Chronic pain refers to pain that persists or recurs for more than 3 months and has a high comorbidity rate with emotions such as depression and anxiety. The complex pathogenesis of comorbid depressive symptoms in chronic pain poses great challenges to clinical diagnosis and treatment. This article reviews the research progress on the effect mechanism on the comorbid depressive symptoms in chronic pain by traditional Chinese medicine monomers， compound formulas， and acupuncture therapy in recent years. It is found that traditional Chinese medicine monomers （flavonoids， phenols， terpenes， coumarins， alkaloids）， traditional Chinese medicine formulas （Aconitum carmichaeli decoction， Chaihu guizhi decoction， etc.）， and acupuncture therapy （acupuncture at acupoints such as Baihui， Yintang， Hegu， and Taichong） can effectively improve comorbid depressive symptoms in chronic pain by regulating the levels of neurotransmitters， brain-derived neurotrophic factors and inflammatory factors， and the activity of glial cells in the central nervous system.

【Objective】 To investigate the effect of polymerized human cord hemoglobin (PolyCHb) in chemoimmunotherapy for breast cancer in mice. 【Methods】 A 4T1 breast cancer in situ tumor model was established, and 15 mice were randomly divided into 3 groups: blank group: no intervention; Control group: doxorubicin + PD-1 inhibitor was given intraperitoneal injection of doxorubicin 5 mg·kg^-1 once a week and PD-1 inhibitor 12.5 mg·kg^-1 once a week; Experimental group: DOX+ a-PD-1+ PolyCHb, the usage of DOX and a-PD-1 was the same as above, PolyCHb: PolyCHb 600 mg·kg^-1 was injected into the tail vein, three times a week; The administration period was 4 weeks. During the administration, the tumor volume was recorded 3 times per week, the tumor growth curve of each group was drawn and the tumor inhibition rate was calculated. The mice were killed on the 29th day, and the tumor was removed and weighed to calculate the tumor inhibition rate. Immunofluorescence, HE staining, TUNEL method and immunohistochemistry was used to detect the expression of HIF-1α, observe the pathological changes of tumor tissue, detect the apoptosis of tumor cells, and detect the expression of tumor proliferation index Ki67. 【Results】 Compared with the blank group and the control group, the tumor volume in the experimental group decreased significantly (P<0.05) and the tumor inhibition rate (%) increased significantly (P<0.05). The content of HIF-1α in tumor tissue in experimental group decreased (P<0.05). In the experimental group, the growth area of tumor tissue decreased, accompanied by the increase of necrosis area; The positive rates (%) of apoptosis in tumor tissues of blank group, control group and experimental group were 18.79±0.62, 20.68±1.19 and 41.65±2.99 respectively (F=135.2, P<0.001). In addition, the results of tumor proliferation index Ki67 showed that there was a statistical difference between the control group and the experimental group (P<0.05). 【Conclusion】 PolyCHb increases the sensitivity of chemoimmunotherapy in breast cancer mouse model, and the mechanism may be related to the decrease of HIF-1α expression, the promotion of apoptosis and the inhibition of cell proliferation.

【Objective】 To prepare liposomes encapsulate hemoglobin and paclitaxel(LEHP)to improve tumor hypoxia resistance. 【Methods】 LEHP were prepared by thin-film method, and the particle size, Zeta potential and polydispersity were investigated by nanoparticle size analyzer, and encapsulation efficiency was investigated by high performance liquid chromatography, and the interaction between the liposomes and tumor cells was evaluated by in vitro cell experiments. 【Results】 The optimal preparation conditions of LEHP was as follows: total phospholipid 36 mM, DPPC∶Dope∶cholesterol molar ratio 7∶2∶1, paclitaxel 3 mg, hydrated with 3 mg·mL^-1 Hb-PBS for 30 min at room temperature; The average particle size was (189.17±8.22) nm, polydispersity was 0.14±0.023, paclitaxel encapsulation efficiency was (58.27±2.55)%, hemoglobin content was (0.63±0.05) mg·mL^-1. In vitro cell experiments, the killing effect of LEHP was about 1.5 times that of LEP, about 1.2 times that of LEP, and ROS production was about 1.8 times that of LEP. 【Conclusion】 The preparation conditions of LEHP was optimized, and cell experiments showed that LEHP can promote tumor cell apoptosis by improving hypoxia and increasing ROS production, which is expected to provide a safe and effective new method for drug resistance caused by tumor hypoxia.

