Objective To investigate the relationship between gentamicin sulfate mediated gut microbi-ota in affecting glucolipid metabolism and inflammation with hypertension improvement.Methods Sprague-Dawley rats (8-weeks-old) were divided into the normal diet group (ND,n=11),high fat diet group (HFD,n=13) and HFD combined with gentamicin sulfate gavage group (GS,n=13).Blood pressure was monitored weekly during 5-13 weeks,and the levels of insulin,IL-1β,IL-6,TNF-α,LPS,TC,TG,LDL-C,HDL-C and homeostasis model assessment of insulin resistance index (HOMA-IR) were assessed at 13 weeks.The met-agenomic analyses were performed on DNA samples from rat colonic feces.Results The blood pressure in 13 weeks had no statistical difference among the three groups (P>0.05).The blood pressure during 5-10 weeks in the GS group was higher than that in the ND group with statistical difference (P<0.05).The blood pressure during 5-13 weeks in the HFD group was higher than that in the ND group,and the blood pressure during 10-13 weeks in the GS group was lower than that in the HFD with statistical difference (P<0.05). Compared with the group ND,the levels of TC,TG,LDL-C and HOMA-IR in the HFD group were higher,the HDL-C level was lower,and the differences were statistically significant (P<0.05).Compared with the HFD group,the levels of TG,LDL-C and HOMA-IR in the GS group were lower,the HDL-C level was higher,and the differences were statistically significant (P<0.05).The levels of LPS,IL-1β,IL-6 and TNF-α in the HFD group were higher than those in the ND group,while the GS group was lower than the HFD group (P<0.05).The partial least squares discriminant analysis showed that the intestinal microbiota in the HFD group and GS group was different in structure from that in the ND group.The family level results showed that the structure of the gut microbiota changed in three groups,including 24 microbiotas with significant changes.The hierarchical analysis showed that the proportion of f-desulphovibrio in the HFD group was higher than that in the ND group,while the GS group was lower the HFD group,and the differences were statistically significant (P<0.05).Conclusion Oral antibiotic gentamicin sulfate could improve the glucose and lipid metabolism ab-normalities and inflammation caused by HFD and its mechanism may be to relieve hypertension by regulating intestinal flora structure,abundance and LPS level.

Objective To evaluate the effects of the multiple factors especially image geometric accuracy of the imaging system on the segmentations of target areas and organs-at-risk.Methods The study used phantoms to test the imaging performance of the 1.5T magnetic resonance(MR)linear accelerator system,including the assessments of MR image geometric distortion and the segmentation errors caused by factors such as image geometric distortion.Model 604-GS large field MR image distortion phantom was used to explore the geometric distortion of the MR images for MR-guided radiotherapy;and CIRS Model 008z upper abdominal phantom was used to analyze the segmentation errors of target areas and organs-at-risk.Results The average geometric distortion and maximum distortion of 3D T1WI-FFE images vs 3D T2WI-TSE images were 0.54 mm vs 0.53 mm and 1.96 mm vs 1.68 mm,respectively;and the control points of the large distortions were distributed at the edges of the phantom,which was consistent with the MR imaging characteristics previously reported.Compared with CT-based segmentation contour,the MDA was 1.17 mm and DSC was 0.91 for 3D T1WI-FFE,while MDA was 0.86 mm and DSC was 0.94 for 3D T2WI-TSE.Conclusion The study quantitatively assesses the geometric accuracy of the imaging system for MR-guided radiotherapy.The phantom-based contour analysis reveals that with CT image as gold standard,the segmentation error in MRI images meets the clinical requirements,and that 3D T2WI-TSE image is advantageous over 3D T1WI-FFE image in segmentation accuracy.

In recent years, the field of genetics has witnessed a burgeoning interest in the non-coding region, an area previously dubbed the"dark matter"of the genome. This once enigmatic domain is now progressively revealing its secrets, emerging as a rich terrain for genetic diagnosis and treatment. This editorial centers on diverse diagnostic analyses and intervention techniques associated with the non-coding region, delving into its significance in the etiology, diagnosis, and treatment of both monogenic and polygenic disorders within the nervous system. In doing so, it offers a comprehensive perspective for the exploration of genetic disorders in the nervous system.

