Conduction system pacing upgrade versus biventricular pacing on pacemaker-induced cardiomyopathy: a retrospective observational study.

Objective: The feasibility of the conduction system pacing (CSP) upgrade as an alternative modality to the traditional biventricular pacing (BiVP) upgrade in patients with pacemaker-induced cardiomyopathy (PICM) remains uncertain. This study sought to compare two modalities of CSP (His bundle pacing (HBP) and left bundle branch pacing (LBBP)) with BiVP and no upgrades in patients with pacing-induced cardiomyopathy. Methods: This retrospective analysis comprised consecutive patients who underwent either BiVP or CSP upgrade for PICM at the cardiac department from 2017 to 2021. Patients with a follow-up period exceeding 12 months were considered for the final analysis. Results: The final group of patients who underwent upgrades included 48 individuals: 11 with BiVP upgrades, 24 with HBP upgrades, and 13 with LBBP upgrades. Compared to the baseline data, there were significant improvements in cardiac performance at the last follow-up. After the upgrade, the QRS duration (127.81 ± 31.89 vs 177.08 ± 34.35 ms, p < 0.001), NYHA class (2.28 ± 0.70 vs 3.04 ± 0.54, p < 0.05), left ventricular end-diastolic diameter (LVEDD) (54.08 ± 4.80 vs 57.50 ± 4.85 mm, p < 0.05), and left ventricular ejection fraction (LVEF) (44.46% ± 6.39% vs 33.15% ± 5.25%, p < 0.001) were improved. There was a noticeable improvement in LVEF in the CSP group (32.15% ± 3.22% vs 44.95% ± 3.99% (p < 0.001)) and the BiVP group (33.90% ± 3.09% vs 40.83% ± 2.99% (p < 0.001)). The changes in QRS duration were more evident in CSP than in BiVP (56.65 ± 11.71 vs 34.67 ± 13.32, p < 0.001). Similarly, the changes in LVEF (12.8 ± 3.66 vs 6.93 ± 3.04, p < 0.001) and LVEDD (5.80 ± 1.71 vs 3.16 ± 1.35, p < 0.001) were greater in CSP than in BiVP. The changes in LVEDD (p = 0.549) and LVEF (p = 0.570) were similar in the LBBP and HBP groups. The threshold in LBBP was also lower than that in HBP (1.01 ± 0.43 vs 1.33 ± 0.32 V, p = 0.019). Conclusion: The improvement of clinical outcomes in CSP was more significant than in BiVP. CSP may be an alternative therapy to CRT for patients with PICM. LBBP would be a better choice than HBP due to its lower thresholds.

End-tidal Carbon Dioxide Trajectory-based Prognostication of Out-of-hospital Cardiac Arrest.

Background: During cardiopulmonary resuscitation (CPR), end-tidal carbon dioxide (EtCO2) is primarily determined by pulmonary blood flow, thereby reflecting the blood flow generated by CPR. We aimed to develop an EtCO2 trajectory-based prediction model for prognostication at specific time points during CPR in patients with out-of-hospital cardiac arrest (OHCA). Methods: We screened patients receiving CPR between 2015-2021 from a prospectively collected database of a tertiary-care medical center. The primary outcome was survival to hospital discharge. We used group-based trajectory modeling to identify the EtCO2 trajectories. Multivariable logistic regression analysis was used for model development and internally validated using bootstrapping. We assessed performance of the model using the area under the receiver operating characteristic curve (AUC). Results: The primary analysis included 542 patients with a median age of 68.0 years. Three distinct EtCO2 trajectories were identified in patients resuscitated for 20 minutes (min): low (average EtCO2 10.0 millimeters of mercury [mm Hg]; intermediate (average EtCO2 26.5 mm Hg); and high (average EtCO2: 51.5 mm Hg). Twenty-min EtCO2 trajectory was fitted as an ordinal variable (low, intermediate, and high) and positively associated with survival (odds ratio 2.25, 95% confidence interval [CI] 1.07-4.74). When the 20-min EtCO2 trajectory was combined with other variables, including arrest location and arrest rhythms, the AUC of the 20-min prediction model for survival was 0.89 (95% CI 0.86-0.92). All predictors in the 20-min model remained statistically significant after bootstrapping. Conclusion: Time-specific EtCO2 trajectory was a significant predictor of OHCA outcomes, which could be combined with other baseline variables for intra-arrest prognostication. For this purpose, the 20-min survival model achieved excellent discriminative performance in predicting survival to hospital discharge.

