ObjectiveTo observe the clinical effectiveness of horticultural therapy involving the planting of Chinese medicinal herbs （mint and lily potted plants） combined with intradermal needling therapy for generalized anxiety disorder （GAD） of liver depression transforming into fire syndrome under transcranial magnetic stimulation and basic psychological therapy， and to explore the possible mechanisms of action. MethodsA total of 180 patients with GAD of liver depression transforming into fire syndrome were randomly divided into three groups， horticultural therapy group， intradermal needling group， and horticultural therapy+intradermal needling group， with 60 patients in each. All groups received basic treatment including basic psychological therapy and transcranial magnetic stimulation. The horticultural therapy group received horticultural therapy in addition to the basic treatment； the intradermal needling group received intradermal needling therapy once a week for 8 weeks in addition to the basic treatment； the horticultural therapy+intradermal needling group received both horticultural therapy and intradermal needling therapy， following the same procedures and duration. Hamilton Anxiety Rating Scale （HAMA）， Self-Rating Anxiety Scale （SAS）， and Pittsburgh Sleep Quality Index （PSQI） scores were assessed at baseline and after 2， 4， 6， and 8 weeks of treatment. Serum levels of adrenocorticotropic hormone （ACTH） and corticosterone （CORT） were measured before treatment and after 8 weeks of treatment. Motor-evoked potential （MEP） baseline levels were recorded before treatment， and MEP amplitude ratios were compared after 1 week and 8 weeks of treatment. Clinical effectiveness and safety were evaluated after 8 weeks of treatment. Pearson correlation analysis was used to examine the relationships between serum ACTH and CORT levels， MEP amplitude， and anxiety. ResultsIn the horticultural therapy group and intradermal needling group， HAMA， SAS and PSQI scores after 4， 6， and 8 weeks treatment were lower than baseline scores （P＜0.05）. In the horticultural therapy+intradermal needling group， these scores showed a significant decline starting after 2 weeks treatment and continuing through 8 weeks after treatment （P＜0.05）. The HAMA， SAS， and PSQI scores in the horticultural therapy+intradermal needling group were significantly lower than those in the other two groups after 2， 4， 6， and 8 weeks treatment （P＜0.05）. After 8 weeks of treatment， serum CORT and ACTH levels in the horticultural therapy+intradermal needling group were significantly lower than baseline levels （P＜0.05） and were also lower than those in the horticultural therapy group and intradermal needling group at the same time point （P＜0.01）. When comparing the level after 8 weeks treatment to that after 1 week treatment， under PAS10 stimulation， the MEP amplitude ratio in the intradermal needling group decreased at 30 minutes， while in the horticultural therapy+intradermal needling group， the MEP amplitude ratio decreased at all time points （P＜0.05 or P＜0.001）； under PAS25 stimulation， the MEP amplitude ratio in the horticultural therapy group increased at 20 minutes， and in the intradermal needle group at 10 minutes （P＜0.05）. In the horticultural therapy+intradermal needling group， the MEP amplitude ratio increased significantly at all time points after treatment （P＜0.001）. The cure rate in the horticultural therapy+intradermal needling group （74.14%， 43/58） was significantly higher than that in the horticultural therapy group （30.00%， 18/60） and the intradermal needling group （48.28%， 28/58， P＜0.05）. Correlation analysis revealed that serum ACTH and CORT levels were positively correlated with HAMA scores （r = 0.488， P＜0.01； r = 0.428， P＜0.01）. Following PAS10 intervention， the MEP amplitude ratio was positively correlated with HAMA scores （r = 0.458， P＜0.01）， whereas after PAS25 intervention， the MEP amplitude ratio was negatively correlated with HAMA scores （r = -0.562， P＜0.01）. ConclusionHorticultural therapy combined with intradermal needling treatment， under transcranial magnetic stimulation and basic psychological therapy， demonstrates significant clinical effectiveness in patients with GAD of liver depression transforming into fire syndrome. Its mechanism of action may be related to the regulation of hyperactivation of the hypothalamic-pituitary-adrenal （HPA） axis and the reduction of cortical excitability.

