%). The prevalence of ADR was 48% (389/811). Three NRTI-associated mutations (M184V/I/L, S68G/N/R and K65R/N) and four NNRTI-associated mutations (V179D/E/T/L, K103N/R/S/T, V106M/I/A and G190A/S/T/C/D/E/Q) were the most common DRMs. These DRMs caused high-level resistance to lamivudine, emtricitabine, efavirenz and nevirapine. The DRM profiles appeared to be significantly different among different subtypes. CONCLUSIONS: We revealed HIV-1 subtype characteristics and the DRM profile in Shanghai, which provide crucial guidance for clinical treatment and management of PLWH.

Impact of Recombinant Human Granulocyte Colony-Stimulating Factor Combined with Aspirin on Clinical Pregnancy Outcomes and Endometrial Receptivity in Patients with Recurrent Abortion: A Retrospective Study.

Objective: This study investigates the impact of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and aspirin on endometrial receptivity and clinical pregnancy outcomes in individuals with a history of recurrent abortions. Methods: In this retrospective study, 131 individuals with recurrent abortions treated at our facility from July 2019 to December 2020 were split into two groups: mixed therapy and control. The mixed therapy group received aspirin and rhG-CSF, while the control group had no specific treatment. Primary endpoint: live birth rate; secondary: pregnancy rate at 20 weeks. We also evaluated abortion rates, newborn weight, pre-eclampsia, premature delivery, fetal/newborn congenital malformations, and maternal drug adverse reactions. Additionally, we analyzed endometrial blood flow three weeks post-treatment. Results: The analysis encompassed 131 individuals, with 65 in the control group and 66 in the mixed therapy group. Notably, the mixed therapy group (n = 54) exhibited a markedly higher live birth rate than the control group (P < .05). In terms of medication-related side effects, the control group showed no adverse reactions, while the mixed therapy group reported mild effects (skin itching in three cases, leukocytosis in seven, and bone pain in one case) that did not significantly impact outcomes. Pre-treatment, the mixed therapy group had a notably lower resistive index, pulsatility index, and systolic-to-diastolic ratio compared to the control group, with statistical significance (P < .05). The control group's indices remained unchanged (P > .05). Conclusions: In women with a history of recurrent abortions, the administration of recombinant human granulocyte colony-stimulating factor and aspirin can effectively and safely improve live birth rates. This improvement may be associated with enhanced endometrial receptivity.

A Multi-Scale Natural Scene Text Detection Method Based on Attention Feature Extraction and Cascade Feature Fusion.

Scene text detection is an important research field in computer vision, playing a crucial role in various application scenarios. However, existing scene text detection methods often fail to achieve satisfactory results when faced with text instances of different sizes, shapes, and complex backgrounds. To address the challenge of detecting diverse texts in natural scenes, this paper proposes a multi-scale natural scene text detection method based on attention feature extraction and cascaded feature fusion. This method combines global and local attention through an improved attention feature fusion module (DSAF) to capture text features of different scales, enhancing the network's perception of text regions and improving its feature extraction capabilities. Simultaneously, an improved cascaded feature fusion module (PFFM) is used to fully integrate the extracted feature maps, expanding the receptive field of features and enriching the expressive ability of the feature maps. Finally, to address the cascaded feature maps, a lightweight subspace attention module (SAM) is introduced to partition the concatenated feature maps into several sub-space feature maps, facilitating spatial information interaction among features of different scales. In this paper, comparative experiments are conducted on the ICDAR2015, Total-Text, and MSRA-TD500 datasets, and comparisons are made with some existing scene text detection methods. The results show that the proposed method achieves good performance in terms of accuracy, recall, and F-score, thus verifying its effectiveness and practicality.