Development and External Validation of Clinical Features-based Machine Learning Models for Predicting COVID-19 in the Emergency Department.

Introduction: Timely diagnosis of patients affected by an emerging infectious disease plays a crucial role in treating patients and avoiding disease spread. In prior research, we developed an approach by using machine learning (ML) algorithms to predict serious acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection based on clinical features of patients visiting an emergency department (ED) during the early coronavirus 2019 (COVID-19) pandemic. In this study, we aimed to externally validate this approach within a distinct ED population. Methods: To create our training/validation cohort (model development) we collected data retrospectively from suspected COVID-19 patients at a US ED from February 23-May 12, 2020. Another dataset was collected as an external validation (testing) cohort from an ED in another country from May 12-June 15, 2021. Clinical features including patient demographics and triage information were used to train and test the models. The primary outcome was the confirmed diagnosis of COVID-19, defined as a positive reverse transcription polymerase chain reaction test result for SARS-CoV-2. We employed three different ML algorithms, including gradient boosting, random forest, and extra trees classifiers, to construct the predictive model. The predictive performances were evaluated with the area under the receiver operating characteristic curve (AUC) in the testing cohort. Results: In total, 580 and 946 ED patients were included in the training and testing cohorts, respectively. Of them, 98 (16.9%) and 180 (19.0%) were diagnosed with COVID-19. All the constructed ML models showed acceptable discrimination, as indicated by the AUC. Among them, random forest (0.785, 95% confidence interval [CI] 0.747-0.822) performed better than gradient boosting (0.774, 95% CI 0.739-0.811) and extra trees classifier (0.72, 95% CI 0.677-0.762). There was no significant difference between the constructed models. Conclusion: Our study validates the use of ML for predicting COVID-19 in the ED and demonstrates its potential for predicting emerging infectious diseases based on models built by clinical features with temporal and spatial heterogeneity. This approach holds promise for scenarios where effective diagnostic tools for an emerging infectious disease may be lacking in the future.

Development of a prediction model for emergency medical service witnessed traumatic out-of-hospital cardiac arrest: A multicenter cohort study.

BACKGROUND/PURPOSE: To develop a prediction model for emergency medical technicians (EMTs) to identify trauma patients at high risk of deterioration to emergency medical service (EMS)-witnessed traumatic cardiac arrest (TCA) on the scene or en route. METHODS: We developed a prediction model using the classical cross-validation method from the Pan-Asia Trauma Outcomes Study (PATOS) database from 1 January 2015 to 31 December 2020. Eligible patients aged ≥18 years were transported to the hospital by the EMS. The primary outcome (EMS-witnessed TCA) was defined based on changes in vital signs measured on the scene or en route. We included variables that were immediately measurable as potential predictors when EMTs arrived. An integer point value system was built using multivariable logistic regression. The area under the receiver operating characteristic (AUROC) curve and Hosmer-Lemeshow (HL) test were used to examine discrimination and calibration in the derivation and validation cohorts. RESULTS: In total, 74,844 patients were eligible for database review. The model comprised five prehospital predictors: age <40 years, systolic blood pressure <100 mmHg, respiration rate >20/minute, pulse oximetry <94%, and levels of consciousness to pain or unresponsiveness. The AUROC in the derivation and validation cohorts was 0.767 and 0.782, respectively. The HL test revealed good calibration of the model (p = 0.906). CONCLUSION: We established a prediction model using variables from the PATOS database and measured them immediately after EMS personnel arrived to predict EMS-witnessed TCA. The model allows prehospital medical personnel to focus on high-risk patients and promptly administer optimal treatment.

