Objective:To investigate the effect of polystyrene microplastics(PS-MPs)combined with high-fat treatment on vascular endothelial cells.Methods:Human umbilical vein endothelial cells(HUVECs)were cultured in the DMEM medium containing 5%fe-tal bovine serum.HUVECs were treated with conventional culture,high-fat treatment,and PS-MPs combined with high-fat treatment.The experiment was conducted in the three groups of control group,high-fat treatment group and PS-MPs+high-fat treatment group.CCK-8 assay was used to measure cell viability,F-actin staining was used to observe cell morphological changes,and flow cytometry,scratch assay,and tube formation assay were used to measure the apoptosis,migration,and tube-forming ability of cells.Results:After HUVECs were exposed to the high-fat environment,there was a significant reduction in cell viability,shrinkage of cells,a signifi-cant increase in cell apoptosis,and significant reductions in cell migration and tube-forming ability.Compared with the high-fat treat-ment group,there were no significant changes in cell viability,cell morphology,cell apoptosis,and cell migration ability after PS-MPs combined with high-fat treatment,but the tube-forming ability of cells was further impaired.Conclusion:High-fat treatment will affect cell viability,change cell morphology,and damage vascular endothelial cell function,and PS-MPs combined with high-fat treat-ment can aggravate the damage of vascular endothelial cell function.

Objective:To investigate the effectiveness and safety of the coaxial needle technique in percutaneous liver biopsy for patients with coagulation function abnormalities.Methods:Clinical data of 210 patients who underwent percutaneous liver biopsy using the coaxial needle technique under ultrasound guidance from December 2018 to May 2021 in 3 centers were collected. A retrospective analysis was conducted to compare the puncture success rate, number of samples obtained, pathology qualification rate, intraoperative and postoperative bleeding rates between the group with coagulation function abnormalities and the group with normal coagulation function.Results:After propensity score matching, there were 105 patients in each group, with a puncture success rate of 100% in both groups. The pathology qualification rate was 100% for all samples.Intraoperative bleeding occurred in 78 cases (74.3%, 78/105) in the coagulation function abnormalities group and in 64 cases (61.0%, 64/105) in the normal coagulation function group, with a statistically significant difference between the two groups ( P=0.006). Postoperative bleeding occurred in 3 cases (2.9%, 3/105) in the coagulation function abnormalities group and in 0 case in the normal coagulation function group, with no statistically significant difference between the two groups ( P=0.081). Conclusions:The use of the coaxial needle technique for percutaneous liver biopsy in patients with coagulation function abnormalities not only allows for obtaining an adequate tissue sample but also demonstrates good safety.

Pain management, listed as the fifth vital sign, has gained increasing attention from clinicians. Conventional analgesics have limited duration, leading to intense monitor and frequent dosing during the early phase in order to prevent the progression of chronic pain. Thus, prolonging the duration of analgesics has become one focus of the pain research. Several strategies, such as adding adjuvants, producing derivatives, and applying extended-release carriers, make it possible for super long-acting analgesics to come into reality. This review briefly introduces the strategies and development of the super long-acting analgesics, including the successful translation and commercialization of the present products of super long-acting analgesics. It also summarizes the application and translation of extended-release drug carriers, providing invaluable reference for the future research on the field of super long-acting analgesics.

