Automated tumor immunophenotyping predicts clinical benefit from anti-PD-L1 immunotherapy.

Cancer immunotherapy has transformed the clinical approach to patients with malignancies, as profound benefits can be seen in a subset of patients. To identify this subset, biomarker analyses increasingly focus on phenotypic and functional evaluation of the tumor microenvironment to determine if density, spatial distribution, and cellular composition of immune cell infiltrates can provide prognostic and/or predictive information. Attempts have been made to develop standardized methods to evaluate immune infiltrates in the routine assessment of certain tumor types; however, broad adoption of this approach in clinical decision-making is still missing. We developed approaches to categorize solid tumors into 'desert', 'excluded', and 'inflamed' types according to the spatial distribution of CD8+ immune effector cells to determine the prognostic and/or predictive implications of such labels. To overcome the limitations of this subjective approach, we incrementally developed four automated analysis pipelines of increasing granularity and complexity for density and pattern assessment of immune effector cells. We show that categorization based on 'manual' observation is predictive for clinical benefit from anti-programmed death ligand 1 therapy in two large cohorts of patients with non-small cell lung cancer or triple-negative breast cancer. For the automated analysis we demonstrate that a combined approach outperforms individual pipelines and successfully relates spatial features to pathologist-based readouts and the patient's response to therapy. Our findings suggest that tumor immunophenotype generated by automated analysis pipelines should be evaluated further as potential predictive biomarkers for cancer immunotherapy. © 2024 The Pathological Society of Great Britain and Ireland.

Acute hospitalizations after proton therapy versus intensity-modulated radiotherapy for locally advanced non-small cell lung cancer in the durvalumab era.

INTRODUCTION: It was hypothesized that use of proton beam therapy (PBT) in patients with locally advanced non-small cell lung cancer treated with concurrent chemoradiation and consolidative immune checkpoint inhibition is associated with fewer unplanned hospitalizations compared with intensity-modulated radiotherapy (IMRT). METHODS: Patients with locally advanced non-small cell lung cancer treated between October 2017 and December 2021 with concurrent chemoradiation with either IMRT or PBT ± consolidative immune checkpoint inhibition were retrospectively identified. Logistic regression was used to assess the association of radiation therapy technique with 90-day hospitalization and grade 3 (G3+) lymphopenia. Competing risk regression was used to compare G3+ pneumonitis, G3+ esophagitis, and G3+ cardiac events. Kaplan-Meier method was used for progression-free survival and overall survival. Inverse probability treatment weighting was applied to adjust for differences in PBT and IMRT groups. RESULTS: Of 316 patients, 117 (37%) received PBT and 199 (63%) received IMRT. The PBT group was older (p < .001) and had higher Charlson Comorbidity Index scores (p = .02). The PBT group received a lower mean heart dose (p < .0001), left anterior descending artery V15 Gy (p = .001), mean lung dose (p = .008), and effective dose to immune circulating cells (p < .001). On inverse probability treatment weighting analysis, PBT was associated with fewer unplanned hospitalizations (adjusted odds ratio, 0.55; 95% CI, 0.38-0.81; p = .002) and less G3+ lymphopenia (adjusted odds ratio, 0.55; 95% CI, 0.37-0.81; p = .003). There was no difference in other G3+ toxicities, progression-free survival, or overall survival. CONCLUSIONS: PBT is associated with fewer unplanned hospitalizations, lower effective dose to immune circulating cells and less G3+ lymphopenia compared with IMRT. Minimizing dose to lymphocytes may be warranted, but prospective data are needed.

(Pro)renin receptor mediates tubular epithelial cell pyroptosis in diabetic kidney disease via DPP4-JNK pathway.

