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Osteoporosis （OP） is a common bone disease affecting the quality of life and causing huge medical burden to the patients and society. The occurrence of OP is mainly caused by excessive bone resorption and insufficient bone formation， which are directly influenced by external calcium ion balance. Calcium imbalance can impair bone integrity， reduce the calcium supply to the bone， and lower the calcium content in the bone， thus triggering OP. Drugs are the main anti-OP therapy in modern medicine， which， however， may cause adverse reactions and drug dependence. Chinese medicines have good clinical effects and high safety in treating OP， being suitable for long-term use. Recent studies have shown that Chinese medicines can alleviate estrogen deficiency， regulate bone cell and calcium metabolism， which is crucial for the formation and development of OP. The transient receptor potential cation channel superfamily V members 5 and 6 （TRPV5 and TRPV6， respectively） affect bone homeostasis by mediating the transmembrane calcium ion transport in the intestine （TRPV6） and kidney （TRPV5）. Therefore， TRPV5/6 is one of the key targets to understand the anti-OP mechanisms of the effective parts of Chinese medicines， which is worthy of further study. This paper summarizes the research results about the anti-OP effects of Chinese medicines in the last two decades， especially the mechanism of regulating calcium metabolism， aiming to provide new ideas for the basic research， clinical application， and drug development of OP treatment.
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In real-time ultrasound,molecular targeted contrast agent is introduced into the blood circulation through peripheral intravenous injection to enhance the imaging signal of target lesions after binding to the corresponding intravascular receptors,which can realize early diagnosis,staging of diseases,assessment of treatment response,and targeted treatment.In addition,molecular targeted ultrasound contrast agents provide a platform for the delivery of drugs and genes via microbubbles,and nanoscale contrast agents can be infiltrated through vascular endothelium into the interstitial space of the lesion for imaging or treatment.The available studies of molecular targeted ultrasound contrast agents mainly focus on the preclinical trials.Some clinical trials have been conducted in humans and preliminarily confirm the safety and feasibility of targeted ultrasound contrast agents.The molecular targeted ultrasound contrast agents enjoy a broad prospect in clinical application.
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Humans , Contrast Media/chemistry , Molecular Targeted Therapy , Ultrasonography/methods , Diagnostic ImagingABSTRACT
OBJECTIVE@#Diffuse large B-cell lymphoma (DLBCL) is often associated with bone marrow infiltration, and 2-deoxy-2-(18F) fluorodeoxyglucose positron emission tomography/computed tomography ( 18F-FDG PET/CT) has potential diagnostic significance for bone marrow infiltration in DLBCL.@*METHODS@#A total of 102 patients diagnosed with DLBCL between September 2019 and August 2022 were included. Bone marrow biopsy and 18F-FDG PET/CT examinations were performed at the time of initial diagnosis. Kappa tests were used to evaluate the agreement of 18F-FDG PET/CT with the gold standard, and the imaging features of DLBCL bone marrow infiltration on PET/CT were described.@*RESULTS@#The total detection rate of bone marrow infiltration was not significantly different between PET/CT and primary bone marrow biopsy ( P = 0.302) or between the two bone marrow biopsies ( P = 0.826). The sensitivity, specificity, and Youden index of PET/CT for the diagnosis of DLBCL bone marrow infiltration were 0.923 (95% CI, 0.759-0.979), 0.934 (95% CI, 0.855-0.972), and 0.857, respectively.@*CONCLUSION@#18F-FDG PET/CT has a comparable efficiency in the diagnosis of DLBCL bone marrow infiltration. PET/CT-guided bone marrow biopsy can reduce the misdiagnosis of DLBCL bone marrow infiltration.
