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.

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.

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 sort out the connotation,pathogenesis and treatment of"wind injuring the heart"in ancient literature,in order to provide theoretical reference for the treatment of refractory diseases such as viral myocarditis and epilepsy.[Methods]Based on the database of the fifth edition of the Chinese Medical Code,this study examines the discourse on"wind injuring the heart"in ancient literature,analyzes the specific connotation of"wind injuring the heart"from three perspectives:"the connotation of the heart""the pronunciation of Zhong"and"the connotation of wind",and summarizes its clinical symptoms,pathogenesis and treatment,in order to better guide clinical practice.[Results]The"heart"in traditional Chinese medicine is the master of the viscera.It not only has the function of controlling blood vessels,but also has the ability to store spirits.At the same time,some ancient physicians often used"heart"to refer to the spleen and stomach in the middle-Jiao.The"wind"in traditional Chinese medicine includes external wind and internal wind.The internal wind is often generated by emotion.Therefore,based on the relevant discussion of ancient and modern literature,the paper briefly expounds the different connotations of"wind injuring the heart",including wind damage to the heart of flesh and blood,wind damage to the heart of the spirit and other types of wind injuring the heart.Wind damage to the heart of flesh and blood and other types of wind injury to the heart are mostly caused by external wind,and wind damaging the heart of the spirit can be caused by external wind or internal wind.The treatment of wind damage to the heart of flesh and blood is mainly composed of drugs for dispelling wind,supplemented by drugs for reinforcing Qi and nourishing blood;wind damaging the heart of the spirit is mainly calming.[Conclusion]Wind damage to the heart of flesh and blood,wind damaging the heart of the spirit and other types of wind injury to the heart are very similar to the viral myocarditis,nervous system diseases,and gastrointestinal diseases in modern medicine,or the clinical prescriptions for these three kinds of diseases can be provided with theoretical basis according to ancient literature.

Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

Objective:To analyze the clinical situation of critically ill children with Montgomery T-tube，aiming to summarize the characteristics of T-tube application in pediatric and the experience of postoperative airway management in PICU.Methods:The etiology，clinical characteristics，complications and ICU admissions of patients with Montgomery T-tube admitted to the Pediatric Hospital of Fudan University from April 2019 to December 2021 were analyzed，and the application of T-tube in patients with critical conditions requiring long-term mechanical ventilation was described in the light of clinical experience.Results:During the study period,seven children were admitted to the PICU after T-tube insertion,including three males and four females,aged 9~75 months.Five children received mechanical ventilation.Among them,there were five cases with congenital laryngeal malformations,one case with tracheoesophageal fistula,and one case with laryngeal papilloma.The main complications were sputum blockage,infection,and granulation proliferation.One child died of secretion blockage,while the other children were successfully evacuated from the T-tube.The longest retention time of the T-tube was 367 days.Five patients experienced hoarseness after removing the T-tube,and upon re-examination with fiberoptic bronchoscopy,no recurrence of subglottic stenosis was observed.There was no respiratory distress or wheezing,and there were no abnormalities observed during regular outpatient follow-up after discharge.After discharge,the quality of life of the six surviving children improved compared to preoperative,and they all resumed oral feeding.There were no complaints of swallowing difficulties or aspiration during outpatient follow-up.But they were all combined with malnutrition.Conclusion:The Montgomery T-tube is a secure and dependable airway stent utilized for airway remodeling and the maintenance of airway patency following interventional surgery.For critically ill children,early management of airway clearance and infection prevention are imperative.

Objective To analyze the concentration and exposure of vancomycin in children with gram-positive coccal infection,and the corresponding clinical efficacy and safety to support rational use of vancomycin in children.Methods We prospectively collected the clinical and laboratory data of 87 children with gram-positive coccal infection in the Children's Hospital of Fudan University from January 2012 to March 2021.Therapeutic drug monitoring(TDM)was conducted for vancomycin simultaneously,to acquire the data of serum through concentration(Cmin),peak concentration(Cmax),the area under the drug concentration-time curve in a 24-h interval(AUC0-24h)and the ratio ofAUC0-24h to the minimum inhibitory concentration(AUC0-24h/MIC).Results The median(P25,P75)age of the children enrolled in this study was 3.60(1.20,20.00)months.The median dose of vancomycin was 39.23(30.00,46.51)mg/kg.The median serum Cmin was 3.30(1.50,7.10)mg/L.Cmin achieved the target(5-15 mg/L)in 23 cases(26.4％).The median AUC0-24h was 213(174,293)mg·h/L and the median AUC0-24h/MIC was 221(128,349).Adaily dose of above 60 mg/kg in children could achieve the median value of AUC0-24h and AUC0-24h/MIC greater than 400,and the corresponding median age was 28.50(6.85,36.00)months.Multivariate logistic analysis showed a good correlation between Cmin and AUC0-24h(P=0.002).At the end of treatment,the clinical efficacy rate was 85.1％(74/87)and the bacterial eradication rate was 95.4％(83/87).No renal injury occurred during the treatment.Conclusions In this study,the median daily dosage,Cmin and A UC0-24h/MIC of vancomycin were below the recommended range at home and abroad.However,good clinical and microbiological efficacy were achieved in children at low vancomycin exposure.The probability of target attainment(PTA)for A UC0-24h and AUC0-24h/MIC ≥400 increased when the daily dose of vancomycin was＞60 mg/kg(corresponding to the median age of 28.50 months)or Cmin ≥ 5 mg/L.