BACKGROUND: (Pro)renin receptor (PRR) is highly expressed in renal tubules, which is involved in physiological and pathological processes. However, the role of PRR, expressed in renal tubular epithelial cells, in diabetic kidney disease (DKD) remain largely unknown. METHODS: In this study, kidney biopsies, urine samples, and public RNA-seq data from DKD patients were used to assess PRR expression and cell pyroptosis in tubular epithelial cells. The regulation of tubular epithelial cell pyroptosis by PRR was investigated by in situ renal injection of adeno-associated virus9 (AAV9)-shRNA into db/db mice, and knockdown or overexpression of PRR in HK-2 cells. To reveal the underlined mechanism, the interaction of PRR with potential binding proteins was explored by using BioGrid database. Furthermore, the direct binding of PRR to dipeptidyl peptidase 4 (DPP4), a pleiotropic serine peptidase which increases blood glucose by degrading incretins under diabetic conditions, was confirmed by co-immunoprecipitation assay and immunostaining. RESULTS: Higher expression of PRR was found in renal tubules and positively correlated with kidney injuries of DKD patients, in parallel with tubular epithelial cells pyroptosis. Knockdown of PRR in kidneys significantly blunted db/db mice to kidney injury by alleviating renal tubular epithelial cells pyroptosis and the resultant interstitial inflammation. Moreover, silencing of PRR blocked high glucose-induced HK-2 pyroptosis, whereas overexpression of PRR enhanced pyroptotic cell death of HK-2 cells. Mechanistically, PRR selectively bound to cysteine-enrich region of C-terminal of DPP4 and augmented the protein abundance of DPP4, leading to the downstream activation of JNK signaling and suppression of SIRT3 signaling and FGFR1 signaling, and then subsequently mediated pyroptotic cell death. CONCLUSIONS: This study identified the significant role of PRR in the pathogenesis of DKD; specifically, PRR promoted tubular epithelial cell pyroptosis via DPP4 mediated signaling, highlighting that PRR could be a promising therapeutic target in DKD.

Does digital technology make people healthier: the impact of digital use on the lifestyle of Chinese older adults.

BACKGROUND: With the arrival of the era of large-scale production, sharing and application of data, digital use has gradually changed people's daily entertainment, consumption, social interaction, learning and other behaviors in its efficient form. This paper mainly discusses whether this fast and convenient behavior leads Chinese older adults to adopt healthier lifestyles. METHODS: Using the most recent information from the Chinese Family Panel Studies (CFPS) in 2020, this paper conducted a descriptive statistical analysis on the basic situation of digital use and lifestyles among Chinese older adults and used a structural equation model to analyse the influence of frequency and types of digital use in a variety of different aspects of the real life of Chinese older adults. RESULTS: Research revealed that the quality of life of Chinese older adults improved significantly as a result of their use of digital technology. The frequency of digital use (FDU) significantly improved Chinese older adults' diet, sleep, exercise, smoking and drinking, and relieved their depression. The types of digital use (TDU) had a significant positive correlation with the lifestyle of Chinese older adults, especially in the influence of digital entertainment (DE), digital consumption (DC) and digital social interaction (DI) on the lifestyle of Chinese older adults. CONCLUSIONS: Digital use can improve the health of Chinese older adults by promoting a healthy lifestyle through various means. The findings of this study have a substantial positive impact on bridging the digital divide that Chinese older adults face, as well as fostering the integration of digital use into their healthy lifestyles.

Clinical Observational Study on the Therapeutic Efficacy of Pirfenidone in Sjögren's Syndrome Complicated with Nonspecific Interstitial Pneumonia.

