Single-cell RNA sequencing reveals recruitment of the M2-like CCL8high macrophages in Lewis lung carcinoma-bearing mice following hypofractionated radiotherapy.

BACKGROUND: Tumor-associated macrophages (TAMs) play a pivotal role in reshaping the tumor microenvironment following radiotherapy. The mechanisms underlying this reprogramming process remain to be elucidated. METHODS: Subcutaneous Lewis lung carcinoma (LLC) murine model was treated with hypofrationated radiotherapy (8 Gy × 3F). Single-cell RNA sequencing was utilized to identify subclusters and functions of TAMs. Multiplex assay and enzyme-linked immunosorbent assay (ELISA) were employed to measure serum chemokine levels. Bindarit was used to inhibit CCL8, CCL7, and CCL2. The infiltration of TAMs after combination treatment with hypofractionated radiotherapy and Bindarit was quantified with flow cytometry, while the influx of CD206 and CCL8 was assessed by immunostaining. RESULTS: Transcriptome analysis identified a distinct subset of M2-like macrophages characterized by elevated Ccl8 expression level following hypofractionated radiotherapy in LLC-bearing mice. Remarkbly, hypofractionated radiotherapy not only promoted CCL8high macrophages infiltration but also reprogrammed them by upregulating immunosuppressive genes, thereby fostering an immunosuppressive tumor microenvironment. Additioinally, hypofractionated radiotherapy enhanced the CCL signaling pathway, augmenting the pro-tumorigenic functions of CCL8high macrophages and boosting TAMs recruitment. The adjunctive treatment combining hypofractionated radiotherapy with Bindarit effectively reduced M2 macrophages infiltration and prolonged the duration of local tumor control. CONCLUSIONS: Hypofractionated radiotherapy enhances the infiltration of CCL8high macrophages and amplifies their roles in macrophage recruitment through the CCL signaling pathway, leading to an immunosuppressive tumor microenvironment. These findings highlight the potential of targeting TAMs and introduces a novel combination to improve the efficacy of hypofractionated radiotherapy.

The effectiveness of various treatment approaches for laryngeal contact granulomas.

OBJECTIVES: To assess and compare the effectiveness of various treatment approaches for laryngeal contact granulomas (LCG). METHODS: A retrospective analysis was conducted on a cohort of 45 patients diagnosed with LCG at the Second Affiliated Hospital of Xi'an Jiaotong University from October 2017 to May 2023. Based on the treatment modalities administered, patients were categorized into three groups: acid suppression alone, hormone injection combined with acid suppression, and surgery combined with acid suppression. Subsequently, the study compared differences in treatment efficacy and average healing time among these three groups, using various indicators. RESULTS: The findings indicate that the granuloma size in LCG patients with hoarseness (0.126, 95% CI 0.087-0.288) was significantly greater compared to LCG patients without hoarseness (0.047, 95% CI 0.014-0.083) (P = 0.001). However, there were no significant variations in age, morphology (unlobulated/lobulated), laterality ratio (left/right), sex ratio (male/female), history of tracheal intubation (non-intubation/intubation), and RFS score (RFS > 7/RFS ≤ 7) (P > 0.05), regardless of the presence of hoarseness symptoms. At the treatment observation endpoint of 3 months, the curative ratio in the group receiving hormone injection combined with acid suppression was found to be significantly higher compared to the group receiving acid suppression alone (P = 0.018). In addition, the average healing time of patients in the hormone injection combined with acid suppression group was notably shorter than that of the acid suppression alone group (P = 0.007). CONCLUSIONS: The combination of hormonal injections and acid suppression may enhance the curative ratio and expedite the healing time of LCG.

The subglottic involvement is an independent risk factor for recurrence of laryngeal amyloidosis.

