Objective To investigate effects of neuromuscular electrical stimulation (NMES) on pulmonary arterial hypertension induced by chronic hypoxic hypercapnia in rats.Methods Eighteen male Sprague-Dawley rats were randomly divided into a normal control group (the control group),a hypoxic hypercapnia group (the model group),and a hypoxic hypercapnia + NMES group (the NMES group),each of 6.The rats in both the model and NMES groups were placed in an isobaric cabin with an O2 concentration of 9％ to 11％ and a CO2 concentration of 5％ to 6％ for 8 hours a day for 4 weeks.After leaving the cabin,NMES was performed on the NMES group's bilateral calf muscles for 30 minutes every day.The heart was removed,and the right ventricle (RV) and the left ventricle plus the septum (LV+S) were dissected.An index of right ventricular hypertrophy was calculated as RVHI=RV/(LV+S).Any changes in the pulmonary vasculature were observed using an optical microscope.WT％ and WA％ were calculated.The expression of hypoxia-inducible factor-1α (HIF-1α),PDH-E1α and PDK1 in the lung tissue were determined using western blotting.The LDH activity and the concentration of PDH in the lung tissue homogenate were measured was measured by spectrophotometric method using the LDH assay kit and ELISA,respectively.Results Compared with the control group,the average RVHI,WT％ and WA％,the protein expression of HIF-lα and PDK1,and LDH activity had all increased significantly in the NMES group,while the average expression of PDH-1Eα had decreased significantly.Compared with the model group,significant decrease was observed in the average RVHI,WT％,WA％,protein expression of HIF-1α and PDK1,and LDH activity in the NMES group,but the average expression of PDH-1Eα increased significantly.No significant differences in PDH concentration were detected among the 3 groups.Conclusions NMES may alleviate pulmonary artery hypertension induced by chronic hypoxic hypercapnia,at least in rats.The mechanism may be attributed to inhibiting the expression of HIF-1α protein,which may inhibit the activity of PDH-E1α and LDH,then the aerobic metabolism into glycolysis,finally improving the remodeling of the pulmonary vascular structure.

OBJECTIVE:To provide reference information for the adoptation of fast drug dispensing model in hospital pharmacy of China.METHODS:The procedure of fast drug dispensing system(FDDS)was analysed and compared with tradi?tional dispensing system in advantages and disadvantages.RESULTS:FDDS could raise the speed,accuracy of drug dispensing and improve the quality of pharmaceutical service.CONCLUSION:FDDS is suitable for drug dispensing in large-scale hospi?tals.

Cardiovascular diseases (CVDs) are major disease burdens with high mortality worldwide. Early prediction of cardiovascular events can reduce the incidence of acute myocardial infarction and decrease the mortality rates of patients with CVDs. The pathological mechanisms and multiple factors involved in CVDs are complex; thus, traditional data analysis is insufficient and inefficient to manage multidimensional data for the risk prediction of CVDs and heart attacks, medical image interpretations, therapeutic decision-making, and disease prognosis prediction. Meanwhile, traditional Chinese medicine (TCM) has been widely used for treating CVDs. TCM offers unique theoretical and practical applications in the diagnosis and treatment of CVDs. Big data have been generated to investigate the scientific basis of TCM diagnostic methods. TCM formulae contain multiple herbal items. Elucidating the complicated interactions between the active compounds and network modulations requires advanced data-analysis capability. Recent progress in artificial intelligence (AI) technology has allowed these challenges to be resolved, which significantly facilitates the development of integrative diagnostic and therapeutic strategies for CVDs and the understanding of the therapeutic principles of TCM formulae. Herein, we briefly introduce the basic concept and current progress of AI and machine learning (ML) technology, and summarize the applications of advanced AI and ML for the diagnosis and treatment of CVDs. Furthermore, we review the progress of AI and ML technology for investigating the scientific basis of TCM diagnosis and treatment for CVDs. We expect the application of AI and ML technology to promote synergy between western medicine and TCM, which can then boost the development of integrative medicine for the diagnosis and treatment of CVDs.

Objective To explore the chain mediating effect of mastery and self-efficacy between optimism and resilience of breast cancer patients.Methods Totally 262 breast cancer patients were investigated with general information questionnaire,resilience scale (RS-14),mastery scale for Chinese version (MSC),general self-efficacy scale (GSES) and revised life orientation test (LOT-R).Causual steps and Bootstrap method were used to test the chain mediating effect of mastery and self-efficacy between optimism and resilience.Results The media score of the participants was 18 for optimism,and the average score of the participants was 27.1±4.6 for mastery,26.0±5.9 for self-efficacy,76.6± 13.9 for resilience.There existed a significant difference in RS-14 scores among the patients with different family relationships,family income,and form of payment (all P＜0.05).Correlation analysis showed that optimism,mastery,self-efficacy,and resilience were positively correlated with each other(r=0.57-0.74,all P＜ 0.01).Mediation modeling analysis showed that optimism had a direct effect on resilience.The effect value was 0.361,and the effect was 49.7％.Mastery and self-efficacy mediation effect value were 0.123 and 0.162,and the mediation effect were 16.9％ and 22.3％.While chain mediating effect of mastery-self-effcacy was also significant,and the mediation effect value was 0.081 and the mediation effect was 11.1％.Conclusion Optimism influences breast cancer patients' resilience,not only through the direct path,but also through the indirect path of mastery and self-efficacy,as well as the chain mediating path between these two variables.