TGFß1-RCN3-TGFBR1 loop facilitates pulmonary fibrosis by orchestrating fibroblast activation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) bears high mortality due to unclear pathogenesis and limited therapeutic options. Therefore, identifying novel regulators is required to develop alternative therapeutic strategies. METHODS: The lung fibroblasts from IPF patients and Reticulocalbin 3 (RCN3) fibroblast-selective knockdown mouse model were used to determine the importance of Rcn3 in IPF; the epigenetic analysis and protein interaction assays, including BioID, were used for mechanistic studies. RESULTS: Reticulocalbin 3 (RCN3) upregulation is associated with the fibrotic activation of lung fibroblasts from IPF patients and Rcn3 overexpression blunts the antifibrotic effects of pirfenidone and nintedanib. Moreover, repressing Rcn3 expression in mouse fibroblasts ameliorates bleomycin-induced lung fibrosis and pulmonary dysfunction in vivo. Mechanistically, RCN3 promotes fibroblast activation by maintaining persistent activation of TGFß1 signalling via the TGFß1-RCN3-TGFBR1 positive feedback loop, in which RCN3 upregulated by TGFß1 exposure detains EZH2 (an epigenetic methyltransferase) in the cytoplasm through RCN3-EZH2 interaction, leading to the release of the EZH2-H3K27me3 epigenetic repression of TGFBR1 and the persistent expression of TGFBR1. CONCLUSIONS: These findings introduce a novel regulating mechanism of TGFß1 signalling in fibroblasts and uncover a critical role of the RCN3-mediated loop in lung fibrosis. RCN3 upregulation may cause resistance to IPF treatment and targeting RCN3 could be a novel approach to ameliorate pulmonary fibrosis.

Spatio-temporal pattern, matching level and prediction of ageing and medical resources in China.

OBJECTIVE: Population ageing, as a hot issue in global development, increases the burden of medical resources in society. This study aims to assess the current spatiotemporal evolution and interaction between population ageing and medical resources in mainland China; evaluate the matching level of medical resources to population ageing; and forecast future trends of ageing, medical resources, and the indicator of ageing-resources (IAR). METHODS: Data on ageing (EPR) and medical resources (NHI, NBHI, and NHTP) were obtained from China Health Statistics Yearbook and China Statistical Yearbook (2011-2020). We employed spatial autocorrelation to examine the spatial-temporal distribution trends and analyzed the spatio-temporal interaction using a Bayesian spatio-temporal effect model. The IAR, an improved evaluation indicator, was used to measure the matching level of medical resources to population ageing with kernel density analysis for visualization. Finally, an ETS-DNN model was used to forecast the trends in population ageing, medical resources, and their matching level over the next decade. RESULTS: The study found that China's ageing population and medical resources are growing annually, yet distribution is uneven across districts. There is a spatio-temporal interaction effect between ageing and medical resources, with higher levels of both in Eastern China and lower levels in Western China. The IAR is relatively high in Northwest, North China, and the Yangtze River Delta, but showed a declining trend in North China and the Yangtze River Delta. The hybrid model (ETS-DNN) gained an R2 of 0.9719, and the predicted median IAR for 2030 (0.99) across 31 regions was higher than the median IAR for 2020 (0.93). CONCLUSION: This study analyzes the relationship between population ageing and medical resources, revealing a spatio-temporal interaction between them. The IAR evaluation indicator highlights the need to address ageing population challenges and cultivate a competent health workforce. The ETS-DNN forecasts indicate higher concentrations of both medical resources and ageing populations in eastern China, emphasizing the need for region-specific ageing security systems and health service industries. The findings provide valuable policy insights for addressing a hyper-aged society in the future.

Herpes simplex virus type 1 infection leads to neurodevelopmental disorder-associated neuropathological changes.

Neonatal herpes simplex virus type 1 (HSV-1) infections contribute to various neurodevelopmental disabilities and the subsequent long-term neurological sequelae into the adulthood. However, further understanding of fetal brain development and the potential neuropathological effects of the HSV-1 infection are hampered by the limitations of existing neurodevelopmental models due to the dramatic differences between humans and other mammalians. Here we generated in vitro neurodevelopmental disorder models including human induced pluripotent stem cell (hiPSC)-based monolayer neuronal differentiation, three-dimensional (3D) neuroepithelial bud, and 3D cerebral organoid to study fetal brain development and the potential neuropathological effects induced by the HSV-1 infections. Our results revealed that the HSV-1-infected neural stem cells (NSCs) exhibited impaired neural differentiation. HSV-1 infection led to dysregulated neurogenesis in the fetal neurodevelopment. The HSV-1-infected brain organoids modelled the pathological features of the neurodevelopmental disorders in the human fetal brain, including the impaired neuronal differentiation, and the dysregulated cortical layer and brain regionalization. Furthermore, the 3D cerebral organoid model showed that HSV-1 infection promoted the abnormal microglial activation, accompanied by the induction of inflammatory factors, such as TNF-α, IL-6, IL-10, and IL-4. Overall, our in vitro neurodevelopmental disorder models reconstituted the neuropathological features associated with HSV-1 infection in human fetal brain development, providing the causal relationships that link HSV biology with the neurodevelopmental disorder pathogen hypothesis.