OBJECTIVE: To analyze the risk factors for recurrence of laryngeal amyloidosis (LA). METHODS: The clinical data of patients with LA admitted in the Otolaryngology Head and Neck Surgery Department of the Second Affiliated Hospital of Xi'an Jiaotong University from August 2009 to June 2022 were analyzed retrospectively; then, the risk factors for recurrence and their impacts on the recurrence time were also analyzed. RESULTS: Of the 44 patients with LA, the majority (38 cases, 86.4%) only involved one anatomical region and the others (6 cases, 13.6%) involved two laryngeal regions concurrently. Overall, the glottic region was the most commonly affected area (28 cases, 63.6%), followed by the supraglottic region (16 cases, 36.4%) and subglottic region (6 cases, 13.6%). In addition, all the lesions were categorized as isolated nodule (31.8%), submucosal localized deposition (52.3%), and submucosal diffuse deposition (15.9%) according to their morphologies under electronic laryngoscope. Finally, six patients (13.6%) had recurrence after operation with a median recurrence time of 24.5 months, and subglottic involvement was confirmed to be an independent risk factor for recurrence of LA by univariate and multivariate logistic regression analyses (P < 0.05). Meanwhile, the patients with subglottic involvement presented as submucosal diffuse deposition had a considerable shorter recurrence time (t = 5.759, P = 0.005). CONCLUSION: The subglottic involvement is an independent risk factor for recurrence of LA.

Improved antioxidant activity of rutin via lipase-mediated esterification with oleic acid.

BACKGROUND: Oxidation is a major problem for oils and fats, which can be mitigated by antioxidants. Rutin has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. In this study, an efficient enzymatic synthesis route of lipophilic rutin ester was established using oleic acid as an acyl donor, and the antioxidant potential of rutin oleate was evaluated for the first time by proton (1 H) nuclear magnetic resonance (NMR) spectroscopy. RESULTS: The synthesized product was finally identified as rutin oleate by Fourier transform infrared, high-performance liquid chromatography-mass spectrometry, and 1 H, carbon-13, and DEPT-135 NMR analyses, and the acylation site was the 4‴-OH of the rhamnose group in the rutin molecule. The maximum conversion was over 93% after 48 h of reaction using Novozym 435 as catalyst under the best conditions among these tests. The conversion of rutin ester decreased with the increase of carbon chain length and the number of carbon-carbon double bonds of the fatty acid molecule. Most importantly, rutin oleate exhibited antioxidant capacity comparable to butylated hydroxytoluene and its counterparts (rutin and oleic acid) at low temperatures (60° C), but had a significant advantage at high temperatures (120° C). CONCLUSION: The antioxidant activity of rutin was significantly enhanced by lipase-mediated esterification with oleic acid. Therefore, rutin oleate could be further developed as a novel antioxidant for use in oil- and fat-based foods. © 2023 Society of Chemical Industry.

Nitrogen-Doped and Surface Functionalized CDs: Fluorescent Probe for Cellular Imaging and Environmental Sensing of ClO.

A novel nitrogen doped and surface functionalized fluorescent CDs (T1) was synthesized by one-step and green hydrothermal method, which exhibits a satisfactory fluorescence quantum yield and a series of admirable features such as good aqueous solubility, narrow particle size distribution, resistance to photobleaching as well as excitation-dependent behavior. Benefitting from above merits, T1 can be employed to serve as an outstanding sensing platform for sensitive and accurate detection of ClO- by remarkable fluorescence "on-off" process with rapid and anti-interference. More notably, the good biocompatibility and photostability can ensure enormous bioimaging potential and successful application of T1 in monitoring of exogenous ClO- in MG-63 cells. Meanwhile, T1 can also be regarded as a filter paper sensor providing a convenient and efficient analyzing technology for monitoring of free residual chlorine in practical environmental samples. All these results demonstrate that there exists promising possibility for practical applications of T1 in bioimaging systems and environmental monitoring.

Overexpression of miR-17 predicts adverse prognosis and disease recurrence for acute myeloid leukemia.