In recent years, an increasing number of emerging environmental pollutants have been identified, garnering widespread attention. Many of these pollutants are characterized by their environmental persistence and bioaccumulation, which pose significant threats to both the ecological environment and human health. However, the molecular mechanisms underlying their effects remain unclear, limiting our ability to assess their adverse impacts and develop effective protective measures. The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor traditionally known to be activated by dioxins and polycyclic aromatic hydrocarbons (PAHs) and is involved in the metabolism of exogenous chemicals. Recent research has shown that the AHR can be activated by a diverse range of exogenous and endogenous chemicals and participates in various biological processes. Studies have demonstrated that AHR mediates the toxic effects of emerging environmental pollutants such as perfluorooctane sulfonamide (PFOSA) and N-(1,3-dimethylbutyl)-N’-phenyl-p-phenylenediamine quinone (6PPDQ). This paper provided an overview of the AHR activation and the toxic effects induced by emerging environmental pollutants, with a focus on how the AHR activation interacts with multiple signaling pathways. The significance of these interactions in environmental risk assessment and toxicological research was also discussed. We aim to provide a scientific basis for environmental protection and risk assessment.

Objective To investigate the effects of an adeno-associated virus(AAV2)vector expressing secretory transforming growth factor-β(TGF-β)type Ⅱ receptor(sTβRⅡ)extracellular domain-IgG2a Fc fusion protein(sTβRⅡ-Fc)on proliferation and migration of triple-negative murine breast cancer 4T1 cells in mice.Methods The pAAV-sTβRⅡ-Fc vector expressing sTβRⅡ-Fc fusion protein constructed by molecular cloning,the capsid protein-expressing vector pAAV2 and the helper vector were co-transfected into HEK 293T cells to prepare the recombinant AAV2-sTβRⅡ virus,which was purified by density gradient centrifugation with iodixanol.Western blotting was used to examine the effects of AAV-sTβRⅡ virus on Smad2/3 phosphorylation in 4T1 cells and on expression levels of E-cadherin,vimentin and p-Smad2/3 in 4T1 cell xenografts in mice.BALB/c mice bearing subcutaneous xenografts of luciferase-expressing 4T1 cells received intravenous injections of AAV-sTβRⅡ virus,AAV-GFP virus or PBS(n=6)through the tail vein,and the proliferation and migration of 4T1 cells were analyzed with in vivo imaging.Ki67 expression in the tumor tissues and sTβRⅡ protein expressions in mouse livers were detected with immunohistochemistry and immunofluorescence staining,and tumor metastases in the vital organs were examined with HE staining.Results The recombinant pAAV-sTβRⅡ-Fc vector successfully expressed sTβRⅡ in HEK 293T cells.Infection with AAV2-sTβRⅡ virus significantly reduced TGF-β1-induced Smad2/3 phosphorylation in 4T1 cells and effectively inhibited proliferation and lung metastasis of 4T1 xenografts in mice(P<0.05).In the tumor-bearing mice,intravenous injection of AAV-sTβRⅡ virus significantly increased E-cadherin expression,reduced vimentin and Ki67 protein expressions and Smad2/3 phosphorylation level in the tumor tissues(P<0.05 or 0.01),and induced liver-specific sTβRⅡ expression without causing body weight loss or heart,liver,spleen or kidney pathologies.Conclusion The recombinant AVV2 vector encoding sTβRⅡ extracellular domain is capable of blocking the TGF-β signaling pathway to inhibit the proliferation and lung metastasis of 4T1 cells in mice.

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.