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.

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.

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 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 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.

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.

OBJECTIVES: To explore the physicochemical characteristics and biocompatibility of calcium peroxide (CPO)-loaded polycaprolactone (PCL) microparticle. METHODS: The CPO/PCL particles were prepared. The morphology and elemental distribution of CPO, PCL and CPO/PCL particles were observed with scanning electron microscopy and energy dispersive spectroscopy, respectively. Rat adipose mesenchymal stem cells were isolated and treated with different concentrations (0.10%, 0.25%, 0.50%, 1.00%) of CPO or CPO/PCL particles. The mesenchymal stem cells were cultured in normal media or osteogenic differentiation media under the hypoxia/normoxia conditions, and the amount of released O₂ and H₂O₂ after CPO/PCL treatment were detected. The gene expressions of alkaline phosphatase (ALP), Runt-associated transcription factor 2 (RUNX2), osteopontin (OPN) and osteocalcin (OCN) were detected by realtime RT-PCR. SD rats were subcutaneously injected with 1.00% CPO/PCL particles and the pathological changes and infiltration of immune cells were observed with HE staining and immunohistochemistry at day 7 and day 14 after injection. RESULTS: Scanning electron microscope showed that CPO particles had a polygonal structure, PCL particles were in a small spherical plastic particle state, and CPO/PCL particles had a block-like crystal structure. Energy dispersive spectroscopy revealed that PCL particles showed no calcium mapping, while CPO/PCL particles showed obvious and uniform calcium mapping. The concentrations of O₂ and H₂O₂ released by CPO/PCL particles were lower than those of CPO group, and the oxygen release time was longer. The expressions of Alp, Runx2, Ocn and Opn increased with the higher content of CPO/PCL particles under hypoxia in osteogenic differentiation culture and normal culture, and the induction was more obvious under osteogenic differentiation conditions (all P<0.05). HE staining results showed that the muscle tissue fibers around the injection site were scattered and disorderly distributed, with varying sizes and thicknesses at day 7 after particle injection. Significant vascular congestion, widened gaps, mild interstitial congestion, local edema, inflammatory cell infiltration, and large area vacuolization were observed in some tissues of rats. At day 14 after microparticle injection, the muscle tissue around the injection site and the tissue fibers at the microparticle implantation site were arranged neatly, and the gap size was not thickened, the vascular congestion, local inflammatory cell infiltration, and vacuolization were significantly improved compared with those at day 7. The immunohistochemical staining results showed that the expressions of CD3 and CD68 positive cells significantly increased in the surrounding muscle tissue, and were densely distributed in a large area at day 7 after particle injection. At day 14 of microparticle injection, the numbers of CD3 and CD68 positive cells in peripheral muscle tissue and tissue at the site of particle implantation were lower than those at day 7 (all P<0.01). CONCLUSIONS CPO/PCL particles have good oxygen release activity, low damage to tissue, and excellent biocompatibility.
Rats ; Animals ; Osteogenesis ; Core Binding Factor Alpha 1 Subunit ; Rats, Sprague-Dawley ; Hydrogen Peroxide/pharmacology* ; Cell Differentiation ; Oxygen ; Hypoxia ; Cells, Cultured

