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Abstract To explore the role of YAP, a key effector of the Hippo pathway, in temporomandibular joint (TMJ) ankylosis. The temporal and spatial expression of YAP was detected via immunohistochemistry and multiplex immunohistochemistry on postoperative Days 1, 4, 7, 9, 11, 14 and 28 in a sheep model. Isolated mesenchymal stem cells (MSCs) from samples of the Day 14. The relative mRNA expression of YAP was examined before and after the osteogenic induction of MSCs. A YAP-silenced MSC model was constructed, and the effect of YAP knockdown on MSC function was examined. YAP is expressed in the nucleus of the key sites that determine the ankylosis formation, indicating that YAP is activated in a physiological state. The expression of YAP increased gradually over time. Moreover, the number of cells coexpressing of RUNX2 and YAP—with the osteogenic active zone labelled by RUNX2—tended to increase after Day 9. After the osteogenic induction of MSCs, the expression of YAP increased. After silencing YAP, the osteogenic, proliferative and migratory abilities of the MSCs were inhibited. YAP is involved in the early development of TMJ bony ankylosis. Inhibition of YAP using shRNA might be a promising way to prevent or treat TMJ ankylosis.

Abstract Introduction Recent studies have suggested a potential association between methotrexate use and an increased risk of dementia. However, the causal relationship between methotrexate and dementia remains unclear. This study aims to investigate the potential causal effect of methotrexate use on the risk of dementia using a two-sample Mendelian randomization (TSMR) approach. Methods We conducted a TSMR study using summary statistics from genome-wide association studies (GWAS) of methotrexate use and dementia. We obtained genetic instruments for methotrexate use from a large-scale GWAS meta-analysis and genetic instruments for dementia from a separate GWAS meta-analysis. We performed several statistical analyses, including inverse-variance weighted (IVW), weighted median (WM1), weighted mode (WM2), and MR-Egger regression methods, to estimate the causal effect of methotrexate on dementia risk. Results Our TSMR analysis showed a significant positive association between genetic predisposition to methotrexate use and dementia risk. The IVW method estimated a causal odds ratio (OR) of 0.476 [95% confidence interval (CI) 0.362–0.626] per unit increase in the log odds ratio of methotrexate use. WM1, WM2, and MR-Egger methods provided consistent results. Conclusion The findings of this mendelian randomization (MR) study suggest a potential causal effect of methotrexate use on the risk of dementia. However, further research is needed to validate these findings and explore the underlying mechanisms. Since methotrexate is widely prescribed for various autoimmune diseases, a better understanding of its potential impact on dementia risk is crucial for optimizing treatment strategies and addressing potential adverse effects.

Critical limb ischemia (CLI) is a devastating disease characterized by the progressive blockage of blood vessels. Although the paracrine effect of growth factors in stem cell therapy made it a promising angiogenic therapy for CLI, poor cell survival in the harsh ischemic microenvironment limited its efficacy. Thus, an imperative need exists for a stem-cell delivery method that enhances cell survival. Here, a collagen microgel (CMG) cell-delivery scaffold (40 × 20 μm) was fabricated via micro-fragmentation from collagen–hyaluronic acid polyionic complex to improve transplantation efficiency. Culturing human adipose-derived stem cells (hASCs) with CMG enabled integrin receptors to interact with CMG to form injectable 3-dimensional constructs (CMG-hASCs) with a microporous microarchitecture and enhanced mass transfer. CMG-hASCs exhibited higher cell survival (p

In this paper, an improved differential evolution algorithm is proposed to improve the positioning accuracy of electronic wristband system. The wristband system is composed of STM32F103 microcontroller, Beidou positioning module, LORA communication module and so on. In the traditional differential evolution algorithm, premature convergence to local optimal will reduce the accuracy of the algorithm. To solve this problem, the method introduces the distance information between known and unknown points and between all unknown points in the fitness function and overall initialization. This reduces the premature convergence of the algorithm and improves the optimization ability of the algorithm. Experimental results using the CICDDoS2019 dataset show that the localization accuracy of the proposed algorithm is improved by 7.6% compared with traditional differential evolution. The method also has good stability. This provides an effective way to improve the positioning accuracy of the wristband, which can be used for applications such as patient monitoring.

