The application of blended teaching in medical practical course of clinical skills training.

BACKGROUND: Blended teaching is an effective approach that combines online and offline teaching methods, leading to improved outcomes in medical education compared to traditional offline teaching. In this study, we examined the impact of blended teaching in clinical skills training, a medical practice course. METHODS: This study involved forty-eight undergraduate students studying clinical medicine in the fifth semester at Wuhan University of Science and Technology. The students were divided into two groups: the control group, which received traditional offline teaching, and the experimental group, which received hybrid teaching. Following the completion of the 4-month course, both groups underwent the Objective Structured Clinical Examination (OSCE) to evaluate their proficiency in clinical skills. Furthermore, the experimental group was given a separate questionnaire to gauge their feedback on the Blended Teaching approach. RESULTS: Based on the OSCE scores, the experimental group outperformed the control group significantly (P<0.05). The questionnaire results indicated that a majority of students (54.2%, 3.71 ± 1.06) believed that blended teaching is superior to traditional offline teaching, and a significant number of students (58.3%, 3.79 ± 1.15) expressed their willingness to adopt blended teaching in other courses. Furthermore, students in the experimental group displayed varying levels of interest in different teaching contents, with emergency medicine (79.2%), internal medicine (70.8%), and surgery (66.7%) being the most popular among them. CONCLUSIONS: This research demonstrates for the first time that blended teaching can achieve a good pedagogical effectiveness in the medical practice course, clinical skills training and practice. Moreover, in different teaching contents, the teaching effects are different. In the content of Emergency Medicine and Surgery, which is more attractive to students, the application of blended teaching could result in a better pedagogical outcome than other contents.

Naringenin enhances the efficacy of ferroptosis inducers by attenuating aerobic glycolysis by activating the AMPK-PGC1α signalling axis in liver cancer.

Liver cancer is a heterogeneous disease characterized by poor responses to standard therapies and therefore unfavourable clinical outcomes. Understanding the characteristics of liver cancer and developing novel therapeutic strategies are imperative. Ferroptosis, a type of programmed cell death induced by lipid peroxidation, has emerged as a potential target for treatment. Naringenin, a natural compound that modulates lipid metabolism by targeting AMPK, shows promise in enhancing the efficacy of ferroptosis inducers. In this study, we utilized liver cancer cell lines and xenograft mice to explore the synergistic effects of naringenin in combination with ferroptosis inducers, examining both phenotypic outcomes and molecular mechanisms. Our study results indicate that the use of naringenin at non-toxic doses to hepatocytes can significantly enhance the anticancer effects of ferroptosis inducers (erastin, RSL3, and sorafenib). The combination index method confirmed a synergistic effect between naringenin and ferroptosis inducers. In comparison to naringenin or ferroptosis inducers alone, the combined therapy caused more robust lipid peroxidation and hence more severe ferroptotic damage to cancer cells. The inhibition of aerobic glycolysis mediated by the AMPK-PGC1α signalling axis is the key to naringenin's effect on reducing ferroptosis resistance in liver cancer, and the synergistic cytotoxic effect of naringenin and ferroptosis inducers on cancer cells was reversed after pretreatment with an AMPK inhibitor or a PGC1α inhibitor. Taken together, these findings suggest that naringenin could boost cancer cell sensitivity to ferroptosis inducers, which has potential clinical translational value.

Impact of Peripheral Anterior Synechiae on the Outcome of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Primary Angle Closure Glaucoma and Cataract: A Multicenter Observational Study.

