Effect of Compatibility of Wujiwan on Pharmacokinetics and Tissue Distribution of Representative Components / 中国实验方剂学杂志

ObjectiveTo study the plasma pharmacokinetics and tissue distribution of five representative components in Wujiwan， and to illustrate the difference of metabolism and tissue distribution before and after compatibility. MethodHealthy male SD rats were divided into four groups， including Wujiwan group（A group， 62.96 g·L-1）， Coptidis Rhizoma group（B group， 38.4 g·L-1）， processed Euodiae Fructus group（C group， 5.88 g·L-1） and fried Paeoniae Radix Alba group（D group， 18.68 g·L-1）， with 65 rats in each group， and were administered the drugs according to the clinical dose of decoction pieces converted into the dose of the extracts. Then plasma， liver， small intestine and brain were taken at pharmacokinetic set time in each group after administration. Ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry was developed for the quantitative analysis of five representative components［berberine（Ber）， palmatine（Pal）， evodiamine（Evo）， rutecarpine（Rut） and paeoniflorin（Pae）］ in Wujiwan， their concentrations in plasma， liver， small intestine and brain were detected at different time， plasma samples were processed by protein precipitation， and tissue samples were pretreated by protein precipitation plus liquid-liquid extraction. Non-atrioventricular model was used to calculate the pharmacokinetic parameters of each component， and the parameters of each group were compared. ResultPharmacokinetic results of A group showed that area under the curve（AUC0-t） of the five representative components were ranked as follows：Ber and Pal were small intestine>liver>blood， Evo and Rut were liver>small intestine>plasma， Pae was small intestine>plasma， which was not detected in the liver， no other components were detected in brain except for Ber. In comparison with plasma and other tissues， peak concentration（Cmax） of Ber， Pal， Evo， and Rut were the highest and time to peak（tmax） were the lowest in the liver of A group. In plasma， the AUC0-t and Cmax of Evo and Rut were increased in A group compared with C group， tmax of Pea was elevated and its Cmax was decreased in A group compared with D group. In the liver， compared with B-D groups， Cmax values of 5 representative components except Pae were elevated， AUC0-t of Pae was decreased and AUC0-t of Evo and Rut were increased in the A group. In the small intestine， half-life（t1/2） of each representative components in A group was elevated and tmax was decreased， and Cmax of each representative ingredient except Pal was decreased， AUC0-t values of Ber and Pal were increased， whereas the AUC0-t values of Evo and Rut were decreased. ConclusionThe small intestine， as the effector organ， is the most distributed， followed by the liver. The pharmacokinetic parameters of the representative components in Wujiwan are changed before and after compatibility， which is more favorable to the exertion of its pharmacodynamic effects.

Effects of Jiaohong Pills and Its Prescription on Scopolamine-induced Alzheimer's Disease Mice / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Jiaohong pills （JHP） and its prescription， Pericarpium Zanthoxyli （PZ） and Rehmanniae Radix （RR） cognitive dysfunction in scopolamine-induced Alzheimer's disease （AD） mice and its mechanism through pharmacodynamic and metabolomics study. MethodThe animal model of AD induced by scopolamine was established and treated with PZ， RG and JHP， respectively. The effects of JHP and its formulations were investigated by open field test， water maze test， object recognition test， avoidance test， cholinergic system and oxidative stress related biochemical test. Untargeted metabolomics analysis of cerebral cortex was performed by ultra-performance liquid chromatography-Quadrupole/Orbitrap high resolution mass spectrometry （UPLC Q-Exactive Orbitrap MS）. ResultThe behavioral data showed that， compared with the model group， the discrimination indexes of the high dose of JHP， PZ and RR groups was significantly increased （P<0.05）. The staging rate of Morris water maze test in the PZ， RR， high and low dose groups of JHP was significantly increased （P<0.05， P<0.01）， the crossing numbers in the PZ， JHP high and low dose groups were significantly increased （P<0.05， P<0.01）； the number of errors in the avoidance test were significantly reduced in the PZ and high-dose JHP groups （P<0.01）， and the error latencies were significantly increased in the JHP and its prescription drug groups （P<0.01）. Compared with the model group， the activities of acetylcholinesterase in the cerebral cortex of the two doses of JHP group and the PZ group were significantly increased （P<0.05， P<0.01）， and the activity of acetylcholinesterase in the high-dose JHP group was significantly decreased （P<0.05）， and the level of acetylcholine was significantly increased （P<0.01）. At the same time， the contents of malondialdehyde in the serum of the two dose groups of JHP decreased significantly （P<0.05， P<0.01）. The results of metabolomics study of cerebral cortex showed that 149 differential metabolites were identified between the JHP group and the model group， which were involved in neurotransmitter metabolism， energy metabolism， oxidative stress and amino acid metabolism. ConclusionJHP and its prescription can antagonize scopolamine-induced cognitive dysfunction， regulate cholinergic system， and reduce oxidative stress damage. The mechanism of its therapeutic effect on AD is related to the regulation of neurotransmitter， energy， amino acid metabolism， and improvement of oxidative stress.