It takes a long time to detect target information in noisy radar information and reduce the probability of false alarm. Therefore, it has become a research direction to reduce the probability of false alarm and the time of effective target detection. This paper introduces a new method to reduce the occurrence of false alarm in non-uniform environment and improve the efficiency of target detection. The proposed method involves a faster and more stable method that involves preprocessing the data set, splitting it into smaller parts, and utilizing a KTH minimum value M determined by an ordered statistics class constant false alarm detection algorithm. Each data point in the small segment is then compared to M, anything above M is classified as a target, and anything below M is ignored as clutter. Then ESVI-CFAR detection was performed on the selected target to obtain the final detection result. Experimental results show that the proposed method is superior to the traditional VI-CFAR and has better target detection performance.

Abstract Background Although great progress has been made in anti-cancer therapy, the prognosis of laryngeal squamous cell carcinoma (LSCC) patients remains unsatisfied. Quantities of studies demonstrate that glycolytic reprograming is essential for the progression of cancers, where triosephosphate isomerase 1 (TPI1) serves as a catalytic enzyme. However, the clinicopathological significance and potential biological functions of TPI1 underlying LSCC remains obscure. Methods We collected in-house 82 LSCC tissue specimens and 56 non-tumor tissue specimens. Tissue microarrays (TMA) and immunohistochemical (IHC) experiments were performed. External LSCC microarrays and bulk RNA sequencing data were integrated to evaluate the expression of TPI1. We used a log-rank test and the CIBERSORT algorithm to assess the prognostic value of TPI1 and its association with the LSCC microenvironment. Malignant laryngeal epithelial cells and immune-stromal cells were identified using inferCNV and CellTypist. We conducted a comprehensive analysis to elucidate the molecular functions of TPI1 in LSCC tissue and single cells using Pearson correlation analysis, high dimensional weighted gene co-expression analysis, gene set enrichment analysis, and clustered regularly interspaced short palindromic repeats (CRISPR) screen. We explored intercellular communication patterns between LSCC single cells and immune-stromal cells and predicted several therapeutic agents targeting TPI1. Results Based on the in-house TMA and IHC analysis, TPI1 protein was found to have a strong positive expression in the nucleus of LSCC cells but only weakly positive activity in the cytoplasm of normal laryngeal cells (p

ObjectiveTo compare the effects of tofacitinib and adalimumab on the risk of adverse lipidaemia outcomes in patients with newly diagnosed rheumatoid arthritis (RA).MethodsData of adult patients newly diagnosed with RA who were treated with tofacitinib or adalimumab at least twice during a 3-year period from 1 January 2018 to 31 December 2020, were enrolled in the TriNetX US Collaborative Network. Patient demographics, comorbidities, medications, and laboratory data were matched by propensity score at baseline. Outcome measurements include incidental risk of dyslipidemia, major adverse cardiac events (MACE) and all-cause mortality.ResultsA total of 7,580 newly diagnosed patients with RA (1998 receiving tofacitinib, 5,582 receiving adalimumab) were screened. After propensity score matching, the risk of dyslipidaemia outcomes were higher in the tofacitinib cohort, compared with adalimumab cohort (hazard ratio [HR] with 95% confidence interval [CI], 1.250 [1.076–1.453]). However, there is no statistically significant differences between two cohorts on MACE (HR, 0.995 [0.760–1.303]) and all-cause mortality (HR, 1.402 [0.887–2.215]).ConclusionTofacitinib use in patients with RA may increase the risk of dyslipidaemia to some extent compared to adalimumab. However, there is no differences on MACE and all-cause mortality.