【Objective】 To prepare microneedles(MNs) loaded with platelet-rich plasma lysate (PL) using Carboxymethyl chitosan (CMCS), and explore the prospect of PL MNs in the treatment of diabetic wounds. 【Methods】 CMCS was used as the basic material, and an appropriate amount of polyvinylpyrrolidone (PVPK-60) was added to prepare needle materials of different concentrations, and the optimal concentration was determined by investigating the needle formation rate, morphological characteristics and mechanical properties, and the growth factor activity in PL MNs was investigated. The diabetic mice were randomly divided into four groups after the back wound was made, the control group did not do any treatment, the PL smear group was treated with PL smearing, the blank MNs group was treated with MNs without PL, and the PL MNs group was treated with PL microneedles. The effect of PL MNs in wound healing in diabetic mice was evaluated through body observation, H&E staining and immunohistochemistry results. 【Results】 When PVPK60 was 40 mg/mL, the needle formation rate was 100%, the array was complete, the needle body was full, and the needle was sharp. According to the results of mechanical-displacement curve and weight pressure change experiment, the prepared PL MNs have good mechanical strength. The results of growth factor analysis indicated that the content of vascular endothelial growth factor (VEGF) in PL was (625±35) pg/mL, and the content of platelet-derived growth factor-BB (PDGF-BB) was (18 741±1 287) pg/mL. After making the MNs, the VEGF content was (183±2) pg/mL, and the PDGF-BB content was (8049±1157) pg/mL. Although the concentration of growth factors decreased, growth factor activity was still preserved.The results of wound healing experiments in diabetic mice showed that the PL MNs group had better healing, and the wound healing rate was different from that of three groups (P<0.01). The results of H&E staining showed that the PL MNs group had fewer inflammatory cell infiltrates and bleeding spots. The number of fibroblasts and new microvascular in the control group was worse than that in the PL MNs group and the PL smear group. The results of immunohistochemistry indicated that the expression of pro-inflammatory factor IL-6 decreased, while anti-inflammatory factor TGF-β and angiogenesis index CD31 increased in the PL MNs group, which were significantly different from those in the other three groups (P<0.01). 【Conclusion】 The PL MNs prepared in this experiment have good mechanical properties, which has a positive effect on the wound healing of diabetic mice, and provides a new idea for diabetic wound healing.

Objective To evaluate the application efficacy of SpyGlass endoscopic direct visualization system in management of complex biliary complications after orthotopic liver transplantation. Methods Clinical data of 369 adult patients with biliary complications after orthotopic liver transplantation who received endoscopic retrograde cholangiopancreatography (ERCP) for the first time were retrospectively analyzed. Preoperative conditions, intraoperative manifestations, treatment outcomes and complications of patients treated with SpyGlass system were analyzed. Results Fifty-six patients were treated with SpyGlass system. The main preoperative symptoms included abdominal discomfort in 38 cases, fever in 8 cases, jaundice in 6 cases and skin itching in 4 cases. Ultrasound examination in 18 patients indicated common bile duct stenosis and significant intrahepatic bile duct dilatation. Preoperative magnetic resonance cholangiopancreatography (MRCP) of 56 patients revealed that 36 cases were diagnosed with common bile duct stenosis complicated with stones, 16 cases of common bile duct stenosis alone and 4 cases of suspected tumors. All patients had definite indications for SpyGlass system treatment. Among 56 patients treated with SpyGlass system, 34 cases were diagnosed with anastomotic stricture complicated with stones, 12 cases of anastomotic stricture alone, 1 case of biliary stone and 4 cases of tumors. Among 48 cases who were successfully treated, the levels of alanine aminotransferase, aspartate aminotransferase, γ-glutamyltransferase, alkaline phosphatase and total bilirubin at postoperative 48 h were all significantly lower than preoperative levels (all P<0.05). No severe complications occurred in 56 patients treated with SpyGlass system. Conclusions Use of SpyGlass system may significantly increase success rate and guarantee surgical safety in the treatment of complex biliary complications after liver transplantation, which is worthy of promotion and application.

