1.Clinical study of optimal positive end-expiratory pressure titration guided by lung stretch index in patients with acute respiratory distress syndrome
Kai HU ; Caixia YIN ; Xuan XIONG ; Yu XIE ; Bujun LI ; Lixin ZHOU
Chinese Critical Care Medicine 2024;36(2):142-146
Objective:To investigate the clinical practicability of positive end-expiratory pressure (PEEP) titrated by lung stretch index (SI) in patients with acute respiratory distress syndrome (ARDS).Methods:A parallel randomized controlled trial was conducted. Patients with moderate to severe ARDS who required mechanical ventilation admitted to the department of critical care medicine of General Hospital of the Yangtze River Shipping from August 2022 to February 2023 were enrolled. They were randomly divide into SI guided PEEP titration group (SI group) and pressure-volume curve (P-V curve) inspiratory low inflection point (LIP) guided PEEP titration group (LIP group). All patients were ventilated in a supine position after admission, with the head of the bed raised by 30°. The primary disease was actively treated, prone position ventilation for 12 h/d, and lung protective ventilation strategies such as controlled lung expansion were used for lung recruitment. On this basis, mechanical ventilation parameters were titrated with SI in the SI group; the LIP group titrated mechanical ventilation parameters with P-V curve inspiratory LIP+2 cmH 2O (1 cmH 2O ≈ 0.098 kPa). The oxygenation index (PaO 2/FiO 2), and respiratory mechanics indicators such as lung dynamic compliance (Cdyn), peak airway pressure (Pip) were monitored before recruitment maneuver and after 1, 3, and 5 days of treatment. The therapeutic effect of the two groups was compared. Results:There were 41 patients in the SI group and 40 patients in the LIP group. There was no significant difference in general information such as gender, age, and disease type between the two groups. The mechanical ventilation time and the length of intensive care unit (ICU) stay in the SI group were significantly shorter than those in the LIP group (days: 9.47±3.36 vs. 14.68±5.52, 22.27±4.68 vs. 27.57±9.52, both P < 0.05). Although the 28-day mortality of the SI group was lower than that of the LIP group, the difference was not statistically significant [19.5% (8/41) vs. 35.0% (14/40), P > 0.05]. On the fifth day, the PaO 2/FiO 2 was higher in SI group [mmHg (1 mmHg≈0.133 kPa): 225.57±47.85 vs. 198.32±31.59, P < 0.05], the Cdyn was higher in SI group (mL/cmH 2O: 47.39±6.71 vs. 35.88±5.35, P < 0.01), the Pip was lower in SI group (mmHg: 35.85±5.77 vs. 43.87±6.68, P < 0.05). The Kaplan-Meier survival curve showed no statistically significant difference in the 28 days cumulative survival rate between the two groups (Log-Rank: χ2 = 2.348, P = 0.125). Conclusion:The application of SI titration with PEEP in the treatment of ARDS patients may improve their prognosis.