Effect of Yiqi Tongmai Formula in Intervening in Liver Inflammation and Lipidosis in ApoE-∕- Mice Based on NF-κB/NLRP3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Yiqi Tongxin formula （YQTM） on liver inflammation in apolipoprotein E-∕- （ApoE-∕-） mice by regulating the nuclear transcription factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway. MethodForty ApoE-∕- mice were randomly divided into a model group， an atorvastatin group （positive drug group）， and low-， medium-， and high-dose YQTM groups （0.39， 0.78， 1.56 g·kg-1）. Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks， oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin （HE） staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in mouse serum， as well as total cholesterol （TC） and triglyceride （TG） in the liver. Interleukin-1β （IL-1β） and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB， NF-κB inhibitory protein （IκB）， IκB kinase β （IKKβ）， phosphorylated NF-κB （p-NF-κB）， phosphorylated IκB （p-IκB）， phosphorylated IKK β （p-IKKβ）， NLRP3， and Caspase-1 in the livers of mice. ResultCompared with the blank group， the model group showed severe aortic lipidosis， and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles（P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly elevated in the mice（P<0.01）. TG and TC levels were elevated in the liver（P<0.01）. The levels of IL-1β and IL-18 in liver tissue， as well as the protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly elevated（P<0.01）. Compared with the model group， the aortic arch plaques of mice in each YQTM group were attenuated， and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated（P<0.05，P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly reduced（P<0.05，P<0.01）. TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue， as well as protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly reduced（P<0.05，P<0.01）. ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.

Lycium barbarian seed oil activates Nrf2/ARE pathway to reduce oxidative damage in testis of subacute aging rats / 中国药理学通报

Aim To explore the effects of Lycium berry seed oil on Nrf2/ARE pathway and oxidative damage in testis of subacute aging rats. Methods Fifty out of 60 male SD rats, aged 8 weeks, were subcutaneously injected with 125 mg • kg"D-galactosidase in the neck for 8 weeks to establish a subacute senescent rat model. The presence of senescent cells was observed using P-galactosidase ((3-gal), while testicular morphology was examined using HE staining. Serum levels of testosterone (testosterone, T), follicle-stimulating hormone ( follicle stimulating hormone, FSH ) , luteinizing hormone ( luteinizing hormone, LH ) , superoxide dis-mutase ( superoxide dismutase, SOD ) , glutathione ( glutathione, GSH) and malondialdehyde ( malondial-dehyde, MDA) were measured through ELISA, and the expressions of factors related to aging, oxidative damage, and the Nrf2/ARE pathway were assessed via immunohistochemical analysis and Western blotting. Results After successfully identifying the model, the morphology of the testis was improved and the intervention of Lycium seed oil led to a down-regulation in the expression of [3-gal and -yH2AX. The serum levels of SOD, GSH, T, and FSH increased while MDA and LH decreased (P 0. 05) . Additionally, there was an up-regulated expression of Nrf2, GCLC, NQOl, and SOD2 proteins in testicular tissue ( P 0. 05 ) and nuclear expression of Nrf2 in sertoli cells. Conclusion Lycium barbarum seed oil may reduce oxidative damage in testes of subacute senescent rats by activating the Nrf2/ARE signaling pathway.

Effects of proprioceptive training on gait and plantar pressure after anterior cruciate ligament reconstruction: study protocol for a randomized controlled trial.