To guide transfusion practice in critically ill children who often need plasma and platelet transfusions, the Transfusion and Anemia Expertise Initiative-Control/Avoidance of Bleeding (TAXI-CAB) developed Recommendations and Expert Consensus for Plasma and Platelet Transfusion Practice in Critically Ill Children. This guideline addresses 53 recommendations related to plasma and platelet transfusion in critically ill children with 8 kinds of diseases, laboratory testing, selection/treatment of plasma and platelet components, and research priorities. This paper introduces the specific methods and results of the recommendation formation of the guideline.

Objective To investigate the effects and related mechanisms of mitochondrial-derived peptide MOTS-c on glycochenodeoxycholic acid (GCDCA)-induced injury in human hepatocytes (THLE-3 cells). Methods THLE-3 cells were cultured in vitro and treated with different concentrations of GCDCA and MOTS-c. The optimal concentrations of GCDCA and MOTS-c were determined by cell counting kit (CCK)-8 method. Subsequently, THLE-3 cells were treated or pre-treated with GCDCA (200 µmol/L), MOTS-c (15, 30, 60 µmol/L), the multidrug resistance protein 2 (MRP2) inhibitor Probenecid (500 µmol/L), and the nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor ML385 (10 µmol/L). Cell proliferation was assessed by CCK-8 method. Lactate dehydrogenase (LDH) levels in the culture medium were measured by biochemical method. Cell apoptosis rates were determined by flow cytometry. MRP2 messenger RNA (mRNA) levels were detected by real-time quantitative polymerase chain reaction (RT-qPCR). MRP2 and Nrf2 protein expression levels were analyzed by Western blotting. Results As the concentration of GCDCA increased, the proliferation activity of THLE-3 cells gradually decreased, while LDH activity in the culture medium and apoptosis levels increased, and the expression levels of MRP2 in the cells decreased (all P<0.05). Treatment with 30 and 60 µmol/L MOTS-c significantly enhanced the proliferation activity of THLE-3 cells exposed to GCDCA, upregulated the expression of MRP2 and Nrf2, and reduced LDH activity and apoptosis levels (all P<0.05). Co-treatment with Probenecid partially reversed the protective effects of MOTS-c on GCDCA-induced THLE-3 cells injury, while co-treatment with ML385 partially inhibited the induction of MRP2 expression by MOTS-c in THLE-3 cells exposed to GCDCA. Conclusions MOTS-c may alleviate GCDCA-induced injury in human hepatocytes (THLE-3 cells), and its mechanism may be related to the upregulation of MRP2 expression mediated by Nrf2.

ObjectiveTo investigate the effect and mechanism of Polygonatum neutral polysaccharides from sibiricum （PSP-NP） on colon injury in mice with chronic obstructive pulmonary disease （COPD）. MethodsMale C57BL/6J mice were randomly divided into a control group， a COPD model group， and a PSP-NP group. The COPD model was established using smoke exposure combined with intranasal LPS administration. The PSP-NP group was simultaneously treated daily with 200 mg/kg of PSP-NP via intragastric gavage， while the other groups received an equal volume of saline. HE staining was used to observe the pathological changes in the colon. ELISA was employed to detect the levels of LPS in serum and the expressions of ZO-1， Occludin， IL-6， and TNF-α in colon tissue. UPLC-MS was used to detect the types and contents of bile acids in colonic content， and to screen for differential bile acids. Differential microbial flora were identified using 16S rRNA gene sequencing， and correlation analysis was conducted with differential bile acids. PSP-NP was combined with the differential bile acids cholic acid （CA）， and deoxycholic acid （DCA） in vitro to analyze the binding capacity of PSP-NP for CA and DCA. PSP-NP was applied to NCM460 normal colonic epithelial cells cultured in CA and DCA. Cell migration ability was assessed using the scratch assay， and the mRNA expression levels of inflammatory cytokines TNF-α， IL-6， and NF-κB were measured by RT-qPCR. ResultsPSP-NP effectively improved colonic damage in COPD model mice， enhanced mechanical barrier function， alleviated inflammatory response， and regulated abnormal changes in colonic flora and bile acid metabolism. Correlation analysis further revealed that PSP-NP regulated colonic bile acid metabolism and reduced the redundancy of secondary bile acids by increasing the relative abundance of Bacteroidota， Verrucomicrobiota， Bacteroides， and Akkermansia， while decreasing the relative abundance of Lactobacillus and Bifidobacterium. Notably， in vitro binding assays demonstrated that PSP-NP bound to differential bile acids DCA and CA， with the strongest binding capacity for DCA at 58.2%. In cellular functional studies， DCA inhibited the migration ability of colonic epithelial cells NCM460 and significantly increased the relative mRNA expression levels of inflammatory factors TNF-α， IL-6， and NF-κB. Importantly， co-treatment with PSP-NP significantly ameliorated the impact of DCA on NCM460 cells. ConclusionsPSP-NP may significantly improve colonic damage in COPD model mice. The mechanism may involve the regulation of colonic bile acid metabolism and bile acid profiles through both microbial modulation and direct binding， thereby reducing the damage caused by secondary bile acids such as DCA to colonic epithelial cells.