Research progress and potential medical applications of anaplastic lymphoma kinase in treatment of non-small cell lung cancer / 中国药理学通报

During the treatment of non-small cell lung cancer ( NSCLC) , many patients have developed drug resistance due to the use of targeted EGFR inhibitors. The main reasons for drug resistance are EGFR site mutations and bypass activation. Activation of ALK pathway is one of the major types of bypass activation. A recent authoritative study indicates that ALK is closely related to immunotherapy. This article reviews the treatment of ALK in tumors from three aspects: the structure and physiological function of ALK, the small molecule inhibitor of ALK, the biological function of ALK and its related treatment methods for NSCLC, and prospects future directions for better application of ALK in the treatment of NSCLC.

Effects of HMGB1 on phenotypes, phagocytosis and ERK/JNK/P38 MAPK signaling pathway in dendritic cells / 中国药理学通报

Aim To explore the impacts of high mobility group box 1 (HMGB1) on the phenotypes, endocy-tosis and extracellular signal-regulated kinase (ERK)/ Jun N-terminal protein kinase (JNK)/P38 mitogen-ac-tivated protein kinase (MAPK) signaling pathway in indoxyl sulfate (IS) -induced dendritic cells (DCs). Methods After treatment with 30, 300 and 600 (xmol · L

Mechanism of action and clinical research progress of iguratimod in connective tissue diseases / 中国药房

As a new type of immunosuppressant，iguratimod can mediate the anti-inflammatory signaling pathway by inhibiting the proliferation of inflammatory cells and reducing the release of inflammatory cytokines， and play the role of anti-inflammatory. It can affect the proliferation of immune cells and the expression of immune factors，reduce the production and deposition of immune complexes in the body，and play the role of immune regulation. It can regulate bone metabolism by mediating signaling pathways such as Wnt/β-catenin，Toll-like receptor 4/nuclear factor-κB and osteoprotegerin/nuclear factor-κB receptor activating factor ligand， and play a role in bone protection. It can inhibit pulmonary fibrosis by inhibiting the expression of transforming growth factor β1/ Smad2/3 signaling pathway，tumor necrosis factor-α，interleukin-1，interleukin-6，matrix metalloproteinase-9 and other inflammatory cytokines in lung tissue，and inhibiting the expression of collagen and fibronectin. Its efficacy and safety have been confirmed in the clinical application of rheumatoid arthritis and primary Sjogren syndrome and included in the diagnosis and treatment of the disease. It has also shown good efficacy in the clinical application of other connective tissue diseases such as systemic lupus erythematosus and ankylosing spondylitis，and no obvious safety risks have been found.

Remyelination Regulated by microRNAs in Neurodegenerative Diseases： A Review / 中国实验方剂学杂志

Demyelination of the central nervous system often occurs in neurodegenerative diseases， such as multiple sclerosis （MS）. The myelin sheath， a layer of myelin membrane wrapping the axon， plays a role in the rapid conduction and metabolic coupling of impulses for neurons. The exposure of the axon will lead to axonal degeneratio， and further neuronal degeneration， which is the main cause of dysfunction and even disability in patients with demyelinating neurodegenerative diseases. In addition to the demyelination of mature myelin sheath， remyelination disorder is also one of the major reasons leading to the development of the diseases. The myelin sheath is composed of oligodendrocytes （OLs） derived from oligodendrocyte progenitor cells （OPCs） which are differentiated from neural stem cells （NSCs）. The process of myelin regeneration， i.e.， remyelination， is the differentiation of NSCs into OLs. Recent studies have shown that this process is regulated by a variety of genes. MicroRNAs， as important regulators of neurodegenerative diseases， form a complex regulatory network in the process of myelin regeneration. This review summarizes the main molecular pathways of myelin regeneration and microRNAs involved in this process and classifies the mechanisms and targets. This review is expected to provide a theoretical reference for the future research on the treatment of demyelinating diseases by targeting the regulation of microRNAs.