BACKGROUND: People who have undergone anterior cruciate ligament reconstruction have an increased risk of osteoarthritis. Abnormality of lower limb kinematics will occur after the operation. This may be related to lower limb muscle strength, the co-excitation of hamstrings and quadriceps femoris, and the weakness of proprioception. Proprioceptive training can improve the proprioception of lower limbs and promote the recovery of lower limb kinematics. Our research objective is to observe whether proprioceptive training can improve the proprioception of lower limbs within 3 months after surgery and whether the recovery of proprioception can correct the abnormal lower limb kinematics. The secondary objective is to explore the underlying mechanism of postoperative lower limb gait abnormalities. METHODS/DESIGN: This study is a prospective single-center randomized clinical trial to be conducted in the Sports Medicine and Orthopedics of Zhongda Hospital Southeast University. Forty participants aged 18-50, preparing to undergo anterior cruciate ligament reconstruction, and initial anterior cruciate ligament reconstruction using hamstring tendons as grafts will be randomly assigned to the intervention or comparator group. People in the intervention group will add proprioceptive training three times a week, 20 min each time. The intervention will be conducted on the first day after surgery. The researcher mainly collects the data of joint of sense, gait, and plantar pressure. The assessment will be divided into three stages: after signing the informed consent form (within 2 weeks before surgery), 6 weeks after surgery, and 12 weeks after surgery. DISCUSSION: The main purpose of our study is to explore whether the proprioception of patients after anterior cruciate ligament reconstruction is weakened, whether the lower limb kinematics is abnormal and whether the lower limb kinematics can be corrected through proprioceptive training. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2200065808. Registered on 15 November 2022; Version 1.

Cardiac screening in school children: Combining auscultation and electrocardiography with a crowdsourcing model.

BACKGROUND/PURPOSE: School-based cardiac screening is useful for identifying children and adolescents with a high risk of sudden cardiac death. However, because of challenges associated with cost, distance, and human resources, cardiac screening is not widely implemented, especially in rural areas with limited medical resources. This study aims to establish a cloud-based system suitable for mass cardiac screening of schoolchildren in rural areas with limited medical resources. METHODS: Students from three schools were included. They or their guardians completed a simple questionnaire, administered in paper or electronic form. Heart sounds were recorded using an electronic stethoscope. Twelve-lead electrocardiograms (ECGs) were recorded and digitalized. The signals were transmitted through Bluetooth to a tablet computer and then uploaded to a cloud server over Wi-Fi. Crowdsourced pediatric cardiologists reviewed those data from a web-based platform and provided remote consultation. In cases in which abnormal heart sounds or ECGs were noted, the students were referred to the hospital for further evaluation. RESULTS: A total of 1004 students were enrolled in this study. Of the 138 students referred, 62 were diagnosed as having an abnormal heart condition and most had previously been undiagnosed. The interrater agreeability was high. CONCLUSION: An innovative strategy combining a cloud-based cardiac screening system with remote consultation by crowdsourced experts was established. This system allows pediatric cardiologists to provide consultation and make reliable diagnoses. Combined with crowdsourcing, the system constitutes a viable approach for mass cardiac screening in children and adolescents living in rural areas with insufficient medical resources.

Effect of using G-FAST to recognize emergent large vessel occlusion: A city-wide community experience.

BACKGROUND/PURPOSE: A prehospital bypass strategy was suggested for large vessel occlusion. This study aimed to evaluate the effect of a bypass strategy using the gaze-face-arm-speech-time test (G-FAST) implemented in a metropolitan community. METHODS: Pre-notified patients with positive Cincinnati Prehospital Stroke Scale and symptom onset <3 h from July 2016 to December 2017 (pre-intervention period) and those with positive G-FAST and symptom onset <6 h from July 2019 to December 2020 (intervention period) were included. Patients aged <20 years and those with missing in-hospital data were excluded. The primary outcomes were the rates of receiving endovascular thrombectomy (EVT) and intravenous thrombolysis (IVT). The secondary outcomes were total prehospital time, door-to-computed tomography (CT) time, door-to-needle (DTN) time, and door-to-puncture (DTP) time. RESULTS: We included 802 and 695 pre-notified patients from the pre-intervention and intervention periods, respectively. The characteristics of the patients in the two periods were similar. In the primary outcomes, pre-notified patients during the intervention period showed higher rates of receiving EVT (4.49% vs. 15.25%, p < 0.001) and IVT (15.34% vs. 21.58%, p = 0.002). In the secondary outcomes, pre-notified patients during intervention period had longer total prehospital time (mean 23.38 vs 25.23 min, p < 0.001), longer door-to-CT time (median 10 vs 11 min, p < 0.001), longer DTN time (median 53 vs 54.5 min, p < 0.001) but shorter DTP time (median 141 vs 139.5 min, p < 0.001). CONCLUSION: The prehospital bypass strategy with G-FAST showed benefits for stroke patients.