OBJECTIVE To analyze chemical components of Yao ethnic medicine Pittosporum pauciflorum， establish its fingerprint and investigate the spectrum-effect relationship of its anti-inflammatory effect. METHODS UHPLC-Q-Orbitrap-MS technology was used to analyze the chemical components of P. pauciflorum （batch S6）. The fingerprints for 10 batches of P. pauciflorum from different producing areas in Guangxi Province （batches S1-S10） were established by HPLC， and similarity assessment and chemometric pattern recognition analysis were conducted. RAW264.7 inflammatory cell model was induced by lipopolysaccharide， and the anti-inflammatory activity of P. pauciflorum was investigated. Using inhibition rates of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β as efficacy indicators， grey relational analysis and partial least squares regression analysis were adopted to evaluate the spectrum-effect relationship of the anti-inflammatory effect of P. pauciflorum. RESULTS There were 60 chemical components， including flavonoids， phenolic acids， lipids， etc.， identified in P. pauciflorum. The fingerprints for 10 batches of P. pauciflorum showed 14 common peaks，with similarity values ranging from 0.883 to 0.991. Three common peaks were assigned neochlorogenic acid （peak 5）， chlorogenic acid （peak 7）， and syringaldehyde （peak 10）. The classification results of the systematic clustering analysis and the principal component analysis were basically consistent. Batches S1 to S10 of P. pauciflorum significantly reduced the levels of NO， TNF-α， IL-6 （except for batch S5） and IL-1β in the cell supernatant （P＜0.05 or P＜0.01）. Inhibition rates of above inflammatory indexes were 10.26%-39.96%， 14.96%-31.36%， 1.38%-21.27%， 18.54%-28.00%， respectively. The contents of neochlorogenic acid， syringaldehyde， as well as the components corresponding to peaks 1， 3， 9， 12 and 14，exhibited a strong correlation with the anti-inflammatory effects of P. pauciflorum. CONCLUSIONS The present study has analyzed the chemical components of P. pauciflorum and established HPLC fingerprints for 10 batches of P. pauciflorum. Each batch of medicinal herbs demonstrates certain anti- inflammatory activities， among which neochlorogenic acid， syringaldehyde， and the components corresponding to peaks 1， 3， 9， 12 and 14 are likely to be the active anti-inflammatory components.