Objective: This study aimed to evaluate the therapeutic impact of pirfenidone in patients with nonspecific interstitial pneumonia (NSIP) secondary to Sjögren's syndrome, comparing its effectiveness against conventional treatments. Methods: A controlled clinical trial was conducted on a cohort of patients diagnosed with primary Sjögren's syndrome complicated by interstitial lung disease. The study included a total of 120 patients, divided equally into two groups: a control group comprising 60 patients and an observation group with another 60 patients. Random assignment placed patients in either a control group receiving hydroxychloroquine and prednisone or an observation group supplemented with pirfenidone. Pulmonary function parameters, Warrick scores from high-resolution CT scans, and Leicester Cough Quality of Life Questionnaire (LCQ) scores were assessed before and after treatment. Adverse reactions were monitored for treatment safety. Results: Before treatment, no statistically significant differences in pulmonary function indicators (FVC%, FEV1%, DLco%) were observed between the groups (P > .05). Post-treatment, both groups showed significant improvements in these parameters (P < .05). Importantly, the observation group demonstrated superior improvements in pulmonary function compared to the control group (P < .05). Warrick's scores improved significantly in both groups after treatment, with the observation group achieving a more substantial reduction in scores compared to the control group (P < .05). LCQ scores showed no significant differences between the groups before treatment (P > .05). However, after treatment, both groups exhibited significant improvements, with the observation group consistently scoring higher (P < .05). Safety assessments revealed a slightly higher incidence of adverse reactions, including neurosensory abnormality and drowsiness, in the observation group compared to the control group. Conclusions: This study suggests that adding pirfenidone to the treatment regimen for NSIP secondary to Sjögren's syndrome leads to significant improvements in pulmonary function, high-resolution CT scores, and quality of life compared to conventional treatments.

Optimizing the Effects of a Comprehensive Emergency Nursing Model on Rescued Patients with Acute Myocardial Infarction in the Cardiology Department.

Background: Acute myocardial infarction (AMI) requires timely and efficient intervention to mitigate adverse events and enhance patient prognosis. However, variations in emergency nursing protocols may impact treatment outcomes. Therefore, assessing the effectiveness of a comprehensive emergency nursing model, encompassing advanced assessment techniques and tailored interventions, is important for refining care strategies. Objective: This study aimed to assess the optimization effect of a comprehensive emergency nursing model on rescued patients diagnosed with acute myocardial infarction (AMI) within the cardiology department. Methods: This retrospective study analyzed data from 80 cases of AMI patients admitted to our hospital between January and June 2023. The study was conducted within our hospital's cardiology department. The participants were divided into two groups: an intervention group (n=40) and a control group (n=40). The intervention group received care under the comprehensive, optimized emergency nursing model, while the control group received standard emergency care. Evaluation parameters comprised rescue time, effectiveness of emergency treatment, and nursing satisfaction. Results: No significant differences in baseline patient characteristics were observed between the two groups. However, the intervention group demonstrated notable reductions in triage assessment time, completion of electrocardiograms, venous blood sampling, administration of intravenous medication, and overall emergency duration compared to the control group (P < .001). Additionally, the clinical complication rate in the intervention group, particularly incidences of heart failure and myocardial infarction recurrence, was significantly lower than that in the control group (P < .05). Patients in the intervention group reported significantly higher nursing satisfaction scores compared to their counterparts in the control group (P < .001). Conclusion: The comprehensive emergency nursing model substantially decreased rescue time for AMI patients, minimized complication rates, and enhanced patient satisfaction with nursing care. This model presents an efficacious strategy for optimizing the rescue process of acute myocardial infarction patients within the cardiology department.

Development of a predictive machine learning model for pathogen profiles in patients with secondary immunodeficiency.

BACKGROUND: Secondary immunodeficiency can arise from various clinical conditions that include HIV infection, chronic diseases, malignancy and long-term use of immunosuppressives, which makes the suffering patients susceptible to all types of pathogenic infections. Other than HIV infection, the possible pathogen profiles in other aetiology-induced secondary immunodeficiency are largely unknown. METHODS: Medical records of the patients with secondary immunodeficiency caused by various aetiologies were collected from the First Affiliated Hospital of Nanchang University, China. Based on these records, models were developed with the machine learning method to predict the potential infectious pathogens that may inflict the patients with secondary immunodeficiency caused by various disease conditions other than HIV infection. RESULTS: Several metrics were used to evaluate the models' performance. A consistent conclusion can be drawn from all the metrics that Gradient Boosting Machine had the best performance with the highest accuracy at 91.01%, exceeding other models by 13.48, 7.14, and 4.49% respectively. CONCLUSIONS: The models developed in our study enable the prediction of potential infectious pathogens that may affect the patients with secondary immunodeficiency caused by various aetiologies except for HIV infection, which will help clinicians make a timely decision on antibiotic use before microorganism culture results return.