BACKGROUND: The clinical significance of miR-17 in patients with acute myeloid leukemia (AML) remains unknown. METHODS: Real-time quantitative reverse transcription-polymerase chain reaction (qPCR) was performed to detect the miR-17 expression in 115 de novo AML patients, 31 patients at complete remission (CR) time, 8 patients at relapse time and 30 normal controls. RESULTS: MiR-17 was upregulated in de novo AML compared with normal controls. Patients with high expression of miR-17 had less CEBPA double mutation, less favorable ELN-risk and lower CR rate. The level of miR-17 was significantly decreased at CR phase and was returned to primary level even higher when in relapse phase. In addition, Cox regression analysis revealed that miR-17 expression retained independent prognostic significance for overall survival (OS). Moreover, the gene-expression profile analysis of miR-17 in AML obtained from TCGA database was involved in multiple biological functions and signal pathways. Among the differential expressed genes (DEGs), we identified FGL2, PLAUR, SLC2A3, GPR65, CTSS, TLR7, S1PR3, OGFRL1, LILRB1, IL17RA, SIGLEC10, SLAMF7, PLXDC2, HPSE, TCF7 and MYCL as potential direct targets of miR-17 according to in silico analysis. CONCLUSIONS: High expression of miR-17 in de novo AML patients pointed to dismal clinical outcome and disease recurrence, which could serve as novel prognostic biomarker for AML patients.

Enhanced antioxidant capacity of lipoic acid in different food systems through lipase-mediated esterification with phytosterols.

BACKGROUND: α-Lipoic acid has excellent antioxidant activity, but its poor lipid solubility greatly limits its practical application. This study was undertaken (i) to develop a novel and efficient enzymatic synthesis of lipophilic lipoic acid esters using Candida sp. 99-125 lipase as a catalyst; and (ii) to systematically evaluate their antioxidant potential against bulk oil, oil-in-water emulsion (O/W) and cooked ground meat. RESULTS: Lipophilic lipoic acid esters were successfully and efficiently synthesized using phytosterols as acyl receptor in the presence of Candida sp. 99-125 lipase. The product was identified as phytosterol lipoate by mass spectrometry, Fourier transform infrared spectroscopy and nuclear magnetic resonance. The maximum conversion of phytosterol lipoate surpassed 90% within 12 h and its final yield exceeded 81%. Interestingly, the oil solubility of lipoic acid was increased at least 25-fold and other physicochemical properties were significantly improved. Most importantly, phytosterol lipoate exhibited higher antioxidant activity than lipoic acid in bulk oil, O/W emulsions and cooked ground meat. CONCLUSION: The antioxidant capacity of lipoic acid can be significantly enhanced by esterification with phytosterols. Therefore, phytosterol lipoate could be further developed as a new antioxidant for use in oil- and fat-based foods. © 2022 Society of Chemical Industry.

Peripheral blood hsa-circRNA5333-4: A novel biomarker for myasthenia gravis.

In this study, the potential of specific Circular RNAs (circRNAs) as novel peripheral blood biomarkers for myasthenia gravis (MG) was explored. We analyzed circRNAs in the peripheral blood of three normal controls and three MG patients using RNA microarray. Candidate circRNAs were validated in three independent cohorts by Quantitative Real-time polymerase chain reaction (qPCR). Eleven differentially expressed circRNAs were initially identified and four were confirmed in the first independent cohort. Hsa_circ_0076490 and hsa-circ_5333-4 had the largest areas under the curve (AUCs) of the receiver operating characteristics (ROC) and were validated in the second cohort. In the third cohort, hsa-circRNA5333-4 had a larger AUC: 0.864 (95% confidence interval [CI] = 0.801-0.928, P < 0.001), a stronger correlation with the Quantitative Myasthenia Gravis Score (qMG): r = 0.505 (P < 0.001) and was correlated with gender and acetylcholine receptor antibody levels (P < 0.05). So hsa-circRNA5333-4 represents a novel biomarker for the diagnosis and monitoring of MG.

Demethyleneberberine promotes apoptosis and suppresses TGF-ß/Smads induced EMT in the colon cancer cells HCT-116.

