Diabetic retinopathy (DR) is a diabetic ocular complication that can lead to poor vision and blindness. This experiment aimed to investigate the ameliorative effect and its mechanism of Panax notoginseng saponins (PNS) eye drops on streptozotocin (STZ)-induced non-proliferative diabetic retinopathy (NPDR) in rats. All experiments were approved by the Animal Research Committee of Shanghai University of Traditional Chinese Medicine. Animal welfare and the animal experimental protocols were strictly consistent with related ethics regulations of Shanghai University of Traditional Chinese Medicine (No. PZSHUTCM 211115004). Diabetes mellitus was induced by a single intraperitoneal injection of STZ into rats. Two months later, PNS solution was dropped binocular twice per day at 6 h intervals at dose of 20, 40, and 80 mg·kg^-1 continuously for 1 month. The morphological structure and activation of microglia of the retina were observed by hematoxylin-eosin staining and immunohistochemical assay. The disruption of the blood-retina barrier (BRB) was conducted by the Evans blue dye leakage assay. The number of acellular capillaries in the retina was assessed by digesting and hematoxylin-eosin staining assay. The number of retinal leukocyte adhesion was observed by fluorescein isothiocyanate-coupled concanavalin A lectin labeling assay. The serum expression of inflammatory factors was measured using enzyme-linked immunosorbent assay. Western blot experiments were used to detect the expression of relevant proteins in retinal tissue and transcriptional activation of nuclear factor kappa-B (NF-κB). The results revealed that PNS eye drops significantly increased the thickness of the retina, decreased the number of acellular capillaries, and up-regulated the expression of the tight junction proteins claudin-1 and occludin, thereby alleviating BRB damage. In addition, PNS eye drops were also able to significantly reduce leukocyte adhesion and microglia activation, the expression of inflammatory factors in serum, and the nuclear translocation of retinal p65 proteins, effectively inhibiting the occurrence of retinal inflammation. The above results showed that PNS eye drops played a role in improving NPDR by inhibiting the activation of the NF-κB signaling pathway and reducing inflammation.

Objective To investigate the clinical efficacy and safety of Yiqi Huatan Tongluo Prescription(mainly composed of Fici Simplicissimae Radix,Notoginseng Radix et Rhizoma,Pinelliae Rhizoma Praeparatum,Poria,Nelumbinis Folium,and Glycyrrhizae Radix et Rhizoma,etc.)combined with drug-coated balloon(DCB)in the treatment of coronary heart disease(CHD)and to observe its effect on low-shear related serological indicators.Methods A total of 106 patients with CHD of qi deficiency and phlegm stasis obstructing collateral type who were scheduled to undergo percutaneous coronary intervention were randomly divided into a treatment group and a control group,with 53 cases in each group.The control group was treated with drug-eluting stent implantation,and the treatment group was treated with DCB.After the operation,the control group was given conventional antiplatelet aggregation drugs,and the treatment group was given oral administration of Yiqi Huatan Tongluo Prescription.The medication for the two groups lasted for 12 weeks.The changes in the serum levels of monocyte chemoattractant protein 1(MCP-1),interleukin 1 β(IL-1β)and vascular endothelial growth factor(VEGF)in the two groups were observed before and after treatment.Moreover,the traditional Chinese medicine(TCM)syndrome efficacy after treatment and the incidence of adverse events one year after operation were compared between the two groups.Results(1)After 12 weeks of treatment,the total effective rate for TCM syndrome efficacy of the treatment group was 88.68％(47/53),and that of the control group was 75.47％(40/53).The intergroup comparison(tested by chi-square test)showed that the TCM syndrome efficacy in the treatment group was significantly superior to that in the control group(P＜0.05).(2)The analysis of indicators related to endothelial dysfunction in the blood flow with low shear stress showed that after treatment,the levels of serum MCP-1,IL-1βand VEGF in the control group presented no obvious changes(P＞0.05),but the serum levels of MCP-1 and IL-1β in the treatment group were significantly lowered compared with those before treatment(P＜0.05).The intergroup comparison showed that the decrease of serum MCP-1,IL-1β and VEGF levels in the treatment group was significantly superior to that in the control group(P＜0.05).(3)The one-year follow-up after the operation showed that the total incidence of adverse events in the treatment group was 18.87％(10/53),and that in the control group was 20.75％(11/53).There was no significant difference between the two groups(P＞0.05).Conclusion Yiqi Huatan Tongluo Prescription combined with DCB has definite action on the targets related to endothelial dysfunction in coronary blood flow with low shear stress,which is conducive to reducing inflammatory response,improving the symptoms of angina pectoris and enhancing clinical efficacy.The incidence of adverse events did not increase one year after operation,indicating good safety and effectiveness.

