Public Heterogeneous Preferences for Low-Dose Computed Tomography Lung Cancer Screening Service Delivery in Western China: A Discrete Choice Experiment.

BACKGROUND: Lung cancer screening (LCS) with low-dose computed tomography (LDCT) is an efficient method that can reduce lung cancer mortality in high-risk individuals. However, few studies have attempted to measure the preferences for LDCT LCS service delivery. This study aimed to generate quantitative information on the Chinese population's preferences for LDCT LCS service delivery. METHODS: The general population aged 40 to 74 in the Sichuan province of China was invited to complete an online discrete choice experiment (DCE). The DCE required participants to answer 14 discrete choice questions comprising five attributes: facility levels, facility ownership, travel mode, travel time, and out-of-pocket cost. Choice data were analyzed using mixed logit and latent class logit (LCL) models. RESULTS: The study included 2529 respondents, with 746 (29.5%) identified as being at risk for lung cancer. Mixed logit model (MLM) analysis revealed that all five attributes significantly influenced respondents' choices. Facility levels had the highest relative importance (44.4%), followed by facility ownership (28.1%), while out-of-pocket cost had the lowest importance (6.4%). The at-risk group placed relatively more importance on price and facility ownership compared to the non-risk group. LCL model identified five distinct classes with varying preferences. CONCLUSION: This study revealed significant heterogeneity in preferences for LCS service attributes among the Chinese population, with facility level and facility ownership being the most important factors. The findings underscore the need for tailored strategies targeting different subgroup preferences to increase screening participation rates and improve early detection outcomes.

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.

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.

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.

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.

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.

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.

Brain regulation of gastric dysfunction induced by stress.

Psychological and physical stressors have been implicated in gastric disorders in humans. The mechanism coupling the brain to the stomach underlying stress-induced gastric dysfunction has remained elusive. Here, we show that the stomach directly receives acetylcholinergic inputs from the dorsal motor nucleus of the vagus (AChDMV), which are innervated by serotonergic neurons in the dorsal raphe nucleus (5-HTDRN). Microendoscopic calcium imaging and multi-tetrode electrophysiological recordings reveal that the 5-HTDRN → AChDMV → stomach circuit is inhibited with chronic stress accompanied by hypoactivate gastric function. Artificial activation of this circuit reverses the gastric dysfunction induced by chronic stress in both male and female mice. Our study demonstrates that this 5-HTDRN → AChDMV → stomach axis drives gastric dysfunction associated with stress, thus providing insights into the circuit basis for brain regulation of the stomach.

Up-regulation of LCN2 in the anterior cingulate cortex contributes to neural injury-induced chronic pain.

Chronic pain caused by disease or injury affects more than 30% of the general population. The molecular and cellular mechanisms underpinning the development of chronic pain remain unclear, resulting in scant effective treatments. Here, we combined electrophysiological recording, in vivo two-photon (2P) calcium imaging, fiber photometry, Western blotting, and chemogenetic methods to define a role for the secreted pro-inflammatory factor, Lipocalin-2 (LCN2), in chronic pain development in mice with spared nerve injury (SNI). We found that LCN2 expression was upregulated in the anterior cingulate cortex (ACC) at 14 days after SNI, resulting in hyperactivity of ACC glutamatergic neurons (ACCGlu) and pain sensitization. By contrast, suppressing LCN2 protein levels in the ACC with viral constructs or exogenous application of neutralizing antibodies leads to significant attenuation of chronic pain by preventing ACCGlu neuronal hyperactivity in SNI 2W mice. In addition, administering purified recombinant LCN2 protein in the ACC could induce pain sensitization by inducing ACCGlu neuronal hyperactivity in naïve mice. This study provides a mechanism by which LCN2-mediated hyperactivity of ACCGlu neurons contributes to pain sensitization, and reveals a new potential target for treating chronic pain.

Green light induces antinociception via visual-somatosensory circuits.

Light has been shown to relieve pain, but the underlying neural mechanisms remain unknown. Here, we show that low-intensity (200 lux) green light treatment exerts antinociceptive effects through a neural circuit from the visual cortex projecting to the anterior cingulate cortex (ACC) in mice. Specifically, viral tracing, in vivo two-photon calcium imaging, and fiber photometry recordings show that green light activated glutamatergic projections from the medial part of the secondary visual cortex (V2MGlu) to GABAergic neurons in the ACC, which drives inhibition of local glutamatergic neurons (V2MGlu→ACCGABA→Glu). Optogenetic or chemogenetic activation of the V2MGlu→ACCGABA→Glu circuit mimics green-light-induced antinociception in both neuropathic and inflammatory pain model mice. Artificial inhibition of ACC-projecting V2MGlu neurons abolishes the antinociception induced by green light. Taken together, our study shows the V2M-ACC circuit as a potential candidate mediating green-light-induced antinociceptive effects.