Research progress on medical image dataset expansion methods / 生物医学工程学杂志

Computer-aided diagnosis (CAD) systems play a very important role in modern medical diagnosis and treatment systems, but their performance is limited by training samples. However, the training samples are affected by factors such as imaging cost, labeling cost and involving patient privacy, resulting in insufficient diversity of training images and difficulty in data obtaining. Therefore, how to efficiently and cost-effectively augment existing medical image datasets has become a research hotspot. In this paper, the research progress on medical image dataset expansion methods is reviewed based on relevant literatures at home and abroad. First, the expansion methods based on geometric transformation and generative adversarial networks are compared and analyzed, and then improvement of the augmentation methods based on generative adversarial networks are emphasized. Finally, some urgent problems in the field of medical image dataset expansion are discussed and the future development trend is prospected.

Specific DNA barcodes, germplasm resources, and genetic diversity of Eleutherococcus senticosus / 中国中药杂志

Eleutherococcus senticosus is one of the Dao-di herbs in northeast China. In this study, the chloroplast genomes of three E. senticosus samples from different genuine producing areas were sequenced and then used for the screening of specific DNA barcodes. The germplasm resources and genetic diversity of E. senticosus were analyzed basing on the specific DNA barcodes. The chloroplast genomes of E. senticosus from different genuine producing areas showed the total length of 156 779-156 781 bp and a typical tetrad structure. Each of the chloroplast genomes carried 132 genes, including 87 protein-coding genes, 37 tRNAs, and 8 rRNAs. The chloroplast genomes were relatively conserved. Sequence analysis of the three chloroplast genomes indicated that atpI, ndhA, ycf1, atpB-rbcL, ndhF-rpl32, petA-psbJ, psbM-psbD, and rps16-psbK can be used as specific DNA barcodes of E. senticosus. In this study, we selected atpI and atpB-rbcL which were 700-800 bp and easy to be amplified for the identification of 184 E. senticosus samples from 13 genuine producing areas. The results demonstrated that 9 and 10 genotypes were identified based on atpI and atpB-rbcL sequences, respectively. Furthermore, the two barcodes identified 23 genotypes which were named H1-H23. The haplotype with the highest proportion and widest distribution was H10, followed by H2. The haplotype diversity and nucleotide diversity were 0.94 and 1.82×10~(-3), respectively, suggesting the high genetic diversity of E. senticosus. The results of the median-joining network analysis showed that the 23 genotypes could be classified into 4 categories. H2 was the oldest haplotype, and it served as the center of the network characterized by starlike radiation, which suggested that population expansion of E. senticosus occurred in the genuine producing areas. This study lays a foundation for the research on the genetic quality and chloroplast genetic engineering of E. senticosus and further research on the genetic mechanism of its population, providing new ideas for studying the genetic evolution of E. senticosus.

UPLC-Q-TOF-MS metabolomic study on improvement of acute myocardial ischemia in rats by Dalbergia cochinchinensis heartwood / 中国中药杂志