2.Non-targeted Metabolomics Analysis of Fuling Yunhua Granules in Treatment of Type 2 Diabetes Mellitus Rats
Mengyao TIAN ; Keke LUO ; Mengxiao WANG ; Tianbao HU ; Hongmei LI ; Zongyuan HE ; Lixin YANG ; Liyu HAO ; Nan SI ; Yuyang LIU ; Baolin BIAN ; Hongjie WANG ; Yanyan ZHOU
Chinese Journal of Experimental Traditional Medical Formulae 2024;30(23):195-204
ObjectiveBased on non-targeted metabolomics, to analyze the regulation of endogenous differential metabolites in serum of type 2 diabetes mellitus(T2DM) rats by Fuling Yunhua granules, and to clarify the metabolic pathways through which this granules exerted its effect on improving T2DM. MethodSeventy SD rats, half male and half female, were randomly divided into the control group, model group, and high, medium, low dose groups of Fuling Yunhua granules(20.70, 10.35, 5.18 g·kg-1 in raw drug amount) and the positive drug group(pioglitazone hydrochloride tablets, 8.1 mg·kg-1). Except for the control group, other groups were fed with high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin(STZ) to establish a T2DM rat model. After successful modeling, the treatment groups were administered the corresponding drugs by gavage, and the control group and model group were treated with an equal volume of saline by gavage, once/d, for 28 d. Fasting blood glucose(FBG) and glycosylated hemoglobin A1c(GHbA1c) levels were measured in all groups of rats during the administration period, and hematoxylin-eosin(HE) staining was used to observe the pathomorphological changes in the pancreatic tissues of rats at the end of the administration period. The endogenous metabolite levels in rat serum were detected by ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap high-resolution mass spectrometry(UPLC-LTQ-Orbitrap MS), and the data were processed using principal component analysis(PCA) and orthogonal partial least squares-discriminant analysis(OPLS-DA). Differential metabolites were identified by the Human Metabolome Database(HMDB) and the Kyoto Encyclopedia of Genes and Genomes(KEGG), and screened for differential metabolites with variable importance in the projection(VIP) value>1, P<0.05, and fold change(FC)<0.6 or FC>1. And the metabolic pathway enrichment analysis of the screened differential metabolites was performed by MetaboAnalyst 5.0, then the screened differential metabolites were diagnosed and evaluated by the receiver operating characteristic(ROC) curves. ResultCompared with the control group, the FBG level of rats in the model group increased significantly(P<0.01), the GHbA1c content tended to increase, but the difference was not statistically significant, and the pancreatic tissue of rats was obviously damaged, the number of pancreatic islets decreased, and the pancreatic β-cells were obviously reduced, atrophied and enlarged. Compared with the model group, the FBG levels of rats in the high dose group of Fuling Yunhua granules and the positive drug group were significantly reduced after 2 weeks of administration(P<0.05, P<0.01), the GHbA1c content of rats in the high dose group of Fuling Yunhua granules was significantly reduced(P<0.05), and the pancreatic tissue lesions of rats in the different dose groups of Fuling Yunhua granules were reduced. The results of non-targeted metabolomics showed that 46 differential metabolites were significantly changed in the model group compared with the blank group. Pathway enrichment analysis found that T2DM mainly affected biological processes including biosynthesis of primary bile acid, D-amino acid metabolism, steroid hormone biosynthesis, and glycerophospholipid metabolism in rats. Compared with the model group, the levels of 8 differential metabolites in the high dose group of Fuling Yunhua granules were significantly adjusted, and the pathway enrichment analysis found that D-amino acid metabolism, retinol metabolism, glycine, serine and threonine metabolism, tryptophan metabolism and other metabolic pathways were mainly involved. ROC curves further analysis revealed that the four characteristic differential markers of 11-cis-retinol, D-piperidinic acid, D-serine, and p-cresol sulfate had high diagnostic value for the treatment of T2DM with Fuling Yunhua granules. ConclusionFuling Yunhua granules can improve the symptoms of T2DM rats by regulating the amino acid metabolic and retinol metabolic pathways through the modulation of endogenous differential metabolites.
3.Process Development and Research Status of Tibetan Medicine Zuotai(Mercury Preparation)
Gaijie DOU ; Lixin WEI ; Wenbin ZHOU ; Xianjia LI
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(1):229-235
Zuotai(mercury preparation)is considered the treasure of Tibetan medicine and is commonly referred to as the"King of Medicines".It is widely utilized in clinical practice as a core ingredient in the precious Tibetan medicine compounds,which possesses multiple therapeutic properties such as disease treatment,detoxification,health maintenance,and tonic effect.This paper conducted a comprehensive review of the classical Tibetan medical literature and recent research literature to elucidate the historical development and modern applications of the"Zuotai"concoction method.There are three main representative approaches of Zuotai concoction,including the mercury concoction method in the"Four Medical Tantras"by Udo-Yundan Pao(708-833),the concoction method in the"Mercury Concoction Classics"by Dongshun Nu Gyatso(13th century),and the mercury concoction method by Master Tsuru Tsering(1926-2004),who has imparted the Zuotai concoction process since the establishment of New China.In addition,Zuotai has been extensively studied by researchers in the fields of modern pharmacochemistry,pharmacokinetics,and toxicology.Overall,this paper provides a comprehensive review of the concoction methods of"Zuotai"in the classical Tibetan medical literature and modern pharmacological and toxicological research,so as to provide important reference value for in-depth understanding of the origin and history of"Zuotai".