PRCIS: The combination of phacoemulsification, goniosynechialysis and goniotomy is an effective treatment for primary angle closure glaucoma patients with cataract, and this is not linked to the extent of preoperative peripheral anterior synechiae. PURPOSE: To evaluate the impact of the extent of peripheral anterior synechiae (PAS) on the effectiveness and safety of combined phacoemulsification (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes with primary angle closure glaucoma (PACG) and cataract. PATIENTS AND METHODS: This study included patients diagnosed with PACG and cataracts who underwent combined PEI and 120 degrees GSL plus GT (PEI+GSL+GT) between April 2020 and October 2022 at 10 ophthalmic institutes. Eligible patients were divided into 3 groups based on the extent of PAS: 180°≤PAS<270°, 270°≤PAS<360°, and PAS=360°. Data on intraocular pressure (IOP), the number of ocular hypotensive medications, and complications were collected and compared. The study defined complete success as postoperative IOP within the 6-18 mm Hg range and a 20% reduction from baseline without the use of topical medications. Qualified success was defined in the same way as complete success, but it allowed for the use of ocular hypotensive medications. RESULTS: Three hundred four eyes of 283 patients were included. The mean follow-up was 12.50±1.24 months. All groups experienced a significant reduction in IOP after the surgery ( P <0.05). There were no significant differences in final IOP, number of medications, and cumulative complete and qualified success rates among the 3 groups ( P >0.05). The groups with 270°≤PAS<360°had a higher frequency of hyphema compared with 180°≤PAS<270° ( P = 0.044). CONCLUSIONS: PEI+GSL+GT has proven to be an effective treatment for PACG with cataracts over a 1 year period. However, the outcome was not correlated with the preoperative extent of PAS.

Phacogoniotomy versus phacotrabeculectomy for advanced primary angle-closure glaucoma with cataract: A randomized non-inferiority trial.

PURPOSE: To investigate the effectiveness and safety of phacogoniotomy versus phacotrabeculectomy (PVP) among patients with advanced primary angle-closure glaucoma (PACG) and cataracts. DESIGN: Multicenter, randomized controlled, non-inferiority trial. METHODS: A total of 124 patients (124 eyes) with advanced PACG and cataracts were enrolled, with 65 in the phacogoniotomy group and 59 in the phacotrabeculectomy group. Patients were followed up for 12 months with standardized evaluations. The primary outcome was the reduction in intraocular pressure (IOP) from baseline to 12 months postoperatively, of which a non-inferiority margin of 4 mmHg was evaluated. Secondary outcomes included the cumulative surgical success rate, postoperative complications, and changes in the number of glaucoma medications. RESULTS: After 12 months, phacogoniotomy demonstrated non-inferiority to phacotrabeculectomy in terms of IOP reduction, with mean IOP reductions of - 26.1 mmHg and - 25.7 mmHg (P = 0.383), respectively, from baseline values of around 40 mmHg. Both groups experienced a significant reduction in the mean number of medications used postoperatively (P < 0.001). The cumulative success rate was comparable between the groups (P = 0.890). However, phacogoniotomy had a lower rate of postoperative complications and interventions (12.3% and 4.6%) compared to phacotrabeculectomy (23.7% and 20.3% respectively). The phacogoniotomy group reported shorter surgery time (22.1 ± 6.5 vs. 38.8 ± 11.1 min; P = 0.030) and higher quality of life (EQ-5D-5 L) improvement at 12 months (7.0 ± 11.5 vs. 3.0 ± 12.9, P = 0.010) than the phacotrabeculectomy group. CONCLUSIONS: Phacogoniotomy was non-inferior to phacotrabeculectomy in terms of IOP reduction for advanced PACG and cataracts. Additionally, phacogoniotomy provided a shorter surgical time, lower postoperative complication rate, fewer postoperative interventions, and better postoperative quality of life.

Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation.

OBJECTIVE: Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of PDIA3 in gastric cancer (GC) and its association with GC development as wells as the underlying mechanisms. METHODS: GC cell lines with PDIA3 knockdown by siRNA, CRISPR-cas9 sgRNAs or a pharmacological inhibitor of LOC14 were prepared and used. PDIA3 knockout GC cells were established by CRISPR-cas9-PDIA3 system. The proliferation, migration, invasion and cell cycle of GC cells were analyzed by cell counting kit-8 assay, wound healing assay, transwell assay and flow cytometry, respectively. Immunodeficient nude mice was used to evaluate the role of PDIA3 in tumor formation. Quantitative PCR and western blot were used for examining gene and protein expressions. RNA sequencing was performed to see the altered gene expression. RESULTS: The expressions of PDIA3 in GC tissues and cells were increased significantly, and its expression was negatively correlated with the three-year survival rate of GC patients. Down-regulation of PDIA3 by siRNA, LOC14 or CRISPR-cas9 significantly inhibited proliferation, invasion and migration of GC cells TMK1 and AGS, with cell cycle arrested at G2/M phase. Meanwhile, decreased PDIA3 significantly inhibited growth of tumor xenograft in vivo. It was found that cyclin G1 (encoded by CCNG1 gene) expression was decreased by downregulation of PDIA3 in GC cells both in vitro and in vivo. In addition, protein levels of other cell cycle related factors including cyclin D1, CDK2, and CDK6 were also significantly decreased. Further study showed that STAT3 was associated with PDIA3-mediated cyclin G1 regulation. CONCLUSION: PDIA3 plays an oncogenic role in GC. Our findings unfolded the functional role of PDIA3 in GC development and highlighted a novel target for cancer therapeutic strategy.