AIM: To explore the optimal concentration of endoplasmic reticulum stress immunohistochemical(IHC)staining antibody in mouse retinitis pigmentosa(RP)model, which provides the corresponding index detection method for studying the pathogenesis and intervention measures of RP.METHODS: Clean male C57BL/6J mice were intraperitoneally injected with N-methyl-N-nitrosourea(MNU, 60mg/kg)to prepare RP mouse model. Electroretinogram(ERG)and hematoxylin-eosin(HE)staining were performed on 7d after modeling to verify the successful modeling. The expression of endoplasmic reticulum stress-related proteins(IRE1, ATF6, PERK, GRP78, Caspase-12)was detected by IHC staining.RESULTS: The following proteins, including IRE1, ATF6, PERK, GRP78 and Caspase-12, were positively expressed in retina of RP mouse. The optimal concentrations of the above proteins were as follows: IRE1 antibody concentration was 1:1000, ATF6 antibody concentration was 1:500 and 1:1000(with no difference in positive expression, P>0.05), PERK antibody concentration was 1:1500, GRP78 antibody concentration was 1:200 and Caspase-12 antibody concentration was 1:100, the proteins were well expressed at the above concentrations, and the positive expressions of corresponding proteins were different from those of other antibody concentrations(P<0.05).CONCLUSION: The optimal concentrations for IHC staining in different proteins of mouse RP models were as follows: the concentrations of endoplasmic reticulum stress-related protein antibodies were 1:1000 in IRE1, 1:500 and 1:1000 in ATF6, 1:1500 in PERK, 1:200 in GRP78, and 1:100 in Caspase-12.

Complicated chemical reactions occur in the decoction of traditional Chinese medicines(TCMs) which features complex components, influencing the safety, efficacy, and quality controllability of TCMs. Therefore, it is particularly important to clarify the chemical reaction mechanism of TCMs in the decoction. This study summarized eight typical chemical reactions in the decoction of TCMs, such as substitution reaction, redox reaction, isomerization/stereoselective reaction, complexation, and supramolecular reaction. With the "toxicity attenuation and efficiency enhancement" of aconitines and other examples, this study reviewed the reactions in decoction of TCMs, which was expected to clarify the variation mechanisms of key chemical components in this process and to help guide medicine preparation and safe and rational use of medicine in clinical settings. The current main research methods for chemical reaction mechanisms of decoction of TCMs were also summed up and compared. The novel real-time analysis device of decoction system for TCMs was found to be efficient and simple without the pre-treatment of samples. This device provides a promising solution, which has great potential in quantity evaluation and control of TCMs. Moreover, it is expected to become a foundational and exemplary research tool, which can advance the research in this field.
Medicine ; Medicine, Chinese Traditional ; Research Design

OBJECTIVE: To explore the characteristics and rules of acupoint sensitization phenomena based on knee osteoarthritis (KOA), one of the clinical dominant diseases of acupuncture-moxibustion. METHODS: In combination with literature and expert experiences, the acupoints with the highest use frequency in treatment of KOA were screened, e.g. Heding (EX-LE 2), Liangqiu (ST 34), Mingmen (GV 4), Neixiyan (EX-LE 4), Ququan (LR 8) and Dubi (ST 35). In 814 patients with KOA and 217 healthy subjects, the acupoint temperature, mechanic pain threshold and pressure pain threshold were detected separately. Using machine learning method, the sensitization was judged at each acupoint. RESULTS: Compared with healthy subjects, the acupoint temperature was increased and the mechanic pain threshold and pressure pain threshold were reduced in KOA patients (P<0.05). Besides, the cut-off value was presented to distinguish whether the acupoint was sensitized or not. The results of machine learning showed that the highest prediction accuracy of acupoint sensitization was 86.7% (Shenshu [BL 23]) and the lowest one was 73.9% (Heding [EX LE 2]). The prediction accuracy at the third clinical stage trial was higher, the highest was 93.3% (Ququan [LR 8]) in KOA patients. CONCLUSION It is confirmed that the acupoint sensitization reflects the characteristics of disease and is correlative with the conditions of illness, which may provide the reference for the auxiliary diagnosis and condition assessment of KOA.
Acupuncture Points ; Acupuncture Therapy ; Humans ; Moxibustion ; Osteoarthritis, Knee/therapy* ; Treatment Outcome