4.Molecular markers of postoperative recurrence and malignant transformation in low-grade gliomas and their predictive value
Xuzhao LI ; Shiqi ZHOU ; Haibin LENG ; Dakuan GAO ; Lixin XU
Journal of Xi'an Jiaotong University(Medical Sciences) 2024;45(2):284-291
【Objective】 To identify the risk factors for recurrence and malignant transformation (MT) in patients with low-grade glioma (LGG) after surgery. 【Methods】 The data of 163 patients who underwent LGG resection and subsequent follow-up from March 2009 to April 2019 were retrospectively collected. Patients who did not experience recurrence or MT after surgery were included in the control group (85 cases), those who experienced recurrence after surgery were included in the observation 1 group (44 cases), and those who experienced MT after surgery were included in the observation 2 group (34 cases). Based on the clinical data of the three groups of patients, their clinical characteristics were analyzed, and the risk factors and predictive value for recurrence and MT were explored using Logistic regression model and receiver operating characteristic (ROC) curve. 【Results】 There were significant differences between the control group and the observation 1 group in preoperative seizure, preoperative Karnofsky performance status (KPS) score, and surgical approach (P<0.05). There were significant differences between the control group and the observation 2 group in gender, preoperative KPS score, tumor size, and surgical approach (P<0.05). There were significant differences between the control group and the observation 1 group in isocitrate dehydrogenase (IDH) mutation, proliferating cell nuclear antigen (PCNA), matrix metalloproteinase-9 (MMP-9), cancer-testis antigen OY-TES-1, OY-TES-1 mRNA protein, tumor suppressor protein p53, mouse double minute 2 (MDM2), vascular endothelial growth factor (VEGF), or epidermal growth factor receptor (EGFR) (P<0.05). There were significant differences between the control group and the observation 2 group in PCNA, MMP-9, cancer-testis antigen OY-TES-1, OY-TES-1 mRNA protein, or VEGF (P<0.05). Logistic regression analysis showed that IDH mutation, MMP-9, and PCNA were independent risk factors for LGG recurrence (P<0.05), while VEGF, MMP-9, and PCNA were independent risk factors for LGG MT (P<0.05). The area under curve (AUC) of PCNA, MMP-9 and IDH mutation for predicting LGG MT after surgery was 0.744, 0.790, and 0.799, respectively. The AUC of PCNA, MMP-9, and VEGF for predicting LGG recurrence after surgery was 0.729, 0.750, and 0.900, respectively. 【Conclusion】 This study found that IDH mutation, MMP-9 and PCNA were independent risk factors for LGG recurrence, while VEGF, MMP-9 and PCNA were independent risk factors for LGG MT by retrospectively analyzing the clinical data and protein expression of 163 patients with LGG after surgery. These proteins have high accuracy in predicting LGG recurrence and MT after surgery. Therefore, the proteins may play an important role in the biological behavior and treatment effect of LGG, and can be used as reference indicators for prognosis evaluation and individualized treatment of LGG patients after surgery.