Clinical characteristics and risk factors for poor prognosis among HIV patients with Talaromyces marneffei bloodstream infection.

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-ß-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 < 0.05. RESULTS: A total of 87 patients were collected, with a median age of 34 years, a median hemoglobin of 94 g/L and CD4 count of 7/µl. The rate of TM bloodstream infection among all in-hospital patients increased from 0.99% in 2015 to 2.09% in 2020(half year). Patients with TM bloodstream infection with CD8 count < 200/µl had a 12.6-fold higher risk of poor prognosis than those with CD8 count > 200/µl (p = 0.04), and those with BDG < 100 pg/mL had a 34.9-fold higher risk of poor prognosis than 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.

Incidence and spectrum of infections among HIV/AIDS patients with lymphoma during chemotherapy.

Introduction Lymphoma is the most common cancer in HIV/AIDS patients. Chemotherapy regiments recommended for lymphomas in HIV-negative patients are also used for lymphomas in HIV/AIDS patients. Little is known about the infections among HIV/AIDS patients with lymphoma undergoing chemotherapy. Methods This retrospective study investigated the incidence, spectrum of and risk factors for infections during chemotherapy in 164 HIV/AIDS patients with lymphoma admitted to Shanghai Public Health Clinical Center from July 2013 to December 2020. Results The median age of the patients was 43 years old; 90.9% (149/164) were male. A total of 112 (68.3%) patients had a CD4 count < 200 cells/µL at lymphoma diagnosis. Diffuse large B-cell lymphoma (56%, 91/164) and Burkitt lymphoma (28%, 46/164) were the two most common subtypes of lymphoma. Among the 137 patients who underwent chemotherapy (total cycles = 749), 58.4% (80/137) of patients experienced a total of 153 episodes of infection, with an incidence rate of 20.4% (153/749). The most commonly seen infections were lung infection (29.2%, 40/137) and febrile neutropenia (27.0%, 37/137). Multivariate analysis showed that grade 4 neutropenia during chemotherapy (OR = 7.128, 95% CI 3.051-16.654, p < 0.001) and duration of antiretroviral treatment at lymphoma diagnosis <6 months (OR = 3.520, 95% CI 1.432-8.653, p = 0.006) were independent risk factors for infection during chemotherapy. Conclusions A large proportion of HIV/AIDS patients with lymphoma may be at risk of infection during chemotherapy. Effective measures should be taken for patients with high risk factors to prevent the occurrence of infection.

Mycobacterium tuberculosis co-infection is associated with increased surrogate marker of the HIV reservoir.

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.

Hydrogeochemical processes and suitability assessment of groundwater in the Jiaodong Peninsula, China.

Groundwater is the primary source of water for domestic use and agricultural irrigation in Jiaodong Peninsula. This study collected 80 groundwater samples from Jiaodong Peninsula to characterize groundwater hydrogeochemical processes and the suitability of groundwater for domestic use and agricultural irrigation. The groundwater of Jiaodong Peninsula was categorized as slightly alkaline freshwater, with a Piper diagram classifying most samples as SO4·Cl-Ca·Mg and HCO3-Ca·Mg types. Major ions were Ca2+, Na+, SO42-, and HCO3-. The major processes driving the hydrochemistry of groundwater were identified as water-rock interactions as well as evaporation. The dissolution of silicate and cation exchange were the predominant hydrogeochemical processes responsible for groundwater chemistry. Four water samples showed seawater intrusion and some indicated pollution from anthropogenic activities such as industry, agriculture, and domestic sewage discharge. Overall, it was found that groundwater in most areas of Jiaodong Peninsula is suitable for domestic use and agricultural irrigation.

Plasma Indoleamine 2,3-Dioxygenase Activity Is Associated With the Size of the Human Immunodeficiency Virus Reservoir in Patients Receiving Antiretroviral Therapy.

BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is an immunoregulatory enzyme that metabolizes tryptophan to immunosuppressive kynurenines. We investigated whether IDO activity is associated with the size of HIV reservoir. METHODS: Total human immunodeficiency virus (HIV) DNA in peripheral blood mononuclear cells (PBMCs) from 127 HIV-infected patients receiving antiretroviral therapy (ART) was quantified. Tryptophan and kynurenine concentrations, as well as microbial translocation markers, were measured in plasma samples. T-cell activation and exhaustion in PBMCs were assessed by flow cytometry. RESULTS: Elevated IDO activity prior to ART correlated with on-ART HIV DNA (r = 0.35, P = .004), but was not associated with pre-ART HIV DNA. A median duration of 15 months of ART significantly decreased IDO activity; however, these levels were still higher than those observed in HIV-uninfected controls. Among treated participants, IDO activity positively correlated with their concurrent HIV DNA (r = 0.36, P < .0001). Multivariate model showed an independent association of pre-ART CD4/CD8 ratio (adjusted odds ratio [aOR], 0.75 per 0.1 increase [95% confidence interval {CI}, .62-.91]) and on-ART IDO activity (aOR, 1.09 per nM/µM increase [95% CI, 1.04-1.14]) with higher levels of HIV DNA on-ART. A lack of association of the microbial translocation markers was observed with the size of HIV reservoir. HIV DNA positively correlated with the proportions of activated CD4 T and CD8 T cells and exhausted CD4 T cells. CONCLUSIONS: We observed a positive correlation between IDO activity and total HIV DNA in blood, highlighting the important role of immunometabolic aberrations in HIV persistence.

Diversity of HIV-1 genotypes and high prevalence of pretreatment drug resistance in newly diagnosed HIV-infected patients in Shanghai, China.

BACKGROUND: Genetic variability and liability to develop drug-resistant mutations are the main characteristics of HIV-1, which can not only increase the risk of antiretroviral treatment (ART) failure, but also can lead to the spread of resistant strains. We aim to investigate the distribution of HIV-1 genotypes and prevalence of pretreatment drug resistance (PDR) in ART-naïve HIV-1 infected patients in Shanghai China. METHODS: A cross-sectional study was performed among the newly diagnosed ART-naive HIV-1 infected patients during the period from January 2017 to November 2017 in Shanghai Public Health Clinical Center. The target fragment of 1316 bp in the pol gene spanning the reverse transcriptase and protease regions was amplified using a nested polymerase chain reaction. HIV-1 genotypes were determined by phylogenetic analysis, and PDR associated mutations were determined according to Stanford University HIV Drug Resistance Database ( http://hivdb.stanford.edu/ ). RESULTS: We successfully amplified pol gene sequences from blood samples of 317 patients, of whom 95.3% were male, and 68.8% were men who have sex with men. The median age was 33 years; and the median CD4 count was 275 cells/µL. The predominant HIV-1 genotype was circulating recombinant form (CRF) 01_AE (53.0%, 168/317), followed by CRF07_BC (29.7%, 94/317), B (7.6%, 24/317), CRF08_BC (1.9%, 6/317), CRF55_01B (1.9%, 6/317), CRF 59_01B (0.9%, 3/317). In addition, 5% (16/317) HIV-1 strains were identified as other subtypes or CRFs/URFs (unique recombinant forms). The overall prevalence of PDR was 17.4% (55/317). PDR frequency to non-nucleoside reverse transcriptase inhibitor (NNRTI, 16.4%) was much higher than that to nucleoside reverse transcriptase inhibitor (NRTI, 4.7%) and protease inhibitor (PI, 0.6%). The most common HIV-1 mutation pattern for NNRTI and NRTI were V179D/E (10.1%, 32/317) and M184 V (2.8%, 9/317), respectively. About half (49.1%, 27/55) of the HIV-1 strains with mutation presented as potential low-level resistant to NNRTI attributed to V179D/E. CONCLUSION: The distribution of HIV-1 genotypes in Shanghai China is diverse and complex. The high prevalence of PDR highlights the significance of baseline HIV-1 drug resistance testing. Non-NNRTI-containing regimen may be the preferred initial therapy for newly diagnosed HIV-1 patients in Shanghai in the absence of PDR test results.