Dysregulation of immunity by cigarette smoking promotes inflammation and cancer: A review.

Smoking is a serious global health issue. Cigarette smoking contains over 7000 different chemicals. The main harmful components include nicotine, acrolein, aromatic hydrocarbons and heavy metals, which play the key role for cigarette-induced inflammation and carcinogenesis. Growing evidences show that cigarette smoking and its components exert a remarkable impact on regulation of immunity and dysregulated immunity promotes inflammation and cancer. Therefore, this comprehensive and up-to-date review covers four interrelated topics, including cigarette smoking, inflammation, cancer and immune system. The known harmful chemicals from cigarette smoking were summarized. Importantly, we discussed in depth the impact of cigarette smoking on the formation of inflammatory or tumor microenvironment, primarily by affecting immune effector cells, such as macrophages, neutrophils, and T lymphocytes. Furthermore, the main molecular mechanisms by which cigarette smoking induces inflammation and cancer, including changes in epigenetics, DNA damage and others were further summarized. This article will contribute to a better understanding of the impact of cigarette smoking on inducing inflammation and cancer.

Improved safety and quality in intravascular brachytherapy: A multi-institutional study using failure modes and effects analysis.

PURPOSE: Highlight safety considerations in intravascular brachytherapy (IVBT) programs, provide relevant quality assurance (QA) and safety measures, and establish their effectiveness. METHODS AND MATERIALS: Radiation oncologists, medical physicists, and cardiologists from three institutions performed a failure modes and effects analysis (FMEA) on the radiation delivery portion of IVBT. We identified 40 failure modes and rated the severity, occurrence, and detectability before and after consideration of safety practices. Risk priority numbers (RPN) and relative risk rankings were determined, and a sample QA safety checklist was developed. RESULTS: We developed a process map based on multi-institutional consensus. Highest-RPN failure modes were due to incorrect source train length, incorrect vessel diameter, and missing prior radiation history. Based on these, we proposed QA and safety measures: ten of which were not previously recommended. These measures improved occurrence and detectability: reducing the average RPN from 116 to 58 and median from 84 to 40. Importantly, the average RPN of the top 10% of failure modes reduced from 311 to 172. With QA considered, the highest risk failure modes were from contamination and incorrect source train length. CONCLUSIONS: We identified several high-risk failure modes in IVBT procedures and practical safety and QA measures to address them.

LncRNA RP11-93B14.5 promotes gastric cancer cell growth through PI3K/AKT signaling pathway.

OBJECTIVE: Emerging evidence indicates that long non-coding RNA (lncRNA) RP11-93B14.5 facilitates tumor progression in variety of malignancies. The present study proposed to study the functional effect of lncRNA RP11-93B14.5 in gastric cancer (GC) as well as the underlying mechanism. METHODS: Bioinformatics analysis was utilized to analyze lncRNA expression in GC tissues. siRNA was used for knockdown of RP11-93B14.5 in GC cells MKN45 and KATO III. The stable knockdown cell lines were constructed by CRISPR-Cas9. Cell counting kit-8 (CCK-8) assay and soft agar colony formation assay were used to analyze GC cell viability. Flow cytometry analysis was performed to analyze the cell cycle distribution of MKN45 and KATO III. RNA sequencing (RNA-seq) was employed to detect differential genes after transfection with siRP11-93B14.5. Quantitative PCR (Q-PCR) was used to examine gene expression in GC cell lines. Western-blot assay was used to measure protein levels. RNA fluorescent in situ hybridization (FISH) was conducted for lncRNA cellular location and expression. RESULTS: Based on the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) database, RP11-93B14.5 was upregulated in GC tissue, which was also verified in GC cell lines in comparison to the normal gastric epithelial HFE145 cells. Knockdown of RP11-93B14.5 decreased cell viability and the colony number of MKN45 and KATO III cells, and altered cell cycle distribution in vitro. RNA-seq analysis revealed RP11-93B14.5 may modulate genes expression of S100A2 and TIMP2 in MKN45 and KATO III cells. Mechanistically, RP11-93B14.5 may drive the progression of GC via S100A2 related-PI3K/AKT signaling pathway. CONCLUSIONS: LncRNA RP11-93B14.5 knockdown alleviated the malignant phenotypes of GC cells through regulating PI3K/AKT. Our results provide evidence for the role of lncRNAs in regulating tumor progression.

