Is low-dose computed tomography for lung cancer screening conveniently accessible in China? A spatial analysis based on cross-sectional survey.

BACKGROUND: Regular Low-Dose Computed Tomography (LDCT) for lung cancer high-risk population has been proved to improve health outcomes and relieve disease burden efficiently for both individual and society. With geographical impedance becoming the major barrier preventing patients from getting timely healthcare service, this study incorporated health seeking behavior in estimating spatial accessibility of relative scarce LDCT resource in China, thus to provide real-world evidence for future government investment and policy making. METHODS: Taking Sichuan Province in southwest China as the study area, a cross-sectional survey was first carried out to collect actual practice and preferences for seeking LDCT services. Using Computed Tomography (CT) registration data reported by owner institutions representing LDCT services capacity, and grided town-level high-risk population as demand, the Nearest Neighbor Method was then utilized to calculate spatial accessibility of LDCT services. RESULTS: A total of 2,529 valid questionnaires were collected, with only 34.72% of the high-risk populations (746 individuals) followed the recommended annual screening. Participants preferred to travel to municipal-level and above institutions within 60 min for LDCT services. Currently, every thousand high-risk populations own 0.0845 CT scanners in Sichuan Province, with 96.95% able to access LDCT within 60 min and over half within 15 min. Urban areas generally showed better accessibility than rural areas, and the more developed eastern regions were better than the western regions with ethnic minority clusters. CONCLUSIONS: Spatial access to LDCT services is generally convenient in Sichuan Province, but disparity exists between different regions and population groups. Improving LDCT capacity in county-level hospitals as well as promoting health education and policy guidance to the public can optimize efficiency of existing CT resources. Implementing mobile CT services and improving rural public transportation may alleviate emerging disparities in accessing early lung cancer detection.

Efficiency evaluation and promoter identification of primary health care system in China: an enhanced DEA-Tobit approach.

BACKGROUND: With Primary Health Care (PHC) being a cornerstone of accessible, affordable, and effective healthcare worldwide, its efficiency, especially in developing countries like China, is crucial for achieving Universal Health Coverage (UHC). This study evaluates the efficiency of PHC systems in a southwest China municipality post-healthcare reform, identifying factors influencing efficiency and proposing strategies for improvement. METHODS: Utilising a 10-year provincial panel dataset, this study employs an enhanced Data Envelopment Analysis (DEA) model integrating Slack-Based Measure (SBM) and Directional Distance Function (DDF) with the Global Malmquist-Luenberger (GML) index for efficiency evaluation. Tobit regression analysis identifies efficiency determinants within the context of China's healthcare reforms, focusing on horizontal integration, fiscal spending, urbanisation rates, and workforce optimisation. RESULTS: The study reveals a slight decline in PHC system efficiency across the municipality from 2009 to 2018. However, the highest-performing county achieved a 2.36% increase in Total Factor Productivity (TFP), demonstrating the potential of horizontal integration reforms and strategic fiscal investments in enhancing PHC efficiency. However, an increase in nurse density per 1,000 population negatively correlated with efficiency, indicating the need for a balanced approach to workforce expansion. CONCLUSIONS: Horizontal integration reforms, along with targeted fiscal inputs and urbanisation, are key to improving PHC efficiency in underdeveloped regions. The study underscores the importance of optimising workforce allocation and skillsets over mere expansion, providing valuable insights for policymakers aiming to strengthen PHC systems toward achieving UHC in China and similar contexts.

Telemedicine-Enhanced Lung Cancer Screening Using Mobile Computed Tomography Unit with Remote Artificial Intelligence Assistance in Underserved Communities: Initial Results of a Population Cohort Study in Western China.