Colorectal cancer (CRC) is one of the most common malignant tumours in the world. Recent reports have revealed natural products displayed inhibition on colon cancer potential by suppressing transforming growth factor-ß/Smads induced epidermal-mesenchymal transition (EMT). In this article, 12 kinds of natural berberine analogues were screened for their effects on the inhibition of the colon cancer cells, the results showed that demethyleneberberine (DM-BBR) exhibited an interesting and potential effect on inducing the apoptosis of HCT-116 cells with drug concentrations of 6, 12 and 18 µM. Particularly, DM-BBR reversed the EMT process by inhibiting the expression of p-Smad2 and p-Smad3 in the transforming growth factor-ß/Smads signal pathway, up-regulated pro-apoptotic protein cleaved caspase-9, and blocked cell cycle at the S phase and increasing the expression of cyclin proteins P27 and P21. Taken together, these findings suggested that DM-BBR could promote apoptosis and suppress TGF-ß/Smads induced EMT in the colon cancer cells HCT-116.

OncoBase: a platform for decoding regulatory somatic mutations in human cancers.

Whole-exome and whole-genome sequencing have revealed millions of somatic mutations associated with different human cancers, and the vast majority of them are located outside of coding sequences, making it challenging to directly interpret their functional effects. With the rapid advances in high-throughput sequencing technologies, genome-scale long-range chromatin interactions were detected, and distal target genes of regulatory elements were determined using three-dimensional (3D) chromatin looping. Herein, we present OncoBase (http://www.oncobase.biols.ac.cn/), an integrated database for annotating 81 385 242 somatic mutations in 68 cancer types from more than 120 cancer projects by exploring their roles in distal interactions between target genes and regulatory elements. OncoBase integrates local chromatin signatures, 3D chromatin interactions in different cell types and reconstruction of enhancer-target networks using state-of-the-art algorithms. It employs informative visualization tools to display the integrated local and 3D chromatin signatures and effects of somatic mutations on regulatory elements. Enhancer-promoter interactions estimated from chromatin interactions are integrated into a network diffusion system that quantitatively prioritizes somatic mutations and target genes from a large pool. Thus, OncoBase is a useful resource for the functional annotation of regulatory noncoding regions and systematically benchmarking the regulatory effects of embedded noncoding somatic mutations in human carcinogenesis.

EpiDenovo: a platform for linking regulatory de novo mutations to developmental epigenetics and diseases.

De novo mutations (DNMs) have been shown to be a major cause of severe early-onset genetic disorders such as autism spectrum disorder and intellectual disability. Over one million DNMs have been identified in developmental disorders by next generation sequencing, but linking these DNMs to the genes that they impact remains a challenge, as the majority of them are embedded in non-coding regions. As most developmental diseases occur in the early stages of development or during childhood, it is crucial to clarify the details of epigenetic regulation in early development in order to interpret the mechanisms underlying developmental disorders. Here, we develop EpiDenovo, a database that is freely available at http://www.epidenovo.biols.ac.cn/, and which provides the associations between embryonic epigenomes and DNMs in developmental disorders, including several neuropsychiatric disorders and congenital heart disease. EpiDenovo provides an easy-to-use web interface allowing users rapidly to find the epigenetic signatures of DNMs and the expression patterns of the genes that they regulate during embryonic development. In summary, EpiDenovo is a useful resource for selecting candidate genes for further functional studies in embryonic development, and for investigating regulatory DNMs as well as other genetic variants causing or underlying developmental disorders.

Release potential, neglected leakage and reduction countermeasures of COD and Ammonia in MSWLs.