Microecology was directly or indirectly involved in the growth and development, metabolism process, and component accumulation of traditional Chinese medicine(TCM) in various ways, which affected the formation and changes of the geoherbalism of TCM. It was one of the main tasks of traditional Chinese medical microecology(TCMM) to reveal the relationship among microecological structure and its change rule and the quality effect of TCM. The heterogeneity of soil environment caused by geographical and climatic factors, as well as the discreteness limitation caused by isolation factors such as distance and host selection, were the main causes of the differentiation of microecological geography of TCM. The microecology of TCM had important influences and contributions on the distinctive origin and quality of Dao-di herbs, which was mainly reflected in the formation of excellent germplasm(including disease and insect resistance, drought resistance, salt resistance, cold resistance, etc.), the increase of yield, the formation of medicinal parts, the metabolism and accumulation of effective components, the time limit of harvesting, and the toxicity, increasing efficiency or reducing toxicity of TCM in the processing, the changes of product efficiency after introduction, and the authenticity of fungus medicine. With the vigorous development of metabonomics and modern information technology, the following aspects would become the future research trends, including the microecologically mediated biogenic pathway of chemical components, the metabolic synthesis reactor of TCM based on the microecological quantitative effect relationship, the cultivation of genuine Chinese medicine based on reconstruction of microecological structure, the origin identification barcode traceability technology, and the toxicity reduction and efficiency enhancement technology of TCM based on the microecological.
Climate ; Drugs, Chinese Herbal ; Geography ; Medicine, Chinese Traditional ; Metabolomics ; Soil/chemistry*

OBJECTIVE: To observe the distribution characteristics and rules of pain sensitivity points on body surface in patients with knee osteoarthritis (KOA). METHODS: A total of 916 patients with KOA were selected in this study, the pain sensitivity points of local site of knee joint were probed by thumb palpation. Tape was used to measure the distance between the pain sensitivity points and the most nearby acupoints. The Wagner tenderness measuring instrument was used to measure the tenderness threshold of pain sensitivity points. RESULTS: A total of 3618 pain sensitivity points were probed, among them, 3338 pain sensitivity points were sensitized. The minimum sensitization degree was 1.00, the maximum sensitization degree was 3.39, while the average sensitization degree was (2.16±0.60). Pain sensitivity points were distributed 0.37-1.73 CONCLUSION The pain sensitivity points of patients with KOA may be the expansion effect of acupoint areas in the disease states, pain sensitivity points are more likely to appear on the medial side of knee joint.
Acupuncture Points ; Humans ; Knee Joint ; Osteoarthritis, Knee/therapy* ; Pain Threshold