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.

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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.

Thalamocortical circuits drive remifentanil-induced postoperative hyperalgesia.

Remifentanil-induced hyperalgesia (RIH) is a severe but common postoperative clinical problem with elusive underlying neural mechanisms. Here, we discovered that glutamatergic neurons in the thalamic ventral posterolateral nucleus (VPLGlu) exhibited significantly elevated burst firing accompanied by upregulation of Cav3.1 T-type calcium channel expression and function in RIH model mice. In addition, we identified a glutamatergic neuronal thalamocortical circuit in the VPL projecting to hindlimb primary somatosensory cortex glutamatergic neurons (S1HLGlu) that mediated RIH. In vivo calcium imaging and multi-tetrode recordings revealed heightened S1HLGlu neuronal activity during RIH. Moreover, preoperative suppression of Cav3.1-dependent burst firing in VPLGlu neurons or chemogenetic inhibition of VPLGlu neuronal terminals in the S1HL abolished the increased S1HLGlu neuronal excitability while alleviating RIH. Our findings suggest that remifentanil induces postoperative hyperalgesia by upregulating T-type calcium channel-dependent burst firing in VPLGlu neurons to activate S1HLGlu neurons, thus revealing an ion channel-mediated neural circuit basis for RIH that can guide analgesic development.

Levels, trends, and determinants of effectiveness on the hierarchical medical system in China: Data envelopment analysis and bootstrapping truncated regression analysis.

Background: The hierarchical medical system (HMS) refers to the classification of treatment according to disease priorities based on severity and difficulty to promote the fairness of medical services for residents, which is regarded as the key to the success of medical reform in China. Methods: In the past decade of "New Medical Reform," the efficiency of HMS, including secondary and tertiary hospitals and primary healthcare centers (PHCs), was measured horizontally and vertically by employing the combination of an output-oriented superefficiency slack-based model-data envelopment analysis (SE-SBM-DEA) model with the Malmquist total factor productivity index (MTFP). In the second stage, the overall technical efficiency (OTE) scores were regressed against a set of environmental characteristics and several managerial factors through bootstrapping truncated regression. Results: On average, the OTE score in tertiary hospitals was 0.93, which was higher than that in secondary hospitals and PHCs (0.9 and 0.92, respectively). In terms of trend, the OTE of tertiary hospitals declined at first and then increased. The opposite was true of secondary hospitals, in which the APC of the OTE was 10.82 and -3.11% in early and late 2012, respectively. The PHCs generally showed a fluctuating downward trend. In the aspects of productivity, all institutions showed a downturn by an annual average rate of 2.73, 0.51, and 2.70%, respectively. There was a significant negative relationship between the ratio of outpatients to inpatients and tertiary hospitals. Additionally, the medical technical personnel per 1,000 population negatively affected PHCs. In contrast, the GDP per capita had a significantly positive effect on tertiary hospitals, and the number of beds per 1,000 population positively influenced PHCs. Conclusion: The efficiency of medical institutions at various levels in HMS was unbalanced and took the form of an "inverted pyramid." Multilateral factors influence the efficiency of HMS, and to address it, multi-intervention packages focusing on sinking high-quality medical resources and improving healthcare capacity, and guiding hierarchical medical practice should be adopted.

Level of knowledge on low-dose CT lung cancer screening in Sichuan province, China: a cross-sectional study.

OBJECTIVES: Low-dose CT (LDCT) can help determine the early stage of lung cancer and reduce mortality. However, knowledge of lung cancer and lung cancer screening among community residents and medical workers, and potential factors that may affect medical institutions to set up LDCT are limited. DESIGN: A cross-sectional study was conducted in Sichuan province, China, in 2021. Community residents, medical workers and medical institutions were randomly selected, and participants responded to related questionnaires. Knowledge of lung cancer and LDCT lung cancer screening was evaluated. Data analyses were performed using SAS V.9.4. RESULTS: A total of 35 692 residents, 6350 medical workers and 81 medical institutions were recruited; 4.05% of the residents were very familiar with lung cancer and 37.89% were (completely) unfamiliar. Characteristics, such as age and level of education, were significantly related to residents who were very familiar with lung cancer. Furthermore, 22.87% of the residents knew that LDCT can effectively screen for early-stage lung cancer, which was correlated with smoking (OR 1.1300; 95% CI 1.0540 to 1.2110; p=0.006) and family history of cancer (OR 1.2210; 95% CI 1.1400 to 1.3080; p<0.0001); 66.06% of medical workers believed that LDCT can detect early-stage lung cancer. Technicians and nurses were less knowledgeable than doctors about whether LDCT can effectively screen for early-stage lung cancer (OR 0.6976; 95% CI 0.5399 to 0.9015; p=0.0059 and OR 0.6970; 95% CI 0.5718 to 0.8496; p=0.0004, respectively). Setting up LDCT in medical institutions was related to grade, administrative rank, number of hospital beds that opened and total number of medical workers. CONCLUSIONS: The knowledge of lung cancer in residents is relatively low, and the knowledge of LDCT in screening (early-stage) lung cancer needs to be improved both in residents and medical workers. Possible factors that affect medical institutions to set up LDCT may need to be incorporated.