Objective:To explore the mechanism of Kechuan'an Oral Liquid in treating asthma based on network pharmacology; To carry out experimental verification.Methods:The effective components and targets of Kechuan'an Oral Liquid were obtained through TCMSP and literature search. The related targets of asthma were screened by GEO database, and the intersection targets of drug and disease were selected. The PPI network was constructed by STRING database, and the GO function and KEGG pathway were enriched and analyzed for key targets by DAVID database. The rats were divided into blank control group, model group and Kechuan'an Oral Liquid group according to the method of random number table. Kechuan'an Oral Liquid group received Kechuan'an Oral Liquid 12.34 ml/kg for gavage, and blank control group and model group were perfused with distilled water of the same volume for gavage, once a day for 3 days. The asthma model of rats was prepared by atomizing the mixture of acetylcholine chloride and histamine phosphate, and HE staining was used to observe the pathological changes of lung tissue; Western blot was used to detect the protein expressions of IL-6, TLR4, MyD88 and TAK1, and the network pharmacological prediction results were verified.Results:A total of 153 active components, 1 896 targets and 2 982 differentially expressed genes of Kechuan'an Oral Liquid were screened out, and 25 intersection targets of drugs and diseases were obtained. The enrichment results showed that toll-like receptor signaling pathway, TNF signaling pathway and Nod-like receptor signaling pathway were the main mechanisms of immune inflammation. Compared with the control group, the lung tissue of rats in the model group showed morphological changes such as thickening of air duct wall and infiltration of inflammatory cells, which were significantly improved in the Kechuan'an Oral Liquid group. Compared with the control group, the expressions of IL-6, TLR4, MyD88 and TAK1 in the model group significantly increased ( P<0.01), and compared with model group, the expressions of IL-6, TLR4, MyD88 and TAK1 in Kechuan'an Oral Liquid group significantly decreased ( P<0.05 or P<0.01). Conclusion:Kechuan'an Oral Liquid can inhibit toll-like receptor signaling pathway and mediate anti-inflammatory effect to treat asthma.

Objective: To analyze the association between short term PM 2.5 exposure and high blood pressure in adolescents and its modification effect of overweight and obesity, and to provide a reference for the refined management of students physical health and the scientific prevention and controlling of air pollution. Methods: A total of 148 956 junior high school students and senior high school students who passed the annual physical examination data of middle school students in Beijing from 2017 to 2018 were selected; The inverse distance weighted interpolation method was used to get the meteorological elements and air quality of the research area; Linear mixed effect model was used to estimate the cumulative lag effect of short term PM 2.5 exposure on systolic and diastolic blood pressure within 7 days, and analyze the modification effect of overweight and obesity on the association between short term PM 2.5 exposure and high blood pressure in adolescents. Results: From September 1, 2017 to June 30, 2018, the average concentration of PM 2.5 was (56.53±45.85)μg/m 3; The detection rate of overweight and obesity was 34.22%, and the detection rate of high blood pressure was 8.03%. The cumulative lag effect of PM 2.5 on systolic blood pressure in overweight and obesity group was the largest at lag07, that is, the daily average concentration of PM 2.5 increased by 10 μg/m 3 was significantly correlated with higher systolic blood pressure ( OR =1.05,95% CI =1.03-1.07); the cumulative lag effect of PM 2.5 on systolic blood pressure in non overweight and obese group was the largest at lag05, that is, the daily average concentration of PM 2.5 increased by 10 μg/m 3 was significantly correlated with higher systolic blood pressure ( OR =1.04,95% CI =1.02-1.06). Short term exposure to PM 2.5 did not affect the high diastolic blood pressure in adolescents. Overweight and obese adolescents were more susceptible to high blood pressure caused by short term PM 2.5 exposure within 3 days of cumulative lag (lag01-lag03). Conclusion The short term exposure of PM 2.5 has a significant positive correlation with adolescent blood pressure, and shows a lag effect. Overweight and obese adolescents have higher blood pressure after PM 2.5 short term exposure.