BackgroundSpondylitis caused by Brucella infection is a rare but challenging condition, and its successful management depends on timely diagnosis and appropriate treatment. This study reports two typical cases of thoracic and lumbar brucellosis spondylitis, highlighting the pivotal roles of real-time polymerase chain reaction (real-time PCR) detection and surgical intervention.Case presentationCase 1 involved a 49-year-old male shepherd who presented with a 6-month history of fever (40°C), severe chest and back pain, and 2-week limited lower limb movement with night-time exacerbation. Physical examination revealed tenderness and percussion pain over the T9 and T10 spinous processes, with grade 2 muscle strength in the lower limbs. CT showed bone destruction of the T9 and T10 vertebrae with narrowing of the intervertebral space, whereas MRI demonstrated abnormal signals in the T9–T10 vertebrae, a spinal canal abscess, and spinal cord compression. The Rose Bengal plate agglutination test was positive. Case 2 was a 59-year-old man who complained of severe thoracolumbar back pain with fever (39.0°C) and limited walking for 2 months. He had a 2.5 kg weight loss and a history of close contact with sheep. The Rose Bengal test was positive, and the MRI showed inflammatory changes in the L1 and L2 vertebrae. Diagnosis and treatment: real-time PCR confirmed Brucella infection in both cases. Preoperative antimicrobial therapy with doxycycline, rifampicin, and ceftazidime-sulbactam was administered for at least 2 weeks. Surgical management involved intervertebral foraminotomy-assisted debridement, decompression, internal fixation, and bone grafting under general anesthesia. Postoperative histopathological examination with HE and Gram staining further substantiated the diagnosis. Outcomes: both patients experienced significant pain relief and restored normal lower limb movement at the last follow-up (4–12 weeks) after the intervention.ConclusionReal-time PCR detection offers valuable diagnostic insights for suspected cases of brucellosis spondylitis. Surgical treatment helps in infection control, decompression of the spinal cord, and restoration of stability, constituting a necessary and effective therapeutic approach. Prompt diagnosis and comprehensive management are crucial for favorable outcomes in such cases.

Summary: Diabetic kidney disease (DKD) is one of the most common complications of diabetes, and no specific drugs are clinically available. We have previously demonstrated that inhibiting microsomal prostaglandin E synthase-2 (mPGES-2) alleviated type 2 diabetes by enhancing β cell function and promoting insulin production. However, the involvement of mPGES-2 in DKD remains unclear. Here, we aimed to analyze the association of enhanced mPGES-2 expression with impaired metabolic homeostasis of renal lipids and subsequent renal damage. Notably, global knockout or pharmacological blockage of mPGES-2 attenuated diabetic podocyte injury and tubulointerstitial fibrosis, thereby ameliorating lipid accumulation and lipotoxicity. These findings were further confirmed in podocyte- or tubule-specific mPGES-2-deficient mice. Mechanistically, mPGES-2 and Rev-Erbα competed for heme binding to regulate fatty acid binding protein 5 expression and lipid metabolism in the diabetic kidney. Our findings suggest a potential strategy for treating DKD via mPGES-2 inhibition.

Parathyroid hormone-related protein (PTHrP) plays a significant role in various tumor types, including prostate cancer. However, its specific role and underlying mechanisms in prostate cancer remain unclear. This study investigates the role of PTHrP and its interaction with the c-Met in prostate cancer. PTHrP was overexpressed and knocked down in prostate cancer cell lines to determine its effect on cell functions. Xenograft tumor models were employed to assess the impact of PTHrP overexpression on tumor growth. To delve into the interaction between PTHrP and c-Met, rescue experiments were conducted. Clinical data and tissue samples from prostate cancer patients were gathered and analyzed for PTHrP and c-Met expression. PTHrP overexpression in prostate cancer cells upregulates c-Met expression and augments cell functions. In contrast, PTHrP-knockdown diminishes c-Met expression and inhibits cell functions. In vivo experiments further demonstrated that PTHrP overexpression promoted tumor growth in xenograft models.Moreover, modulating c-Met expression in rescue experiments led to concurrent alterations in prostate cancer cell functions. Immunohistochemical analysis of clinical samples displayed a significant positive correlation between PTHrP and c-Met expression. Additionally, PTHrP expression correlated with clinical parameters like prostate-specific antigen (PSA) levels, tumor stage, lymph node involvement, distant metastasis, and Gleason score. PTHrP plays a crucial role in prostate cancer progression by upregulating c-Met expression. These insights point to PTHrP as a promising potential biomarker for prostate cancer.

Adonis pseudoamurensis W.T. Wang 1980 is an important traditional medicinal plant used for the treatment of cardiac diseases. The complete chloroplast (cp) genome of Adonis pseudoamurensis is reported for the first time in this study. The circular cp genome is 156,917 bp in length, consisting of a large single-copy region (86,262 bp), a small single-copy region (18,067 bp), and two inverted repeat regions (26,294 bp). The genome encodes 129 genes, comprising 84 protein-coding genes, 37 transfer RNA (tRNA) genes, and 8 ribosomal RNA (rRNA) genes. Phylogenetic analysis showed that A. pseudoamurensis is closely related to A. amurensis.