Effect of anodal or cathodal transcranial direct current stimulation on upper limb function of stroke patients / 中国康复理论与实践

ObjectiveTo observe the clinical efficacy of anodal or cathodal transcranial direct current stimulation (atDCS and ctDCS) on upper limb function of stroke patients with moderate to severe upper extremity impairment. MethodsFrom January to September, 2022, 69 patients in Zhongda Hospital Southeast University were randomly divided into control group (n = 23), atDCS group (n = 23) and ctDCS group (n = 23). All the groups received conventional rehabilitation. Moreover, atDCS group received atDCS over the M1 area of the affected hemisphere, ctDCS group received ctDCS over the M1 area of the unaffected hemisphere, and the control group received placebo stimulation. Before and four weeks after treatment, they were assessed with Fugl-Meyer Assessment-Upper Extremities (FMA-UE), Wolf Motor Function Test (WMFT) and modified Barthel index (MBI). ResultsBefore treatment, there was no significant difference in the scores of FMA-UE, WMFT and MBI among groups (F < 1.165, P > 0.05). After treatment, all the scores improved significantly in all the groups (|t| > 6.412, P < 0.001), and were higher in the atDCS group and ctDCS group than in the control group (P < 0.05), however, no significant difference was found between the atDCS group and ctDCS group (P > 0.05). ConclusionBoth atDCS and ctDCS could improve the upper limb motor function and activities of daily living of stroke patients with moderate to severe upper extremity impairment.

Percutaneous foraminal endoscopy for the treatment of lumbar lateral recess stenosis in elderly / 中国骨伤

OBJECTIVE@#To investigate the clinical efficacy and safety of percutaneous foraminal endoscopy in the treatment of lumbar lateral recess stenosis in elderly.@*METHODS@#The clinical data of 31 elderly patients with lumbar lateral recess stenosis treated by percutaneous foraminal endoscopic decompression from March 2018 to August 2019 were retrospectively analyzed. Including 16 males and 15 females, aged from 65 to 81 years with an average of (71.13±5.20) years, the course of disease ranged from 3 months to 7 years with an average of (14.36±6.52) months. Visual analogue scale (VAS) and Oswestry disability index (ODI) were used to assess clinical symptom and functional status before operation and 1, 6, 12 months after operation. At the final follow-up, the modified Macnab standard was used to evaluate clinical efficacy.@*RESULTS@#All patients were completed the operation successfully. The operation time was from 75 to 120 min with an average of (97.84±11.22 ) min. All 31 patients were followed up from 12 to 28 months with an average of (17.29±5.56) months. Postoperative lumbago-leg pain VAS and ODI were significantly improved at 1, 6, and 12 months(P<0.01). At the final follow-up, according to the modified Macnab standard to evaluate the effect, 23 got excellent results, 5 good, 3 fair. One patient had severe adhesions between peripheral tissues and nerve root, and postoperative sensory abnormalities in the lower extremities were treated conservatively with traditional Chinese medicine and neurotrophic drugs, which recovered at 2 weeks after surgery. No complications such as nerve root injury and infection occurred.@*CONCLUSION@#The intervertebral foraminal endoscopy technique, which is performed under local anesthesia for a short period of operation, ensures adequate decompression while minimizing complications, and is a safe and effective surgical procedure for elderly patients with lumbar lateral recess stenosis.