Discontinuous phase transition switching induced by a power-law function between dynamical parameters in coupled oscillators.

In biological or physical systems, the intrinsic properties of oscillators are heterogeneous and correlated. These two characteristics have been empirically validated and have garnered attention in theoretical studies. In this paper, we propose a power-law function existed between the dynamical parameters of the coupled oscillators, which can control discontinuous phase transition switching. Unlike the special designs for the coupling terms, this generalized function within the dynamical term reveals another path for generating the first-order phase transitions. The power-law relationship between dynamic characteristics is reasonable, as observed in empirical studies, such as long-term tremor activity during volcanic eruptions and ion channel characteristics of the Xenopus expression system. Our work expands the conditions that used to be strict for the occurrence of the first-order phase transitions and deepens our understanding of the impact of correlation between intrinsic parameters on phase transitions. We explain the reason why the continuous phase transition switches to the discontinuous phase transition when the control parameter is at a critical value.

ER Stress-Perturbed Intracellular Protein O-GlcNAcylation Aggravates Podocyte Injury in Diabetes Nephropathy.

Diabetes nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide, and podocyte injury is the central contributor to the progression of DN. Despite the emerging evidence that has established the importance of podocyte endoplasmic reticulum (ER) stress in the pathogenesis of DN, abnormal protein O-GlcNAcylation is also augmented. Currently, the mechanism associating these two hyperglycemia-induced disorders remains poorly understood. This study intended to elucidate whether ER stress drives hyper-protein O-GlcNAcylation to cause podocyte injury in DN. We used both type 1 and type 2 DN models to confirm the occurrence of ER stress and excessive protein O-GlcNAcylation, and then podocyte purification was also conducted for further investigation. Nephroseq V5 data were mined and in vitro studies were applied to reveal the involvement of ER stress and hyper-O-GlcNAcylation in podocyte injury. Our results indicated that ER stress was induced in both type 1 and type 2 DN, and the human RNA-seq data from Nephroseq V5 showed that O-GlcNAcylation-related genes were significantly upregulated in the DN patients. We further demonstrated that ER stress occurred prior to hyper-O-GlcNAc modification and that pharmacologically inhibited protein O-GlcNAcylation can help decrease the podocyte apoptosis induced by hyperglycemia. Together, these discoveries will aid in uncovering the activation of the ER stress-O-GlcNAcylation axis in podocyte injury under DN, which will help open up new therapeutic approaches for preventing DN progression.

Solvable dynamics of the three-dimensional Kuramoto model with frequency-weighted coupling.

The presence of coupling heterogeneity is deemed to be a natural attribute in realistic systems comprised of many interacting agents. In this work, we study dynamics of the 3D Kuramoto model with heterogeneous couplings, where the strength of coupling for each agent is weighted by its intrinsic rotation frequency. The critical coupling strength for the instability of incoherence is rigorously derived to be zero by carrying out a linear stability analysis of an incoherent state. For positive values of the coupling strength, at which the incoherence turns out to be unstable, a self-consistency approach is developed to theoretically predict the degree of global coherence of the model. Our theoretical analyses match well with numerical simulations, which helps us to deepen the understanding of collective behaviors spontaneously emerged in heterogeneously coupled high-dimensional dynamical networks.

Effects of electroacupuncture on postoperative cognitive dysfunction and its underlying mechanisms: a literature review of rodent studies.

With the aging of the population, the health of the elderly has become increasingly important. Postoperative cognitive dysfunction (POCD) is a common neurological complication in elderly patients following general anesthesia or surgery. It is characterized by cognitive decline that may persist for weeks, months, or even longer. Electroacupuncture (EA), a novel therapy that combines physical nerve stimulation with acupuncture treatment from traditional Chinese medicine, holds potential as a therapeutic intervention for preventing and treating POCD, particularly in elderly patients. Although the beneficial effects of EA on POCD have been explored in preclinical and clinical studies, the reliability of EA is limited by methodological shortcomings, and the underlying mechanisms remain largely unexplored. Therefore, we have synthesized existing evidence and proposed potential biological mechanisms underlying the effects of EA on neuroinflammation, oxidative stress, autophagy, the microbiota-gut-brain axis, and epigenetic modification. This review summarizes recent advances in EA and POCD, provides a theoretical foundation, explores potential molecular mechanisms for the prevention and treatment of POCD, and offers a basis for conducting relevant clinical trials.