Introduction: Lung cancer is a leading cause of cancer deaths globally. Despite favorable recommendations, low-dose computed tomography (LDCT) lung screening adoption remains low in China. Barriers such as limited infrastructure, costs, distance, and personnel shortages restrict screening access in disadvantaged regions. We initiated a telemedicine-enabled lung cancer screening (LCS) program in a medical consortium to serve people at risk in underserved communities. The objective of this study was to describe the implementation and initial results of the program. Methods: From 2020 to 2021, individuals aged 40-80 years were invited to take LCS by mobile computed tomography (CT) units in three underserved areas in Western China. Numerous CT scans were remotely reported by radiologists aided by artificial intelligence (AI) diagnostic systems. Abnormal cases were tracked through an integrated hospital network for follow-up. A retrospective cohort study documented participant demographics, health history, LDCT results, and outcomes. Descriptive analysis was conducted to report baseline characteristics and first-year follow-up results. Results: Of the 28,728 individuals registered in the program, 19,517 (67.94%) participated in the screening. The study identified 2.68% of participants with high-risk pulmonary nodules and diagnosed 0.55% with lung cancer after a 1-year follow-up. The majority of high-risk participants received timely treatment in hospitals. Conclusions: This study demonstrated mobile CT units with remote AI assistance improved access to LCS in underserved areas, with high participation and early detection rates. Our implementation supports the feasibility of deploying telemedicine-enabled LCS to increase access to a large scale of basic radiology and diagnostic services in resource-limited settings. Clinical Trial Registration Number: ChiCTR1900024623.

Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain.

Pain is a multidimensional perception that includes unpleasant somatosensory and affective experiences; however, the underlying neural circuits that mediate different components of pain remain elusive. Although hyperactivity of basolateral amygdala glutamatergic (BLAGlu) neurons is required for the somatosensory and emotional processing of pain, the precise excitatory inputs to BLAGlu neurons and their roles in mediating different aspects of pain are unclear. Here, we identified two discrete glutamatergic neuronal circuits in male mice: a projection from the insular cortex glutamatergic (ICGlu) to BLAGlu neurons, which modulates both the somatosensory and affective components of pain, and a projection from the mediodorsal thalamic nucleus (MDGlu) to BLAGlu neurons, which modulates only the aversive-affective component of pain. Using whole-cell recording and fiber photometry, we found that neurons within the IC→BLA and MD→BLA pathways were activated in mice upon inflammatory pain induced by injection of complete Freund's adjuvant (CFA) into their paws. Optical inhibition of the ICGlu→BLA pathway increased the nociceptive threshold and induced behavioral place preference in CFA mice. In contrast, optical inhibition of the MDGlu→BLA pathway did not affect the nociceptive threshold but still induced place preference in CFA mice. In normal mice, optical activation of the ICGlu→BLA pathway decreased the nociceptive threshold and induced place aversion, while optical activation of the MDGlu→BLA pathway only evoked aversion. Taken together, our results demonstrate that discrete ICGlu→BLA and MDGlu→BLA pathways are involved in modulating different components of pain, provide insights into its circuit basis, and better our understanding of pain perception.

Up-regulation of microglial chemokine CXCL12 in anterior cingulate cortex mediates neuropathic pain in diabetic mice.

Diabetic patients frequently experience neuropathic pain, which currently lacks effective treatments. The mechanisms underlying diabetic neuropathic pain remain unclear. The anterior cingulate cortex (ACC) is well-known to participate in the processing and transformation of pain information derived from internal and external sensory stimulation. Accumulating evidence shows that dysfunction of microglia in the central nervous system contributes to many diseases, including chronic pain and neurodegenerative diseases. In this study, we investigated the role of microglial chemokine CXCL12 and its neuronal receptor CXCR4 in diabetic pain development in a mouse diabetic model established by injection of streptozotocin (STZ). Pain sensitization was assessed by the left hindpaw pain threshold in von Frey filament test. Iba1+ microglia in ACC was examined using combined immunohistochemistry and three-dimensional reconstruction. The activity of glutamatergic neurons in ACC (ACCGlu) was detected by whole-cell recording in ACC slices from STZ mice, in vivo multi-tetrode electrophysiological and fiber photometric recordings. We showed that microglia in ACC was significantly activated and microglial CXCL12 expression was up-regulated at the 7-th week post-injection, resulting in hyperactivity of ACCGlu and pain sensitization. Pharmacological inhibition of microglia or blockade of CXCR4 in ACC by infusing minocycline or AMD3100 significantly alleviated diabetic pain through preventing ACCGlu hyperactivity in STZ mice. In addition, inhibition of microglia by infusing minocycline markedly decreased STZ-induced upregulation of microglial CXCL12. Together, this study demonstrated that microglia-mediated ACCGlu hyperactivity drives the development of diabetic pain via the CXCL12/CXCR4 signaling, thus revealing viable therapeutic targets for the treatment of diabetic pain.

Perceived knowledge, attitudes and practices regarding the medical consortium among medical staff in Sichuan, China: a cross-sectional survey.

