The dysfunction of qi, blood, and fluid underlies the pathology of diabetes mellitus. The symptoms, signs, and physical and chemical indexes of diabetes mellitus patients reflect the duration, degree, primary and secondary pathological state of the abnormal metabolism of qi, blood, and fluid. It is necessary to construct a three-dimensional syndrome differentiation system of diabetes mellitus based on spatial and temporal dimensions. According to the four stages of depression, heat, deficiency, and damage, the location of the disease can be locked into qi, ying, and blood levels. The process reflects the pathological trend of the abnormal metabolism of qi, blood, and fluid: qi depression (prodromal stage: asymptomatic metabolic disorder/early stage of qi level) → qi heat (initial stage: index stage/late stage of qi level) → deficiency of both qi and yin (middle stage: symptom stage of three more and one less/stage of ying level) → damage of zang-fu viscera and meridians (late stage: complication stage/stage of blood level). According to the time process, the treatment principles are proposed as follows: during the early stage of qi level, treatment should focus on strengthening the spleen to regulate qi flow, to prevent the accumulation of glucose; during the late stage of qi level, treatment should focus on clearing heat and resolving turbidity, to remove the stagnated heat caused by glucose; during the stage of ying level, treatment should focus on benefiting qi and nourishing yin, to improve the symptoms about deficiency of both qi and yin; during the stage of blood level, treatment should focus on promoting blood circulation and removing blood stasis, to remove the complication. According to the etiology and pathogenesis of diabetes mellitus, the sequential treatment strategy is thus proposed, which is strengthening the spleen to regulate qi flow, clearing heat and resolving turbidity, benefiting qi and nourishing yin, and promoting blood circulation and removing blood stasis. The compound prescriptions such as Houpo Sanwu Decoction, Baihu Jia Renshen Decoction, Danggui Liuhuang Decoction, and Taohong Siwu Decoction are used with modification in the stage-based treatment.

Objective To explore the targets and mechanism of Buyang Huanwu Decoction in preventing and treating atherosclerosis through network pharmacology,molecular docking and animal experiment.Methods The main active components and related targets of Buyang Huanwu Decoction were obtained and screened through databases such as TCMSP,HERB,UniProt,PubChem,SwissADME and SwissTargetPrediction.Six disease databases such as DrugBank,GeneCards,DisGeNET,OMIM,PharmGKB and TTD were used to obtain AS related targets.R language was used to obtain common targets for the drug and disease.STRING 11.5 database was used for protein interaction network analysis,and Cytoscape 3.9.1 software was used to conduct network topology parameters and obtain core targets.GO and KEGG enrichment analysis were performed on the common targets using DAVID platform.Molecular docking of core genes with the main active components of Buyang Huanwu Decoction was conducted using AutoDock Vina 1.5.6 software.An AS mouse model was established and intervened with Buyang Huanwu Decoction.The lipid content of the mouse aortic sinus was observed using Oil Red O staining.Western blot was used to detect the expression of PI3K/AKT/p38 signaling pathway,and ELISA was used to detect the contents of TNF-α and IL-17 in mouse serum.Results A total of 104 main active components and 283 action targets of Buyang Huanwu Decoction were obtained,as well as 5 347 AS related targets and 218 common targets for drugs and disease.Buyang Huanwu Decoction may use key active components such as quercetin,kaempferol and baicalin as core targets for TP53,MAPK1,AKT1,and exert its therapeutic effect on AS through PI3K-Akt signaling pathway,TNF signaling pathway and IL-17 signaling pathway,etc.Molecular docking indicated that quercetin,luteolin,kaempferol and baicalin had good affinity with TP53,HSP90AA1,MAPK1,AKT1 and RELA targets.MAPK1 had strong binding activity with baicalin and luteolin.The experimental results showed that Buyang Huanwu Decoction could reduce the lipid content in aortic sinus of AS mice,reduce the contents of TNF-α and IL-17 in serum(P<0.01)and significantly down-regulate the expression levels of PI3K,p-AKT and p-p38 proteins(P<0.05,P<0.01).Conclusion The mechanism of Buyang Huanwu Decoction for preventing and treating AS may be related to regulating the expression of the PI3K/AKT/p38 signaling pathway,thereby reducing inflammatory response.

Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200 μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1α related to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

This paper summarizes the clinical experience in applying jiao （角） medicine to treat diabetes mellitus from the perspective of qi， blood， and fluids. It is believed that impaired spleen transportation and transformation is the key pathomechanism of diabetes， leading to metabolic disturbances in qi， blood， and fluids， and resulting in a sequential pathological progression of "qi → thick fluids → thin fluids → blood". At the qi level， the disease is mainly characterized by spleen qi deficiency and stagnation， and is commonly treated with Hongshen （Panax Ginseng）， Huangqi （Astragalus Mongholicus）， and Baizhu （Atractylodes Macrocephala） to tonify the spleen and regulate qi. At the thick fluids level， the condition manifests as abdominal distension， internal heat， and turbid pathogens， requiring Zexie （Alisma Orientale）， Huanglian （Coptis Chinensis）， and Dahuang （Rheum Palmatum） to clear the spleen and drain turbidity. At the thin fluids level， with qi and yin deficiency and predominant yin damage， Gegen （Pueraria Lobata）， Wuweizi （Schisandra Chinensis）， and Maidong （Ophiopogon Japonicus） are used to nourish yin and generate fluids. At the blood level， where vascular damage is predominant， Shuizhifen （Whitmania Pigra Powder）， Danshen （Salvia Miltiorrhiza）， and Sanqifen （Panax Notoginseng Powder） are applied to activate blood circulation， resolve stasis， and unblock the channels. Clinicians may flexibly select appropriate jiao medicine based on the specific pathological layer affected in each patient.

Sepsis is a life-threatening organ dysfunction syndrome caused by a dysregulated host response to infection. Due to different infection sources, pathogens and basic conditions of patients, there is significant heterogeneity in clinical manifestations, response to treatment and prognosis of patients with sepsis. Accurate classification and individualized treatment of sepsis will help to further improve the prognosis of patients with sepsis. In recent years, the integration of artificial intelligence and bioinformatics has brought new opportunities for the research of sepsis classification. This review systematically introduces a variety of sepsis classification methods and their clinical application value. The clinical data in the electronic medical record, such as the dynamic changes of vital signs such as body temperature, can be used as the basis for sepsis classification. Different subtypes of body temperature trajectories have differences in physiological characteristics and prognosis, which contributes to predict the prognosis of patients and guide fluid management strategies. Biomarker classification can more comprehensively reflect the pathophysiological state of patients. Immune index classification is helpful to identify immunocompromised patients so as to carry out targeted immunotherapy. Transcriptome data and genotyping reveal the heterogeneity of sepsis at the molecular level and provide a new perspective for precision medicine. In addition, a detailed systematic review of sepsis-related organ function damage, such as acute respiratory distress syndrome (ARDS), acute kidney injury (AKI), and acute liver injury, has also been conducted, which is helpful to develop targeted organ protection and treatment strategies. These typing methods have shown good application prospects in clinical practice. However, there are still limitations in the current research, such as typing stability and biomarker selection, which need to be further explored. Future research should focus on the development of stable and efficient typing tools to achieve precise treatment of sepsis and improve the prognosis of patients.
Humans ; Sepsis/classification* ; Multiple Organ Failure/classification* ; Prognosis ; Artificial Intelligence ; Biomarkers ; Computational Biology ; Respiratory Distress Syndrome

Objective To observe the effects of Yitangkang on brown fat thermogenesis and mitochondrial biogenesis of PGC1α-NRF1/2-TFAM pathway in db/db mice;To explore its mechanism of regulating glucose and lipid metabolism.Methods Totally 27 six-week-old db/db mice were randomly divided into model group,Yitangkang group(30 g/kg)and liraglutide group(200 μg/kg),another 9 db/m mice of the same age were set as normal group.All groups received intervention with drugs or saline for 6 weeks.The body mass and FBG were measured weekly.After intervention,oral glucose tolerance test(OGTT)was carried out,the contents of serum TC,TG,LDL-C and HDL-C were detected by biochemical analyzer,HE staining was used to observe the morphology of brown adipose tissue(BAT)in scapular region,RT-qPCR and Western blot were used to detect the expressions of UCP1,PRDM16,PGC1α related to BAT thermogenesis and NRF1,Nrf2,TFAM related to mitochondrial biogenesis.Results Compared with the normal group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C content of model group significantly increased(P<0.01),the content of HDL-C significantly decreased(P<0.01);the diameter of BAT cells in scapular region was larger,white vacuoles appeared,lipid droplets increased,and the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT decreased significantly(P<0.01).Compared with the model group,the body mass,FBG,area under the curve of OGTT and serum TG,TC,LDL-C contents of Yitangkang group and liraglutide group significantly decreased(P<0.01),the content of HDL-C increased(P<0.01);BAT cells were smaller in diameter,more closely arranged,more regular in shape,and more abundant in capillary,the mRNA and protein expressions of UCP1,PRDM16,PGC-1α,NRF1,NRF2 and TFAM in BAT increased significantly(P<0.01).Conclusion Yitangkang can regulate mitochondrial biogenesis through PGC1α-NRF1/2-TFAM pathway to activate brown fat in db/db mice and improve glucose and lipid metabolism in db/db mice.