5.Multi-level ranking classification algorithm for nuclear cataract based on AS-OCT image
Lixin FANG ; Yu ZHOU ; Yuanyuan GU ; Ziyuan JIANG ; Lei MOU ; Yang WANG ; Fang LIU ; Yitian ZHAO
Chinese Journal of Experimental Ophthalmology 2024;42(3):264-270
Objective:To investigate the diagnostic value of an intelligent assisted grading algorithm for nuclear cataract using anterior segment optical coherence tomography (AS-OCT) images.Methods:A diagnostic test study was conducted.AS-OCT image data were collected from 939 cases of 1 608 eyes of nuclear cataract patients at the Shanghai Tenth People's Hospital of Tongji University from November 2020 to September 2021.The data were obtained from the electronic case system and met the requirements for clinical reading clarity.Among them, there were 398 cases of 664 male eyes and 541 cases of 944 female eyes.The ages of the patients ranged from 18 to 94 years, with a mean age of (65.7±18.6) years.The AS-OCT images were labelled manually from one to six levels according to the Lens Opacities Classification System Ⅲ (LOCS Ⅲ grading system) by three experienced clinicians.This study proposed a global-local cataract grading algorithm based on multi-level ranking, which contains five basic binary classification global local network (GL-Net).Each GL-Net aggregates multi-scale information, including the cataract nucleus region and original image, for nuclear cataract grading.Based on ablation test and model comparison test, the model's performance was evaluated using accuracy, precision, sensitivity, F1 and Kappa, and all results were cross-validated by five-fold.This study adhered to the Declaration of Helsinjki and was approrved by Shanghai Tenth People's Hospital of Tongji University (No.21K216).Results:The model achieved the results with an accuracy of 87.81%, precision of 88.88%, sensitivity of 88.33%, F1 of 88.51%, and Kappa of 85.22% on the cataract dataset.The ablation experiments demonstrated that ResNet18 combining local and global features for multi-level ranking classification improved the accuracy, recall, specificity, F1, and Kappa metrics.Compared with ResNet34, VGG16, Ranking-CNN, MRF-Net models, the performance index of this model were improved.Conclusions:The deep learning-based AS-OCT nuclear cataract image multi-level ranking classification algorithm demonstrates high accuracy in grading cataracts.This algorithm may help ophthalmologists in improving the diagnostic accuracy and efficiency of nuclear cataract.
6.Strengthening the integration of traditional Chinese and Western medicine to promote the construction of a Chinese characteristic wound repair and regeneration system
Yu LIU ; Xiaohui QIU ; Na YANG ; Hong YANG ; Lixin XU ; Jian WANG ; Lu ZHANG ; Ke CAO ; Ke TAO ; Wu XIONG ; Jianda ZHOU
Journal of Chinese Physician 2024;26(3):321-325
To promote the construction of a wound repair and regeneration system with Chinese characteristics, it is necessary to follow the principle of combining traditional Chinese and Western medicine, and integrate theory, clinical practice, and teaching. Traditional Chinese medicine emphasizes a holistic concept and the principle of dialectical treatment, while Western medicine focuses on etiological analysis and local treatment. The combination of Chinese and Western medicine can complement each other's advantages and improve treatment effectiveness. The key technological innovations in repairing and regenerating systems cover areas such as drug therapy, physical therapy, and the application of biomaterials. This article discusses the development potential and challenges of combining traditional Chinese and Western medicine in the field of wound repair and regeneration, providing new ideas and methods for the development of wound repair and regeneration. It is expected to bring better medical services and treatment effects to patients undergoing repair and regeneration.
7.Explore the mechanism of Huangqi Jiedu decoction in the treatment of breast cancer syndrome of Zheng-deficiency and toxic-incandescence based on network pharmacology and molecular docking technology
Lingjia TIAN ; Zihao YIN ; Liang ZHOU ; Qin ZHANG ; Lixin LIANG ; Yongjie CAO ; Hua WANG ; Lifang LIU
Journal of Chinese Physician 2024;26(3):360-365
Objective:To explore the mechanism of Huangqi Jiedu Decoction (HQJD) in the treatment of breast cancer with the syndrome of Zheng deficiency and toxic incandescence by network pharmacology and molecular docking technology.Methods:The main active ingredients and targets of HQJD were screened through the traditional Chinese medicine (TCM) systematic pharmacology database and analysis platform. The relevant targets of breast cancer with the syndrome of Zheng-deficiency, toxic-incandescence were obtained using OMIM, GeneGards and Drugbank databases, and the relevant targets of HQJD for the treatment of breast cancer with the syndrome of Zheng-deficiency and toxic incandescence were obtained by intersection; The Cytoscape 3.9.1 software was used to build the protein protein interaction (PPI) network and the " drug active component target disease" network on the basis of String 11.0 database, and the core active components and core targets of HQJD in treating breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence were inferred according to the topological parameters. gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed on core targets using R language; and molecular docking verification on the main active ingredients and core targets were conducted.Results:230 effective targets of active ingredients of HQJD were screened, and 15 467 active ingredients of breast cancer with syndrome of Zheng-deficiency/toxic-incandescence were obtained; 217 intersection targets; GO function enrichment analysis showed that the treatment of HQJD for breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence mainly involved oxidative stress and cytochemical stress; The enrichment analysis of KEGG pathway showed that HQJD treatment of breast cancer with the syndrome of Zheng-deficiency and toxic-incandescence was mainly related to phosphatidylinositol 3-protein kinase B (PI3K-Akt), interleukin-17 (IL-17) and other signal pathways. The molecular docking results showed that the main active ingredients such as β-sitosterol, stigmasterol, luteolin had good binding ability with core targets.Conclusions:HQJD has the characteristics of multi-component, multi target and multi pathway in the treatment of breast cancer with syndrome of Zheng-deficiency and toxic-incandescence, and its main mechanism may be related to PI3K-Akt, IL-17, P53 and other signal pathways.