Implementing failure mode and effect analysis to improve the safety of volumetric modulated arc therapy for total body irradiation.

PURPOSE: Volumetric-modulated arc therapy for total body irradiation (VMAT-TBI) is a novel radiotherapy technique that has been implemented at our institution. The purpose of this work is to investigate possible failure modes (FMs) in the treatment process and to develop a quality control (QC) program for VMAT-TBI following TG-100 guidelines. METHODS: We formed a multidisciplinary team to map out the complete treatment process of VMAT-TBI following the AAPM TG-100 guidelines. This process map gives a visual representation of the VMAT-TBI workflow from the CT simulation, image processing, contouring, treatment planning, to treatment delivery. From the process map, potential FMs were identified. The occurrence (O), detectability (D), and severity of impact (S) of each FM were assigned according to scoring criteria (1-10) by the multidisciplinary team. A risk priority number (RPN) was calculated from average O, S, and D of each FM (RPN = O x S x D). High risk FMs were identified as 20% of the FMs having the highest RPN scores. After the FMEA analysis, fault-tree analysis (FTA) was performed for each major step of the treatment process to determine the effects of potential failures to the treatment outcome. Effective QC methods were identified to prevent the high risk failures and to improve the safety of the VMAT-TBI program. RESULTS: We identified a total of 55 sub-processes and 128 FMs from the VMAT-TBI workflow. The top five high-risk FMs were: (1) Prescription and/or OAR constraints changed during planning and not communicated to the planner, (2) Patient moves or breathes too heavily during the upper body CT scan (3) Patient moves during the lower body CT scan, (4) Treatment planning system not calculating total body DVH metrics correctly for TBI, (5) Improper optimization criteria used or not sufficient optimization, resulting in suboptimal dose coverage, OAR sparing or excessive hotspots during treatment planning. Two FMs have average severity scores ≥8: Incorrect PTV subdivision/isocenter placement and Prescription and/or OAR constraints changed during planning and not communicated to the planner. Quality assurance and QC interventions including staff training, standard operating procedures, and quality checklists were implemented based on the FMEA and FTA. CONCLUSION: FM and effect analysis was performed to identify high-risk FMs of our VMAT-TBI program. FMEA and FTA were effective in identifying potential FMs and determining the best quality management (QM) measures to implement in the VMAT-TBI program.

Antigen-specific B cells direct T follicular-like helper cells into lymphoid follicles to mediate Mycobacterium tuberculosis control.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), is a global cause of death. Granuloma-associated lymphoid tissue (GrALT) correlates with protection during TB, but the mechanisms of protection are not understood. During TB, the transcription factor IRF4 in T cells but not B cells is required for the generation of the TH1 and TH17 subsets of helper T cells and follicular helper T (TFH)-like cellular responses. A population of IRF4+ T cells coexpress the transcription factor BCL6 during Mtb infection, and deletion of Bcl6 (Bcl6fl/fl) in CD4+ T cells (CD4cre) resulted in reduction of TFH-like cells, impaired localization within GrALT and increased Mtb burden. In contrast, the absence of germinal center B cells, MHC class II expression on B cells, antibody-producing plasma cells or interleukin-10-expressing B cells, did not increase Mtb susceptibility. Indeed, antigen-specific B cells enhance cytokine production and strategically localize TFH-like cells within GrALT via interactions between programmed cell death 1 (PD-1) and its ligand PD-L1 and mediate Mtb control in both mice and macaques.

Sequential monoscopic image-guided motion compensation in tomotherapy stereotactic body radiotherapy (SBRT) for prostate cancer.