BACKGROUND: In China, fragmented and inefficient health care systems are common while quality resources are limited. To promote an organized, efficient system, the government launched a medical consortium policy to vertically integrate health care through the collaboration of different levels of medical care. Logically, medical staff's knowledge, attitudes and practices (KAP) regarding the consortium are critical for its development. The objective of this study was to explore the KAP regarding the medical consortium among medical staff in a medical consortium in Sichuan Province, China. METHODS: A cross-sectional survey was conducted. In total, 690 medical staff members in 3 cities of Sichuan Province, China, were interviewed from November 2018 to December 2018. The questionnaire consisted of 18 items, including 4 items related to perceived knowledge, 4 items related to attitudes and 2 items related to practices, and was rated on a 5-point Likert scale (one = strongly disagree/do not know, five = strongly agree/know). RESULTS: The effective response sample was 640 copies of the questionnaire, and most medical staff members (92.50%) knew about the cooperation with other hospitals in the medical consortium. Medical staff scored differently on each item in the questionnaire, with the highest score being the item 'agreeing with the ward rounds and clinical teaching and training organized by the leading hospital' (4.54 ± 0.76), and the lowest score being the item 'frequency in participating in ward rounds and clinical teaching organized by the leading hospital' (2.83 ± 1.36). In addition, the effect of demographic characteristics on KAP was evaluated by stepwise multiple regression analysis, and a significant positive correlation was found between all the studied variables by Spearman's correlation (p < 0.05). CONCLUSIONS: This study showed that the attitudes toward and knowledge of the medical consortium significantly contribute to practices, satisfaction with the support work performed by the leading hospital and agreement of improvement after joining the medical consortium. Thus, to improve medical staff's KAP and satisfaction, publicity and educational programs in medical consortia are necessary, and the leading hospital should attach importance to the informatization construction and demand of different medical staff members. CLINICAL TRIAL REGISTRATION: There are no clinical trials in this study.

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Patient navigation is an effective intervention measure to promote the integration of medical systems and services. By providing individualized, coordinated, and continuous care, patient navigation offers a way to address the problem of fragmented services across institutions and levels of care in the whole-process management of lung cancer, providing assistance to patients with complex healthcare needs. Herein, we reviewed the origin, the development, the models, and the application status of patient navigation in China and other countries. We also analyzed the considerations regarding introducing patient navigation in the whole-process management of lung cancer against the background of medical consortiums in China, discussing why patient navigation should be introduced, how to introduce patient navigation, as well as potential challenges and coping strategies. Patient navigation meets the current needs for equitable, accessible, systematic, continuous, and integrated prevention and treatment services for chronic diseases in the context of the Healthy China Strategy. It helps fill the gaps in the continuity and coordination of whole-process management of lung cancer patients in the context of medical consortiums. However, introducing patient navigation in medical consortiums involving multiple institutions and levels of care may face challenges, including incompatibility between the health information systems of different institutions, poor cross-institutional collaboration and communication, and limited resources. Further improvement is needed in medical informatization, coordination and communication mechanisms, and benefit distribution mechanisms within the medical consortiums. In this paper, we intend to provide insights and suggestions for developing patient navigation models that suit China's local characteristics and for promoting the implementation and development of whole-process management of lung cancer in the context of the medical consortium system.

Switching of delta opioid receptor subtypes in central amygdala microcircuits is associated with anxiety states in pain.

Anxiety is often comorbid with pain. Delta opioid receptors (DORs) are promising targets for the treatment of pain and mental disorders with little addictive potential. However, their roles in anxiety symptoms at different stages of pain are unclear. In the current study, mice with inflammatory pain at the fourth hour following complete Freund's adjuvant (CFA) injection displayed significant anxiety-like behavior, which disappeared at the seventh day. Combining electrophysiology, optogenetics, and pharmacology, we found that activation of delta opioid receptor 1 (DOR1) in the central nucleus amygdala (CeA) inhibited both the anxiolytic excitatory input from the basolateral amygdala (BLA) and the anxiogenic excitatory input from the parabrachial nucleus (PBN). In contrast, activation of delta opioid receptor 2 (DOR2) did not affect CeA excitatory synaptic transmission in normal and 4-h CFA mice but inhibited the excitatory projection from the PBN rather than the BLA in 7-day CFA mice. Furthermore, the function of both DOR1 and DOR2 was downregulated to the point of not being detectable in the CeA of mice at the 21st day following CFA injection. Taken together, these results suggest that functional switching of DOR1 and DOR2 is associated with anxiety states at different stages of pain via modulating the activity of specific pathways (BLA-CeA and PBN-CeA).