Horizontal Integration and Financing Reform of Rural Primary Care in China: A Model for Low-Resource and Remote Settings.

Primary health care (PHC) systems are compromised by under-resourcing and inadequate governance, and fail to provide high-quality health care services in most low- and middle-income countries (LMICs). As a response to solve the problems of underfunding and understaffing, Pengshui County, an impoverished area in rural Chongqing, China, implemented a profound reform of its PHC delivery system in 2009, focusing on horizontal integration and financing mechanisms. This paper aims to present new evidence from the Pengshui model, and to assess the relevant changes over the past 10 years (2009-2018). An inductive approach was adopted, based on analysis of national and local policy documents and administrative data. From 2009 to 2018, the proportion of outpatients who sought first-contact care in rural community or township health centers increased from 29% (522,700 of 1,817,600) in 2009, to 40% (849,900 of 2,147,800) in 2018 (the national average in 2018 was 23%). Our findings suggest that many positive results have been achieved through the reform, and that innovations in financial governance and incentive mechanisms are the main driving forces behind the improvement. Pengshui County's experience has proven to be a successful experiment, particularly in rural and low-income areas.

Sound induces analgesia through corticothalamic circuits.

Sound-including music and noise-can relieve pain in humans, but the underlying neural mechanisms remain unknown. We discovered that analgesic effects of sound depended on a low (5-decibel) signal-to-noise ratio (SNR) relative to ambient noise in mice. Viral tracing, microendoscopic calcium imaging, and multitetrode recordings in freely moving mice showed that low-SNR sounds inhibited glutamatergic inputs from the auditory cortex (ACxGlu) to the thalamic posterior (PO) and ventral posterior (VP) nuclei. Optogenetic or chemogenetic inhibition of the ACxGlu→PO and ACxGlu→VP circuits mimicked the low-SNR sound-induced analgesia in inflamed hindpaws and forepaws, respectively. Artificial activation of these two circuits abolished the sound-induced analgesia. Our study reveals the corticothalamic circuits underlying sound-promoted analgesia by deciphering the role of the auditory system in pain processing.

The effect of transdermal 17ß-estradiol combined with norethisterone acetate treatment on the lipid profile in postmenopausal women: A meta-analysis and systematic review of randomized controlled trials.

BACKGROUND AND AIM: The effect of transdermal 17ß-estradiol and norethisterone acetate co-administration on the lipid profile in postmenopausal women remains controversial as randomized controlled trials (RCTs) conducted to investigate this research question have produced conflicting results. Consequently, to clarify this issue, we conducted a systematic review and meta-analysis of RCTs that evaluated the impact of transdermal 17ß-estradiol combined with norethisterone acetate treatment on the concentrations of serum lipids in postmenopausal women. METHODS: Relevant articles published before February 1st, 2022 were identified by searching the PubMed/Medline, Scopus, and Embase, and Web of Science electronic databases. A random-effects model, employing the method of DerSimonian and Laird, was used to evaluate effect sizes, and results were expressed as weighted mean difference (WMD) and 95% confidence intervals (CIs). RESULTS: Pooled results from 7 RCTs with 9 intervention arms demonstrated that transdermal 17ß-estradiol combined with norethisterone acetate administration significantly decreased total cholesterol (TC) (WMD: -13.43 mg/dL, 95% CI: -18.11 to -8.75, P < 0.001) and low-density lipoprotein cholesterol (LDL-C) (WMD: -13.90 mg/dL, 95% CI: -20.40 to -7.41, P < 0.001). In the subgroup analyses, a notable reduction in TC was observed in subjects with baseline TC concentrations ≥ 130 mg/dL (WMD -14.49 mg/dL), when treatment duration was ≤ 6 months (WMD: -17.21 mg/dL), and in participants with a body mass index (BMI) ≥ 25 kg/m2 (WMD: -21.71 mg/dL). Moreover, in the subgroup analyses, transdermal 17ß-estradiol combined with norethisterone acetate decreased triglycerides (TG) levels when the treatment duration was ≤ 6 months (WMD: -21.37 mg/dL). However, the prescription of transdermal 17ß-estradiol combined with norethisterone acetate in postmenopausal women did not change high-density lipoprotein cholesterol (HDL-C) values. CONCLUSIONS: Based on our findings, the co-administration of transdermal 17ß-estradiol and norethisterone acetate in postmenopausal females can decrease TC and LDL-C levels, as well as TG values, but does not influence HDL-C concentrations.