PURPOSE: To manage intra-fractional motions, recent developments in tomotherapy enable a unique capability of adjusting MLC/jaw to track the moving target based on the intra-fractional motions detected by sequential monoscopic imaging. In this study, we evaluated the effectiveness of motion compensation with a realistic imaging rate for prostate stereotactic body radiotherapy (SBRT). The obtained results will guide optimizing treatment parameters and image-guided radiation therapy (IGRT) in tomotherapy using this approach. METHODS: Ten retrospective prostate cases with actual prostate motion curves previously recorded through the Calypso system were used in this study. Based on the recorded peak-to-peak motion, these cases represented either large (> 5 mm) or median (≤ 5 mm) intra-fractional prostate motions. All the cases were re-planned on tomotherapy using 35 Gy/5 fractions SBRT regimen and three different jaw settings of 1 cm static, 2.5 cm static, and 2.5 cm dynamic jaw. Two motion compensation methods were evaluated: a complete compensation that adjusted the jaw and MLC every 0.1 s (the same rate as the Calypso motion trace), and a realistic compensation that adjusted the jaw and MLC at an average imaging interval of 6 s from sequential monoscopic images. An in-house 4D dose calculation software was then applied to calculate the dosimetric outcomes from the original motion-free plan, the motion-contaminated plan, and the two abovementioned motion-compensated plans. During the process, various imaging rates were also simulated in one case with unusually large motions to quantify the impact of the KV-imaging rate on the effectiveness of motion compensation. RESULTS: The effectiveness of motion compensation was evaluated based on the PTV coverage and OAR sparing. Without any motion-compensation, the PTV coverage (PTV V100%) of patients with large prostate motions decreased remarkably to 55%-82% when planning with the 1 cm jaw but to a less level of 67-94% with the 2.5 cm jaw. In contrast, motion compensation improved the PTV coverage (>92%) when combined with the 2.5 cm jaw, but less effective, around 75%-94%, with the 1 cm jaw. For OAR sparing, the bladder D1cc, bladder D10cc, and rectum D1cc all increased in the motion-contaminated plans. Motion compensation improved OAR sparing to the equivalent level of the original motion-free plans. For patients with median prostate motion, motion-induced degradation in PTV coverage was only observed when planning with the 1 cm jaw. After motion compensation, the PTV coverage improved to better than 94% for all three jaw settings. Additionally, the effectiveness of motion compensation depends on the imaging rate. Motion compensation with a typical rate of two KV images per gantry rotation effectively reduces motion-induced dosimetric uncertainties. However, a higher imaging rate is recommended when planning with a 1 cm jaw for patients with large motions. CONCLUSION: Our results demonstrated that the performance of sequential monoscopic imaging-guided motion compensation on tomotherapy depends on the amplitude of intra-fractional prostate motion, the plan parameter settings, especially jaw setting, gantry rotation, and the imaging rate for motion compensation. Creating a patient-specific imaging guidance protocol is essential to balance the effectiveness of motion compensation and achievable imaging rate for intra-fractional motion tracking.

One-Year Results of a Multicenter Study: Intraocular Pressure-Lowering Effect of Combined Phacoemulsification, Goniosynechialysis, and Goniotomy for Cases of Advanced Primary Angle-Closure Glaucoma With Cataract.

PURPOSE: To evaluate the intraocular pressure (IOP)-lowering effect of the combination of phacoemulsification with intraocular lens implantation (PEI), goniosynechialysis (GSL), and goniotomy (GT) in eyes of advanced primary angle-closure glaucoma (PACG) with cataract. DESIGN: Multicenter observational study. METHODS: We enrolled 83 eyes of 83 patients with advanced PACG who received combined PEI+GSL+GT at 8 ophthalmic institutes. Each patient was assessed before treatment and at 1, 7 days, 1, 3, 6, and 12 months postsurgery. The criteria for complete success were IOP within 6 to 18 mm Hg and at least 20% of reduction in IOP from baseline without ocular hypotensive medications or reoperation. The definition of qualified success was similar to that of complete success, except for the need for ocular hypotensive medications. The potential prognostic factors for surgical success were investigated using a multivariate logistic model. RESULTS: All participants completed 1 year of follow-up. Complete and qualified success were achieved in 74 (89.1%) and 79 (95.2%) of 83 eyes, respectively. The mean preoperative and postsurgical IOPs were 27.4±7.3 and 14.2±2.6 mm Hg, respectively. Participants used an average of 2.0 and 0.3 types of ocular hypotensive medications before and after surgery, respectively. The chief complications included hyphema (n=9), IOP spike (n=9), and corneal edema (n=8). None of the eyes required reoperation or developed vision-threatening complications. Multivariate analysis showed that older age was associated with a higher probability of complete success (odds ratio=1.13; 95% CI: 1.02-1.25; P=0.020). CONCLUSIONS: The 1-year results of combination of PEI+GSL+GT in treating advanced PACG cases with cataract appear to be safe and effective. Further large-scale multination and multicenter studies are warranted.