Direct auditory cortical input to the lateral periaqueductal gray controls sound-driven defensive behavior.

Threatening sounds can elicit a series of defensive behavioral reactions in animals for survival, but the underlying neural substrates are not fully understood. Here, we demonstrate a previously unexplored neural pathway in mice that projects directly from the auditory cortex (ACx) to the lateral periaqueductal gray (lPAG) and controls noise-evoked defensive behaviors. Electrophysiological recordings showed that the lPAG could be excited by a loud noise that induced an escape-like behavior. Trans-synaptic viral tracing showed that a great number of glutamatergic neurons, rather than GABAergic neurons, in the lPAG were directly innervated by those in layer V of the ACx. Activation of this pathway by optogenetic manipulations produced a behavior in mice that mimicked the noise-evoked escape, whereas inhibition of the pathway reduced this behavior. Therefore, our newly identified descending pathway is a novel neural substrate for noise-evoked escape and is involved in controlling the threat-related behavior.

Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior.

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world's population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA-mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.

Cost-utility analysis of palliative care in patients with advanced cancer: a retrospective study.

BACKGROUND: Aging population and other factors have led to a rapid rise in cancer incidence in China. However, under the influence of traditional perception of diseases, deaths and economic factors, many patients who are unresponsive to radical treatment are still adherent to excessive and unnecessary treatment, which may lead to poor quality of life (QoL) and increase unnecessary medical burden. AIM: Compare the difference of the quality of life and cost-utility value between patients who received palliative care (PC) and patients who were adherent to conventional anticancer treatment (CAT) and provides empirical evidence of clinical and economic value for hospital-based PC. METHODS: Chinese Quality of Life Questionnaire (CQLQ) Scale was used to collect advanced cancer patients' QoL on admission and discharge days. Paired and independent samples' statistical analysis were used to compare inter- and intra- QoL between PC and CAT group. Delphi and Analytic Hierarchy Process were used to weight QoL scores and converted the QoL to quality-adjusted life years (QALYs). Propensity Score Matching (PSM) for 1:1 was used to compare average hospitalization expenses between two groups. The expense per QALYs was used for Cost-Utility analysis between the two treatments. RESULTS: A total of 248 hospitalized patients diagnosed with metastatic disease at stage IV were recruited from West China Fourth Hospital between January 2018 and August 2018, including 128 patients receiving PC and 120 patients receiving CAT. Although both treatments had positive effects on improving QoL for patients, the QoL in the PC group were significantly higher than that in the CAT group (55.90 ± 18.80 vs 24.00 ± 8.60, t = 7.51, p < 0.05). The QALY (days) of pre- and post- treatment increased by 55.9 and 24.0 days in PC and CAT group respectively. Compared average hospitalization expense in 613 pairs of advanced cancer inpatients after PSM 1:1, the per capita expense of PC group was higher (13,743.5 ± 11,574.1 vs 11,689.0 ± 8876.8, t = 3.44, p < 0.05), while each unit of QALYs paid by PC group was only 50% of that paid by those receiving CAT. CONCLUSIONS: PC played a positive role in improving the QoL for patients diagnosed with advanced cancer and alleviating economic burdens of both patient families and the society from the viewpoint of cost-utility. Our findings imply that PC should be recognized as a proactive care model in China that helps patients with some terminal diseases.

Comparison of User-Oriented Information Services on the Websites of Large Hospitals in China and the United States: Cross-sectional Study.

BACKGROUND: Many people use the internet to access health care information to support health care decisions, and hospital websites can be the first point of contact to provide health care information services for consumers. However, little is known about the current information services provided by the websites of large Chinese hospitals. OBJECTIVE: The aim of this study is to evaluate and compare the information services of the websites of large hospitals in China and the United States. We hope that our findings will benefit hospital managers worldwide in providing service information on the web. METHODS: This study adopted a cross-sectional analytical approach to evaluate the websites of large hospitals in China and the United States in 2020. A total of 300 large hospitals were randomly selected, of which half were in China and half were in the United States. Based on the 7Ps marketing mix, we identified 39 items that represent typical hospital website information services, covering the following seven dimensions: product, price, place, propagation, people, process, and physical evidence. RESULTS: Most of the items (34/39, 87%) related to information services offered by hospital websites were less covered in China than in the United States; however, 5 items (appointments by a third-party platform, mobile payment, hospital value, hospital environment display, and physicians' profiles) had higher coverage in China. The average scores for hospital websites in China and the United States were 13.25 (SD 2.99) points and 23.16 (SD 2.76) points, respectively. Generally, high scores were given to the south areas of China and north areas of the United States. CONCLUSIONS: Hospital websites in China lagged behind those in the United States with regard to information services offered. We recommend that hospital managers in China place more emphasis on the people, product, and propagation dimensions of the 7Ps marketing mix in the construction of information services on hospital websites. Through the comparison of the websites of large hospitals in China and the United States, our study findings can provide suggestions for forming standard hospital website construction guidelines worldwide.