Abstract Carbon supported intermetallic compound nanoparticles with high activity and stability are promising cathodic catalysts for oxygen reduction reaction in proton-exchange-membrane fuel cells. However, the synthesis of intermetallic catalysts suffers from large diffusion barrier for atom ordering, resulting in low ordering degree and limited performance. We demonstrate a low-melting-point metal doping strategy for the synthesis of highly ordered L10-type M-doped PtCo (M = Ga, Pb, Sb, Cu) intermetallic catalysts. We find that the ordering degree of the M-doped PtCo catalysts increases with the decrease of melting point of M. Theoretic studies reveal that the low-melting-point metal doping can decrease the energy barrier for atom diffusion. The prepared highly ordered Ga-doped PtCo catalyst exhibits a large mass activity of 1.07 A mgPt −1 at 0.9 V in H2-O2 fuel cells and a rated power density of 1.05 W cm−2 in H2-air fuel cells, with a Pt loading of 0.075 mgPt cm−2.

Abstract Background The main subtypes of idiopathic inflammatory myopathies (IIMs)—polymyositis (PM) and dermatomyositis (DM)—are often presented as interstitial lung disease (ILD) in clinical practice; therefore, many researchers have combined the three studies into PM/DM with ILD. Methods Using bibliometrics, the research status, progress, and hotspots of PM/DM with ILD between 2000 and 2022 were studied. Literature data on PM/DM with ILD were retrieved from the Web of Science (WoS) database for the research period. Visualization software, including VOSviewer, Pajek, CiteSpace, and Scimago Graphica were used for bibliometric analysis. Results A total of 1555 relevant articles were obtained, and the overall research in this field showed an increasing trend. Regarding contributing countries and venues, Japan published the most articles while Rheumatology was the most prolific journal. Regarding authors, the most published article was by Wang Guochun from Changchun University of Technology in China. Keyword analysis and cocited literature cluster analysis showed that diagnosis, classification, autoantibodies, antibodies, prognosis, complications, and treatment of PM/DM with ILD have been hot topics in this field recently. Moreover, our study shows that anti‐mda5 antibody, mortality, gene 5 antibody, IIMs, double‐blind, and prognostic factors, among others, may be new hot topics. Conclusion This study found that research on PM/DM with ILD has increased over time, and scholars are paying more attention to this field. The development of new drugs for the management, treatment, and prevention of PM/DM with ILD is the primary task of researchers and a direction for future research in this field.

ObjectiveAt present, the structure of knowledge in the field of childhood thyroid cancer is not clear enough, and scholars lack a sufficient understanding of the developing trends in this field, which has led to a shortage of forward-looking outputs. The purpose of this research is to help scholars construct a complete knowledge framework and identify current challenges, opportunities, and development trends.MethodsWe searched the literature in the Web of Science Core Collection database on August 7, 2023 and extracted key information from the top 100 most cited articles, such as the countries, institutions, authors, themes, and keywords. We used bibliometric tools such as bibliometrix, VOSviewer, and CiteSpace for a visualization analysis and Excel for statistical descriptions.ResultsThe top 100 most cited articles fluctuated over time, and the research was concentrated in European countries, the United States, and Japan, among which scientific research institutions and scholars from the United States made outstanding contributions. Keyword analysis revealed that research has shifted from simple treatment methods for pediatric thyroid cancer (total thyroidectomy) and inducing factors (the Chernobyl power station accident) to the clinical applications of genetic mutations (such as the BRAF and RET genes) and larger-scale genetic changes (mutation studies of the DICER1 gene). The thematic strategy analysis showed an increasing trend towards the popularity of fusion oncogenes, while the popularity of research on traditional treatments and diagnostics has gradually declined.ConclusionExtensive research has been conducted on the basic problems of pediatric thyroid cancer, and there has been significant outputs in the follow-up and cohort analysis of conventional diagnostic and treatment methods. However, these methods still have certain limitations. Therefore, scholars should focus on exploring fusion genes, the clinical applications of molecular targets, and novel treatment methods. This study provides a strong reference for scholars in this field.