Subject(s)
Humans , Positron Emission Tomography Computed Tomography/methods , Fluorodeoxyglucose F18 , Bone Marrow/pathology , Retrospective Studies , Positron-Emission Tomography/methods , Lymphoma, Large B-Cell, Diffuse/pathologyABSTRACT
Objective:To investigate the effect of dwell time deviation constraint of inverse optimization on the quality and position error robustness of three-dimensional (3D) brachytherapy plans for cervical cancer.Methods:A total of 20 patients with cervical cancer receiving 3D brachytherapy treatment in Xiangya Hospital Central South University from August 2020 to August 2021 were retrospectively selected. All plans were designed using the Eclipse treatment planning system, and the dwell time deviation constraint parameter smooth value in the system were set to 0.00, 0.25, 0.50, 0.75, and 1.00, respectively. An inverse dose volume optimization algorithm was used to generate plans with various smooth values, and the optimization conditions were the same as the original clinical plans. Key dosimetric metrics and total dwell time differences were comparatively analyzed. The applicators were intentionally subjected to position errors (0.2-1.0 cm) in 6 directions (left-right, anterior-posterior, head-foot), and the effect of various smooth values on plan quality and robustness was assessed. There were 133 plans per case and 2 660 plans for 20 patients. The results were statistically analyzed using the Wilcoxon signed-rank nonparametric test.Results:As the smooth value was increased, the modulation factor was gradually decreased and the D 2 cm3 of the bladder and rectum was increased. Plans with smooth values of 0.25, 0.50, 0.75, 1.00 had modulation factors of 0.72±0.09, 0.63±0.08, 0.55±0.08, 0.51±0.06, respectively, lower than 0.75±0.05 of the plan with the smooth value of 0.00, and all differences were statistically significant ( P=0.004, 0.002, 0.002, 0.002). The bladder D 2 cm3 of plans with smooth values of 0.50, 0.75, 1.00 were (475.4±41.0) cGy, (483.7±46.2) cGy, and (489.0±46.8) cGy, respectively, higher than (469.8±41.8) cGy of the plan with the smooth value of 0.00, with statistically significant differences (all P=0.002). The rectum D 2 cm3 of plans with smooth values of 0.50 and 0.75 plans were (413.2±93.3) cGy and (418.6±96.4) cGy, both higher than (410.2±91.5) cGy of the plan with the smooth value of 0.00, with statistically significant differences ( P=0.006, 0.010). When positional errors were introduced, the high risk clinical target volume (HR-CTV) D 90% was close for different smooth plans at most positional errors, and the differences were not statistically significant. The organs at risk D 2 cm3 of plans with the smooth value of 0.00 was lower than those of plans with other smooth values, and for the bladder and rectum, the differences were statistically significant at most positional errors (all P<0.01). Conclusions:The dwell time deviation constraint parameter exerts significant effect on the plan quality, and the smaller the value of the constraint parameter, the higher quality of the plan. The dwell time deviation constraint parameter has slight impact on the positional error robustness of dosimetric indices of targets and key organs at risk.
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Objective:To investigate the effects of off-target isocenter plans with different off-target distances on the plan quality and delivery accuracy of stereotactic body radiotherapy (SBRT) for lung cancer, aiming to provide a reference for the clinical plan design of SBRT for lung cancer.Methods:For 10 lung cancer patients treated with SBRT, isocenter reference plans were designed by setting the plan isocenters at the mass centers of tumors and 60 off-target isocenter plans by setting the isocenters at distances of 1, 3, 5, 8, and 10 cm from the mass centers of tumors. The dosimetric differences between the off-target isocenter plans and the reference plans. Subsequently was analyzed, under different positional errors (0-5 mm). The gamma pass rates (GPRs) of these plans were measured using the Octavius 4D high-resolution dose verification system, and 240 verifications of these plans were completed. The robustness of the delivery accuracy of the reference plans and off-target isocenter plans were analyzed under different positional errors.Results:The off-target isocenter plans yielded slightly worse dose gradient indices than the isocenter reference plans, but there was no statistically significant differences. With an increase in the off-target distance, the mean lung dose (MLD), V20 of normal lungs, as well as the Dmax of bronchi, showed slight upward trends. Compared with the isocenter reference plans, the MLD of the off-target isocenter plans increased by 0.8%, 0.8%, and 1.9% at off-target distances of 1, 3, and 10 cm, respectively, with statistically significant differences ( z = -2.34 to -1.99, P < 0.05), and the V20 of the off-target isocenter plans increased by 2.0%, 2.5%, and 3.7% at off-target distances of 1, 5, and 10 cm, respectively, with statistically significant differences ( z =-2.11 to -1.99, P < 0.05). In the case of a positional error of up to 5 mm, the GPRs of plans with off-target distances of 5 cm and above decreased by more than 1.0% on average and up to a maximum of 3.5%, showing statistically significant differences ( z = 2.13-2.75, P < 0.05). Conclusions:Compared to the reference plans, the off-target isocenter plans showed slightly lower dosimetric quality and less robust delivery accuracy under different positional errors. Therefore, it is necessary to avoid the plans and treatment with too large off-target distances (≥ 5 cm) as far as possible for SBRT of lung cancer.