Rahnella aquatilis JZ-GX1 alleviates iron deficiency chlorosis in Cinnamomum camphora by secreting desferrioxamine and reshaping the soil fungal community.

Plant growth-promoting rhizobacteria are important for improving plant iron nutrition, but the interactions among inoculants, host plants and soil microorganisms have not been greatly explored. Rahnella aquatilis JZ-GX1 was applied to treat the increasingly serious iron deficiency chlorosis in Cinnamomum camphora, and the resulting improvement in chlorosis was determined by assessing the contents of chlorophyll, active iron, Fe2+ and antioxidant enzymes in leaves, the effects on the soil microbial community and the metabolism in the rhizosphere by high-throughput sequencing techniques and liquid chromatography-mass spectrometry (LC-MS). The results showed that inoculation with JZ-GX1 significantly increased the chlorophyll content of C. camphora, which promoted the redistribution of active iron in roots and leaves, increased the activities of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT) and ascorbate peroxidase (APX), and thus reduced membrane damage in iron-deficient C. camphora caused by reactive oxygen species. According to genome prediction and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) analysis, the JZ-GX1 strain could secrete desferrioxamine (DFO), and the concentration of DFO in C. camphora rhizosphere was 21-fold higher than that in uninoculated soil. The exogenous application of DFO increased the SPAD and Fe2+ contents in leaves. In addition, the inoculant affected the fungal community structure and composition in the C. camphora rhizosphere soil and increased the abundances of specific taxa, such as Glomus, Mortierella, Trichoderma, and Penicillium. Therefore, R. aquatilis JZ-GX1 application promoted iron absorption in C. camphora trees by secreting DFO and alleviated iron deficiency chlorosis through interactions with the local fungal community.

Effect of Acupuncture along Meridians on Pain Degree and Treatment of Acute Lumbar Sprain.

Aim: This study is aimed at investigating the effect of acupuncture along meridians on pain degree and treatment of acute lumbar sprain. Methods: A total of 96 patients with acute lumbar sprain from May 2019 to March 2021 in our hospital were selected and divided into the study and control groups. The patients in the control group were administered conventional western medicine and massage therapy, while the study group underwent acupuncture along meridians based on the control group. The therapeutic effect, visual analogue scale (VAS), Roland-Morris Disability Questionnaire (RMDQ), and lumbar range of motion (ROM) scores, emG inversion times, emG amplitude of the sacrospinalis muscle, and the serum TNF-α and IL-6 levels were determined. Results: The total effective rate of the study group was significantly higher than that of the control group. After treatment, the VAS, RMDQ, and ROM scores of the study group were significantly lower than those of the control group. Before the intervention, the EMG inversion times and the EMG amplitude of the spinous process muscle in the study group were not significantly different from those in the control group. After the intervention, the number and amplitude of EMG reversal in the study group were significantly higher than those in the control group. After the intervention, the serum levels of TNF-α (pg/ml) and IL-6 (pg/ml) in the study group were significantly lower than those in the control group. Conclusion. Meridian acupuncture for acute lumbar sprain can effectively improve body function, relieve pain, regulate serum inflammatory factors, and improve the overall therapeutic effect.

Overexpression of BDNF in the ventrolateral periaqueductal gray regulates the behavior of epilepsy-migraine comorbid rats.