A Central Amygdala-Ventrolateral Periaqueductal Gray Matter Pathway for Pain in a Mouse Model of Depression-like Behavior.

BACKGROUND: The mechanisms underlying depression-associated pain remain poorly understood. Using a mouse model of depression, the authors hypothesized that the central amygdala-periaqueductal gray circuitry is involved in pathologic nociception associated with depressive states. METHODS: The authors used chronic restraint stress to create a mouse model of nociception with depressive-like behaviors. They then used retrograde tracing strategies to dissect the pathway from the central nucleus of the amygdala to the ventrolateral periaqueductal gray. The authors performed optogenetic and chemogenetic experiments to manipulate the activity of this pathway to explore its roles for nociception. RESULTS: The authors found that γ-aminobutyric acid-mediated (GABAergic) neurons from the central amygdala project onto GABAergic neurons of the ventrolateral periaqueductal gray, which, in turn, locally innervate their adjacent glutamatergic neurons. After chronic restraint stress, male mice displayed reliable nociception (control, mean ± SD: 0.34 ± 0.11 g, n = 7 mice; chronic restraint stress, 0.18 ± 0.11 g, n = 9 mice, P = 0.011). Comparable nociception phenotypes were observed in female mice. After chronic restraint stress, increased circuit activity was generated by disinhibition of glutamatergic neurons of the ventrolateral periaqueductal gray by local GABAergic interneurons via receiving enhanced central amygdala GABAergic inputs. Inhibition of this circuit increased nociception in chronic restraint stress mice (median [25th, 75th percentiles]: 0.16 [0.16, 0.16] g to 0.07 [0.04, 0.16] g, n = 7 mice per group, P < 0.001). In contrast, activation of this pathway reduced nociception (mean ± SD: 0.16 ± 0.08 g to 0.34 ± 0.13 g, n = 7 mice per group, P < 0.001). CONCLUSIONS: These findings indicate that the central amygdala-ventrolateral periaqueductal gray pathway may mediate some aspects of pain symptoms under depression conditions.

The health service capacity of primary health care in West China: different perspectives of physicians and their patients.

BACKGROUND: Many countries, including China, have identified the primary health care system as a reform priority. The purpose of this study is to compare the perceived service capacity of primary care from the perspectives of physicians and their patients in Sichuan province of China. METHODS: A cross-sectional survey was conducted through Quality and Costs of Primary Care (QUALICOPC) questionnaires. A representative sample of 319 primary care physicians and 641 patients in 48 primary healthcare settings were recruited to take part in the study. RESULTS: Physicians perceived equity of care the best, while quality of care was rated the highest from the perspective of patients. They both regarded coordination as the weakest dimension of primary care service capacity. CONCLUSIONS: Although primary health care reform may have been effective in helping patients acquire better primary care services, our results suggest that coordination is still perceived to be problematic for both physicians and patients. Improving the coordination of care has to be one of the main goals in the future primary care reforms in China.

MeCP2 repression of G9a in regulation of pain and morphine reward.

Opioids are commonly used for pain relief, but their strong rewarding effects drive opioid misuse and abuse. How pain affects the liability of opioid abuse is unknown at present. In this study, we identified an epigenetic regulating cascade activated by both pain and the opioid morphine. Both persistent pain and repeated morphine upregulated the transcriptional regulator MeCP2 in mouse central nucleus of the amygdala (CeA). Chromatin immunoprecipitation analysis revealed that MeCP2 bound to and repressed the transcriptional repressor histone dimethyltransferase G9a, reducing G9a-catalyzed repressive mark H3K9me2 in CeA. Repression of G9a activity increased expression of brain-derived neurotrophic factor (BDNF). Behaviorally, persistent inflammatory pain increased the sensitivity to acquiring morphine-induced, reward-related behavior of conditioned place preference in mice. Local viral vector-mediated MeCP2 overexpression, Cre-induced G9a knockdown, and CeA application of BDNF mimicked, whereas MeCP2 knockdown inhibited, the pain effect. These results suggest that MeCP2 directly represses G9a as a shared mechanism in central amygdala for regulation of emotional responses to pain and opioid reward, and for their behavioral interaction.