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Objective:To establish a metaheuristics-based automatic radiotherapy treatment planning method (ATP-STAR) and verify its effectiveness.Methods:The main process of the ATP-STAR method was as follows. First, the optimization parameters were vectorized for encoding and corrected using Gaussian convolution. Then, the candidate optimization parameter vector set was selected through simulated annealing. Finally, the optimal combination of optimization parameters was determined by combining the field fluence optimization to achieve automatic trial-and-error. Twenty cases with large individual differences in tumors were selected for testing. Clinical physicists with more than five years of experience were invited to perform manual planning. Both the manual and ATP-STAR plans were made utilizing the matRad open source software for radiation treatment planning, with the fields and prescribed doses consistent with those of the clinical treatment plans. The dosimetric differences of target volumes and organs at risk between the ATP-STAR and manual plans for different diseases were analyzed.Results:For the target volumes, the ATP-STAR plans showed superior homogeneity compared with the manual plans (brain tumors: z = 2.28, P = 0.022; lung cancers: z = 2.29, P = 0.022; liver cancers: z = 2.11, P = 0.035). The conformability of the ATP-STAR plans was comparable to that of the manual plans for brain tumors and liver cancer and was slightly lower than that of the manual plans for lung cancer ( z = 2.29, P = 0.022). The comparison result of doses to organs at risk (OARs) between the manual plans and STAR plans were as follows. For OARs of brain tumors, the ATP-STAR plans decreased the mean left lens Dmean from 2.19 Gy to 1.76 Gy ( z = 2.28, P = 0.022), decreased left optic nerve Dmean from 11.36 Gy to 10.22 Gy ( z = 2.28, P = 0.022), decreased right optic nerve Dmax from 32.92 Gy to 29.97 Gy ( z = 2.10, P = 0.036), and decreased pituitary Dmax from 39.53 Gy to 35.21 Gy ( z = 2.29, P = 0.022). For OARs of lung cancer, the ATP-STAR plans decreased the mean spinal cord Dmax from 38.00 Gy to 31.17 Gy ( z = 2.12, P = 0.034), decreased the bilateral lungs Dmean from 8.51 Gy to 8.07 Gy ( z = 2.29, P = 0.022), and decreased cardiac Dmean from 3.21 Gy to 2.69 Gy ( z =2.29, P = 0.022). For OARs of liver cancer, the ATP-STAR plans decreased spinal cord Dmax from 18.19 Gy to 14.76 Gy ( z = 2.11, P = 0.035), decreased liver Dmean from 15.61 Gy to 14.45 Gy ( z = 2.11, P = 0.035), and decreased kidneys Dmean from 4.76 Gy to 4.04 Gy ( z = 2.10, P = 0.036). Conclusions:The proposed ATP-STAR method relies little on the experience of manual planning and thus is easy to be widely applied. This method is expected to improve the quality and consistency of IMRT plans and save clinical labor and time costs.
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To train homogeneous and excellent anesthesiologists who understand basic theory and clinical specialty, and response quickly and precisely to the emergency clinical condition. The Department of Anesthesiology, The First Affiliated Hospital of Army Medical University applied the integrated medical education mode combined with problem-based learning (PBL) to conduct the teaching of standardized residency training. We have always integrated relevant knowledge with "the alteration of pathophysiology" as the core, and standardized training teaching ideas with cases as the main line. A patient case bank has been set up based on the concept of integrated medical education, PBL training as the center, and the pathophysiological changes during anesthesia operation as the main line, which effectively achieves the goal of integrating theoretical knowledge with clinical practice. It is not only train high-quality anesthesiologists, but also improve their ability to find, analyze, and solve problems, so that the trainees form a habit of self-learning and continuous learning through the training.
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Purpose@#Gastric cancer (GC) is the second most lethal cancer globally and is associated with poor prognosis. Fatty acid-binding proteins (FABPs) can regulate biological properties of carcinoma cells. FABP5 is overexpressed in many types of cancers; however, the role and mechanisms of action of FABP5 in GC remain unclear. In this study, we aimed to evaluate the clinical and biological functions of FABP5 in GC. @*Materials and Methods@#We assessed FABP5 expression using immunohistochemical analysis in 79 patients with GC and evaluated its biological functions following in vitro and in vivo ectopic expression. FABP5 targets relevant to GC progression were determined using RNA sequencing (RNA-seq). @*Results@#Elevated FABP5 expression was closely associated with poor outcomes, and ectopic expression of FABP5 promoted proliferation, invasion, migration, and carcinogenicity of GC cells, thus suggesting its potential tumor-promoting role in GC. Additionally, RNA-seq analysis indicated that FABP5 activates immune-related pathways, including cytokinecytokine receptor interaction pathways, interleukin-17 signaling, and tumor necrosis factor signaling, suggesting an important rationale for the possible development of therapies that combine FABP5-targeted drugs with immunotherapeutics. @*Conclusions@#These findings highlight the biological mechanisms and clinical implications of FABP5 in GC and suggest its potential as an adverse prognostic factor and/or therapeutic target.
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Objective:To explore the application of expanded polytetrafluoroethylene (ePTFE) as the main support combined with a small amount of ear cartilage in rhinoplasty.Methods:Through a nasal opening approach, the ePTFE was used as a support implant for the nasal dorsum and columella, and unilateral concha cartilage was used as a nasal tip modification graft.Results:This method was applied in 56 cases of rhinoplasty (36 cases of initial nose, 20 cases of silicone augmentation rhinoplasty). The wounds of 55 patients healed at one stage without complications, with satisfactory results (average follow-up of 6 months). In one case, nasal mucosa was damaged early after surgery, and the ePTFE was partially exposed, which healed after debridement and suture.Conclusions:For most primary rhinoplasty and simple repair of the nose, using ePTFE as the main support combined with a small amount of ear cartilage, has the advantages of fewer materials, rapid surgery, mild trauma, and stable postoperative results.