Due to its traditional fermentation, there are obvious limits on the quality improvements in black tea. However, microbial fermentation can provide an abundance of metabolites and improve the flavor of tea. The “golden flower” fungi are widely used in the microbial fermentation of tea and has unique uses in healthcare. To further explore the improvements in black tea quality achieved via microbial fermentation, we used widely targeted metabolomics and metagenomics analyses to investigate the changes in and effects of metabolites and other microorganisms during the interaction between the “golden flower” fungi and black tea. Five key flavor metabolites were detected, the levels of catechin, epigallocatechin gallate, (−)-epicatechin gallate were decreased by different degrees after the inoculation of the “golden flower” fungus, whereas the levels of caffeine and (+)-gallocatechin increased. Botryosphaeriaceae, Botryosphaeriales, Dothideomycetes, Aspergillaceae, Trichocomaceae, and Lecanoromycetes play a positive role in the black tea fermentation process after inoculation with the “golden flower” fungi. D-Ribose can prevent hypoxia-induced apoptosis in cardiac cells, and it shows a strong correlation with Botryosphaeriaceae and Botryosphaeriales. The interaction between microorganisms and metabolites is manifested in tryptophan metabolism, starch and sucrose metabolism, and amino sugar and nucleotide sugar metabolism. In conclusion, the changes in metabolites observed during the fermentation of black tea by “golden flower” fungi are beneficial to human health. This conclusion extends the knowledge of the interaction between the “golden flower” fungi and black tea, and it provides important information for improving the quality of black tea.

The prevalence of human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) has emerged as a major public health concern in China. When patients with HIV infection undergo surgical treatment, there are two main challenges. Firstly, medical staff face a high risk of HIV infection due to occupational exposure. Secondly, the patient’s immune function is impaired, increasing the risk of opportunistic infections and postoperative complications. The surgical treatment of such patients is unique, and the risk of occupational exposure during the operation primarily depends upon the viral load of HIV/AIDS patients. Therefore, perioperative antiretroviral therapy is of paramount importance in order to standardize the perioperative antiretroviral therapy (ART) for HIV/AIDS patients. The Surgery Group of the Chinese Association of STD and AIDS Prevention and Control, in collaboration with the Treatment Association, and Surgery Group of the Chinese Medical Association of Tropical Diseases and Parasitology, has developed an expert consensus on perioperative antiretroviral therapy for HIV/AIDS patients. This consensus encompasses various aspects, including surgical risk assessment, selection of perioperative antiretroviral therapy regimens, prevention of opportunistic infections, and the crucial focus on rapid preoperative viral load reduction and immune function reconstruction for HIV/AIDS patients.

Presently, there is limited data on the potential survival benefits of transurethral resection of the prostate (TURP) in patients with metastatic hormone-sensitive prostate cancer (mHSPCa). In this study, we aimed to assess the effects of TURP on the survival of mHSPCa patients. Of the 59 patients diagnosed with mHSPCa included, 28 received androgen deprivation therapy (ADT) alone, and the remaining received TURP plus ADT. Their time to biochemical progression (TBCP) and progression-free survival (PFS) were analyzed. Our results showed that for a median follow-up time of 15 (range, 3–40) months and 21 (range, 6–39) months for the ADT group and the TURP group, respectively, the TURP group exhibited significantly longer TBCP than the ADT group (p = 0.020). In addition, patients in the TURP group had numerically longer PFS, although the difference between the two groups was not significantly different (p = 0.110). Cox multivariate analysis indicated that longer TBCP was independently associated with TURP (p = 0.032) and lower Gleason scores (p = 0.001). Altogether this study showed that TURP could prolong TBCP and potentially improve the PFS of mHSPCa patients. However, further studies with a larger sample size are needed to confirm these findings.