This paper aimed to study the effect of Dalbergia cochinchinensis heartwood on plasma endogenous metabolites in rats with ligation of the left anterior descending coronary artery, and to analyze the mechanism of D. cochinchinensis heartwood in improving acute myocardial ischemic injury. The stability and consistency of the components in the D. cochinchinensis heartwood were verified by the establishment of fingerprint, and 30 male SD rats were randomly divided into a sham group, a model group, and a D. cochinchinensis heartwood(6 g·kg~(-1)) group, with 10 rats in each group. The sham group only opened the chest without ligation, while the other groups established the model of ligation. Ten days after administration, the hearts were taken for hematoxylin-eosin(HE) staining, and the content of heart injury indexes in the plasma creatine kinase isoenzyme(CK-MB) and lactate dehydrogenase(LDH), energy metabolism-related index glucose(Glu) content, and vascular endothelial function index nitric oxide(NO) was determined. The endogenous metabolites were detected by ultra-high-performance liquid chromatography-time-of-flight-mass spectrometry(UPLC-Q-TOF-MS). The results showed that the D. cochinchinensis heartwood reduced the content of CK-MB and LDH in the plasma of rats to relieve myocardial injury, reduced the content of Glu in the plasma, improved myocardial energy metabolism, increased the content of NO, cured the vascular endothelial injury, and promoted vasodilation. D. cochinchinensis heartwood improved the increase of intercellular space, myocardial inflammatory cell infiltration, and myofilament rupture caused by ligation of the left anterior descending coronary artery. The metabolomic study showed that the content of 26 metabolites in the plasma of rats in the model group increased significantly, while the content of 27 metabolites decreased significantly. Twenty metabolites were significantly adjusted after the administration of D. cochinchinensis heartwood. D. cochinchinensis heartwood can significantly adjust the metabolic abnormality in rats with ligation of the left anterior descending coronary artery, and its mechanism may be related to the regulation of cardiac energy metabolism, NO production, and inflammation. The results provide a corresponding basis for further explaining the effect of D. cochinchinensis on the acute myocardial injury.

Eleven new sesquiterpenoids from peeled stems of Syringa pinnatifolia / 中国中药杂志

The peeled stems of Syringa pinnatifolia(SP) is a representative Mongolian folk medicine with the effects of anti-depression, heat clearance, pain relief, and respiration improvement. It has been clinically used for the treatment of coronary heart disease, insomnia, asthma, and other cardiopulmonary diseases. As part of the systematic study on pharmacological substances of SP, 11 new sesquiterpenoids were isolated from the terpene-containing fractions of the ethanol extract of SP by liquid chromatography-mass spectrometry(LC-MS) and proton nuclear magnetic resonance(~1H-NMR) guided isolation methods. The planar structures of the sesquiterpenoids were identified by MS, 1D NMR, and 2D NMR data analysis, and were named pinnatanoids C and D(1 and 2), and alashanoids T-ZI(3-11), respectively. The structure types of the sesquiterpenoids included pinnatane, humulane, seco-humulane, guaiane, carryophyllane, seco-erimolphane, isodaucane, and other types. However, limited to the low content of compounds, the existence of multiple chiral centers, the flexibility of the structure, or lack of ultraviolet absorption, the stereoscopic configuration remained unresolved. The discovery of various sesquiterpenoids enriches the understanding of the chemical composition of the genus and species and provides references for further analysis of pharmacological substances of SP.

"Component-target-efficacy" network analysis and experimental verification of Qingkailing Oral Preparation / 中国中药杂志

This study aims to explore the mechanism of Qingkailing(QKL) Oral Preparation's heat-clearing, detoxifying, mind-tranquilizing effects based on "component-target-efficacy" network. To be specific, the potential targets of the 23 major components in QKL Oral Preparation were predicted by the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and SwissTargetPrediction. The target genes were obtained based on UniProt. OmicsBean and STRING 10 were used for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the targets. Cytoscape 3.8.2 was employed for visualization and construction of "component-target-pathway-pharmacological effect-efficacy" network, followed by molecular docking between the 23 main active components and 15 key targets. Finally, the lipopolysaccharide(LPS)-induced RAW264.7 cells were adopted to verify the anti-inflammatory effect of six monomer components in QKL Oral Preparation. It was found that the 23 compounds affected 33 key signaling pathways through 236 related targets, such as arachidonic acid metabolism, tumor necrosis factor α(TNF-α) signaling pathway, inflammatory mediator regulation of TRP channels, cAMP signaling pathway, cGMP-PKG signaling pathway, Th17 cell differentiation, interleukin-17(IL-17) signaling pathway, neuroactive ligand-receptor intera-ction, calcium signaling pathway, and GABAergic synapse. They were involved in the anti-inflammation, immune regulation, antipyretic effect, and anti-convulsion of the prescription. The "component-target-pathway-pharmacological effect-efficacy" network of QKL Oral Preparation was constructed. Molecular docking showed that the main active components had high binding affinity to the key targets. In vitro cell experiment indicated that the six components in the prescription(hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide) can reduce the expression of nitric oxide(NO), TNF-α, and interleukin-6(IL-6) in cell supernatant(P<0.05). Thus, the above six components may be the key pharmacodynamic substances of QKL Oral Preparation. The major components in QKL Oral Prescription, including hyodeoxycholic acid, baicalin, chlorogenic acid, isochlorogenic acid C, epigoitrin, geniposide, cholic acid, isochlorogenic acid A, and γ-aminobutyric acid, may interfere with multiple biological processes related to inflammation, immune regulation, fever, and convulsion by acting on the key protein targets such as IL-6, TNF, prostaglandin-endoperoxide synthase 2(PTGS2), arachidonate 5-lipoxygenase(ALOX5), vascular cell adhesion molecule 1(VCAM1), nitric oxide synthase 2(NOS2), prostaglandin E2 receptor EP2 subtype(PTGER2), gamma-aminobutyric acid receptor subunit alpha(GABRA), gamma-aminobutyric acid type B receptor subunit 1(GABBR1), and 4-aminobutyrate aminotransferase(ABAT). This study reveals the effective components and mechanism of QKL Oral Prescription.