OBJECTIVE: To investigate the effects of brain-derived neurotrophic factor (BDNF) overexpression in the ventrolateral periaqueductal gray (vlPAG) on behavioral changes in epilepsy-migraine comorbid rats. METHOD: We used an adeno-associated virus (AAV)-mediated vector to supplement BDNF in the vlPAG area prior to the establishment of a pilocarpine-nitroglycerin (Pilo-NTG) combination-induced comorbid model of epilepsy and migraine. Seizure- and migraine-related behaviors were analyzed. Cell loss and apoptosis in vlPAG were detected through hematoxylin-eosin (HE) and TUNEL staining. Immunofluorescence staining analyses were employed to detect expressions of BDNF and its receptor, tyrosine kinase B (TrkB), in vlPAG. Immunohistochemical staining was conducted to detect expressions of c-Fos and calcitonin gene-related peptide (CGRP) in the trigeminal nucleus caudalis (TNC) and trigeminal ganglion (TG). RESULTS: Comparing to control group, AAV-BDNF injected comorbid group showed lower pain sensitivity, scratching head, and spontaneous seizures accompanied by the downregulation of c-Fos labeling neurons and CGRP immunoreactivity in the TNC and TG. However, these changes were still significantly higher in the comorbid group than those in both epilepsy and migraine groups under the same intervention. CONCLUSION: These data demonstrated that supplying BDNF to vlPAG may protect structural and functional abnormalities in vlPAG and provide an antiepileptic and analgesic therapy.

Hydrostatic pressure stimulates the osteogenesis and angiogenesis of MSCs/HUVECs co-culture on porous PLGA scaffolds.

In native bone tissue regeneration, blood vessels, providing oxygen and nutrition for tissues, can promote the regeneration of bone and accelerate the repair of a defected area. In this study, Poly(D, L-lactic-co-glycolic acid) (PLGA) inverse opal scaffolds with high pore interconnectivity were fabricated and further modified with vascular endothelial growth factor (VEGF). The rat bone marrow derived mesenchymal stem cells (rMSCs) and human umbilical vein endothelial cells (HUVECs) were co-cultured onto the scaffolds to enhance vascularization for bone tissue regeneration. Cell attachment, viability, proliferation, and morphology were detected by cell counting kit-8 (CCK-8) assay, live and dead staining and scanning electron microscopy (SEM). Hydrostatic pressure with 0-279 KPa and 1 Hz one hour per day for 7 days was applied to tissue engineered bone constructs to investigate whether the loading stimulation can promote osteogenesis and angiogenesis mutually evaluated in parallel by multiple in vitro assays and in an in vivo chicken chorioallantoic membrane (CAM) model. The results indicated that the immobilization of VEGF can improve biocompatibility of PLGA scaffolds and promote cell attachment and proliferation. The cell-scaffold constructs showed higher CD31 expression because of the angiogenic differentiation of rMSCs in hydrostatic loading culture condition in vitro. The in vivo CAM model experiment demonstrated that hydrostatic loading stimulated angiogenic differentiation of rMSCs can accelerate tubulogenesis. Furthermore, the new capillaries formed in cell-scaffold constructs were conducive to calcium deposition in vivo.

Faecal microbiome and metabolic signatures in rectal neuroendocrine tumors.

Background: The prevalence of rectal neuroendocrine tumors (RNET) has increased substantially over the past decades. Little is known on mechanistic alteration in the pathogenesis of such disease. We postulate that perturbations of human gut microbiome-metabolome interface influentially affect the development of RNET. The study aims to characterize the composition and function of faecal microbiome and metabolites in RNET individuals. Methods: We performed deep shotgun metagenomic sequencing and untargeted liquid chromatography-mass spectrometry (LC-MS) metabolomic profiling of faecal samples from the discovery cohort (18 RNET patients, 40 controls), and validated the microbiome and metabolite-based classifiers in an independent cohort (15 RNET participants, 19 controls). Results: We uncovered a dysbiotic gut ecological microenvironment in RNET patients, characterized by aberrant depletion and attenuated connection of microbial species, and abnormally aggregated lipids and lipid-like molecules. Functional characterization based on our in-house and Human Project Unified Metabolic Analysis Network 2 (HUMAnN2) pipelines further indicated a nutrient deficient gut microenvironment in RNET individuals, evidenced by diminished activities such as energy metabolism, vitamin biosynthesis and transportation. By integrating these data, we revealed 291 robust associations between representative differentially abundant taxonomic species and metabolites, indicating a tight interaction of gut microbiome with metabolites in RNET pathogenesis. Finally, we identified a cluster of gut microbiome and metabolite-based signatures, and replicated them in an independent cohort, showing accurate prediction of such neoplasm from healthy people. Conclusions: Our current study is the first to comprehensively characterize the perturbed interface of gut microbiome and metabolites in RNET patients, which may provide promising targets for microbiome-based diagnostics and therapies for this disorder.