Aroma is an important factor in the measurement of the quality and market value of oolong tea. However, it is hard to develop an oolong tea with good aroma quality using unsuitable tea varieties. To explore the key factors of tea varieties in the formation of oolong tea aromas, the fresh leaves of the Chungui variety (CG, suitable for oolong tea, Camellia sinensis (L.) O. Kuntze) and the Fuyun No. 6 variety (F6, unsuitable for oolong tea, Camellia sinensis (L.) O. Kuntze) were harvested and treated by withering and mechanical stress in order. Then, aroma, transcriptome, and jasmonate (JA) contents, and weighted gene co-expression network analysis (WGCNA), of samples were investigated. The contents of characteristic oolong tea aromas, including indole, (E)-β-ocimene, (E)-nerolidol, α-farnesene, and jasmine lactone, were all accumulated in much higher quantities in the CG variety after withering and mechanical stress. Accordingly, the coding genes of aroma formation synthases TSB2, OCS, NES, AFS, and LOX1, and related genes in MVA, MEP, and ALA pathways, were all much more highly activated. These differential reactions are mainly caused by the higher accumulation of jasmonates, especially methyl jasmonate, a type of important plant signal chemical, in CG after mechanical stress. WGCNA analysis indicated 34 different transcription factors from different families are predicted to be involved in this jasmonate-responsive reaction.

With shared routes of transmission, HBV and HCV co-infection are estimated to occur more in subjects with HIV. This study aimed to characterize and describe the prevalence of HBV and HCV co-infections in a cohort of newly diagnosed HIV+ subjects living in China. We conducted a cross-sectional study among newly diagnosed HIV+ subjects aged 18–100 who participated in surveys on the national HIV molecular epidemiology in 2015 and 2023. (The epidemiological table survey is located in the national database alongside serologic testing). The chi-square test was used to identify changes in infections between the studying populations in 2015 and 2023, and conditional logistic regression models were fit to identify risk factors for each co-infection. Among the 11,024 newly diagnosed HIV+ subjects who were surveyed (n = 4501 in 2015; n = 6523 in 2023), the prevalence of HBV, HCV, and HBV/HCV in 2023 was lower than that in 2015, respectively. No decrease was observed in HCV co-infection in men who had sex with men (MSM) in North China, Northeast China, and East China. Increasing recognition among those at high risk of heterosexual transmission and those with low educational backgrounds is paramount to the prevention and control of HIV/HBV/HCV infections.

Transition metal doping is an ideal strategy to construct multifunctional and efficient nanozymes for biosensing. In this work, a metal-doped CoMnOx nanozyme was designed and synthesized by hydrothermal reaction and high-temperature calcination. Based on its oxidase activity, an “on-off-on” smartphone sensing platform was established to detect ziram and Cu2+. The obtained flower-shaped CoMnOx could exhibit oxidase-, catalase-, and laccase-like activities. The oxidase activity mechanism of CoMnOx was deeply explored. O2 molecules adsorbed on the surface of CoMnOx were activated to produce a large amount of O2·-, and then, O2·- could extract acidic hydrogen from TMB to produce blue oxTMB. Meanwhile, TMB was oxidized directly to the blue product oxTMB via the high redox ability of Co species. According to the excellent oxidase-like activity of CoMnOx, a versatile colorimetric detection platform for ziram and Cu2+ was successfully constructed. The linear detection ranges for ziram and Cu2+ were 5~280 μM and 80~360 μM, and the detection limits were 1.475 μM and 3.906 μM, respectively. In addition, a portable smartphone platform for ziram and Cu2+ sensing was established for instant analysis, showing great application promise in the detection of real samples including environmental soil and water.

BackgroundEmerging HIV drug resistance caused by increased usage of antiretroviral drugs (ARV) could jeopardize the success of standardized HIV management protocols in resource-limited settings. ObjectiveWe aimed to characterize pretreatment HIV drug resistance (PDR) among HIV-positive individuals and risk factors in China in 2022. MethodsThis cross-sectional study was conducted using 2-stage systematic sampling according to the World Health Organization’s surveillance guidelines in 8 provincial-level administrative divisions in 2022. Demographic information and plasma samples were obtained from study participants. PDR was analyzed using the Stanford HIV drug resistance database, and the Tamura-Nei 93 model in HIV-TRACE was used to calculate pairwise matches with a genetic distance of 0.01 substitutions per site. Logistic regression was used to identify and estimate factors associated with PDR. ResultsPDR testing was conducted on 2568 participants in 2022. Of the participants, 34.8% (n=893) were aged 30-49 years, 81.4% (n=2091) were male, and 3.2% (n=81) had prior ARV exposure. The prevalence of PDR to protease and reverse transcriptase regions, nonnucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 7.4% (n=190), 6.3% (n=163), 1.2% (n=32), and 0.2% (n=5), respectively. Yunnan, Jilin, and Zhejiang had much higher PDR incidence than did Sichuan. The prevalence of nonnucleoside reverse transcriptase inhibitor–related drug resistance was 6.1% (n=157) for efavirenz and 6.3% (n=163) for nevirapine. Multivariable logistic regression models indicated that participants who had prior ARV exposure (odds ratio [OR] 7.45, 95% CI 4.50-12.34) and the CRF55_01B HIV subtype (OR 2.61, 95% CI 1.41-4.83) were significantly associated with PDR. Among 618 (24.2%) sequences (nodes) associated with 253 molecular transmission clusters (size range 2-13), drug resistance mutation sites included K103, E138, V179, P225, V106, V108, L210, T215, P225, K238, and A98. ConclusionsThe overall prevalence of PDR in China in 2022 was modest. Targeted genotypic PDR testing and medication compliance interventions must be urgently expanded to address PDR among newly diagnosed people living with HIV in China.