Identification and biological characteristics of violet root rot pathogen of Pseudostellaria heterophylla in Fujian province / 中国中药杂志

Violet root rot is one of the main root diseases in the production process of Pseudostellaria heterophylla. To clarify the pathogenic species that cause the violet root rot of P. heterophylla in Fujian province, the roots and the sclerotia with violet root rot symptoms were collected from the main producing areas of P. heterophylla(Fujian province) from 2017 to 2021, and the pathogens were isolated by tissue separation method and identified by morphology and multi-gene phylogenetic analysis. Additionally, the biological characteristics of the pathogens were studied and the fungicides were determined. The results showed that 78 strains of violet root rot were isolated from the collected root samples, which belonged to one type after preliminary morphological identification. Two represen-tative strains were selected from the pathogens for multi-gene phylogenetic analysis, and they were clustered with Helicobasidium mompa together. The suitable culture conditions for the mycelium were OA medium, 25 ℃, pH 6, and ammonium oxalate as the nitrogen source. The lethal temperature of the mycelium was 50 ℃ for 10 minutes. Moreover, 99.1% propiconazole and 98.7% azoxystrobin had the optimal bacteriostatic effect, and the concentrations with the 50% bacteriostatic rate were 16.85 and 12.24 μg·mL~(-1), respectively. On the basis of the above results, the pathogen causing violet root rot of P. heterophylla in Fujian province was H. mompa. The medium type, growth temperature, pH value, nitrogen source, etc. had significant effect on the growth of mycelium.

Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling / 中国中药杂志

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

Study on relationship between platelet transfusion efficacy and KIR-HLA receptor-ligand compatibility / 中国输血杂志

【Objective】 To study the correlation between platelet transfusion efficacy and KIR receptor-HLA ligand. 【Methods】 Thirty-three leukemia patients with positive HLA antibody were tested for cross-matching with donor platelets. Platelets from suitable donors were selected for transfusion, and the 24-hour platelet corrected count increment (CCI) was used to determine the transfusion effect. KIR and ligand genotyping were performed on blood samples from patients and donors by PCR-SSP method, and the relationship between platelet transfusion effects and KIR receptor-HLA ligand was analyzed. 【Results】 In 74 occasions of platelet transfusion, 42 were ineffective and 32 were effective. When the donor had C2 gene and HLA-B Bw4-80T gene, the frequency of ineffective platelet transfusion in the recipient was 69.0% (29/42) and 52.4% (22/35), respectively, which was significantly higher than that in the effective group [25.0% (8/32) and 25.0% (8/32)]. When the donor had C1 gene, and the frequency of effective platelet transfusion in the recipient was 100.0%(32/32), which was higher than that in the ineffective group [83.3%(35/42)]. When the recipient-donor matching mode was KIR2DL1-C2 and KIR3DL1-(HLA-B Bw4-80T), the frequency of ineffective platelet transfusion was 69.0%(29/42) and 40.5%(22/42),higher than that of the effective group [25% (8/32) and 18.8% (6/32)]. When the recipient-donor matching model was KIR2DL3-C1, the rate of effective platelet transfusion in 32 patients (100.0%), which was higher than that (35 patients 83. 3%) in the ineffective group. When the mismatch mode of recipient iKIR+donor HLA ligand receptor was KIR2DL1-C2, the frequency of effective platelet transfusion in the recipient was 78.1% (25/32), which was much higher than that in the ineffective group [31.0% (13/42)]. When the mismatch mode was KIR3DL1-(HLA-B Bw4-80T), the rate of effective platelet transfusion in the recipient was 68.8% (22/32), which was higher than that in the ineffective group (42.9%, 18/42). The difference between the above groups was statistically significant(P<0.05). 【Conclusion】 HLA-C1 and HLA-C2 genes are the key factors affecting the efficacy of platelet transfusion.For platelet refractorines, HLA-C1 is the protective gene, while HLA-C2 and HLA-B Bw4-80T are the susceptible genes. The recipient iKIR+donor HLA ligand receptor model may play an important role in platelet refractoriness.