Objective:To investigate the clinical epidemiological data of children with prolonged mechanical ventilation (PMV) in pediatric intensive care unit(PICU), and analyze the primary disease of children with PMV as well as the disease characteristics and prognosis of children with PMV under different kinds of primary disease.Methods:The clinical data of hospitalized children with PMV in PICU at Children′s Hospital of Fudan University from January 2019 to December 2020 were retrospectively collected.Results:A total of 46 children with PMV were collected.There were 18 males (39.1%) and 28 females (60.9%). The median age was 37 (8, 86) months and the median body weight was 15 (7, 20) kg.The average pediatric critical illness score at admission was 84.2±7.7, PaO 2/FiO 2 was (245.5±99.8)mmHg.The primary diseases leading to PMV were as follows: there were 14 cases of severe pneumonia, eight cases of severe encephalitis, five cases of bronchopulmonary dysplasia, three cases of upper airway obstruction/craniofacial deformity, three cases of myasthenia, three cases of brain stem tumor, three cases of mitochondrial encephalomyopathy, two cases of spinal muscular atrophy, two cases of Prader-Willi syndrome, one case of dermatomyositis, one case of severe brain injury, and one case of central hypoventilation.The causes of unable to withdraw ventilator were respiratory dysfunction in 24 cases, brain dysfunction in 16 cases, and diaphragm dysfunction in six cases.Compared with neuromuscular diseases, children with PMV caused by respiratory diseases had lower month age, higher preterm birth rate, lower PaO 2/FiO 2 ratio, higher parameters for ventilator treatment, and the differences were statistically significant ( P<0.05). Children with PMV caused by neuromuscular diseases had lower Glasgow coma score and higher coma rate, and the differences were statistically significant ( P<0.05). A total of nine (19.6%) cases underwent tracheotomy.A total of 23 (50.0%) cases were successfully extubated from ventilator, six (13.0%) cases were dependent on invasive ventilator, and six (13.0%) cases were breathing with tracheotomy tube.The median mechanical ventilation time was 33 (28, 40) days, the median PICU hospital stay was 42 (34, 56) days, and the median hospital stay was 51 (41, 65) days.A total of 27 (58.7%) cases were improved and discharged, four (8.7%) cases were transferred to rehabilitation hospital, four (8.7%) cases were transferred to local hospital, and 11 (23.9%) cases died in hospital or at home after giving up. Conclusion:The main causes of PMV in PICU children are respiratory dysfunction, brain dysfunction and diaphragm dysfunction.50.0% of the children with PMV could be discharged from the ventilator, and 23.9% died or died after giving up.

Objective To explore the different diagnostic values of acid-fast staining, tuberculosis culture, tuberculosis DNA detection (TB-DNA), tuberculosis RNA constant temperature amplification technology (SAT-TB) in the detection of Mycobacterium tuberculosis in sputum specimens. Methods A total of 200 pulmonary tuberculosis patients and 80 non-tuberculosis patients who were hospitalized in Hebei Chest Hospital between September 2015 and September 2019 were selected for this study. Sputum samples were collected after admission, and the detection values of acid-fast staining, tuberculosis culture, TB-DNA, and SAT-TB in sputum samples were statistically analyzed. Results The differences in the sensitivity, accuracy, positive predictive value, and negative predictive values of the four diagnostic methods of acid-fast staining, tuberculosis culture, TB-DNA, and SAT-TB were statistically significant (P <0.05). In terms of diagnostic sensitivity, accuracy and negative predictive value, the values were SAT-TB> TB-DNA> tuberculosis culture> acid-fast staining. In terms of the positive predictive value of diagnosis, the values of SAT-TB, TB-DNA, and tuberculosis culture were higher than that of acid-fast staining. The Kappa values of the four methods and the gold standard were: Kappa (acid-fast staining) = 0.145, Kappa (tuberculosis culture) = 0.395, Kappa (TB-DNA) = 0.602, and Kappa (SAT-TB) = 0.770. Conclusion The four diagnostic methods of acid-fast staining, tuberculosis culture, TB-DNA, and SAT-TB all had certain detection value with their advantages and disadvantages. SAT-TB was a better detection method with high specificity, good sensitivity, and a short detection timer, which could quickly identify bacteria and distinguish live bacteria.

Objective:To explore the reproducibility of ultrasound measurements of children′s anterior, middle and posterior diaphragm motions.Methods:Thirty children admitted to a pediatric intensive care unit were positioned supine and a 5MHz ultrasound probe was placed over the intersection of their right midclavicular line with the costal margin. M-mode ultrasound was used to record the excursion and contraction velocity of the anterior, middle and posterior diaphragm during respiration. The observations were duplicated so the repeatability of the measurements could be evaluated using intra-group correlation coefficients calculated for the diaphragm excursions and the contraction velocities. Analysis of variance was used to explore the differences in excursion and contraction velocity among different parts of the diaphragm.Results:The intra-group correlation coefficients calculated for the anterior, middle and posterior diaphragm were 0.89, 0.95 and 0.90 respectively. The corresponding values for the contraction velocities were 0.90, 0.94 and 0.95 respectively. Both variables measured by ultrasound showed high repeatability. The average anterior, middle and posterior diaphragm excursion values (in mm) were 8.1±3.1, 7.4±3.0 and 5.5±2.3, and the corresponding average contraction velocities (in mm/s) were 12.5±4.8, 11.5±6.3 and 8.9±4.0.Conclusions:Measurements of children′s diaphragm motions using ultrasound show high repeatability. The excursions and contraction velocities of the anterior, middle and posterior diaphragm differ in children. The motion of one part of the diaphragm cannot represent the functioning of the entire diaphragm.