Brainstem brain-derived neurotrophic factor signaling is required for histone deacetylase inhibitor-induced pain relief.

Our previous study demonstrated that persistent pain can epigenetically suppress the transcription of Gad2 [encoding glutamic acid decarboxylase 65 (GAD65)] and consequently impair the inhibitory function of GABAergic synapses in central pain-modulating neurons. This contributes to the development of persistent pain sensitization. Histone deacetylase (HDAC) inhibitors increased GAD65 activity considerably, restored GABA synaptic function, and rendered sensitized pain behavior less pronounced. However, the molecular mechanisms by which HDAC regulates GABAergic transmission through GAD65 under pain conditions are unknown. This work showed that HDAC inhibitor-induced increases in colocalization of GAD65 and synaptic protein synapsin I on the presynaptic axon terminals of the nucleus raphe magnus (NRM) were blocked by a TrkB receptor antagonist K252a [(9S,10R,12R)-2,3,9,10,11,12-hexahydro-10-hydroxy-9-methyl-1-oxo-9,12-epoxy-1H-diindolo[1,2,3-fg:3',2',1'-kl]pyrrolo[3,4-i][1,6]benzodiazocine-10-carboxylic acid methyl ester], indicating that BDNF-TrkB signaling may be required in GAD65 modulation of GABA synaptic function. At the brain-derived neurotrophic factor (BDNF) promoter, HDAC inhibitors induced significant increases in H3 hyperacetylation, consistent with the increase in BDNF mRNA and total proteins. Although exogenous BDNF facilitated GABA miniature inhibitory postsynaptic currents and GAD65 accumulation in NRM neuronal synapses in normal rats, it failed to do so in animals subjected to persistent inflammation. In addition, blockade of the TrkB receptor with K252a has no effect on miniature inhibitory postsynaptic currents and synaptic GAD65 accumulation under normal conditions. In addition, the analgesic effects of HDAC inhibitors on behavior were blocked by NRM infusion of K252a. These findings suggest that BDNF-TrkB signaling is required for drugs that reverse the epigenetic effects of chronic pain at the gene level, such as HDAC inhibitors.

Persistent inflammation-induced up-regulation of brain-derived neurotrophic factor (BDNF) promotes synaptic delivery of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor GluA1 subunits in descending pain modulatory circuits.

The enhanced AMPA receptor phosphorylation at GluA1 serine 831 sites in the central pain-modulating system plays a pivotal role in descending pain facilitation after inflammation, but the underlying mechanisms remain unclear. We show here that, in the rat brain stem, in the nucleus raphe magnus, which is a critical relay in the descending pain-modulating system of the brain, persistent inflammatory pain induced by complete Freund adjuvant (CFA) can enhance AMPA receptor-mediated excitatory postsynaptic currents and the GluA2-lacking AMPA receptor-mediated rectification index. Western blot analysis showed an increase in GluA1 phosphorylation at Ser-831 but not at Ser-845. This was accompanied by an increase in distribution of the synaptic GluA1 subunit. In parallel, the level of histone H3 acetylation at bdnf gene promoter regions was reduced significantly 3 days after CFA injection, as indicated by ChIP assays. This was correlated with an increase in BDNF mRNA levels and BDNF protein levels. Sequestering endogenous extracellular BDNF with TrkB-IgG in the nucleus raphe magnus decreased AMPA receptor-mediated synaptic transmission and GluA1 phosphorylation at Ser-831 3 days after CFA injection. Under the same conditions, blockade of TrkB receptor functions, phospholipase C, or PKC impaired GluA1 phosphorylation at Ser-831 and decreased excitatory postsynaptic currents mediated by GluA2-lacking AMPA receptors. Taken together, these results suggest that epigenetic up-regulation of BDNF by peripheral inflammation induces GluR1 phosphorylation at Ser-831 sites through activation of the phospholipase C-PKC signaling cascade, leading to the trafficking of GluA1 to pain-modulating neuronal synapses.