Advanced intrahepatic cholangiocarcinoma (ICC) is a rare malignant tumor of biliary epithelial cells, known for its extremely unfavorable prognosis. In the absence of intervention, patients typically survive for less than 5 months. Current guidelines from the Chinese Society of Clinical Oncology (CSCO), National Comprehensive Cancer Network (NCCN), and European Society for Medical Oncology (ESMO) recommend chemotherapy-based systemic therapy as the standard treatment for advanced ICC. However, the first-line regimen, consisting of gemcitabine in combination with cisplatin, generally results in a median survival of approximately one year, which is considered suboptimal. Significant progress has been made in radiotherapy techniques, molecular diagnostics, and tumor immune microenvironments. The integration of immune and radiation therapies has revolutionized treatment strategies for cholangiocarcinoma. Moreover, combined therapeutic regimens have shown promising results in improving survival rates among patients with advanced ICC. In this study, we present a case report of a 70-year-old male patient diagnosed with stage IV ICC, featuring metastases to the retroperitoneal, left adrenal, and left supraclavicular lymph nodes. The patient exhibited a high tumor mutational load, significant microsatellite instability, and hyper-expression of PD-L1 (90%), along with positive Epstein-Barr virus-encoded RNA (EBER). Pembrolizumab, a programmed cell death 1 (PD-1) inhibitor, was administered in conjunction with radiotherapy. As a result, considerable shrinkage and inactivation of the primary foci were observed, accompanied by the disappearance of metastases. Ultimately, the patient achieved complete remission and maintained progression-free survival for 41 months following the initial treatment. To the best of our knowledge, this represents the longest case of complete remission using a combination of immunotherapy and radiotherapy as a first-line regimen for the high tumor mutational load, microsatellite instability, and PD-L1 expression (90%) subtype of Epstein-Barr virus-associated ICC (EBVaICC). These findings suggest that the combination of PD-1 inhibitors with radiotherapy may serve as a promising therapeutic strategy for treating this particular cancer subtype.

The effects of 5 MeV Au3+ ions irradiation damage on surface blistering and deuterium (D) retention behaviors in tungsten (W) and W-0.5 wt% ZrC alloy (WZC) have been studied after exposure to a low energy (38 eV D-1) D plasma under the fluence of ∼1 × 1025 D m−2 at about 400 K. It is found that Au3+ ions irradiation significantly reduces the surface density of blisters for both W and WZC. However, the size of blisters becomes larger due to Au3+ ions irradiation. With increasing dpa, the surface density and average size of blisters on the surface of the WZC noticeably decrease. In the case of the W, the average size of blisters also decreases with dpa, but the surface density of blisters changes less. Most of the D (>60%) are trapped at the depth less than ∼3.5 µm and the D concentration increases with dpa for both WZC and W. Compared to W, the D concentration in the sub-surface region of WZC is higher at the same damage level. For both W and WZC, a new high-temperature desorption peak appears at ∼800 K, which is ascribed to the D trapping at vacancy-type defects induced by Au3+ ions irradiation. The D retention in both samples increases with dpa and saturates at a damage level between ∼0.4–1.7 dpa. The growth rate of D retention caused by ion irradiation damage in WZC is less than that in W, while the D retention in WZC is slightly higher than that in W.