Efficacy and safety of domestic Paliperidone extended-release tablets in the treatment of stable schizophrenia / 中国药房

OBJECTIVE To investigate the efficacy and safety of domestic Paliperidone extended-release tablets as a substitute for original Paliperidone extended-release tablets in the treatment of stable schizophrenia. METHODS A total of 65 patients with schizophrenia， who were treated with single original Paliperidone extended-release release tablets for 2 months or more in the outpatient or inpatient department of Shandong Daizhuang Hospital from June 2021 to June 2022， were collected and randomly divided into the domestic group （33 cases） and the original group （32 cases）. The domestic group was treated with the same dose of domestic Paliperidone extended-release tablets instead for 2 months， and the original group continued to use the previous dose of the original drug for 2 months. Positive and negative syndrome scale （PANSS） and treatment emergent symptom scale （TESS） were used to evaluate the two groups at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment. The incidence of ADR was calculated at the end of 2 months after enrollment. The fasting blood glucose， blood lipid indicators （triglyceride， total cholesterol， low-density lipoprotein， high-density lipoprotein， very-low-density lipoprotein）， serum prolactin levels， and paliperidone blood concentration were determined after the intravenous blood sample was collected. The ratio of paliperidone blood concentration to dose （C/D value） was calculated， and an electrocardiogram was performed. RESULTS There were 31 and 30 patients in the domestic group and the original group who completed the trial， respectively. There were no statistical significances in PANSS score， TESS score or C/D value at the time of enrollment and the end of 1 week， 1 month and 2 months after enrollment； there were no statistical significances in the levels of fasting blood glucose， blood lipid or serum prolactin at the time of enrollment and at the end of 2 months after enrollment （P＞0.05）. PANSS scores of both groups significantly decreased at the end of 1 month and 2 months after enrollment （P＜0.01）. The incidences of ADR were 25.81% in the domestic group and 30.00% in the original group， without significant difference （P＞0.05）， and there were no significant abnormalities in the electrocardiograms of the two groups. CONCLUSIONS Domestic Paliperidone extended-release tablets can directly replace the original tablets in the treatment of stable schizophrenia， and their clinical efficacy and safety are comparable.

Contribution of Traditional Chinese Medicine Combined with Conventional Medicine Treatment for a Long-Term Survivor of Heart Transplant with Severe COVID-19： A Case Report / 中医杂志

We report a case of a long-term survivor of heart transplant who developed severe COVID-19 and was treated with a traditional Chinese medicine combined with conventional medicine. Throughout the treatment， the patient received active conventional medical treatment， and traditional Chinese medicine interventions included tonifying qi， invigorating the spleen and transforming phlegm， promoting yang and eliminating stagnation， resolving dampness and dissipating phlegm， and promoting blood circulation and eliminating stasis. The main therapeutic principles adopted were to recuperating depleted yang and rescuing the patient from collapse and to resolve phlegm and promote water. Pogezilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications was administered. In summary， it is crucial to the timely adjust the immunosuppressive regimen， combine use of various anti-infective agents with a focus on COVID-19， to protect of cardiac and renal function， and to integrate traditional Chinese medicine in the entire treatment process. As this case is rare， the diagnostic and therapeutic methods in traditional Chinese medicine， the use of immunosuppressive agents， and follow-up monitoring strategies can be a valuable reference.