Technical overview of magnetic resonance fingerprinting and its applications in radiation therapy.

Magnetic resonance fingerprinting (MRF) is an emerging imaging technique for rapid and simultaneous quantification of multiple tissue properties. The technique has been developed for quantitative imaging of different organs. The obtained quantitative measures have the potential to improve multiple steps of a typical radiotherapy workflow and potentially further improve integration of magnetic resonance imaging guided clinical decision making. In this review paper, we first provide a technical overview of the MRF method from data acquisition to postprocessing, along with recent development in advanced reconstruction methods. We further discuss critical aspects that could influence its usage in radiation therapy, such as accuracy and precision, repeatability and reproducibility, geometric distortion, and motion robustness. Finally, future directions for MRF application in radiation therapy are discussed.

Efficacy and safety of phacotrabeculectomy versus phacogoniotomy in advanced primary angle-closure glaucoma: study protocol for a multicentre non-inferiority randomised controlled trial (PVP Study).

INTRODUCTION: Primary angle-closure glaucoma (PACG) has a high prevalence and blinding rate across Asia. The first-line treatment of PACG is surgery, and phacotrabeculectomy remains the mainstream surgery for advanced PACG. However, it may cause vision-threatening complications with long learning curve. Minimally invasive glaucoma surgery has been gradually used in PACG combined with cataract surgery and achieved efficacy without excessive injury, of which goniotomy is the most commonly performed. Therefore, this study aimed to conduct a multicentre, non-inferiority randomised controlled clinical trial to compare the efficacy and safety of phacotrabeculectomy versus phacogoniotomy in advanced PACG. METHODS AND ANALYSIS: This is a non-inferiority multicentre randomised controlled trial and will be conducted at eight ophthalmic departments and institutes in China. 124 patients with advanced PACG will be enrolled and randomised to undergo phacotrabeculectomy or phacogoniotomy. Comprehensive ophthalmic examinations will be performed before and after the surgery. The primary outcome is the change of intraocular pressure at 12 months after surgery compared with the baseline intraocular pressure. An extended follow-up period of 36 months will be required. Cumulative success rate of surgery, intraoperative and postoperative complications, and number of anti-glaucomatous medications will also be compared between the groups as secondary outcomes. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the ethical committee of Zhongshan Ophthalmic Center, Sun Yat-sen University, China (ID: 2021KYPJ090) and all subcentres. All the participants will be required to provide written informed consent. The results will be disseminated through scientific meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT04878458.

Image-guided volumetric-modulated arc therapy of total body irradiation: An efficient workflow from simulation to delivery.

INTRODUCTION: Using multi-isocenter volumetric-modulated arc therapy (VMAT) for total body irradiation (TBI) may improve dose uniformity and vulnerable tissue protection compared with classical whole-body field technique. Two drawbacks limit its application: (1) VMAT-TBI planning is time consuming; (2) VMAT-TBI plans are sensitive to patient positioning uncertainties due to beam matching. This study presents a robust planning technique with image-guided delivery to improve dose delivery accuracy. In addition, a streamlined sim-to-treat workflow with automatic scripts is proposed to reduce planning time. MATERIALS: Twenty-five patients were included in this study. Patients were scanned in supine head-first and feet-first directions. An automatic workflow was used to (1) create a whole-body CT by registering two CT scans, (2) contour lungs, kidneys, and planning target volume (PTV), (3) divide PTV into multiple sub-targets for planning, and (4) place isocenters. Treatment planning included feathered AP/PA beams for legs/feet and VMAT for the body. VMAT-TBI was evaluated for plan quality, planning/delivery time, and setup accuracy using image guidance. RESULTS: VMAT-TBI planning time can be reduced to a day with automatic scripts. Treatment time took around an hour per fraction. VMAT-TBI improved dose coverage (PTV V100 increased from 76.8 ± 10.5 to 88.5 ± 2.6; p < 0.001) and reduced lung dose (lung mean dose reduced from 10.8 ± 0.7 Gy to 9.4 ± 0.8 Gy, p < 0.001) compared with classic AP/PA technique. CONCLUSION: A VMAT-TBI sim-to-treat workflow with robust planning and image-guided delivery was proposed. VMAT-TBI improved the plan quality compared with classical whole-body field techniques.