ObjectiveTo investigate the quality markers of Xiaoqinglong granules（XQLG） for treating bronchial asthma using the analytic hierarchy process（AHP）-entropy weight method（EWM）， network pharmacology and high performance liquid chromatography（HPLC） content determination. MethodsEffectiveness， testability and peculiarity component data of XQLG in treating bronchial asthma were constructed through database retrieval， literature review， and network pharmacology. Subsequently， AHP-EWM was used to quantitatively identify and weight the control layer and element layer， the relevant compounds were selected as candidate quality markers based on comprehensive scores. Further comparison of reference substances and establishment of HPLC content determination method were used to determine the potential quality markers of XQLG， which were verified by molecular docking with disease targets. ResultsA total of 13 components， including glycyrrhizic acid， paeoniflorin， schisandrol A， isoliquiritigenin， 6-gingerol， ephedrine， liquiritin， albiflorin， liquiritigenin， 6-shogaol， pseudoephedrine， cinnamic acid and cinnamaldehyde， were identified as potential quality markers of XQLG by AHP-EWM. Quantitative analysis indicated that all aforementioned quality markers could be detected in 13 batches of XQLG， indicating that it had stable testability as a quality marker. Among these 13 batches of samples， ephedrine and paeoniflorin exhibited good consistency in content， while pseudoephedrine and cinnamaldehyde showed poor consistency. Molecular docking analysis revealed that the 13 compounds exhibited binding energies with the core targets -2.11 kcal·mol^-1， indicating that the 13 compounds could spontaneously bind to the disease targets， which may be the material basis for the treatment of bronchial asthma with XQLG. ConclusionIn this study， 13 compounds were screened by AHP-EWM combined with network pharmacology and HPLC as quality markers for the treatment of bronchial asthma by XQLG， laying the foundation for enhancing the quality standards of this preparation.

The assessment of adverse drug events is an important basis for clinical safety evaluation and post-marketing risk control of drugs,and its causality assessment is gaining increasing attention.The existing methods for assessing the causal relationship between drugs and the occurrence of adverse reactions can be broadly classified into three categories:global introspective methods,standardized methods,and probabilistic methods.At present,there is no systematic introduction of the operational details of the various methods in the domestic literature.This paper compares representative causality assessment methods in terms of definition and concept,methodological steps,industry evaluation and advantages and disadvantages,clarifies the basic process of determining the causality of adverse drug reactions,and discusses how to further improve the adverse drug reaction monitoring and evaluation system,with a view to providing a reference for drug development and pharmacovigilance work in China.

Objective To investigate the effect of Yiqi Huoxue Tongluo Decoction on microRNA-126a-5p(miR-126a-5p)and vascular endothelial growth factor(VEGF)signaling pathway in cervical spondylotic myelopathy model rats.Methods Thirty healthy male SD rats were divided into the sham operation group,the model group and the traditional Chinese medicine(TCM)group by random number table method.Cervical spondylotic myelopathy models were prepared in the model group and the TCM group.The TCM group was given intragastric administration of Yiqi Huoxue Tongluo Decoction,while the sham operation group and the model group were given intragastric administration of normal saline for 12 weeks.After intervention,the threshold of mechanical stimulation and retraction time of thermal stimulation in each group were measured by behavior tests.Rats were sacrificed to collect intervertebral disc tissue for hematoxylin-eosin(HE)staining and observe the number of vascular buds in intervertebral disc.Rat intervertebral disc annulus fibrosus cells were subjected to terminal dexynucleotidyl transferase-mediated dUTP nick end labeling(TUNEL)staining.The miR-126a-5p and VEGF mRNA of rat intervertebral disc tissue were detected by real-time fluorescence quantitative polymerase chain reaction(RT-PCR).The expression of VEGF protein of rat intervertebral disc tissue was detected by Western blot assay.Results Compared with the sham operation group,the number of vascular buds in intervertebral disc was decreased in the model group and the TCM group.The cell destruction of intervertebral disc annulus was obvious in rats,and apoptosis was high and cell density decreased.Mechanical stimulation threshold decreased,and mechanical stimulation threshold decreased.The level of miR-126a-5p was decreased,and the expression levels of VEGF mRNA and protein were increased.Compared with the model group,the number of vascular buds in intervertebral disc was increased in the TCM group.The destruction of intervertebral disc annulus cells was alleviated in rats.The apoptosis of annulus fibrosus cells in intervertebral disc decreased and cell density increased.The threshold of mechanical stimulation increased,and the retraction time of thermal stimulation was prolonged.The level of miR-126a-5p increased,and the expression levels of VEGF mRNA and protein decreased(P＜0.05).Conclusion The mechanism of Yiqi Huoxue Tongluo Decoction in the treatment of cervical spondylotic myelopathy may be related to the up-regulation of miR-126a-5p expression and the down-regulation of VEGF expression.