The role of gut microorganisms and metabolites in intracerebral hemorrhagic stroke: a comprehensive review.

Intracerebral hemorrhagic stroke, characterized by acute hemorrhage in the brain, has a significant clinical prevalence and poses a substantial threat to individuals' well-being and productivity. Recent research has elucidated the role of gut microorganisms and their metabolites in influencing brain function through the microbiota-gut-brain axis (MGBA). This article provides a comprehensive review of the current literature on the common metabolites, short-chain fatty acids (SCFAs) and trimethylamine-N-oxide (TMAO), produced by gut microbiota. These metabolites have demonstrated the potential to traverse the blood-brain barrier (BBB) and directly impact brain tissue. Additionally, these compounds have the potential to modulate the parasympathetic nervous system, thereby facilitating the release of pertinent substances, impeding the buildup of inflammatory agents within the brain, and manifesting anti-inflammatory properties. Furthermore, this scholarly analysis delves into the existing dearth of investigations concerning the influence of gut microorganisms and their metabolites on cerebral functions, while also highlighting prospective avenues for future research.

A tale of lockdown policies on the transmission of COVID-19 within and between Chinese cities: A study based on heterogeneous treatment effect.

During the early outbreak phase of COVID-19 in China, lockdowns prevailed as the only available policy tools to mitigate the spread of infection. To evaluate the impact of lockdown policies in the context of the first phase of COVID-19 pandemic, we leverage data on daily confirmed cases per million people and related characteristics of a large set of cities. The study analyzed 369 Chinese cities, among which 188 implemented lockdowns of varying severity levels from January 23 to March 31, 2020. We use nationwide Baidu Mobility data to estimate the impact of lockdown policies on mitigating COVID-19 cases through reducing human mobility. We adopt a heterogeneous treatment effect model to quantify the effect of lockdown policies on containing confirmed case counts. Our results suggest that lockdowns substantially reduced human mobility, and larger reduction in mobility occurred within-city compared to between-city. The COVID-19 daily confirmed cases per million people decreased by 9% - 9.2% for every ten-percentage point fall in within-city travel intensity in t+7 timeframe. We also find that one city's lockdowns can effectively reduce the spillover cases of the traveler's destination cities. We find no evidence that stricter lockdowns are more effective at mitigating COVID-19 risks. Our findings provide practical insights about the effectiveness of NPI during the early outbreak phase of the unprecedented pandemic.

Efficacy and safety of acupuncture treatment for post-stroke depression: A protocol for systematic review and meta-analysis.

BACKGROUND: Post-stroke depression is a common complication of stroke, with a high incidence rate and low recognition rate. Many patients do not receive effective intervention at the onset, which affects subsequent treatment outcomes. Post-stroke depression not only impacts the patient's mental well-being but also increases the risk of stroke recurrence and poor prognosis. Therefore, it has become a significant public health concern. Acupuncture has gained significant popularity in the treatment of post-stroke depression. However, there are inconsistent clinical research results regarding its efficacy and safety. This systematic review aims to gather and critically assess all available evidence regarding the effectiveness and safety of acupuncture in the treatment of post-stroke depression in patients. METHODS: We will conduct thorough searches for relevant studies in multiple electronic databases (PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, VIP Database, Wan-fang Data and China Biomedical Database). Our search scope will encompass studies published from the inception of each database until September 2023. To evaluate the potential bias in all the included studies, we will adhere to the guidelines offered in the Cochrane Handbook. The total effective rate will be the primary outcome. To conduct a systematic review, we will employ RevMan 5.4 software. RESULTS: This study will obtain efficacy and safety of acupuncture for the treatment of post-stroke depression. CONCLUSIONS: The conclusions of this study will provide evidence-based perspectives that can guide clinical decision-making regarding the practicality and recommended timing of using acupuncture to treat post-stroke depression. Furthermore, this study will help advance the clinical application of acupuncture treatment for post-stroke depression and enhance its efficacy while ensuring patient safety.