The aim of this paper was to investigate the effect of Faeces Bombycis(FB) on the intestinal microflora in rats with syndrome of damp retention in middle-jiao, and to explore its mechanism in regulating intestinal microflora from the perspective of microorganisms contained in FB. The contents of antidiuretic hormone(ADH) and C-reactive protein(CRP) in serum and aquaporin 3(AQP3) in jejunum were determined by enzyme-linked immunosorbent assay(ELISA). Illumina Miseq platform was used for high-throughput sequencing of the rat feces and FB. The ELISA results showed that as compared with the normal control group, the contents of ADH and CRP in the model group were significantly increased(P<0.05), and the content of AQP3 was significantly decreased(P<0.05). After drug administration, the ADH, CRP and AQP3 contents were recovered. Sequencing of rat feces showed that the ACE, Chao1 and Shannon indexes of the intestinal microflora were the lowest in the model group. As compared with the normal control group, the levels from phylum to genus were all significantly changed in model group, and Proteobacteria, Acinetobacter, Anaerobacter, Pseudomonas, and Parabacteroides levels were significantly increased(P<0.05), while Marvinbryantia level was significantly decreased(P<0.05). As compared with the model group, Proteobacteria was significantly decreased in the FB low and high dose groups(P<0.05), and Acinetobacter, Anaerobacter, Pseudomonas, Parabacteroides levels were significantly decreased in the low, medium and high dose groups(P<0.05), while Lachnoanaerobaculum, Intestinimonas and Marvinbryantia were increased significantly in the high dose group(P<0.05). Sequencing analysis of FB showed that the relative abundance of Leclercia, Pantoea, Brachybacterium, Shimwellia, Hartmannibacter, Klebsiella, Serratia, Aurantimonas, Paenibacillus and Bacillus was high in the FB, but they were basically not present or little in the rat feces. In conclusion, FB may play a role in the treatment of "syndrome of damp retention in middle-jiao" by balancing the intestinal microflora, and this effect may be related to the metabolites of microorganisms in the FB.
Animals ; Aquaporin 3/analysis* ; Bombyx/chemistry* ; C-Reactive Protein/analysis* ; Feces/chemistry* ; Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Medicine, Chinese Traditional ; Rats ; Vasopressins/blood*

Objective: To evaluate the model with spleen deficiency and dampness stagnancy by bioelectrical impedance analysis (BIA) and traditional indicators. Method: The forty rats were divided into blank group and model group, with 20 rats in each group. The rats in the blank group were fed with normal feed, the rats in model group were prepared with the spleen deficiency and dampness stagnancy model for 14 days. Observe the general condition of the rats, measure the water content of the feces in the dry method, measure the water load index by weighing method, and detect the urinary D-xylose excretion total protein (TP), albumin (Alb) content, by enzyme-linked immunosorbent assay (ELISA). Western blot analysis of renal aquaporin 1 (AQP1) content, and the use of experimental animal body composition analyzer to determine the total water content (TBW), extracellular fluid (ECF), intracellular fluid (ICF), fat mass (FM), free fat mass (FFM) and body mass bioelectrical impedance index such as body mass index (BMI). Result: Compared with blank group, the rats in model group lost weight, gradually loose stools occasionally, the anus temperature was basically unchanged, body mass, D-xylose excretion, water load index, TP and Alb content decreased (P<0.01). The feces contained water,the rate and the content of AQP1 in the renal pulp were increased (P<0.01). The TBW, ECF and FFM were increased, and the ICF, FM and BMI were decreased (P<0.01). Conclusion: Rats with spleen deficiency and dampness stagnancy induced a combination of factors such as diet and excessive fatigue. The bioelectrical impedance method can be more intuitive and comprehensive.

Objective: To evaluate the efficacy and safety of a domestic human plasma derived coagulation Factor Ⅸ concentrate (pd-FⅨ) in patients with hemophilia B. Methods: The study was a multicenter, open-label and single-arm study. The efficacy of pd-F Ⅸ was evaluated by objective performance criteria. The doses of pd-FⅨ were calculated according to the bleeding symptom and disease severity. The infusion efficiency of pd-FⅨ and improvement of bleeding symptoms were measured at 30 minutes and (24±4) h after the first infusion, respectively. Adverse events were recorded. Viral infection and FⅨ inhibitor were detected 90 d after the first infusion. Results: All 36 subjects with hemophilia B were enrolled in the study. The median age of these patients was 31 years old and the median injection doses were 4 (1-17) times. The hemostatic effect of 27/36 (75.00%) and 9/36 (25.00%) acute bleeding events were rated as "excellent" and "better" , respectively. The recovery rate was 111.92% (65.55%-194.28%) at 30 minutes after infusion of FⅨ. There was no adverse event related to FⅨ. No reactivation of HBV, HCV or HIV and FⅨ inhibitor was detected at 90-104 d after the first FⅨ infusion. Conclusion: This domestically made human plasma derived FⅨ concentrate is safe and effective in the treatment of acute bleeding in patients with hemophilia B. Clinical trial registration: China food and Durg Administration, 2016L08027.
Adult ; China ; Factor IX ; Hemophilia A ; Hemophilia B/therapy* ; Hemorrhage ; Humans ; Plasma