Objective:To construct the risk prediction nomogram model of acute kidney injury (AKI) with R language and traditional statistical methods based on the large sample clinical database, and verify the accuracy of the model.Methods:It was a a retrospective case control study. The patients who met the diagnostic criteria of AKI in Tongji Hospital of Tongji University from January 1 to December 31, 2021 were screened in the clinical database, and the patients with monitored serum creatinine within 48 hours but without AKI were included as the control group. The demographic data, disease history, surgical history, medication history and laboratory test data were collected to screen the risk factors of AKI in clinic.Firstly, based on multivariate logistic regression analysis and forward stepwise logistic regression analysis, the selected risk factors were included to construct the nomogram model. At the same time, cross validation, bootstrap validation and randomly split sample validation were used for internal verification, and clinical data of patients in the sane hospital after one year (January to December, 2022) were collected for external verification. The receiver-operating characteristic curve was used to determine the discrimination of the model, and calibration curve and decision curve analysis were carried out to evaluate the accuracy and clinical net benefit, respectively.Results:A total of 5 671 patients were enrolled in the study, with 1 884 AKI patients (33.2%) and 3 787 non-AKI patients (66.7%). Compared with non-AKI group, age, and proportions of surgical history, renal replacement therapy, hypertension, diabetes, cerebrovascular accident,chronic kidney disease, drug use histories and mortality in AKI group were all higher (all P<0.05). Multivariate logistic regression analysis showed that the independent influencing factors of AKI were surgical history, hypertension, cerebrovascular accident, diabetes, chronic kidney disease, diuretics, nitroglycerin, antidiuretic hormones, body temperature, serum creatinine, C-reactive protein, red blood cells, white blood cells, D-dimer, myoglobin, hemoglobin, blood urea nitrogen, brain natriuretic peptide, aspartate aminotransferase, alanine aminotransferase, triacylglycerol, lactate dehydrogenase, total bilirubin, activated partial thromboplastin time, blood uric acid and potassium ion (all P<0.05). Finally, the predictive factors in the nomogram were determined by forward stepwise logistic regression analysis, including chronic kidney disease, hypertension, myoglobin, serum creatinine and blood urea nitrogen, and the area under the curve of the prediction nomogram model was 0.926 [95% CI 0.918-0.933, P<0.001]. The calibration curve showed that the calibration effect of nomogram was good ( P>0.05). The decision curve showed that when the risk threshold of nomogram model was more than 0.04, the model construction was useful in clinic. In addition, the area under the curve of receiver-operating characteristic curve predicted by nomograph model in external validation set was 0.876 (95% CI 0.865-0.886), which indicated that nomograph model had a high discrimination degree. Conclusion:A nomogram model for predicting the occurrence of AKI is established successfully, which is helpful for clinicians to find high-risk AKI patients early, intervene in time and improve the prognosis.

The advent of digital times promotes the evolution of clinical research from traditional mode to digital mode. Digital technologies， which are introduced to clinical research of traditional Chinese medicine （TCM）， can optimize the research design， improve research quality， and save research funds and time. The digital and remote control of clinical research recruitment and screening， disease diagnosis and treatment， informed consent， indicator measurement， and other processes can be realized by computers， networks， sensors， and other technologies. Artificial intelligence （AI） algorithms， wearable monitoring devices， data management tools， blockchain， and virtual clinical trials （VCTs） are key innovation technologies and research design methods. On this basis， this study summarized relevant literature on key digital technologies and research methods such as AI algorithms， wearable monitoring devices， data management tools， blockchain， and VCT， and the following discoveries were obtained： The future development of clinical research of TCM requires to attach importance to the changes in clinical research brought by digital technologies and to promote the utilization of digital technologies in clinical research of TCM. Digital technologies realize the medical ethical ideas of ''putting people first''， promote the decentralization of clinical research， simplify the participation process of participants， reduce the time and cost of clinical research， improve the efficiency of clinical research of TCM， and enhance the objectivity， authenticity， and stability of clinical research of TCM. Deepening the application of digital technologies in clinical research and realizing the interaction and fusion of various digital technologies are inevitable trends of future development of clinical research of TCM. Under the background of digitization， the digital innovation of clinical research of TCM can accelerate the development of clinical research of TCM and promote the internationalization of TCM.