Dihydrofolate reductase-like protein inactivates hemiaminal pharmacophore for self-resistance in safracin biosynthesis

Dihydrofolate reductase (DHFR), a housekeeping enzyme in primary metabolism, has been extensively studied as a model of acid-base catalysis and a clinic drug target. Herein, we investigated the enzymology of a DHFR-like protein SacH in safracin (SAC) biosynthesis, which reductively inactivates hemiaminal pharmacophore-containing biosynthetic intermediates and antibiotics for self-resistance. Furthermore, based on the crystal structure of SacH-NADPH-SAC-A ternary complexes and mutagenesis, we proposed a catalytic mechanism that is distinct from the previously characterized short-chain dehydrogenases/reductases-mediated inactivation of hemiaminal pharmacophore. These findings expand the functions of DHFR family proteins, reveal that the common reaction can be catalyzed by distinct family of enzymes, and imply the possibility for the discovery of novel antibiotics with hemiaminal pharmacophore.

Preparation of monodisperse microspheres by electrospray and their biomedical applications / 国际生物医学工程杂志

Electrospray technology is a method to prepare microspheres by electrostatic force. Electrospray technology has the advantages of simple operation and mild reaction conditions. The polymer microspheres prepared by electrospray technology have uniform morphology and good monodispersity, which is a new and promising method. In this paper, the devices and principles of electrospray technology, the factors affecting the morphology and particle size of the prepared polymer microspheres by the electrospray process, and the types of polymer solutions commonly used in electrospray technology were described, and the applications of electrospray technology for drug delivery, loaded nanoparticles, cell therapy, and bioactive substance delivery were reviewed. It can be concluded that electrospray technology has a broad application prospect and potential application value.

Research on total time prediction method of MRI examination based on BP neural network / 医疗卫生装备

Objective To propose a total time prediction method of MRI examination based on BP neural network.Methods The clinical data of MRI equipment in some tertiary grade A hospital was mined deeply.Totally 63 examination sites and 26 examination methods were combined into several examination sequences,and the examination sequence vector and total examination time were used as the input and output of BP neural network,respectively,so as to construct a BP neural network model.The BP neural network model established was compared with the ridge regression model and Lasso regression model with the mean absolute error(MAE)as the evaluation index when used for predicting MRI examinations.Results The BP neural network model behaved better than the ridge regression model and Lasso regression model with the predicted value close to the measured value and MAE being 53.14 s.Conclusion The proposed method accurately predicts the total MRI examination time and can assist hospital staff in scheduling patient examinations.[Chinese Medical Equipment Journal,2023,44(10):13-16]

Effects of rhubarb ethanol extract on hemin-induced autophagy and apoptosis of HT22 cells / 中成药

AIM To explore the effects of rhubarb ethanol extract on autophagy and apoptosis of HT22 cells after hemin-induced injury.METHODS The HT22 cells were divided into the blank group,the model group,and the high,medium and low dose rhubarb ethanol extract groups(25,12.5 and 6.25 μg/mL).After the 24 hours corresponding drug intervention,3 hours induction of 40 μmol/L hemin was used for the modeling of cell cerebral hemorrhage injury.Subsequently,the cells had their cell viability detected by CCK-8 method;their leakage rate of lactate dehydrogenase(LDH)detected by kit;their apoptosis rate detected by flow cytometry;and their apoptosis and autophagy related protein expressions of cysteine protease-3(caspase-3),Bcl-2 related X protein(Bax),B cell lymphoma-2(Bcl-2)and microtubule related protein light chain 3(LC3)detected by Western blot.RESULTS Compared with the normal group,the model group displayed decreased cell viability(P<0.01);increased LDH leakage rate,apoptosis rate and the protein expressions of Bax/Bcl-2,caspase-3,Beclin1 and LC3(P<0.01);and decreased protein expression of P62(P<0.01).Compared with the model group,all of the groups intervened with rhubarb ethanol extract showed increased cell viability(P<0.05,P<0.01),decreased LDH leakage rate,apoptosis rate and protein expressions of Bax/Bcl-2,caspase-3,Beclin1 and LC3(P<0.05,P<0.01),in addition to the decreased protein expression of P62 increased(P<0.05,P<0.01)in the high and middle dose rhubarb ethanol extract groups.CONCLUSION The ethanol extract of rhubarb may protect neurons and reduce cell damage through its efficacy in regulating their autophagy and apoptosis.