Genetic relatedness of human immunodeficiency virus-1 (HIV-1) strains in a 12-year-old daughter and her father in a household setting.

Modalities of intra-familial transmission of HIV-1 are not always clear. Here we describe an uncommon case of HIV transmission in a family setting, analyzed using clinical, epidemiological and nucleic-acid-based methods, and assess risk factors for intrafamilial transmission of HIV-1 infection. All sequences from the father and the daughter were grouped in the same cluster with a 100 % bootstrap value, which means that the father and his daughter were infected with highly homologous CRF01_AE. The diversity of genetic clones between env and pol genes was insignificant (p > 0.05). Moreover, the results of analysis of drug-resistance-associated mutation positions of the two viral isolates were almost identical, indicating that both were susceptible to the first-line anti-HIV drugs prior to the initiation of antiretroviral treatment (ART), and this presented additional evidence of a high similarity between the two family members' HIV-1 quasispecies. In this family, HIV-1 isolates from a father and his daughter had very highly genetic relatedness. By combining their clinical histories, we could draw the conclusion that the daughter was probably infected via contact with her father's blood or other body fluids, but no obvious transmission route was found, suggesting that HIV-1 infection in similar household settings should be taken into consideration whenever the origin of HIV-1 infection cannot be identified.

Comparative evaluation of mechanical injury methods for establishing stable tracheal stenosis animal models.

The study aimed to assess the stability of various mechanical injury techniques in creating tracheal stenosis animal models using endoscopic assistance and investigate the viability of tracheal stoma in this process. Twenty-six healthy adult New Zealand white rabbits were randomly assigned to an experimental and control group. The experimental group underwent tracheal incision followed by steel brush scraping with endoscopic assistance, while the control group received nylon brush scraping. Within the control group, two subgroups were formed: Group A underwent scraping without tracheal stoma, and Group B underwent scraping followed by tracheal stoma. Additionally, a sham operation was performed on a separate group without subsequent scratching, resulting in no stenosis formation. Endoscopic observations were conducted at 7, 14, and 21 days post-scraping, followed by histological examinations of euthanized rabbits on the 21st day. Notably, all rabbits in the non-stoma group survived without complications, whereas Group B rabbits faced mortality post-operation. Histological assessments revealed inflammatory cell infiltration, fibroblast proliferation, and collagen fiber deposition in narrowed tracheal specimens. Steel brush scraping with endoscopic assistance proved more effective in inducing stable tracheal stenosis compared to nylon brush scraping. However, the survival challenges of rabbits with tracheal fistula require further investigation.

Carbon export from submarine groundwater discharge in a semi-enclosed bay: Impact for the buffering capacity against coastal ocean acidification.

Submarine groundwater discharge (SGD) serves as an important pathway for the transport of dissolved carbon from land to ocean, significantly affecting the coastal biogeochemical cycles. However, the impact of SGD-derived dissolved carbon on the coastal carbon budget remains poorly understood. This study first quantified SGD and associated dissolved organic carbon (DOC), dissolved inorganic carbon (DIC) and total alkalinity (TA) fluxes in Daya Bay using mass balance models based on radium isotopes (223Ra, 224Ra, 226Ra and 228Ra). We then constructed carbon mass balance models to evaluate the impact of SGD-derived carbon on the buffering capacity against coastal ocean acidification. The estimated SGD fluxes ranged from 0.80 × 107 to 2.64 × 107 m3d-1. The DIC, DOC and TA fluxes from SGD were 17.90-36.44 mmol m-2d-1, 0.93-2.13 mmol m-2d-1, and 21.19-28.47 mmol m-2d-1, respectively. Based on carbon mass balances, the DIC flux from SGD was 19-39 times the riverine input, accounting for 27.16 % ∼ 37.64 % of the total carbon source. These results suggest that SGD is a major contributor to DIC, significantly affecting the coastal carbon budget. Furthermore, the average TA:DIC ratio of groundwater discharging into Daya Bay was approximately 1.13. High TA exports enhance the buffering capacity of the coastal ocean and contribute bicarbonate to the ocean, playing a significant role in the ocean carbon sequestration process. This study demonstrates the importance of SGD-derived dissolved carbon in the assessment of coastal carbon budgets.