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Objective:To observe and evaluate the safety and efficacy of anti-vascular endothelial growth factor (VEGF) in the treatment of eyes with macular edema (ME) secondary to branch retinal vein occlusion (BRVO) in Lhasa, Tibet.Methods:A retrospective case series. From September 2018 to January 2022, a total of 41 patients (41 eyes) with BRVO-ME, who were diagnosed in Department of Ophthalmology of Tibet Autonomous Region People’s Hospital, were included in this study. There were 21 eyes in 21 males and 20 eyes in 20 females. The median age was 53 (31,75) years. There were 24 patients with hypertension (58.8%, 24/41). Best corrected visual acuity (BCVA), ocular pressure, fundus color photography and optical coherence tomography (OCT) were performed in all eyes. The BCVA was performed using the international standard logarithmic visual acuity chart, which was converted into logarithm of the minimum angle of resolution (logMAR) BCVA for record. The foveal macular thickness (CMT) was measured by OCT. All eyes were treated with intravitreous injection of anti-VEGF drugs, once a month, among which 23 eyes (56.1%, 23/41) received intravitreous injection of ranibizumab (IVR), and 18 eyes (43.9%, 18/41) received intravitreous injection of conbercept (IVC), and were grouped accordingly. There was no significant difference in age ( Z=-0.447), gender composition ( Z=-0.485), logMAR BCVA ( t=-1.591), intraocular pressure ( t=-0.167) and CMT ( t=-1.290) between two groups ( P>0.05). During the follow-up, the same devices and methods were used at baseline to perform relevant examinations, and the changes of BCVA, intraocular pressure, CMT and new cardiovascular and cerebrovascular events were compared between baseline and the last follow-up. logMAR BCVA, intraocular pressure and CMT were compared between baseline and last follow-up using Student t test. The comparison of injection times and follow-up time between IVR group and IVC group was conducted by Mann-Whitney U test. Results:At baseline, logMAR BCVA, intraocular pressure, and CMT were 0.852±0.431, (12.5±2.5) mm Hg (1 mm Hg= 0.133 kPa), and (578.1±191.1) μm, respectively. At the last follow-up, the number of anti-VEGF drug treatments was (2.7±1.2) times; logMAR BCVA and CMT were 0.488±0.366 and (207.4±108.7) μm, respectively, with CMT > 250 μm in 14 eyes (34.1%, 14/41). Compared with baseline, BCVA ( t=4.129) and CMT ( t=-0.713) were significantly improved, with statistical significance ( P<0.001). The injection times of IVR group and IVC group were (2.6±0.9) and (3.0±1.5) times, respectively. There were no significant differences in the number of injection times ( t=-1.275), logMAR BCVA ( t=-0.492), intraocular pressure ( t=0.351) and CMT ( t=-1.783) between the two groups ( P>0.05). No new hypertension, cardiovascular and cerebrovascular events occurred in all patients during follow-up. At the last follow-up, there were no eye complications related to treatment modalities and drugs. Conclusion:Short-term anti-VEGF treatment can improve the visual acuity of BRVO secondary ME patients and alleviate ME in Lhasa, Tibet. The safety and efficacy of ranibizumab and conbercept were similar.
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ObjectiveTo observe the therapeutic effect and underlying mechanism of Linggui Zhugantang on lipopolysaccharide （LPS）-induced acute lung injury （ALI） in mice. MethodSeventy-two 7-week-old C57BL/6 mice of SPF grade were randomly divided into a normal group， a model group， a dexamethasone group （5 mg·kg-1）， and high-， medium-， and low-dose Linggui Zhugantang groups （9.36， 4.68，2.34 g·kg-1）， with 12 mice in each group. Except for the normal group， the remaining groups underwent intranasal instillation of LPS （50 μg per mouse） for the induction of the ALI model. The treatment groups received oral administration for 7 days prior to modeling. After 12 hours of modeling， mouse lung tissues were taken to measure the wet/dry weight ratio （W/D）. Hematoxylin-eosin （HE） staining was performed to observe the pathological morphological changes in lung tissues. Bronchoalveolar lavage fluid （BALF） was collected for total cell count using a cell counter， and Wright-Giemsa staining was conducted to classify and quantify inflammatory cells （neutrophils and macrophages）. Enzyme-linked immunosorbent assay （ELISA） was used to determine the expression levels of inflammatory cytokines tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in BALF. Western blot analysis was performed to detect the expression of nuclear factor-κB （NF-κB） inhibitory protein α （IκBα）， NF-κB p65， and their phosphorylated proteins， and the ratio of phosphorylated protein/total protein was calculated. ResultCompared with the normal group， the model group exhibited severe lung tissue damage， disrupted alveolar structure， thickened alveolar walls， infiltration of extensive inflammatory cells and red blood cells， and significantly aggravated lung edema （P<0.01）. The total cell count， inflammatory cell count， expression levels of IL-6， and TNF-α in BALF， as well as NF-κB p65 and phosphorylated IκBα in lung tissues， were significantly upregulated in the model group （P<0.01）. Compared with the model group， high-， medium-， and low-dose Linggui Zhugantang groups， as well as the dexamethasone group， showed improved lung injury， reduced lung edema （P<0.01）， downregulated total cell count， neutrophil count， expression levels of IL-6 and TNF-α in BALF， and NF-κB p65 and phosphorylated IκBα in lung tissues （P<0.01）， and reduced macrophage count （P<0.05）. ConclusionLinggui Zhugantang has anti-inflammatory and protective effects on LPS-induced ALI in mice， effectively reducing inflammation and promoting diuresis and edema elimination. Its mechanism may be related to the inhibition of NF-κB pathway activation.