In response to the Opinions of the CPC Central Committee and the State Council on Promoting the Inheritance， Innovation， and Development of traditional Chinese medicine（TCM） and the spirit of the National Conference on TCM， Chinese Association of Chinese Medicine organized experts in Otorhinolaryngology Head and Neck Surgery of traditional Chinese and western medicine to discuss the clinical advantages of TCM and integrated traditional Chinese and western medicine in the treatment of allergic rhinitis （AR） and they reached a basic consensus. In recent years， the prevalence of AR has been on the rise， threatening the quality of life of patients and giving rise to a heavy burden to both the patients and the society. AR is resulted from immune imbalance rather than reduced immunity or hyperimmunity， and the imbalance is similar to the Yin-yang disharmony in TCM. In the treatment of this disease， western medicine features rapid onset. However， it is cost-intensive and causes severe surgical trauma， and the recurrence is common. TCM boasts diverse methods for AR， which can be used in all stages of this disease. It has advantages in controlling symptoms such as nasal congestion， runny nose， or dysosmia in the attack stage， preventing recurrence in the remission stage， and treating refractory AR or steroid-resistant AR. In particular， acupuncture enjoys a reputation in treatment of AR， which has been supported by evidence-based medicine and recommended by guidelines. While treating local symptoms of AR， TCM regulates the psychosomatic conditions， which facilitates chronic disease management and long-term follow-up. We should integrate the advantages of TCM and western medicine， give full play to the unique nonnegligible and irreplaceable advantages of TCM， formulate a comprehensive diagnosis and treatment scheme for learning and promotion， and summarize the research outcomes to promote the theoretical innovation of TCM on AR from the perspective of integrated traditional Chinese and western medicine.

This study aims to investigate the impact of hepatocyte nuclear factor 1β (HNF1b) on macrophage sortilin-mediated lipid metabolism and aortic atherosclerosis and explore the role of the flavone of Polygonatum odoratum (PAOA-flavone)-promoted small ubiquitin-related modifier (SUMO) modification in the atheroprotective efficacy of HNF1b. HNF1b was predicted to be a transcriptional regulator of sortilin expression via bioinformatics, dual-luciferase reporter gene assay, and chromatin immunoprecipitation. HNF1b overexpression decreased sortilin expression and cellular lipid contents in THP-1 macrophages, leading to a depression in atherosclerotic plaque formation in low-density lipoprotein (LDL) receptor-deficient (LDLR^-/-) mice. Multiple SUMO1-modified sites were identified on the HNF1b protein and co-immunoprecipitation confirmed its SUMO1 modification. The SUMOylation of HNF1b protein enhanced the HNF1b-inhibited effect on sortilin expression and reduced lipid contents in macrophages. PAOA-flavone treatment promoted SUMO-activating enzyme subunit 1 (SAE1) expression and SAE1-catalyzed SUMOylation of the HNF1b protein, which prevented sortilin-mediated lipid accumulation in macrophages and the formation of atherosclerotic plaques in apolipoprotein E-deficient (ApoE^-/-) mice. Interference with SAE1 abrogated the improvement in lipid metabolism in macrophage cells and atheroprotective efficacy in vivo upon PAOA-flavone administration. In summary, HNF1b transcriptionally suppressed sortilin expression and macrophage lipid accumulation to inhibit aortic lipid deposition and the development of atherosclerosis. This anti-atherosclerotic effect was enhanced by PAOA-flavone-facilitated, SAE1-catalyzed SUMOylation of the HNF1b protein.
Mice ; Animals ; Polygonatum/metabolism* ; Sumoylation ; Hepatocyte Nuclear Factor 1-beta/metabolism* ; Atherosclerosis/metabolism* ; Flavones ; Lipids

The nucleus tractus solitarii (NTS) is one of the morphologically and functionally defined centers that engage in the autonomic regulation of cardiovascular activity. Phenotypically-characterized NTS neurons have been implicated in the differential regulation of blood pressure (BP). Here, we investigated whether phenylethanolamine N-methyltransferase (PNMT)-expressing NTS (NTS^PNMT) neurons contribute to the control of BP. We demonstrate that photostimulation of NTS^PNMT neurons has variable effects on BP. A depressor response was produced during optogenetic stimulation of NTS^PNMT neurons projecting to the paraventricular nucleus of the hypothalamus, lateral parabrachial nucleus, and caudal ventrolateral medulla. Conversely, photostimulation of NTS^PNMT neurons projecting to the rostral ventrolateral medulla produced a robust pressor response and bradycardia. In addition, genetic ablation of both NTS^PNMT neurons and those projecting to the rostral ventrolateral medulla impaired the arterial baroreflex. Overall, we revealed the neuronal phenotype- and circuit-specific mechanisms underlying the contribution of NTS^PNMT neurons to the regulation of BP.
Solitary Nucleus/metabolism* ; Blood Pressure/physiology* ; Phenylethanolamine N-Methyltransferase/metabolism* ; Neurons/metabolism* ; Paraventricular Hypothalamic Nucleus/metabolism*