Diagnostic value of a combined serology-based model for minimal hepatic encephalopathy in patients with compensated cirrhosis / 中华检验医学杂志

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

A diagnostic prediction nomogram for small gastric stromal tumors based on features under endoscopic ultrasonography / 中华消化内镜杂志

Objective:To establish a nomogram based on features under endoscopic ultrasonography (EUS) for predicting the diagnosis of small gastric stromal tumors.Methods:The clinicopathological data of 189 patients with gastric submucosal tumors (diameter less than 2 cm) who underwent endoscopic resection at the Department of Gastroenterology, Tongji Hospital of Tongji University from June 2015 to August 2021 were retrospectively collected. All patients were divided into the modeling group ( n=126) and the validation group ( n=63) at 2∶1 by random function of software R. Independent influencing factors for the diagnosis of small gastric stromal tumors under EUS screened by univariable and multivariable logistic regression analysis were used to establish the diagnostic prediction nomogram. The receiver operator characteristic (ROC) curves were drawn to evaluate the discrimination of the model both in the modeling group and the validation group. Hosmer-Lemeshow test and calibration curve were used to evaluate the calibration of the model in both groups. Results:The age of patients >60 years ( OR=2.815, 95% CI:1.148-6.900, P=0.024), the lesions located in cardia/fundus ( OR=5.210, 95% CI:1.225-22.165, P=0.025), originated in muscularis propria ( OR=6.404, 95% CI:2.262-18.135, P<0.001) and of external growth ( OR=6.024, 95% CI:1.252-28.971, P=0.025) were independent influencing factors for the diagnosis of small gastric stromal tumors under EUS. The diagnostic prediction nomogram was established based on the four factors above. The areas under ROC curve of the modeling group and validation group were 0.834 (95% CI:0.765-0.903) and 0.780 (95% CI:0.667-0.893). Hosmer-Lemeshow test indicated that this model fit the data well ( χ2=10.23, P=0.176 in the modeling group; χ2=2.62, P=0.918 in the validation group). Calibration charts of the model drawn by Bootstrap method showed that the calibration curves fit well with the standard curves in both groups. Conclusion:The nomogram based on features under EUS for predicting the diagnosis of small gastric stromal tumors provides a visual reference for endoscopists to diagnose small gastric stromal tumors under EUS with good discrimination and calibration.

Case analysis of multiple endocrine adverse reactions associated with immune checkpoint inhibitors / 中华内分泌代谢杂志

Objective:To investigate the clinical features of multiple endocrine gland dysfunction in patients with tumors after using immune checkpoint inhibitors(ICIs).Methods:Cases with two or more abnormalities of endocrine gland function after immunotherapy were collected from the Department of Endocrinology, Zhongshan Hospital, Fudan University between January 2019 and January 2022. Clinical manifestations, laboratory tests, imaging, treatment and prognosis were analyzed.Results:A total of 12 patients were included, 6 males and 6 females, aged(61.2±10.0) years old. All patients received programmed cell death protein-1(PD-1) monoclonal antibody therapy, and the time to endocrine abnormality ranged from 9 to 94 weeks after administration. All patients developed primary hypothyroidism, 11 of them had isolated adrenocorticotropic hormone deficiency, and 1 had primary adrenal insufficiency.Conclusion:ICIs can involve multiple endocrine glands simultaneously or successively, mainly manifested as primary hypothyroidism and isolated adrenocorticotropic hormone deficiency. It is essential to assess the function of the pituitary and target glands in patients treated with ICIs to improve the safety of immunotherapy.

Moderate and vigorous aerobic exercise reduces the 10-year risk of diabetes in adults with obesity / 中华内分泌代谢杂志

This article introduced the research design and main results of the article " Effect of Moderate and Vigorous Aerobic Exercise on Incident Diabetes in Adults with Obesity: A 10-Year Follow-up of a Randomized Clinical Trial" recently published in JAMA Internal Medicine, and addressed the scientific significance of the study. The importance of obesity management has been well discussed recently. This study investigated obesity management strategies for obese individuals and their long-term metabolic benefits.