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ObjectiveTo investigate the mechanism of Renshentang， recorded in Synopsis of Golden Chamber， in the treatment of atherosclerosis （AS） based on the autophagic effect of transient receptor potential vanilloid subtype 1 （TRPV1） on arterial smooth muscle. MethodFourteen SPF-grade 8-week-old male C57BL/6J mice were assigned to the normal group and 70 8-week-old apolipoprotein E knockout （ApoE-/-） mice were assigned to the experimental group. The AS model was induced by a high-fat diet in the mice in the experimental group for eight weeks. The model mice were then randomly divided into model group， low-， medium-， and high-dose Renshentang groups （2.715， 5.43， and 10.68 g·kg-1·d-1）， and simvastatin group （0.02 g·kg-1·d-1）. Drug treatment lasted eight weeks. Serum was taken and serum total cholesterol （CHO）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， and high-density lipoprotein cholesterol （HDL-C） levels were measured by assay kits to observe the changes in lipid levels in mice. The aorta was stained with hematoxylin-eosin （HE） to observe the overall pathology of the aortic root and oil red O staining was used to detect the lipid deposition in the aortic plaque and calculate the percentage of the aortic root area to the lumen area. The protein expression of TRPV1， adenylate-activated protein kinase （AMPK）， phosphorylated AMPK （p-AMPK）， autophagy effector-1 （Beclin-1）， and microtubule-associated protein 1 light chain 3 （LC3Ⅱ） in mouse aortic tissues was determined by Western blot. ResultCompared with the normal group， the model group showed increased serum CHO， TG， and LDL-C levels， decreased HDL-C， and increased aortic root plaque area （P<0.01）. Compared with the model group， the Renshentang groups showed decreased levels of CHO， TG， and LDL-C in serum （P<0.05， P<0.01）， especially in the low- and medium-dose Renshentang groups （P<0.01）. Compared with the normal group， the simvastatin group and the Renshentang groups showed reduced aortic root plaque area （P<0.05）， especially in the high-dose Renshentang group （P<0.01）. Compared with the normal group， the model group showed decreased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（P<0.05， P<0.01）. Compared with the model group， the medium- and high-dose Renshentang groups showed increased relative expression levels of TRPV1， p-AMPK/AMPK， Beclin-1， and LC3Ⅱ/LC3Ⅰ（P<0.05，P<0.01）. ConclusionThe anti-AS effect of Renshentang recorded in Synopsis of Golden Chamber may be achieved by up-regulating TRPV1 expression to restore the level of autophagy mediated by AMPK.