8.Mechanism of lncRNA-N1LR in blood-brain barrier injury during cerebral ischemia reperfusion
Yun HU ; Lixin ZHOU ; Li TONG ; Xintai LI ; Jianwen YANG
Chinese Journal of Geriatric Heart Brain and Vessel Diseases 2024;26(2):217-220
Objective To investigate the action mechanism of long non-coding RNA(lncRNA)-N1LR on blood-brain barrier(BBB)after cerebral ischemia-reperfusion(I/R)injury.Methods Primary rat brain microvascular endothelial cells(BMECs)were cultured and treated with OGD/R to simulate cerebral I/R injury.The experiment was divided into normal control group,ln-cRNA-N1LR OGD group,overexpression group(lncRNA-N1LR overexpression after OGD treat-ment)and silence group(lncRNA-N1LR silence after OGD treatment).The mRNA levels of ln-cRNA-N1LR,claudin-5 and occludin in each group were detected by RT-qPCR.The BBB permea-bility was detected by FITC-dextran infiltration assay.The expression of claudin-5 and occludin were detected by Western blotting.Results The mRNA levels of lncRNA-N1LR,occludin and claudin-5 were significantly decreased(0.31±0.01 vs 1.00±0.10,0.42±0.03 vs 1.01±0.13,0.38±0.03 vs 1.00±0.15,P<0.05),and the BBB permeability was significantly increased(58.79± 3.04 vs 8.87±0.63,P<0.05)in the OGD group than the control group.The lncRNA-N1LR over-expression group increased the mRNA expression of lncRNA-N1LR,occludin and claudin-5(0.67±0.07 vs 0.31±0.01,0.92±0.02 vs 0.42±0.03,0.70±0.08 vs 0.38±0.03,P<0.05),and decreased the BBB permeability(41.57±2.43 vs 58.79±3.04,P<0.05)than the OGD group.lncRNA-N1LR silence resulted in lower mRNA levels of lncRNA-N1LR,occludin and claudin-5(0.21±0.02 vs 0.31±0.01,0.31±0.03 vs 0.42±0.03,0.22±0.02 vs 0.38±0.03,P<0.05),and enhanced BBB permeability(72.34±1.43 vs 58.79±3.04,P<0.05)when compared with the OGD group.Conclusion Up-regulation of lncRNA-N1LR may play a neuroprotective role by reducing BBB permeability.