Objective:To investigate the workflow, efficacy and safety of MR-Linac in liver malignancies.Methods:Clinical data of 15 patients with hepatocellular carcinomas (HCC) or liver metastases treated with MR-Linac between November 2019 and July 2021 were retrospectively analyzed. The workflow of MR-Linac was investigated and image identification rate was analyzed. Patients were followed up for response and toxicity assessment.Results:Fifteen patients (6 HCC, 8 liver metastases from colorectal cancer, 1 liver metastasis from breast cancer) were enrolled. A total of 21 lesions were treated, consisting of 10 patients with single lesion, 4 patients with double lesions and 1 patient with triple lesions. The median tumor size was 2.4 cm (0.8-9.8 cm). The identification rate for gross tumor volume (GTV) in MR-Linac was 13/15. Although GTV of two patients were unclearly displayed in MR-Linac images, the presence of adjacent blood vessel and bile duct assisted the precise registration. All the patients were treated with stereotactic body radiation therapy (SBRT). For HCC, the median fraction dose for GTV or planning gross tumor volume (PGTV) was 6 Gy (5-10 Gy) and the median number of fractions was 9(5-10). The median total dose was 52 Gy (50-54 Gy) and the median equivalent dose in 2 Gy fraction (EQD 2Gy) at α/ β= 10 was 72 Gy (62.5-83.3 Gy). For liver metastases, the median fraction dose for GTV or PGTV was 5 Gy (5-10 Gy) and the median number of fractions was 10(5-10). The median total dose was 50 Gy (40-50 Gy) and the median EQD 2Gy at α/ β=5 was 71.4 Gy (71.4-107.1 Gy). At 1 month after SBRT, the in-field objective response rate (ORR) was 8/13 and the disease control rate was 13/13. At 3-6 months after SBRT, the in-filed ORR was increased to 6/6. During the median follow-up of 4.0 months (0.3-11.6), 4-month local progression-free survival, progression-free survival and overall survival were 15/15, 11/15 and 15/15, respectively. Toxicities were mild and no grade 3 or higher toxicities were observed. Conclusions:MR-Linac provides a platform with high identification rates of liver lesions. Besides, the presence of adjacent blood vessel and bile duct also assists the precise registration. It is especially suitable for liver malignancies with promising local control and well tolerance.

Objective:To describe a prospective study of pre-operative tumor-bed boost performed at the 1.5 T MR-Linac in combination with adjuvant whole breast irradiation, and a first case, with an accentuation on clinical feasibility and safety.Methods:A phase II, single arm study recruiting early stage patients follows a paradigm that first boosts the tumor bed and then undergoes breast conservative surgery in 2 weeks, and last irradiates the whole breast in 6 weeks. The primary endpoint is ≥ grade 2 acute breast toxicity. A 43 years old patient affected by a breast carcinoma, not special type of the right-sided lateral quadrant, staged cT 2N 0M 0, was planned and treated. The dose, 8 Gy for one time, was calculated by Monaco on CT simulation images. Both the air electron stream effect (ESE) and the electron return effect (ERE) at the presence of 1.5 T magnetic field were evaluated. During the pre-treatment evaluation, we carried out adaptation-to-position adjustment. Results:The normal organ dosimetry is within toleration. The Dmax to the skin, the chin and the right upper arm was 8.44 Gy, 28.5 cGy and 17.8 cGy, respectively. There was no increased toxicity from ERE and ESE, and the treatment was well tolerated without > grade 1 acute toxicity. The patient received breast conservative surgery on day 7 without delayed wound healing.Conclusions:This is the first case successfully treated within a clinical trial by pre-operative tumor-bed boost under 1.5 T MR-Linac in our institution. More participants are needed to validate and optimize the paradigm.

With aligned MR registration, the MR-Linac provides superior soft tissue resolution for prostate cancer. No fiducial markers or electromagnetic transponders insertion is needed to guarantee high-precision radiotherapy. The highly-recommended Adapt-To-Shape (ATS) workflow can resolve all the problems encountered during prostate cancer radiotherapy, including prostate volume changes and adjacent organs motion, both inter-fractionally and intra-fractionally. With all the above advantages, MR-Linac performs outstandingly than conventional linac in prostate cancer RT delivery, and probably helps us to reduce the CTV-PTV margin safely in the near future. Nevertheless, it is difficult to implement the ATS workflow in clinical practice. In this article, the standard ATS workflow for prostate cancer was summarized based on our own experience.

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTS^LepRb) neurons notably activated breathing. Moreover, stimulation of NTS^LepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTS^LepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTS^LepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTS^LepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca²⁺ transients in most NTS^LepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.
Leptin/pharmacology* ; Membrane Potentials ; Neurons/metabolism* ; Solitary Nucleus/metabolism*