Improving access to primary health care through financial innovation in rural China: a quasi-experimental synthetic difference-in-differences approach.

BACKGROUND: Inadequate financing constrains primary healthcare (PHC) capacity in many low- and middle-income countries, particularly in rural areas. This study evaluates an innovative PHC financing reform in rural China that aimed to improve access to healthcare services through supply-side integration and the establishment of a designated PHC fund. METHODS: We employed a quasi-experimental synthetic difference-in-differences (SDID) approach to analyze county-level panel data from Chongqing Province, China, spanning from 2009 to 2018. The study compared the impact of the reform on PHC access and per capita health expenditures in Pengshui County with 37 other control counties (districts). We assessed the reform's impact on two key outcomes: the share of outpatient visits at PHC facilities and per capita total PHC expenditure. RESULTS: The reform led to a significant increase in the share of outpatient visits at PHC facilities (14.92% points; 95% CI: 6.59-23.24) and an increase in per capita total PHC expenditure (87.30 CNY; 95% CI: 3.71-170.88) in Pengshui County compared to the synthetic control. These effects were robust across alternative model specifications and increased in magnitude over time, highlighting the effectiveness of the integrated financing model in enhancing PHC capacity and access in rural China. CONCLUSIONS: This research presents compelling evidence demonstrating that horizontal integration in PHC financing significantly improved utilization and resource allocation in rural primary care settings in China. This reform serves as a pivotal model for resource-limited environments, demonstrating how supply-side financing integration can bolster PHC and facilitate progress toward universal health coverage. The findings underscore the importance of sustainable financing mechanisms and the need for policy commitment to achieve equitable healthcare access.

Screening for lung cancer using thin-slice low-dose computed tomography in southwestern China: a population-based real-world study.

OBJECTIVES: Lung cancer is one of the most common malignant tumors threatening human life and health. At present, low-dose computed tomography (LDCT) screening for the high-risk population to achieve early diagnosis and treatment of lung cancer has become the first choice recommended by many authoritative international medical organizations. To further optimize the lung cancer screening method, we conducted a real-world study of LDCT lung cancer screening in a large sample of a healthy physical examination population, comparing differences in lung nodules and lung cancer detection between thin and thick-slice LDCT scanning. METHODS: A total of 29 296 subjects who underwent low-dose thick-slice CT scanning (5 mm thickness) from January 2015 to December 2015 and 28 058 subjects who underwent low-dose thin-slice CT scanning (1 mm thickness) from January 2018 to December 2018 in West China Hospital were included. The positive detection rate, detection rate of lung cancer, pathological stage of lung cancer, and mortality rate of lung cancer were analyzed and compared between the two groups. RESULTS: The positive rate of LDCT screening in the thin-slice scanning group was significantly higher than that in the thick-slice scanning group (20.1% vs. 14.4%, p < 0.001). In addition, the lung cancer detection rate in the thin-slice LDCT screening positive group was significantly higher than that in the thick-slice scanning group (78.0% vs. 52.9%, p < 0.001). CONCLUSIONS: The screening positive rate of low-dose thin-slice CT scanning is higher and more early-stage lung cancer (IA1 stage) can be detected in the screen-positive group.

Somatosensory cortex and central amygdala regulate neuropathic pain-mediated peripheral immune response via vagal projections to the spleen.

Pain involves neuroimmune crosstalk, but the mechanisms of this remain unclear. Here we showed that the splenic T helper 2 (TH2) immune cell response is differentially regulated in male mice with acute versus chronic neuropathic pain and that acetylcholinergic neurons in the dorsal motor nucleus of the vagus (AChDMV) directly innervate the spleen. Combined in vivo recording and immune cell profiling revealed the following two distinct circuits involved in pain-mediated peripheral TH2 immune response: glutamatergic neurons in the primary somatosensory cortex (GluS1HL)→AChDMV→spleen circuit and GABAergic neurons in the central nucleus of the amygdala (GABACeA)→AChDMV→spleen circuit. The acute pain condition elicits increased excitation from GluS1HL neurons to spleen-projecting AChDMV neurons and increased the proportion of splenic TH2 immune cells. The chronic pain condition increased inhibition from GABACeA neurons to spleen-projecting AChDMV neurons and decreased splenic TH2 immune cells. Our study thus demonstrates how the brain encodes pain-state-specific immune responses in the spleen.