Recent advance in role of cAMP signaling pathway in axonal regeneration after peripheral nerve injury / 中华神经医学杂志

The recovery of motor and sensory functions after peripheral nerve injury has been an important concern in the medical field, and axonal regeneration and re-innervation of the corresponding target organs is important prerequisites for recovery of motor and sensory functions. Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger that affects the damage repair in human tissues. Protein kinase A (PKA) and exchange protein activated by cAMP (EPAC), downstream factors of cAMP, are closely related to nerve regeneration, and they are involved in and play a key role in axonal regeneration. In this paper, we review the effect of cAMP signaling pathway on myelin debris removal, axon guidance, and growth cone regeneration after peripheral nerve injury.

Protective mechanism of Yinchenzhufu decoction against cholestatic liver injury induced by lithic acid based on network pharmacology / 药学学报

Yinchenzhufu decoction (YCZFD) is a classic formula for treating Yin Huang syndrome, which can improve liver injury caused by cholestasis. However, the mechanism of action of YCZFD still remains unclear. This article used network pharmacology, molecular docking, animal experiments, and molecular biology methods to explore the mechanism of YCZFD in treating liver injury caused by cholestasis. A mouse model of acute cholestasis induced by lithocholic acid was used to investigate the effects of YCZFD on liver injury. The experimental procedures described in this paper were reviewed and approved by the Ethical Committee at the Shanghai University of Traditional Chinese Medicine (approval NO. PZSHUTCM190823002). The results showed that YCZFD could reduce the levels of blood biochemical indicators and improve hepatocyte damage of cholestatic mice. Then, multiple databases were used to predict the corresponding targets of YCZFD active components on cholestatic liver injury. An intersection target protein-protein interaction (PPI) networks based on String database and Cytoscape software was used to demonstrate the possible core targets of YCZFD against cholestatic liver injury. The results indicated that core targets of YCZFD include tumor necrosis factor, interleukin-1β, non-receptor tyrosine kinase Src, interleukin-6, etc. GO (gene ontology) and KEGG (kyoto encyclopedia of genes and genomes) enrichment analysis indicated that YCZFD may regulate the tumor necrosis factor signaling pathway, nuclear factor-κB signaling pathway, bile secretion, and other related factors to ameliorate the cholestatic liver injury. AutoDockTools software was used to perform molecular docking verification on the core targets and components of YCZFD. To verify the results of network pharmacology, UPLC-MS/MS method was used to determine the effect of YCZFD on levels of bile acid profiles in mouse liver tissues. It was found that treatment with YCZFD significantly reduced the content of free bile acids, taurine bound bile acids, and total bile acids in the liver tissues of cholestatic mice. Then, results from real time PCR and Western blot also found that YCZFD can upregulate the expression of hepatic nuclear receptor farnesoid X receptor, metabolizing enzyme (UDP glucuronidase transferase 1a1), and efflux transporters (bile salt export pump, multidrug resistance-associated protein 2, multidrug resistance-associated protein 3, etc) in cholestasis mice, promote bile acid metabolism and excretion, and improve bile acid homeostasis. Moreover, YCZFD can also inhibit pyroptosis and inflammation by regulating NOD-like receptors 3 pathway, thereby inhibiting cholestatic liver injury.

Investigation on the pharmacological mechanisms of Shirebi granules in treating gouty arthritis with damp-heat syndrome based on crosstalk of Wnt/β-catenin signaling / 药学学报