  Objective  To explore the mechanism of Wnt5a on keratinocyte involved in the peripheral sensitization of complex regional pain syndrome type-Ⅰ (CRPS-Ⅰ) by regulating the expression of MMP9, and search for potential therapeutic strategies.  Methods  Cultured HaCaT cells were treated with oxygen glucose deprivation/re-oxygenation (OGD/R). The early stage of mitochondrial damage and membrane potential changes after OGD/R and the effects of Box5 (Wnt5a inhibitor) at different concentrations (20 μmol/L, 40 μmol/L) on MMP9 were explored. Adult male Sprague-Dawley rats were divided into Control group(n=8), CPIP group (n=8), Box5 (20) group (n=8) and Box5 (40) group (n=8). The rat chronic post-ischemia pain (CPIP) model was established to mimic the pathophysiological process of CRPS-Ⅰ. Box5 (20) group and Box5 (40) group were treated with intraplantar injection of 20 μmol/L and 40 μmol/L Box5 100 μL, respectively. The changes of mechanical withdrawal threshold and thermal withdrawal latency were measured within two weeks, and the skin inflammatory infiltration and keratosis were observed by HE staining. The expression of MMP9 was observed by immunofluorescence, and the levels of IL-1β and TNF-α in dorsal root ganglion of different groups were detected by ELISA.  Results  Vitro experiment: After OGD/R treatment, the mitochondrial atrophy was observed in OGD/R group under transmission electron microscope and the average fluorescence intensity of MMP9 was found to increase significantly (P<0.001). Compared with Control group, the mitochondrial membrane potential in OGD/R group decreased significantly by JC-1 detection (P=0.027). Compared with OGD/R group, only Box5 (40) group had a statistically significant increase in mitochondrial membrane potential (P=0.046). Animal experiment: Behavioral tests showed that the mechanical pain threshold and thermal pain threshold of CPIP group were significantly decreased at each time point (D1, D2, D4, D10, D14) (all P<0.05). HE staining indicated that there was a large-scale infiltration of inflammatory cell in the dermis and excessive keratosis in the epidermis, and the thickness of stratum granulosum and stratum spinosum increased significantly (P < 0.001). Immunofluorescence analysis showed that the expression of MMP9 in CPIP group was significantly increased (P<0.001). Compared with CPIP group, the fluorescence intensity of MMP9 in Box5 (20) group (P=0.002) and Box5 (40) group (P<0.001) were significantly decreased. ELISA results showed that the concentrations of IL-1β (P=0.048) and TNF-α (P=0.002) in CPIP group were significantly increased. Compared with CPIP group, the concentrations of IL-1β (P=0.047) and TNF-α (P=0.047) were significantly decreased in Box5 (40) group.  Conclusions  Peripheral ischemia reperfusion injury leads to overexpression of MMP9 on keratinocytes, resulting in CRPS-Ⅰ peripheral sensitization. Targeted inhibition of Wnt5a/MMP9 pathway can reverse pain behavior in rat model of CPIP, thus providing a strategy for clinical treatment of chronic pain.

  Objective  To elucidate whether coffee consumption and caffeine intake was associated with various subtypes of pain based on extensive data from publicly accessible databases.  Methods  The information was extracted from three cycles of the American National Health and Nutrition Examination Survey (1999—2000, 2001—2002, 2003—2004), encompassing data on coffee consumption, pain information, and 11 covariates (including age, gender, race, etc.). Multinomial logistic regression in three models were utilized for analysis.  Results  A total of 13 428 participants were included in this study, with a mean age of (49.79±19.06)years and a male-to-female ratio of 0.9∶1. Daily coffee intake: non-drinker 7794(58.0%), > 0-2 cups 2077(15.5%), > 2 cups 3557(26.5%); daily caffeine intake: without intake 7794(58.0%), > 0-200 mg 3152(23.5%), > 200 mg 2482(18.5%); pain situation: no pain or pain duration < 24 h 10 202(76.0%), acute pain 910(6.8%), subacute pain 369(2.7%), chronic pain 1947(14.5%). After weighting, 13 428 participants were expected to represent 190 million(190 709 157) U.S. citizens aged ≥20 years, and the overall prevalence of acute, subacute, and chronic pain in the U.S. population during that period was estimated to be 8%, 3%, and 16%, respectively. Without adjusting for covariates, individuals who consumed more than 2 cups of coffee or 200 mg of caffeine per day exhibited an elevated risk of chronic pain compared to non-coffee/caffeine drinkers, with an odds ratio of 1.354(95% CI: 1.187-1.544) and 1.372(95% CI: 1.185-1.587), respectively. After adjusting for partial covariates including age, sex, and race, individuals who consumed more than 2 cups of coffee or more than 200 mg of caffeine per day still demonstrated an increased risk of chronic pain with an odds ratio of 1.243(95% CI: 1.083-1.427) and 1.249 (95% CI: 1.072-1.456), respectively. However, after all covariates were adjusted, there was no significant association between coffee/caffeine consumption and chronic pain. Furthermore, the number of cups of coffee consumed or caffeine intake showed no significant correlation with acute and subacute pain.  Conclusions  Compared with nondrinkers, heavy daily coffee drinkers may be more likely to have chronic pain, but it is affected by multiple factors. Basic research and prospective clinical studies are needed to further determine the causality in this association.