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Objective:To evaluate and compare the clinical efficacy and safety of three different medicated eye patches in the treatment of Demodex blepharitis. Methods:A multicenter, randomized, double-blind, parallel-controlled clinical trial was conducted.A total of 140 patients (280 eyes) with Demodex blepharitis were recruited in Shanghai Jing'an District Shibei Hospital, Xi'an Fourth Hospital and Kunming First People's Hospital from July 2021 to December 2022.The affected eyes were randomly divided into tea tree oil group, okra oil group, basal fluid control group and metronidazole group by the random number table method.Eye patches containing 20% tea tree oil, 1% okra oil, prepared base solution and 2% metronidazole were applied to the eyes for 28 days by the double-blind method.The count of Demodex was evaluated before treatment and on days 14 and 28 of treatment.Ocular surface symptoms were scored according to Ocular Surface Disease Index (OSDI). The degree of congestion at the eyelid margin and cylindrical dandruff at the root of eyelashes were scored under a slit lamp microscope.The effective rate was calculated according to the comprehensive scores above, and the adverse reactions of the subjects were observed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Shanghai Jing'an District Shibei Hospital (No.YL-20200320-05). All the subjects were informed of the significance, purpose and method of the study.Written informed consent was obtained from each subject before any medical examination. Results:All subjects completed the treatment and follow-up, and the loss to follow-up rate was 0%.After 14 and 28 days of treatment, the Demodex count was significantly decreased in all groups compared with before treatment (all at P<0.05). After 28 days of treatment, the number of Demodex in tea tree oil group, okra oil group and metronidazole group were significantly lower than that in basal fluid control group, with statistically significant differences (all at P<0.05). The OSDI score, palpebral margin congestion score and cylindrical dandruff score on 14 and 28 days after treatment in tea tree oil group, okra oil group and metronidazole group were significantly lower than before treatment, showing statistically significant differences (all at P<0.05). After 28 days of treatment, the effective rates of tea tree oil group, okra oil group and metronidazole group were 71.4%, 71.4% and 62.9%, respectively, which were significantly higher than 25.7% in basal solution control group.No serious local or systemic adverse reactions were found during the treatment and follow-up. Conclusions:Eye patches containing tea tree oil, okra oil and metronidazole have significant effects on the treatment of Demodex blepharitis, which can improve the biological environment of the palpebral margin and eliminate the inflammation related to blepharitis.
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Atherosclerosis is a chronic inflammatory disease caused by lipid accumulation and vascular endothelial dysfunction. The Toll-like receptor （TLR）/nuclear transcription factor-κB （NF-κB） pathway and the NOD-like receptor protein 3 （NLRP3） inflammasome pathway play a proinflammatory role， while the transient receptor potential vanilloid subtype 1 （TRPV1） and transient receptor potential ankyrin 1 （TRPA1） play a protective role in the occurrence of atherosclerosis. We reviewed the relevant studies published in the last 10 years. The results showed that activation of TRPV1/TRPA1 could activate endothelial-type nitric oxide synthase （eNOS） and inhibit the generation of reactive oxygen species （ROS） and cholesterol crystal （CC） to modulate the TLR/NF-κB and NLRP3 inflammasome pathways， thereby inhibiting TLR/NLRP3-mediated inflammatory response. A variety of compound prescriptions and active components of Chinese medicinal materials can activate TRPV1/TRPA1 or its downstream pathway to regulate the TLR/NLRP3 pathway in atherosclerosis. This paper introduces the mechanisms of compound prescriptions and active components of Chinese medicinal materials in regulating the TLR/NLRP3 pathway via TRPV1/TRPA1 in atherosclerosis. This review provides new ideas for the research on the interactions between Chinese medicines in the treatment of atherosclerosis and provides a new strategy for the clinical treatment of atherosclerosis with traditional Chinese medicine.
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Objective To explore the efficacy, safety, and factors that might influence the efficacy of antiPD-1 antibody-based therapy in advanced hepatocellular carcinoma in the real world. Methods The clinical features, efficacy, and safety in patients with advanced hepatocellular carcinoma who received anti-PD-1 antibody-based therapy were retrospectively analyzed. The survival status was followed-up. Results The objective response and the disease control rate were 21.8% and 76.4%, respectively. The overall incidence of adverse events during treatment was 81.8%, of which the incidence of grade 3/4 adverse events was 14.5%. The incidence of immune-related adverse events was 58.2% and the incidence of grade 3/4 immune-related adverse events was 3.6%, and no treatment-related death was observed. The median PFS of the 55 patients was 5.0 (95%CI: 3.9-6.1) months, and the median OS was 11.4 (95%CI: 6.5-16.3) months. Univariate and multivariate analyses showed that liver function Child-Pugh scores and performance status ECOG score were the influencing factors of the objective response rate and survival. Conclusion In the real world anti-PD-1 antibody-based therapy is safe and effective in patients with advanced hepatocellular carcinoma, in which the performance status ECOG score and liver function Child-Pugh score before treatment are independent prognostic factors influencing survival.
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Objective To investigate the effect of GHET1 on the biological behavior of gallbladder cancer cells and the regulatory mechanism of GHET1 on miR-27b. Methods The expression of GHET1 and miR-27b in 50 samples of gallbladder cancer was detected by real-time quantitative PCR. The si-NC vector, si-GHET1 vector, miR-27b inhibitor, and si-GHET1 vector+miR-27b inhibitor were transfected into SGC-996 cells and set as the control group, GHET1 interference group, miR-27b interference group, and GHET1+miR-27b interference group. Cell proliferation, apoptosis, and metastasis in each group were detected by MTT, flow cytometry, and Transwell assays. The regulatory effect of GHET1 on miR-27b was validated by luciferase reporter gene assay. Results GHET1 expression was higher in cancer tissues than that in paracancerous ones. miR-27b expression was lower in cancer tissues than that in paracancerous tissues. GHET1 was negatively correlated with miR-27b expression (P<0.05), and GHET1 expression was associated with TNM staging and lymph node metastasis (P<0.05). High GHET1 expression was associated with poor prognosis of patients with gallbladder cancer (P<0.05). Compared with the control group, the GHET1 interference group showed decreased cell-proliferation ability, increased apoptosis rate, and reduced number of cell metastasis. The miR-27b interference group showed increased cell-proliferation ability, decreased apoptosis rate, and increased number of cell metastasis (P<0.05). Compared with the GHET1 interference group, the GHET1+miR-27b interference group showed increased cell-proliferation ability, decreased apoptosis rate, and increased number of cell metastasis (P<0.05). GHET1 inhibited miR-27b expression by acting as a sponge of miR-27b. Conclusion GHET1 promotes the proliferation and metastasis and inhibits the apoptosis of gallbladder cancer cells by targeting miR-27b, suggesting that GHET1/miR-27b axis plays a role in gallbladder cancer progression.