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

Modified Sanpiantang Treats Nitroglycerin-induced Migraine in Rats via p38 MAPK/iNOS Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo decipher the mechanism of modified Sanpiantang in the treatment of nitroglycerin-induced migraine in rats. MethodSeventy-two Wistar rats were randomized into the control， model （nitroglycerin， 10 mg·kg-1）， positive control （rizatriptan， 0.89 mg·kg-1）， and high- （12.96 g·kg-1）， medium- （6.48 g·kg-1）， and low-dose （3.24 g·kg-1） modified Sanpiantang groups. The rat model of migraine was established by intraperitoneal injection of 10 mg·kg-1 nitroglycerin. The behavioral test was carried out to measure the mechanical pain thresholds （MPT） of the periorbital region and hindpaw after successful modeling. The serum levels of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， and interleukin-1β （IL-1β） in rats were determined by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was employed to determine the expression of inducible nitric oxide synthase （iNOS） in the trigeminal nucleus caudalis （TNC）. Western blot was employed to determine the protein levels of iNOS and phospho-p38 mitogen-activated protein kinase （p-p38 MAPK） in the TNC. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to measure the mRNA levels of iNOS， p38 MAPK， and IL-1β in the TNC. ResultCompared with the control group， the model group showed decreased MPT （P<0.01）， elevated serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.01）， and up-regulated expression levels of p38 MAPK， iNOS， and IL-1β in the TNC （P<0.05， P<0.01）. Compared with the model group， modified Sanpiantang increased the MPT （P<0.05）， and the medium-dose group showed the most significant effect （P<0.01）. In addition， modified Sanpiantang down-regulated the mRNA levels of iNOS， p38 MAPK， and IL-1β and the protein levels of p-p38 MAPK and iNOS in the TNC of migraine rats （P<0.05， P<0.01） and lowered the serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.05， P<0.01）. ConclusionModified Sanpiantang may treat migraine by down-regulating the expression of pro-inflammatory factors such as NO， TNF-α， IFN-γ， and IL-1β in the p38 MAPK/iNOS signaling pathway to reduce the neurogenic inflammation.

The expression and significance of protease activated receptor 2 in ovarian epithelial carcinoma / 中华肿瘤杂志

Objective: To investigate the expression and significance of protease activated receptor 2 (PAR2) in ovarian epithelial carcinoma. Methods: PAR2 mRNA expression levels in 410 cases of epithelial ovarian carcinoma and 88 cases of human normal ovary were analyzed from cancer Genome Atlas (TCGA) database and tissue genotypic expression database (GTEx). Immunohistochemical (IHC) staining of PAR2 protein was performed in 149 patients with ovarian cancer who underwent primary surgical treatment at Cancer Hospital of Chinese Academy of Medical Sciences. Then the relationship between mRNA/protein expression of PAR2 and clinicopathological features and prognosis was analyzed. Gene functions and related signaling pathways involved in PAR2 were studied by enrichment analysis. Results: The mRNA expression of PAR2 in epithelial ovarian carcinoma was significantly higher than that in normal ovarian tissue (3.05±0.72 vs. 0.33±0.16, P=0.004). There were 77 cases showing positive and 19 showing strong positive of PAR2 IHC staining among the 149 patients, accounting for 64.4% in total. PAR2 mRNA/protein expression was closely correlated with tumor reduction effect and initial therapeutic effect (P<0.05). Survival analysis showed that the progression free survival time (P=0.033) and overall survival time (P=0.011) in the group with high PAR2 mRNA expression was significantly lower than that in the low PAR2 mRNA group. Multivariate analysis showed tumor reduction effect, initial therapeutic effect were independent prognostic factors on both progression-free survival and overall survival (P<0.05). The progression-free survival (P=0.016) and overall survival (P=0.038) of the PAR2 protein high expression group was significantly lower than that of the low group. Multivariate analysis showed PAR2 expression, initial treatment effect and chemotherapy resistance were independent prognostic factors on both progression-free survival and overall survival (P<0.05). Based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), PAR2 target genes were mainly enriched in function related to intercellular connection, accounting for 40%. Gene enrichment analysis (GSEA) showed that the Wnt/β-catenin signaling pathway (P=0.023), the MAPK signaling pathway (P=0.029) and glycolysis related pathway (P=0.018) were enriched in ovarian cancer patients with high PAR2 mRNA expression. Conclusions: PAR2 expression is closely related to tumor reduction effect, initial treatment effect and survival of ovarian cancer patients. PAR2 may be involved in Wnt/β-catenin signaling pathway and intercellular connection promoting ovarian cancer invasion and metastasis.