In order to eliminate the impact of the industrial revolution on the environment and improve the water ecological environment, pollutant discharge reduction is imperative. With the acceleration of global discharge reduction process, the huge pollutant release potential and potential environmental effects of municipal solid waste landfills gradually appear, but its release amount and intensity have not been quantitatively revealed. We propose a coupling method of parameter stochastic simulation and physical process model simulation to estimate the hidden leakage of large-scale regional municipal solid waste landfills, and provide a methodology for estimating the hidden leakage of landfills in other countries and even in the whole world by taking China, which has the largest amount of waste generation among developing countries, as an example. Prior to the implementation of stringent construction quality control and assurance management requirements, the average annual leachate generation potential over the entire life cycle of 2600 landfills in China was estimated to be 4.66 × 108 m3, in which the concentrations of COD and NH3-N are 5.38 × 102-6.48 × 104 mg/L and 6.10-3.50 × 103 mg/L, respectively, and the total amounts are 5.21 × 103-7.81 × 108 t and 8.09 × 102-6.65 × 107 t, respectively. About 14 % of these pollutants may leak into the environmental media through the landfill liner with the average number of holes of 21.5/ha. For different regions, the overall release, discharge and leakage of COD and NH3-N in East China account for 35.70 %, 36.68 % and 29.60 % respectively, making it the region with the highest potential for discharge and risk of leakage. Meanwhile, the implementation of mandatory regulations related to leachate generation and control has led to a significant reduction in the leakage of pollutants. For instance, comprehensively detecting and repair of holes in the impermeable liner has reduced the number of holes to 2/ha, resulting in a reduction of >90 % in the leakage of pollutants.

A cooperative control method and application for series multivariable coupled system.

Series multivariable coupled system is a typical controlled object in process control industry. The interaction of various state variables between multiple inputs and outputs in the system forms a complex series multivariable coupled structure. This coupled structure makes the control of a controlled object in the system affect the controlled object in the upper and lower control loop. As a result, it is difficult to control one or more control loops in the system without changing the state of other links in the system. In this paper, a cooperative control method for series multivariable coupled system is proposed. A decoupling controller is designed to remove the coupling effect caused by the interaction between stages, and the system is decoupled into several independent control loops. Differential leading PI (proportional-integral) error compensation method is introduced to ensure the following performance of the controller without static error. The proposed cooperative control method satisfies the Lyapunov stability, and has been successfully applied in the simulation experiment of cascade pumping station system of Beijing East-to-West water transfer project. The proposed method reduces the difficulty to controlling the water level of forebay of each pumping station and ensures the efficient operation of the cascade pumping station system.

The cryo-EM structure of homotetrameric attachment glycoprotein from langya henipavirus.

Langya Henipavirus (LayV) infection is an emerging zoonotic disease that has been causing respiratory symptoms in China since 2019. For virus entry, LayV's genome encodes the fusion protein F and the attachment glycoprotein G. However, the structural and functional information regarding LayV-G remains unclear. In this study, we revealed that LayV-G cannot bind to the receptors found in other HNVs, such as ephrin B2/B3, and it shows different antigenicity from HeV-G and NiV-G. Furthermore, we determined the near full-length structure of LayV-G, which displays a distinct mushroom-shaped configuration, distinguishing it from other attachment glycoproteins of HNV. The stalk and transmembrane regions resemble the stem and root of mushroom and four downward-tilted head domains as mushroom cap potentially interact with the F protein and influence membrane fusion process. Our findings enhance the understanding of emerging HNVs that cause human diseases through zoonotic transmission and provide implication for LayV related vaccine development.

Novel Synthesis of Phytosterol Ferulate Using Acidic Ionic Liquids as a Catalyst and Its Hypolipidemic Activity.

Phytosterol ferulate (PF) is quantitively low in rice, corn, wheat, oats, barley, and millet, but it is potentially effective in reducing plasma lipids. In this study, PF was synthesized for the first time using acidic ionic liquids as a catalyst. The product was purified, characterized using Fourier transform infrared, mass spectroscopy, and nuclear magnetic resonance, and ultimately confirmed as the desired PF compound. The conversion of phytosterol surpassed an impressive 99% within just 2 h, with a selectivity for PF exceeding 83%. Plasma lipid-lowering activity of PF was further investigated by using C57BL/6J mice fed a high-fat diet as a model. Supplementation of 0.5% PF into diet resulted in significant reductions in plasma total cholesterol, triacylglycerols, and nonhigh-density lipoprotein cholesterol by 13.7, 16.9, and 46.3%, respectively. This was accompanied by 55.8 and 36.3% reductions in hepatic cholesterol and total lipids, respectively, and a 22.9% increase in fecal cholesterol excretion. Interestingly, PF demonstrated a higher lipid-lowering activity than that of its substrates, a physical mixture of phytosterols and ferulic acid. In conclusion, an efficient synthesis of PF was achieved for the first time, and PF had the great potential to be developed as a lipid-lowering dietary supplement.