Scalp acupuncture for post-stroke spastic hemiparesis: A systematic review and meta-analysis.

BACKGROUND: Spastic paralysis is one of the most common sequelae of stroke, severely affecting patients' limb function and reducing their quality of life. Scalp acupuncture (SA) has been shown to significantly improve cerebral blood supply and reduce the severity of limb spasticity. This meta-analysis aims to systematically evaluate the clinical efficacy of SA in the treatment of post-stroke spastic paralysis, providing evidence-based medicine for clinical management of this condition. METHODS: We comprehensively searched databases including China National Knowledge Infrastructure, Wanfang Data, VIP Chinese Science and Technology Periodical Database, China Biomedical Literature Database, PubMed, Embase, and Cochrane Library. Randomized controlled trials investigating the efficacy of SA in post-stroke spastic paralysis were identified until July 28, 2023. Meta-analysis was conducted using RevMan 5.4 and Stata17.0. RESULTS: A total of 16 studies were included. Meta-analysis showed that the modified Ashworth spasticity assessment scale in the SA group was significantly higher than that in the rehabilitation group (mean difference [MD] = -0.56, 95% confidence interval [CI] [-0.75, -0.37], Z = 5.67, P < .00001). The simplified Fugl-Meyer motor function assessment scale in the SA group was significantly higher than that in the rehabilitation group (MD = 5.86, 95% CI [3.26, 8.46], Z = 4.41, P < .0001). The modified Barthel index assessment scale in the SA group was significantly higher than that in the rehabilitation group (MD = 5.79, 95% CI [4.73, 6.84], Z = 10.77, P < .00001). Additionally, the clinical effective rate in the SA group was significantly higher than that in the rehabilitation group (relative risk = 1.25, 95% CI [1.16, 1.36], Z = 5.42, P < .00001). CONCLUSION: SA combined with rehabilitation therapy has certain advantages in reducing limb spasticity, improving limb function, and enhancing activities of daily living in patients with post-stroke spastic paralysis. This study provides reference and theoretical support for the promotion of SA in the treatment of this condition.

Mechanism research progress of acupuncture for regulating axon regeneration after stroke. / é’ˆåˆºè°ƒæŽ§è„‘å’ä¸­åŽè½´çªå†ç”Ÿçš„æœºåˆ¶ç ”ç©¶è¿›å±•.

Stroke brings the pathological changes of brain tissues such as hematoma formation or ischemia and hypoxia, which leads to neuronal death and axon degeneration. Axon regeneration after its injury is mainly dependent on the surrounding microenvironment and the related proteins, including glial scar, myelin associated inhibitory factors, axon guidance molecules, and neurotrophic factors. All of them affect axon growth by regulating the morphology and orientation of growth cones, the synaptic stability, and the proliferation and differentiation of neural stem cells. This article summarizes the mechanism of acupuncture in regulating axon regeneration after stroke. Acupuncture inhibits glial scar formation, alleviates the inhibitory effects of its physical and chemical barriers on axon growth, reverses the inhibitory effects of myelin-related inhibitory factors on axon growth, and adjusts the level of axon guidance molecules to promote the proliferation and differentiation of neural stem cells and the regeneration of injured axons, and up-regulates neurotrophic factors. Eventually, post-stroke nerve injury can be ameliorated.

Mechanism and treatment of intracerebral hemorrhage focus on mitochondrial permeability transition pore.