OBJECTIVE To investigate the effects of astaxanthin on oxidative stress and inflammatory reaction in rats with traumatic brain injury （TBI）. METHODS Male SD rats were randomly divided into sham operation group， model group， astaxanthin low-dose group （20 mg/kg）， astaxanthin high-dose group （40 mg/kg）， astaxanthin+ML385 group [astaxanthin 40 mg/kg+ nuclear factor-erythroid 2-related factor 2 （Nrf2） inhibitor ML385 30 mg/kg]， with 14 rats in each group. Except for the sham operation group， TBI model was induced by the modified Feeney free-fall impact method in other groups. The rats in each drug group were given the corresponding drug intragastrically or intraperitoneally， and the rats in the sham operation group and model group were intragastrically given a constant volume of normal saline. The neurological function of rats in each group was scored on the 1st， 3rd and 7th day after drug intervention； on the 7th day of drug intervention， the changes of cerebral histomorphology and inflammatory infiltration score were observed in each group， and the ultrastructure of nerve cells in brain tissue was also observed. The contents of oxidative stress indexes [superoxide dismutase （SOD）， catalase （CAT）， glutathione peroxidase （GSH-Px）， malondialdehyde （MDA）， nitric oxide （NO）] and inflammatory reaction indexes [tumor necrosis factor-α， interleukin-1β （IL-1β）， IL-6， inducible nitric oxide synthase] as well as protein and mRNA expressions of Nrf2， heme oxygenase-1 （HO-1） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were detected in cerebral tissue. RESULTS Compared with the sham operation group， the brain edema of rats in the model group was obvious， accompanied by a large number of inflammatory cells infiltrated， the shape of organelles was damaged and their number was reduced， and the ultrastructure of nerve cells was seriously damaged. The neurological function score， the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1 and NQO1 protein and mRNA in brain tissue were significantly decreased， while the inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes were significantly increased （P＜0.05）. Compared with the model group， low-dose and high-dose astaxanthin could significantly improve the pathological status of brain tissue and nerve cells and neurological function scores （except for the first day of drug intervention in the astaxanthin low-dose group）， increase the contents of SOD， CAT， GSH-Px and NO and the relative expression levels of Nrf2， HO-1， NQO1 protein and mRNA in brain tissue in a dose-dependent manner， and reduce inflammatory infiltration scores， the contents of MDA and inflammatory reaction indexes （P＜0.05）. ML385 could significantly inhibit the above effects of astaxanthin （P＜0.05）. CONCLUSIONS Astaxanthin may reduce the oxidative stress of TBI model rats， alleviate the neurological damage and reduce the level of inflammation reaction by activating the Nrf2/HO-1 signaling pathway.

Objective To investigate the current situation of perioperative pain treatment and management using questionnaire survey.Methods A questionnaire was designed by ourselves and sent to anesthesiologists in each hospital all over China via the WeChat platform within 1 month.The system automatically recorded the situation of questionnaires.Results A total of 8 447 anesthesiologists involved in the investigation,the number of valid questionnaires retrieved was 6 778,anesthesiologists in the survey came from 847 hospitals in China,distributing across China 31 provinces and cities,and there were 526 tertiary hospitals (62.1％) and 321 hospitals under tertiary grade (37.9％).Among the medication for perioperative analgesia (not including medication for anesthesia),the following analgesics (applied alone or in combination) were used by anesthesiologists,and the application rate was as follows:opioids 79.74％,nonsteroidal anti-inflammatory drugs 53.78％,paracetamol 25.76％,local analgesics for analgesia (for nerve blockade) 25.44％,other drugs (such as ketamine,gabapentin) 12.39％;combination of two or more drugs 63.65％.Six hundred forty-nine hospitals (76.6％) carried out therapy with analgesic pump after operation,and the constituent ratio of hospitals using patient-controlled analgesia (PCA) pump was 43.8％.Four hundred seventy-five hospitals (56.1％) established Acute Pain Service (APS),the organizing rate of APS was significantly higher in tertiary hospitals than in hospitals under tertiary grade (P＜ 0.01),and the majority of APS personnel was anesthesiologists (72.4％).Conclusion Multimodal analgesia and PCA technique are not widely adopted and the requirement for non-steroidal anti-inflammatory drugs and nerve blockade is lower in perioperative pain treatment in China;analgesic pump is widely used after operation,but the application rate of PCA technique is not high;APS establishment is relatively weak in pain management and anesthesiologists play a leading role in APS.