9.The Prescription Regularity Investigation of Mercury(Zuotai)Detoxification Formula in Tibetan Classic Medical Literatures Based on Data Mining
Gaijie DOU ; Lamao SUONAN ; Yingying LIU ; Lixin WEI ; Xianjia LI ; Wenbin ZHOU
World Science and Technology-Modernization of Traditional Chinese Medicine 2024;26(3):777-786
Objective This study aimed to explore the prescription regularity of Mercury(Zuotai)detoxification formula in Tibetan classic medical literatures based on data mining.Methods Mercury(Zuotai)detoxification formula of were collected from 22 ancient Tibetan medical literatures including the Four Medical Tantras,Medicine of Moon King,One Hundred Thousand Fists and Eight Essential Collections of Medicine,et al.The database of drugs,medicinal properties,five-source,six-flavor,and three-chemical flavor was established.R 4.2.2,IBM SPSS Modeler 18.0,Origion 2024 and other software were used to conduct frequency statistical analysis,Apriori association rule analysis and cluster analysis of the category,property and flavor,and five-source of Mercury(Zuotai)detoxification compound drugs,and interpret the statistical results in combination with the theory of Tibetan medicine.Results A total of 52 formulas were collected,containing 213 Tibetan medicines,with a cumulative frequency of 1066 times.The medicines involved in the prescription are mainly plant-based,and most of them are"cold"drugs;the medicinal flavor of drugs is mainly bitter,sweet,and pungent,with the five sources of emptiness,wind and water predominating;the most frequently occurring medicine was Mercury(Zuotai),followed by Terminalia Chebula,Musk,Geranium,Saffron,and Nutmeg.High-frequency medicines such as Mercury(Zuotai),Musk,Strychni Semen,Aconitum Tanguticum,Pedicularis Trichoglossa,Swertia Verticillifolia,and Sinapis Alba have detoxification effects.Musk also has the effect of aromatherapy,Terminalia Chebula can reconcile the nature of the medicine and the three causes of the disease effectively.The"six good medicines",including Geranium,Saffron,Nutmeg,White cardamom,Cloves,and Tsaoko Amomum Fruit,can harmonize qi and blood,and treat diseases of internal organs of the body.The analysis of association rules showed 24 pairs of medicines combinations with a support degree exceeding 59.62,and 9 groups of three-drug combinations,predominantly involving Mercury(Zuotai),Terminalia Chebula,Musk,and"six good medicines".The cluster analysis of medicines with a frequency of>10 produced 7 clustered formulas,primarily characterized by their efficacy in clearing away heat and toxins,as well as regulating the five internal organs and six viscera.Conclusion Most medicines in the Mercury(Zuotai)detoxification formula are primarily composed of botanicals,cold and bitter drugs,which is consistent with the heat-clearing and detoxifying therapy in Tibetan medicine.The medication pattern of the Mercury(Zuotai)detoxification formula is characterized by the use of Terminalia Chebula to reconcile the medicinal properties,detoxifying medicines to detoxify,aromatic drugs to rapidly eliminate or expel toxins,and six good medicines to protect the viscera.The combined use of these medicines plays a role in clearing away heat and toxins,opening up the orifices and collaterals,and harmonizing the functions of the viscera.The study provides data to support the medication rules of the Tibetan medicine Mercury(Zuotai)detoxification prescription.
10.Near Peer Learning in Neurology Residency Training on Electromyography
Ying TAN ; Yuehui HONG ; Jia LI ; Dongchao SHEN ; Jiayu SHI ; Hexiang YIN ; Lixin ZHOU ; Jun NI ; Yicheng ZHU
Medical Journal of Peking Union Medical College Hospital 2024;16(1):263-268
To explore the effectiveness of "near peer learning" (NPL) in the electromyography(EMG)teaching module for neurology residents. The Department of Neurology, Peking Union Medical College Hospital implemented an NPL instructional design for a course on EMG for residents from November 2020 to March 2024. This teaching session was held annually, in which senior residents instructed juniors who were 1 or 2 years earlier in their training. The residents participated in the pre-course/post-course tests and completed a feedback survey at the end of the session. This evaluation method was used to understand the effectiveness of the NPL intervention in EMG teaching. Over four years, a total of 83 residents participated. Among them, there were 24 postdoctoral students, 52 postgraduates and 7 junior residents. The results showed that the post-course test scores were significantly improved compared with pre-course test scores (74.33±2.43 The NPL intervention is suitable for the teaching of EMG, because of its contribution to knowledge acquisition and basic clinical skills improvement. The NPL is worth replicating in other teaching and learning programs.

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