Cryo-EM structures of the human NaS1 and NaDC1 transporters revealed the elevator transport and allosteric regulation mechanism.

The solute carrier 13 (SLC13) family comprises electrogenic sodium ion-coupled anion cotransporters, segregating into sodium ion-sulfate cotransporters (NaSs) and sodium ion-di- and-tricarboxylate cotransporters (NaDCs). NaS1 and NaDC1 regulate sulfate homeostasis and oxidative metabolism, respectively. NaS1 deficiency affects murine growth and fertility, while NaDC1 affects urinary citrate and calcium nephrolithiasis. Despite their importance, the mechanisms of substrate recognition and transport remain insufficiently characterized. In this study, we determined the cryo-electron microscopy structures of human NaS1, capturing inward-facing and combined inward-facing/outward-facing conformations within a dimer both in apo and sulfate-bound states. In addition, we elucidated NaDC1's outward-facing conformation, encompassing apo, citrate-bound, and N-(p-amylcinnamoyl) anthranilic acid (ACA) inhibitor-bound states. Structural scrutiny illuminates a detailed elevator mechanism driving conformational changes. Notably, the ACA inhibitor unexpectedly binds primarily anchored by transmembrane 2 (TM2), Loop 10, TM11, and TM6a proximate to the cytosolic membrane. Our findings provide crucial insights into SLC13 transport mechanisms, paving the way for future drug design.

Proposals for the delineation of neck clinical target volume for definitive Radiation therapy in patients with oral/ oropharyngeal squamous cell cancer based on lymph node distribution.

PURPOSE/OBJECTIVE(S): To establish the distribution pattern of cervical lymph node metastasis (LNM) and propose optimized clinical target volume (CTV) boundaries specific to oral/ oropharyngeal squamous cell cancer (OSCC/OPSCC). MATERIALS/METHODS: 531 patients with pathologically confirmed OSCC/OPSCC were enrolled from January 2013 to June 2022. Patients were stratified into two groups based on the minimal distance from the lesion's edge to the body's midline: ≤1 cm or > 1 cm. The geometric center of cervical metastatic LN was marked on a template CT. LN distribution probability maps were established. The relationships between the LN distribution and consensus guidelines were analyzed to propose modifications for CTV boundaries specific to OSCC/OPSCC. RESULTS: A total of 1962 positive LNs were enrolled. Compared with the > 1 cm group, the ≤ 1 cm group has following feature tendencies: male smokers, younger, median organs, large gross lesion, infiltrative growth pattern, contralateral LNM. The most frequently involved level of LNM was ipsilateral II, but ipsilateral Ib had the highest involvement rate in the > 1 cm OSCC group. In addition, tongue cancer had a higher incidence of LN extranodal extension (ENE), which mainly distributes in ipsilateral level II. The skip metastasis was prone to from level III to Vb (3.5 %) in LN(+)/ENE (-), and level Ib to VIa (3.7 %) in LN(+)/ENE (+). Accordingly, we proposed the following modifications: 1. only including lateral and posterior margin of submandibular gland within 5 mm; 2. retracting posterior boundary of level II to front edge of levator scapula muscle, and descending the upper boundary to transverse process of C2 vertebra only for OSCC; 3. including posterior third of thyroglossal muscle or anterior edge of sternocleidomastoid muscle; 4. sparing level Va in case of only level II involvement; 5. including upper area of the thyroid cartilage plate in case of level Ib LN(+)/ENE (+); 6. sparing level VIIa is considered. CONCLUSION: This is the first description of LN topographic spread patterns for OSCC/OPSCC. Modified CTV for prophylactic irradiation was proposed to spare the organs at risk and minimize adverse effects.

Exploring the impact mechanism of low-carbon multivariate coupling system in Chinese typical cities based on machine learning.