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Zhishi Xiebai Guizhitang is a classical prescription for the treatment of chest impediment with the method of warming Yang. It is included in the Catalogue of Ancient Classical Prescriptions issued by the National Administration of Traditional Chinese Medicine （First Batch）， with the effect of activating Yang， dissipating mass， moving Qi and resolving phlegm. Its main symptoms include chest fullness and pain， or even chest pain radiating to the back， wheezing， coughing， shortness of breath， and Qi reversal from the hypochondrium. In modern traditional Chinese medicine， Zhishi Xiebai Guizhitang is clinically used in the treatment of cardiovascular system， digestive system， respiratory system and other diseases， among which coronary heart disease， unstable angina pectoris， myocardial infarction， sinus bradycardia and other cardiovascular diseases have particularly significant effects. This paper reviewed the pharmacological studies of Zhishi Xiebai Guizhitang in the past 10 years. The results showed that each single medicine and the whole prescription alleviated the above cardiovascular diseases to a certain extent， with the pharmacological effects of improving intravascular environment， myocardial ischemia， myocardial ischemia-reperfusion injury， and myocardial hypoxia， anti-inflammation， plaque stabilisation， etc.， and the pharmacological mechanism involved the regulation of relevant active substances in vivo as well as related signaling pathways and ion channels， mainly including thromboxane B2 （TXB2）， prostacyclin I2（PGI2） and phosphatidylinositol 3-kinases/protein kinase B/endothelial nitric oxide synthase （PI3K/Akt/eNOS） signaling pathways， and ATP-sensitive potassium channels. In addition， the relationship between the pharmacological effects of some single medicines and transient receptor potential ankyrin 1 （TRPA1） has been reported that TRPA1 is a key to understanding the mechanism of Zhishi Xiebai Guizhitang in treating cardiovascular diseases， which is worth of further study.
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This study aimed to compare the efficacy of Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke with network Meta-analysis. CNKI, Wanfang, VIP, SinoMed, PubMed, EMbase, and Cochrane Library were searched from database inception to October 2022 for randomized controlled trial(RCT) on 11 Qi-benefiting and blood-activating Chinese patent medicines in the treatment of ischemic stroke. The risk of bias plot was made by RevMan 5.3, and network Meta-analysis and efficacy ranking were performed by Stata 17. Ninety-two RCTs were included, involving 10 608 patients. According to the network Meta-analysis, in terms of the clinical total effective rate, surface under the cumulative ranking curve(SUCRA) as followed: Qilong Capsules+conventional western medicine>Zhishe Tongluo Capsules+conventional western medicine>Longshengzhi Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Tongsaimai Tablets+conventional western medicine>Naoan Capsules+conventional western medicine>Naoluotong Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine=Tongxinluo Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine. In terms of the improvement in National Institute of Health stroke scale(NIHSS) score, SUCRA as followed: Longshengzhi Capsules+conventional western medicine>Naomaitai Capsules+conventional western medicine>Naoxintong Capsules+conventional western medicine>Dengzhan Shengmai Capsules+conventional western medicine>Xiaoshuan Changrong Capsules+conventional western medicine>Naoluotong Capsules+conventional western medi-cine>Tongxinluo Capsules+conventional western medicine>Naoan Capsules+conventional western medicine>Qilong Capsules+conventional western medicine. In terms of safety, the overall adverse reactions/events of Qi-benefiting and blood-activating Chinese patent medicines + conventional western medicine were less than those of the control group. Since Qilong Capsules+conventional western medicine and Zhishe Tongluo Capsules+conventional western medicine were preferred to improve the clinical total effective rate. In the aspect of improving NIHSS score, Longshengzhi Capsules+conventional western medicine and Naomaitai Capsules+conventional western medicine were first options. Due to the lack of direct comparisons between drugs, the overall quality of RCT was not high, so more studies are needed to verify the strength of the evidence.