NECA alleviates inflammatory responses in diabetic retinopathy through dendritic cell toll-like receptor signaling pathway.

Introduction: This study examined the impact of 5'-(N- ethylcarboxamido)adenosine (NECA) in the peripheral blood of healthy individuals, those with diabetes mellitus, diabetic retinopathy (DR), and C57BL/6 mice, both in vivo and in vitro. Methods: Enzyme-linked immunosorbent assay (ELISA) and flow cytometry (FCM) were used to evaluate the effects of NECA on dendritic cells (DCs) and mouse bone marrow-derived dendritic cells (BMDCs) and the effects of NECA-treated DCs on Treg and Th17 cells. The effect of NECA on the Toll-like receptor (TLR) pathway in DCs was evaluated using polymerase chain reaction (PCR) and western blotting (WB). Results: FCM and ELISA showed that NECA inhibited the expression of surface markers of DCs and BMDCs, increased anti-inflammatory cytokines and decreased proinflammatory cytokines. PCR and WB showed that NCEA decreased mRNA transcription and protein expression in the TLR-4-MyD88-NF-kß pathway in DCs and BMDCs. The DR severity in streptozocin (STZ) induced diabetic mice was alleviated. NECA-treated DCs and BMDCs were co-cultivated with CD4+T cells, resulting in modulation of Treg and Th17 differentiation, along with cytokine secretion alterations. Conclusion: NECA could impair DCs' ability to present antigens and mitigate the inflammatory response, thereby alleviating the severity of DR.

Prevalence and transmission of pretreatment drug resistance in people living with HIV-1 in Shanghai China, 2017-2021.

The implementation of pretreatment drug-resistance (PDR) surveillance among people living with HIV-1 (PLWH) is a top priority in countries using efavirenz (EFV)/nevirapine (NVP) for first-line ART. In this study, we assessed the prevalence of PDR among PLWH in Shanghai, China during 2017-2021, and to reveal PDR transmission between Shanghai and other regions of China. A total of 5050 PLWH not on ART during 2017-2021 were included. Partial HIV-1 pol sequences were amplified, sequenced, and analysed for drug-resistance mutations (DRMs). Besides, transmission network of PDR variants was inferred using HIV-TRACE. The overall prevalence of PDR was 4.8% (242/5050; 95% CI, 4.2-5.4). Prevalence of NNRTI-associated PDR was 3.9% (95% CI, 3.4-4.5), higher than those of NRTI-associated (0.8%; 95% CI, 0.5-1.1) and PI-associated PDR (0.9%; 95% CI, 0.6-1.2). High prevalence of PDR (especially high-level resistance) to EFV (132/5050, 2.6%) and NVP (137/5050, 2.7%) were found. CRF01_AE (46.0%) was the predominant HIV-1 genotype with any DRMs, followed by CRF55_01B (21.0%), and CRF07_BC (15.1%). Two NRTI-associated (S68G/N/R and T215A/N/S/Y), five NNRTI-associated (V179D/E/T/L, K103N/R/S/T, E138A/G/K, V106M/I/A and Y181C/I) and two PI-associated mutations (M46I/L/V and Q58E) were the most common observed DRMs in PDR patients in Shanghai. The vast majority of S68G occurred in CRF01_AE (45%). M46I/L/V and Q58E showed a relatively high prevalence in CRF01_AE (4.1%) and CRF07_BC (12.6%). Transmission network analyses demonstrated cross-regional transmission links of PDR variants between Shanghai and other regions of China, which was mainly driven by the potential low-level DRM V179D/E. These results provide crucial information for clinical decision making of first-line ART in PLWH with PDR.

Seawater intrusion-triggered high fluoride groundwater development on the eastern coast of China.