Low-carbon city construction is one of the key issues that must be addressed for China to achieve high-quality economic development and meet the Sustainable Development Goals. This study creates a comprehensive evaluation index system of low-carbon city multivariate system based on carbon emission data from 30 typical Chinese cities from 2006 to 2017 and evaluates and analyzes the trend of city low-carbon levels using the CRITIC-TOPSIS technique and MK method. Meanwhile, the influence mechanism of the multi-coupled system is investigated using the coupling coordination degree model and random forest algorithm.The results show that there are 8 cities with a significant increasing trend of low-carbon level, 19 cities with no significant monotonic change trend, and 3 cities with a decreasing trend of low-carbon level. By analyzing the coupling coordination degree, we found that the coupling coordination degree between low-carbon level and economic development in most cities tends to increase year by year, from the initial antagonistic effect to a good coordination development trend, which confirms the "inverted U-shaped" relationship between economy and carbon emission. In addition, industrial pollutant emissions, foreign direct investment, and economic output are the core drivers of low-carbon levels in cities.

Construction of Urban Environmental Performance Evaluation System Based on Multivariate System Theory and Comparative Analysis: A Case Study of Chengdu-Chongqing Twin Cities, China.

Based on the related environmental data of Chengdu and Chongqing from 2011 to 2020, this paper constructs a multivariate environment performance evaluation system, combines the self-built indicator system determination criteria and rules, evaluates and compares the environmental performance of Chengdu and Chongqing, and also discusses the impact of COVID-19 on urban environmental performance. The research results show that the overall environmental performance increased from 2011 to 2020, but there are differences between different subsystems, mainly manifested in the best water environment performance, followed by air environment and solid waste; moreover, the noise environment maintains a relatively stable level. By comparing the average levels of various subsystems of the Chengdu-Chongqing dual cities from 2011 to 2020, it can be seen that Chengdu City has better environmental performance in air environment and solid waste, while Chongqing City has better environmental performance in the water environment and noise environment. In addition, this paper also found that the impact of the epidemic on urban environmental performance mainly comes from the impact on the air environment. At present, the overall environmental performance of the two places has shown a trend of environmentally coordinated development. In the future, Chengdu and Chongqing should further optimize and improve their relatively weak environmental subsystems, deepen the joint action mechanism between the two places, and build a green and high-quality development economic circle for the Chengdu-Chongqing twin cities.

PAllidal versus SubThalamic deep brain Stimulation for Cervical Dystonia (PASTS-CD): study protocol for a multicentre randomised controlled trial.

INTRODUCTION: Deep brain stimulation (DBS) has been validated as a safe and effective treatment for refractory cervical dystonia (CD). Globus pallidus internus (GPi) and subthalamic nucleus (STN) are the two main stimulating targets. However, there has been no prospective study to clarify which target is the better DBS candidate for CD. The objective of this trial is to compare directly the efficacy and safety of GPi-DBS and STN-DBS, thereby instructing the selection of DBS target in clinical practice. METHODS AND ANALYSIS: This multicentre, prospective, randomised, controlled study plans to enrol 98 refractory CD patients. Eligible CD patients will be randomly allocated to GPi-DBS group or STN-DBS group, with the DBS electrodes implanted into the posteroventral portion of GPi or the dorsolateral portion of STN, respectively. The primary outcome will be the improvement of symptomatic severity, measured by the changes in the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) severity subscale and the Tsui scale at 3 months, 6 months and 12 months after surgery. The secondary outcomes include the improvement of the TWSTRS-disability subscale, TWSTRS-pain subscale, quality of life, mental and cognitive condition, as well as the differences in stimulation parameters and adverse effects. In addition, this study intends to identify certain predictors of DBS efficacy for CD. ETHICS AND DISSEMINATION: The trial has been approved by the Medical Ethics Committee of Chinese PLA General Hospital (S2022-613-01). The results of this study will be published in international peer-reviewed journals and shared in professional medical conferences. TRIAL REGISTRATION NUMBER: NCT05715138.