Objective To make classification and segment measurement for the cases with tibiofibular and ankle fractures in parachuting landing, and investigate main classification types of parachuting fractures and fracture segments of high risk.Methods A total of 56 fracture cases in parachuting landing were collected, and the tibiofibula and ankle fractures were classified according to AO-OTA or Lauge-Hansen classification standards respectively based on their digital X-ray images. The medium plane between talus and tibia joint planes in ankle joint was defined as the reference plane. The highest and lowest injury points of tibia and fibula were marked respectively, and the fracture segment was defined between the highest and lowest point for statistical analysis.Results For tibiofibular and ankle fracture cases in parachuting landing, fracture at both tibia and fibula accounted for 80.4%. The major classification of tibiofibula fracture was 42-D/5.2 (45.8%) and 42-D/5.1 (16.7%). The major classification for ankle fracture was pronation-external rotation (PER, 59.4%) and supination-external rotation (SER, 37.5%). When tibiofibular and ankle fracture cases in parachuting landing occurred, the fracture segment of the tibia was mainly from 57 to 143 mm above the reference plane and from 6 mm below the reference plane to 24 mm above the reference plane, while the fracture segment of the fibula was 4-45 mm and 74-83 mm above the reference plane. Injury risks of all above segments were higher than 50%.Conclusions For protection of lower limbs in parachuting landing, the fracture at both tibia and fibula should be highly noticed. The ankle motion of PER and SER should be especially restricted in parachuting ankle protection.

Objective: To analyze the relationship between short term exposure of PM 2.5 and the vital capacity of children and adolescents and the modification effect of overweight and obesity, and to provide a scientific reference for appropriate outdoor activities and strengthening prevention of air pollution. Methods: A total of 1 036 273 students who qualified in the annual health examination data of primary and secondary school students in a city from 2017 to 2018 were selected; the meteorological factors and air quality of the study area were obtained by inverse distance weighted interpolation method; the generalized linear mixed model was used to estimate the individual lag effect and average lag effect of PM 2.5 short term exposure on lung capacity with in 7 days, and to analyze the modification effect of overweight and obesity on the relationship between short term PM 2.5 exposure and vital capacity in children and adolescents. Results: From September 1, 2017 to June 30, 2018, the average PM 2.5 concentration in this city was 66.36 μg/m 3, the detection rate of overweight and obesity was 33.38%, and the average lung capacity was (2 286.72±956.77)mL. The single lag effect of PM 2.5 on vital capacity was the biggest when lag6, the average daily PM 2.5 concentration increased by 10 μg/m 3 and the decrease of vital capacity of children and adolescents by 2.81(95% CI =2.60-3.03)mL. The average lag effect of PM 2.5 on lung capacity was the largest when lag07, the average concentration of PM 2.5 sliding was significantly correlated with the decrease of lung capacity of children and adolescents by 5.82(95% CI =5.37-6.27)mL every 10 μg/m 3 increase. The prevalence of PM 2.5 short term exposure to pulmonary capacity decreased in overweight and obese children and adolescents was higher ( P ＜0.01). Conclusion The short term exposure of PM 2.5 has a significant negative correlation with the lung capacity of children and adolescents, and there is a lag effect. The decrease of the vital capacity of overweight and obese children and adolescents after PM 2.5 short term exposure is more significant.

Objective To investigate the prenatal imaging features of fetal congenital esophageal atresia and to further evaluate the value of MRI and ultrasound scan in the same condition.Methods This study recruited 12 singleton gravidas whose fetuses were initially suspected with congenital esophageal atresia by prenatal ultrasound scan and then confirmed by surgery and/or upper gastrointestinal angiography after birth at Guangzhou Women and Children's Medical Center from May 2011 to May 2017.Imaging features of prenatal MRI and ultrasonography of the 12 fetuses were retrospectively analyzed.Differences in imaging findings of these two methods were analyzed by Chi-square test.Results All 12 women received prenatal ultrasound examination and eight of them underwent MRI scan when fetal congenital esophageal atresia was suggested by ultrasound.Both ultrasound and MRI were capable of identifing polyhydramnios and absent or small stomach bubble (12/12 and 8/8,respectively).However,MRI was superior to ultrasound in detecting "pouch sign "/"oral filling sign" or poor filling of small intestine (7/8 vs 3/12 and 8/8 vs 0/12,x2 were 7.500 and 20.000,both P＜0.01).While,no statistical difference was shown in detecting curved tracheal between MRI and ultrasound (2/8 vs 0/12,x2=3.333,P=0.067).For Gross Ⅰ or Gross Ⅲ congenital esophageal atresia fetuses,no statistically significant difference was found in their imaging features (all P＞0.05).The total detection rates after 32 weeks of gestation of Gross Ⅰ and Gross Ⅲ cases were both 3/6.Conclusions Prenatal MRI is a vital supplement to ultrasound due to its high display rate of characterized features of congenital esophageal atresia.Thus,the combined use of ultrasound and MRI is of great importance for prenatal diagnosis of this fetal abnormality.