Subject(s)
Humans , Capsules , Ischemic Stroke , Medicine , Network Meta-Analysis , QiABSTRACT
Objective: To explore the predictive values of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score on the death risk of severe burn patients. Methods: A retrospective case series study was conducted. From February 2018 to November 2019, 260 severe burn patients who met the inclusion criteria were admitted to the Department of Burns of the First Affiliated Hospital of Nanchang University, including 158 males and 102 females, aged 36 (3, 53) years. According to the final outcome, the patients were divided into survival group (n=229) and death group (n=31). Data of patients were compared and statistically analyzed with chi-square test or Mann-Whitney U test between the two groups, including the gender, age, cause of burn, site of burn, total burn area, depth of burn, combined inhalation injury, and combined underlying diseases on admission, and the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score calculated based on part of the aforementioned data. The Kendall tau-b coefficient method was used to analyze the consistency of the above-mentioned three scores in 260 severe burn patients. The receiver operating characteristic (ROC) curves of the above-mentioned three scores predicting the death risk of 260 severe burn patients were drawn, and the area under the curve (AUC), the optimal threshold, and the sensitivity and specificity under the optimal threshold were calculated. The quality of AUC of the above-mentioned three scores was compared by Delong test. Results: The gender, site of burn, and depth of burn of patients between the two groups were all similar (P>0.05). The age, total burn area, proportion of flame burn, proportion of combined inhalation injury, and proportion of combined underlying diseases of patients in death group were significantly higher than those in survival group (with Z values of 5.53 and 17.78, respectively, χ2 values of 16.23, 15.89, and 17.78, respectively, P<0.01); the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score of patients in death group were 142 (115, 155), 7 (5, 7), 2 (2, 3), all significantly higher than 64 (27, 87), 1 (0, 3), 0 (0, 1) in survival group (with Z values of 7.91, 7.64, and 7.61, respectively, P<0.01). In 260 severe burn patients, the results between the modified Baux score and Ryan score, modified Baux score and Belgian Outcome in Burn Injury score, Ryan score and Belgian Outcome in Burn Injury score were significantly consistent (with Kendall tau-b coefficients of 0.75, 0.71, and 0.86, respectively, P<0.01). The AUCs of ROC curves of the modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score for predicting the death risk of 260 severe burn patients were 0.92, 0.89, and 0.85, respectively (with 95% confidence intervals of 0.86-0.98, 0.83-0.95, and 0.78-0.93, respectively, P<0.01); the optimal thresholds were 106.5, 4.5, and 1.5 points, respectively; the sensitivity under the optimal threshold were 88.5%, 76.9%, and 73.1%, respectively, and the specificity under the optimal threshold were 88.5%, 87.2%, and 86.3%, respectively. The modified Baux score was similar to Belgian Outcome in Burn Injury score in the AUC quality (z=1.25, P>0.05), which were both significantly better than the AUC quality of Ryan score (with z values of 2.35 and 2.11, respectively, P<0.05). Conclusions: The modified Baux score, Belgian Outcome in Burn Injury score, and Ryan score have good ability in predicting the death risk of severe burn patients. From the perspective of clinical practice, the modified Baux score is more suitable as a predictive tool for the prognosis of severe burn patients.
Subject(s)
Adult , Female , Humans , Male , Burns , Hospitalization , Prognosis , ROC Curve , Retrospective StudiesABSTRACT
OBJECTIVES@#To study the correlation between CT imaging features of acceleration and deceleration brain injury and injury degree.@*METHODS@#A total of 299 cases with acceleration and deceleration brain injury were collected and divided into acceleration brain injury group and deceleration brain injury group according to the injury mechanism. Subarachnoid hemorrhage (SAH) and Glasgow coma scale (GCS), combined with skull fracture, epidural hematoma (EDH), subdural hematoma (SDH) and brain contusion on the same and opposite sides of the stress point were selected as the screening indexes. χ2 test was used for primary screening, and binary logistic regression analysis was used for secondary screening. The indexes with the strongest correlation in acceleration and deceleration injury mechanism were selected.@*RESULTS@#χ2 test showed that skull fracture and EDH on the same side of the stress point; EDH, SDH and brain contusion on the opposite of the stress point; SAH, GCS were correlated with acceleration and deceleration injury (P<0.05). According to binary logistic regression analysis, the odds ratio (OR) of EDH on the same side of the stress point was 2.697, the OR of brain contusion on the opposite of the stress point was 0.043 and the OR of GCS was 0.238, suggesting there was statistically significant (P<0.05).@*CONCLUSIONS@#EDH on the same side of the stress point, brain contusion on the opposite of the stress point and GCS can be used as key indicators to distinguish acceleration and deceleration injury mechanism. In addition, skull fracture on the same side of the stress point, EDH and SDH on the opposite of the stress point and SAH were relatively weak indicators in distinguishing acceleration and deceleration injury mechanism.