High-fluoride groundwater is commonly found in coastal areas worldwide, while its formation mechanism remains elusive. Herein, a comprehensive study was performed to identify the major controlling factor of high-fluoride groundwater occurrence along the eastern coast of China. Hydrogeochemical methods were employed to examine the distribution patterns of seawater intrusion and fluoride concentration and the impact of seawater intrusion on the fluoride concentration. The results indicate that seawater intrusion significantly influences the groundwater evolution process in the study areas. The groundwater in Laizhou Bay was affected by brine, and the groundwater in Tianjin and Jiangsu was affected by seawater with a mixing ratio lower than 40% and 20%, respectively. And the fluoride concentration in groundwater from Tianjin, Laizhou Bay, and Jiangsu generally exceeded 1 mg/L, with the average of 2.3 mg/L, 24.9 mg/L, and 34.6 mg/L, respectively. Both the degree of seawater intrusion and the fluoride concentration exhibit a consistent pattern: Laizhou Bay > Tianjin > Jiangsu. Cl- concentration in groundwater varies positively with the F- concentration (y = 0.66x - 1.31). Moreover, the spatial distribution of areas with high-fluoride groundwater mirrors that of seawater intrusion. The high-fluoride groundwater varies spatially and is related to the degree, stage, and type of seawater intrusion. In other words, when seawater intrusion intensifies more or groundwater in the freshwater renewal phase with higher Na+/Ca2+ or the presence of paleo-seawater intrusion with higher fluoride concentration of brine, the concentration of fluoride in groundwater is higher. As seawater intrusion intensifies, the high-fluoride groundwater in the study areas generally poses a higher health risk to human. These findings enhance our comprehension of the mechanisms underpinning high-fluoride groundwater in coastal regions and the environmental ramifications of seawater intrusion.

Trends in and Risk Factors for Drug Resistance in Mycobacterium tuberculosis in HIV-Infected Patients.

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 <60 years old was a risk factor for streptomycin resistance, mono-drug resistance, and any-drug resistance (RR 4.139, 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.

Prevalence and associated factors of low bone mineral density in people living with HIV: a cross-sectional study.

This study examined low bone mineral density (BMD) prevalence and associated factors among Chinese people living with HIV (PLWH), uncovering a persistent high BMD risk in older individuals, even after adjusting for age and body mass index (BMI). Notably, lopinavir/ritonavir (LPV/r) therapy was linked to reduced BMD, highlighting the imperative need for regular BMD monitoring and interventions in older PLWH. PURPOSE: HIV infection and antiretroviral therapy (ART) have been shown to contribute to lower BMD, resulting in an increased susceptibility to osteopenia and osteoporosis. However, there is limited knowledge about the prevalence of reduced BMD and its associated factors among Chinese PLWH. In this cross-sectional study, we aimed to investigate the prevalence and factors associated with low BMD among PLWH in China. METHODS: We retrospectively enrolled PLWH and non-HIV volunteers who underwent dual-energy X-ray absorptiometry (DXA) scans to measure bone density. Demographic information, laboratory test results, ART regimens, and treatment duration were collected. Univariate and multiple regression analyses were performed to identify factors influencing abnormal bone mass in PLWH. RESULTS: A total of 829 individuals were included in this study, comprising the HIV group (n = 706) and the non-HIV group (n = 123). The prevalence of low BMD among all PLWH was found to be 13.88% (98 out of 706). However, among PLWH aged 50 years and above, the prevalence increased to 65.32% (81 out of 124). In contrast, control subjects in the same age group had a prevalence of 38.21% (47 out of 123). After adjusting for age and BMI, older PLWH still demonstrated a higher prevalence of low BMD compared to the non-HIV group (68.24% vs 34.94%, P < 0.001). Multivariate analysis revealed that older age was strongly associated with a higher risk of low BMD among PLWH, with an odds ratio (OR) of 6.28 for every 10-year increase in age in the ART-naïve population (95% confidence intervals [CIs], 3.12-12.65; P < 0.001) and OR of 4.83 in the ART-experienced population (3.20-7.29, P < 0.001). Within the ART-experienced group, current LPV/r treatment was associated with an increased risk of low BMD (OR = 3.55, 1.24-10.14, P < 0.05), along with lower BMI (OR = 0.84, 0.75-0.95, P < 0.05), and elevated alkaline phosphatase (OR = 1.02, 1.01-1.03, P < 0.01). CONCLUSION: The prevalence of low BMD is higher among PLWH aged 50 years and above compared to non-HIV individuals. The use of LPV/r for ART is associated with reduced BMD. These findings emphasize the importance of regular monitoring of BMD in older PLWH and the need for appropriate interventions to mitigate the risks of osteopenia and osteoporosis in this population.