Objective To explore the targets and mechanism of Buyang Huanwu Decoction in preventing and treating atherosclerosis through network pharmacology,molecular docking and animal experiment.Methods The main active components and related targets of Buyang Huanwu Decoction were obtained and screened through databases such as TCMSP,HERB,UniProt,PubChem,SwissADME and SwissTargetPrediction.Six disease databases such as DrugBank,GeneCards,DisGeNET,OMIM,PharmGKB and TTD were used to obtain AS related targets.R language was used to obtain common targets for the drug and disease.STRING 11.5 database was used for protein interaction network analysis,and Cytoscape 3.9.1 software was used to conduct network topology parameters and obtain core targets.GO and KEGG enrichment analysis were performed on the common targets using DAVID platform.Molecular docking of core genes with the main active components of Buyang Huanwu Decoction was conducted using AutoDock Vina 1.5.6 software.An AS mouse model was established and intervened with Buyang Huanwu Decoction.The lipid content of the mouse aortic sinus was observed using Oil Red O staining.Western blot was used to detect the expression of PI3K/AKT/p38 signaling pathway,and ELISA was used to detect the contents of TNF-α and IL-17 in mouse serum.Results A total of 104 main active components and 283 action targets of Buyang Huanwu Decoction were obtained,as well as 5 347 AS related targets and 218 common targets for drugs and disease.Buyang Huanwu Decoction may use key active components such as quercetin,kaempferol and baicalin as core targets for TP53,MAPK1,AKT1,and exert its therapeutic effect on AS through PI3K-Akt signaling pathway,TNF signaling pathway and IL-17 signaling pathway,etc.Molecular docking indicated that quercetin,luteolin,kaempferol and baicalin had good affinity with TP53,HSP90AA1,MAPK1,AKT1 and RELA targets.MAPK1 had strong binding activity with baicalin and luteolin.The experimental results showed that Buyang Huanwu Decoction could reduce the lipid content in aortic sinus of AS mice,reduce the contents of TNF-α and IL-17 in serum(P<0.01)and significantly down-regulate the expression levels of PI3K,p-AKT and p-p38 proteins(P<0.05,P<0.01).Conclusion The mechanism of Buyang Huanwu Decoction for preventing and treating AS may be related to regulating the expression of the PI3K/AKT/p38 signaling pathway,thereby reducing inflammatory response.

By analysing the conceptual connotations of phenotype and traditional Chinese medicine （TCM） symptoms， the relationship between TCM symptoms， phenotypes and diseases is explained. It is believed that phenotypes and TCM syndromes have certain similarities， both of which elaborate the physiological and pathological mechanisms of the human body through external manifestations， and have the temporal and spatial characteristics of both phases and wholeness， as well as focusing on the connection between the innate and the acquired. Summarising the current status of the application of phenomics technology in the studies of TCM syndromes， it is concluded that the study of the intrinsic biological mechanisms of TCM syndromes with the help of phenomics technology has achieved certain results， but there are still problems such as difficulties in matching between traditional Chinese medicine syndromes and phenotypes， the incompleteness of the existing disease phenotype system， and the inconsistency of the understanding about "syndromes". It is proposed that in the future， large-scale clinical databases could be used to collect a wide range of TCM syndromes and phenotypes that are closely related to specific diseases. The phenomics technology could make preliminary correspondence and identification between a single syndrome and the corresponding phenotype， and then further carry out a more accurate phenotypic detection of the composite syndromes， and finally realise the standardization and intelligence of the diagnosis of TCM syndromes with the help of the artificial intelligence technology. By elaborating the modern scientific connotation of TCM syndromes from the perspective of phenotypes， we can provide scientific basis for the determination of TCM syndromes and the clarification of modern biomarkers of syndromes， as well as ideas for the modernisation research of TCM syndromes.

Objective To investigate the effects of Yitangkang on browning of white adipose and PINK1/Parkin pathway of mitophagy in adipose tissue of db/db mice.Methods Totally 30 six-week db/db mice were randomly divided into model group,Yitangkang Group(30 g/kg)and liraglutide group(200 μg/kg),and another 10 C57BL/6 mice of the same age were set as normal group.All groups were treated with corresponding drugs or normal saline for 5 weeks.During the period of administration,the body mass and fasting blood glucose(FBG)of mice in each group were detected regularly,the samples of liver,white and brown adipose of mice were weighed,the contents of serum triglyceride cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical analyzer,HE staining was used to observe the pathological changes of inguinal white adipose tissue(iWAT),immunohistochemical staining was used to detect the expression of browning marker protein uncoupling protein-1(UCP1)in iWAT,Western blot was used to detect the expressions of browning-related proteins UCP1,PRDM16,PGC-1α and mitophagy-related proteins PINK1,Parkin,Beclin-1,p62 in iWAT.Results Compared with the normal group,the body mass,liver,white adipose and brown adipose mass of the model group significantly increased(P<0.01),the FBG and serum TG,TC and LDL-C contents significantly increased(P<0.01),and the content of HDL-C significantly decreased(P<0.01);large vacuoles in iWAT adipocytes,the diameter of adipocytes increased obviously,some adipocytes were extruded and deformed,and the edge of adipocytes was not clear,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins decreased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins increased(P<0.01).Compared with the model group,the body mass,liver and white adipose mass significantly decreased in Yitangkang group and the liraglutide group(P<0.01),FBG and serum contents of TC,TG and LDL-C were significantly decreased(P<0.05,P<0.01),while HDL-C content significantly increased(P<0.01);the diameter of iWAT adipocytes decreased,the number increased,and the morphology was regular,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins increased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins decreased(P<0.05,P<0.01).Conclusion Yitangkang can improve glucose and lipid metabolism and promote browning of white adipose in db/db mice,which may be related to mitophagy mediated by PINK1/Parkin pathway.