OBJECTIVE To study the mitochondrial toxicity effect of Radix Aconiti Lateralis Praepa?rata(Fuzi)on H9c2 cardiomyocytes. METHODS H9c2 cells were exposed to Fuzi decoction 6.25, 12.5,25,50 and 100 g·L-1 for 24 h. Fluorescence staining and CCK-8 assay were used to detect cell viability. H9c2 cells were exposed to Fuzi decoction 6.25,12.5 and 25 g · L-1 for 24 h,while the effect on mitochondrial membrane potential and reactive oxygen species(ROS)was detected by flow cytometry. The fluorescence molecular probe and laser scanning confocal microscope were used to observe the effect on Ca2+ in cells,Ca2+ and superoxide in mitochondria. The effect on ATP concentration in cells was detected via firefly luciferin and the expression of Pgc-1α,Bcl-2 and Bax mRNA evaluated by real-time PCR,while the expression of Pgc-1α protein was measured by Western blotting. RESULTS H9c2 cell viability was significantly inhibited by Fuzi decoction 12.5-100 g · L-1(P<0.05,P<0.01). The IC50 value was 47.4669 g · L-1,while the 95%confidence limit was 32.5997-69.1145 g · L-1. After treatment with Fuzi decoction 25 g · L-1 ,the fluorescence intensity of ROS in the normal control group increased from 204±67 to 454±78(P<0.05),that of mitochondrial superoxide increased from 5.4±1.8 to 26.8±8.5 (P<0.01),mitochondrial membrane potential decreased from 1.7±0.5 to 0.8±0.4(P<0.05),the fluores?cence intensity of intracellular Ca2+increased from 7.8±0.8 to 22.1±0.5(P<0.05)while that of mitochon?drial Ca2+decreased from 38.0±4.3 to 9.2±1.6(P<0.01),and intracellular ATP concentration decreased from (10.6 ± 0.4)μmol · g-1 to (5.3 ± 1.1)μmol · g-1 protein (P<0.05). qPCR and Western blotting test results showed that compared with the normal control group ,Pgc-1αand Bcl-2 mRNA relative expression level in Fuzi decoction 25 g·L-1 group was decreased from 1.00±0.10 and 1.00±0.10 to 0.09±0.06(P<0.01)and 0.43±0.06(P<0.01),respectively, while the relative expression of Bax mRNA was increased from 1.00 ± 0.03 to 1.17 ± 0.06 (P<0.05),and the expression of Pgc-1α protein was decreased from 0.906±0.034 to 0.541±0.003(P<0.01). CONCLUSION Fuzi has some mitochondrial toxicity to cardiomy?opathy. This effect arises from the combined action of different mechanisms. Mitochondrial toxicity of myocytes may account for the cardiac toxicity of Fuzi.

Objective Toinvestigateserumalanineaminotransferase(ALT)andtotalbilirubin(TB)concentrationsofchildrenin Panyu district of Guangzhou ,and establish the reference ranges for ALT and TB tests for healthy children of different gender and different age .Methods 4 065 children were chosen randomly ,and their serum ALT and TB were determined .After excluding the outliers ,the results were analyzed statistically .Results After excluding outliers ,a total of 4 000 children were enrolled in the stud-y ,including 2 241 males ,1 759 females ,aged 2- <9 years old .According to statistical analysis ,reference ranges were established . For male the ALT reference ranges were as follows ,2- <3 years old :5 .0-36 .0 U/L ,3- <4 years old :7 .0-21 .0 U/L ,4- <8 years old :6 .0-21 .0 U/L ,8- <9 years old :5 .0-24 .0 U/L ;TB reference ranges of male were as follows ,2- <3 years old :3-12μmol/L ,3- <7 years old :4-15 μmol/L ,7- <8 years old :4-16 μmol/L ,8- <9 years old :7-12 μmol/L .ALT reference range of female were as follows ,2- <3 years old :6 .0-30 .0 U/L ,3- <4 years old:7 .0-22 .0 U/L ,4- <9 years old :6 .0-19 .0 U/L ;female TB reference range ,2- <3 years old :3 .0-12 .0 μmol/L ,3- <4 years old :3 .0-13 .0 μmol/L ,4- <9 years old:4 .0-16 . 0 μmol/L .Conclusion Established the reference ranges of ALT and TB test for healthy children in Panyu district .

This study was aimed to investigate the theoretical basis of Jian-Shen Li-Shui (JSLS) formula. Knowledge
of acute phase of cerebral hemorrhage in ancient Chinese medicine literature, modern pathophysiology theories, experimental researches and clinical results were studied, in order to discuss theoretical basis of JSLS formula. The results showed that JSLS formula embodied basic theories of traditional Chinese medicine (TCM) and experiences of physicians from different generations. It also reflected modern pharmacology research results. It was supported by animal experiments and clinical research results. It was concluded that JSLS formula was in accordance with essence of TCM syndrome differentiation. There were enough evidences for the formation of the formula. It was worthy of further study.