Intracerebral hemorrhage (ICH) is the second most common subtype of stroke, characterized by high mortality and a poor prognosis. Despite various treatment methods, there has been limited improvement in the prognosis of ICH over the past decades. Therefore, it is imperative to identify a feasible treatment strategy for ICH. Mitochondria are organelles present in most eukaryotic cells and serve as the primary sites for aerobic respiration and energy production. Under unfavorable cellular conditions, mitochondria can induce changes in permeability through the opening of the mitochondrial permeability transition pore (mPTP), ultimately leading to mitochondrial dysfunction and contributing to various diseases. Recent studies have demonstrated that mPTP plays a role in the pathological processes associated with several neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease, ischemic stroke and ischemia-reperfusion injury, among others. However, there is limited research on mPTP involvement specifically in ICH. Therefore, this study comprehensively examines the pathological processes associated with mPTP in terms of oxidative stress, apoptosis, necrosis, autophagy, ferroptosis, and other related mechanisms to elucidate the potential mechanism underlying mPTP involvement in ICH. This research aims to provide novel insights for the treatment of secondary injury after ICH.

HIV/HBV coinfection: understanding the complex interactions and their impact on spontaneous HBV clearance, chronic liver damage, cirrhosis, and hepatocellular carcinoma.

Compared to either HIV or hepatitis B virus (HBV) monoinfected individuals, HIV/HBV-coinfected individuals have a decreased probability of spontaneous HBV clearance and a greater risk of developing chronic liver damage and a faster progression to cirrhosis and hepatocellular carcinoma. This manuscript attempts to provide a comprehensive review of the landscape of current HIV/HBV coinfection research with a focus on the intricate interactions between these two viruses. Our review will help understand the disease dynamics of HIV/HBV coinfection and has important implications for designing public health strategies.

Astrocytes in intracerebral hemorrhage: impact and therapeutic objectives.

Intracerebral hemorrhage (ICH) manifests precipitously and profoundly impairs the neurological function in patients who are affected. The etiology of subsequent injury post-ICH is multifaceted, characterized by the intricate interplay of various factors, rendering therapeutic interventions challenging. Astrocytes, a distinct class of glial cells, interact with neurons and microglia, and are implicated in a series of pathophysiological alterations following ICH. A comprehensive examination of the functions and mechanisms associated with astrocytic proteins may shed light on the role of astrocytes in ICH pathology and proffer innovative therapeutic avenues for ICH management.

Serum cell division cycle 42 reflects the development and progression of diabetic nephropathy in patients with diabetes mellitus.

Cell division cycle 42 (CDC42) regulates podocyte apoptosis to take part in the development and progression of diabetic nephropathy (DN), but currently the clinical evidence is limited. The aim of the present study was to investigate the capability of serum CDC42 expression level to estimate the development and progression of DN in patients with diabetes mellitus (DM). Patients with type 2 DM (n=306) were enrolled and divided into normoalbuminuria (n=185), microalbuminuria (n=72) and macroalbuminuria (n=49) groups based on the urinary albumin-to-creatinine ratio. Serum CDC42 was measured in all subjects using enzyme-linked immunosorbent assay. The median (interquartile range) CDC42 in patients with DM was 0.461 (0.314-0.690) ng/ml (range, 0.087-1.728 ng/ml). CDC42 was positively associated with the estimated glomerular filtration rate (P<0.001), but negatively correlated with body mass index, systolic blood pressure, hemoglobin A1c, serum creatine, serum uric acid and C reactive protein (all P<0.050). CDC42 levels were lowest in the macroalbuminuria group, followed by the microalbuminuria group, and were highest in the normoalbuminuria group (P<0.001). CDC42 indicated that it was a favorable estimator for the presence of albuminuria [area under the curve (AUC), 0.792; 95% confidence interval (CI), 0.736-0.848] and macroalbuminuria (AUC, 0.845; 95% CI, 0.775-0.915). By analyses in four different multivariate logistic regression models, increased CDC42 was independently associated with the presence of microalbuminuria (all P<0.001), macroalbuminuria (most P<0.001) and microalbuminuria + macroalbuminuria (all P<0.001). Serum CDC42 level negatively correlated with microalbuminuria and macroalbuminuria in patients with DM, suggesting its ability for estimating the development and progression of DN.