Objective:To investigate the risk factors for postoperative fever in patients with negative preoperative urine culture undergoing flexible ureteroscopy (fURS), and construct a nomogram prediction model to predict the risk of postoperative fever.Methods:The clinical data of 308 patients who underwent flexible ureteroscopy (fURS) at the Second Affiliated Hospital of Zhengzhou University from January 2019 to March2023, were retrospectively analyzed. Among these patients, there were 235 males and 73 females, with an average age of (46.4±12.1) years old. Additionally, 86 cases had concomitant hypertension, 41 cases had diabetes, and 12 cases had coronary heart disease. A history of urinary stone surgery was present in 57 cases, and 91 cases exhibited severe hydronephrosis. The distribution of stones included 164 cases on the left side and 144 cases on the right side, with 88 cases of renal stones, 124 cases of ureteral stones, and 96 cases of renal-ureteral stones. Among them, 243 cases had ≤2 stones, while 65 cases had >2 stones, with a maximum stone diameter of 12.0 (9.0, 15.0) mm. Urine leukocyte-positive cases were 109, and urine leukocyte-negative cases were 199. Two cases were positive for nitrite, and 308 cases were negative. The occurrence of postoperative fever within 48 hours was recorded, and differences between the fever and non-fever groups were compared. Logistic regression analysis was employed to identify risk factors for post-fURS fever. A nomogram prediction model based on independent risk factors was constructed, and internal validation was conducted using 1 000 bootstrap resamples. The predictive performance of the model was evaluated using receiver operating characteristic (ROC) curves and the area under the curve (AUC). Model stability was assessed using calibration curves.Results:The surgeries for all 308 cases were successfully completed with a median operative time of 60.0 (40.0, 75.0) minutes. Complete stone clearance was achieved in 221 cases. Among them, 14 cases (4.5%) experienced postoperative fever, while 294 cases did not. The fever group had a higher proportion of females [57.1% (8/14) vs. 22.1% (65/294), P=0.007], more cases with comorbid diabetes [50.0% (7/14) vs. 11.6% (34/294), P<0.001], a higher proportion of renal stones [64.3% (9/14) vs. 26.9% (79/294), P=0.022], a lower intraoperative stone clearance rate [42.9% (6/14) vs. 73.1% (215/294), P=0.031], larger stone diameter [15.5 (12.5, 19.3) mm vs. 11.0 (9.0, 15.0) mm, P=0.004], longer operative time [87.5 (58.8, 106.3) min vs. 55.0 (40.0, 75.0) min, P<0.001], higher platelet count [267.0 (225.8, 354.0) ×10 9/L vs. 233.0 (197.8, 272.0) ×10 9/L, P=0.026], lower creatinine levels [67.5 (52.5, 72.3) umol/L vs. 73.0 (62.0, 84.0) umol/L, P=0.026], and a higher platelet lymphocyte ratio [148.8 (118.3, 189.3) vs. 119.5 (93.2, 156.0), P=0.030]. Results of univariate analysis showed that female gender, diabetes, stone location, incomplete stone clearance, maximum stone diameter, operative time, platelet count, creatinine, platelet lymphocyte ratio, and positive nitrite in urine (all P<0.05)were risk factors for postoperative fever. Multivariate regression analysis revealed that female gender ( OR=11.073, 95% CI 1.623-75.521, P=0.014), diabetes ( OR=5.995, 95% CI 1.441-24.952, P=0.014), and operative time ( OR=1.024, 95% CI 1.003-1.046, P=0.024) were independent risk factors for post-fURS fever. The nomogram exhibited excellent predictive performance (AUC=0.866, 95% CI 0.781-0.935), and the calibration curve demonstrated good consistency. Conclusions:Female gender, longer operative time, and diabetes are risk factors for post-fURS fever in patients with preoperative negative urine culture. The nomogram demonstrates excellent predictive performance.