Objective:1. To detect any change in the PTEN/Akt/FoxO1 signaling pathway in the muscles of rats with chronic hypoxia-hypercapnia treated using neuromuscular electrical stimulation (NMES), and 2. To document the role of chronic hypoxia-hypercapnia in inducing muscle atrophy.Methods:Thirty-two male Sprague-Dawley rats were randomly divided into a control group, a model group, a mock stimulation group, and an NMES group, each of eight. All of the rats in the model group, the mock stimulation group and the NMES group were placed in a hypoxia-hypercapnia chamber with a 9-11% O 2 and 5.5-6.5% CO 2 atmosphere for 8h per day and 7d per week, lasting 4 weeks. The control group were placed in a similar chamber with normal air. In the last 2 weeks, after the 8h in the chamber, the NMES group were given 30min of electrical stimulation at 100Hz to the calf muscles of their bound lower limbs. The mock stimulation group were only bound without any electrical stimulation. After the 4-week intervention, the gastrocnemius muscles were resected and their cross-sectional areas (CSAs) were observed using hematoxylin-eosin staining. Immunohistochemistry and western blotting were employed to detect the protein expression of phosphatase and tensin (PTEN), p-Akt, Akt and FoxO1. Results:Compared with the control group, a significant decrease was observed in the average CSA and in the expression of p-Akt and Akt in the model group, while a significant increase was found in the average protein expression of PTEN and FoxO1. Compared with the model group, there was a significant increase in the average CSA, as well as the average expression of p-Akt and Akt in the NMES group, but a significant decrease in the average expression of PTEN and FoxO1.Conclusion:Neuromuscular electrical stimulation can relieve muscle atrophy from chronic hypoxia-hypercapnia by inducing skeletal muscle protein synthesis through regulating the PTEN/Akt/FoxO1 signaling pathway, at least in rats.

Objective:To establish a method for determining the concentration of gatifloxacin in rabbit ocular tissue and compare the ocular pharmacokinetics of 0.3% gatifloxacin eye gel after a single and multiple topical instillations in rabbits.Methods:Ninety-four healthy New Zealand rabbits were selected.Ten rabbits were randomly selected without any treatment for blank tissue collection, and the remaining 84 rabbits were randomly divided into a single-dose group (36 rabbits) and a multiple-dose group (48 rabbits) equally between males and females using a random number table.The left eye was taken as the experimental eye.The single-dose group was given one drop of 0.3% gatifloxacin eye gel into the left eyes, and the rabbits were divided evenly into six subgroups.In each subgroup, tear specimens and blood specimens were collected at 0.5, 1, 3, 5, 7, 10 hours after gel application, then cardiac blood samples were taken, after which animals were sacrificed immediately to collect ocular tissue including aqueous humor, conjunctiva, cornea, sclera, iris-ciliary body, lens, vitreous body, retina, and choroid.The multiple-dose group was given 1 drop of gatifloxacin ophthalmic gel in the left eye three times a day.At 0.5 hour after the first administration days 4 and 6, and 0.5, 1, 3, 5, 7, and 10 hours after the first administration on day 7, the cardiac blood sampling and ocular tissue collection were performed.The methanol precipitation protein method was used to pretreat samples, and the concentration of gatifloxacin in rabbit plasma and eye tissue was measured and calculated by high-performance liquid chromatography-tandem mass spectrometry method to obtain pharmacokinetic-related parameters such as peak concentration (C max), peak time (T max), and area under curve (AUC).The mobile phase was a methanol-0.1% acetic acid aqueous solution (volume ratio=70∶30), and a positive ion multiple reaction detection mode was used.Ciprofloxacin was used as the internal standard, the selectivity, standard curve and lower limit of quantification, accuracy and precision, extraction recovery rate, matrix effect, and stability of the method were validated in accordance with the 9012 Guidelines for Validation of Quantitative Analysis Methods for Biological Samples in Chinese Pharmacopoeia ( 2020 edition).Combined with the minimum inhibitory concentration (MIC 90) of gatifloxacin on common ocular infectious bacteria, C max/MIC 90 and AUC/MIC 90 were calculated.The study protocol was reviewed and approved by the Animal Ethics Committee of Shenyang Xingqi Pharmaceutical Co., Ltd.(No.XQ-2016-011). Results:Gatifloxacin has a good linear relationship in various eye tissues and plasma.The between-run precision in corneal tissue is within the range of -1.5%-6.0%, and the daytime precision was not greater than 15%.The extraction recovery rate in corneal tissue ranged from 92.0% to 94.8%, and the precision of the matrix effect at low, medium, and high concentrations calculated by internal standard normalization was not greater than 3.3%.After a single topical instillation, gatifloxacin reached a high concentration in anterior and posterior segment ocular tissues and its distribution ranked in order from the highest to the lowest by AUC 0-t as follows, tears, cornea, conjunctiva, iris-ciliary body, sclera, aqueous humor, choroid, retina, lens and vitreous body, with the C max of 94.90 μg/g, 7.34 μg/g, 3.65 μg/g, 1.81 μg/g, 1.75 μg/g, 1.31 μg/ml, 0.86 μg/g, 0.53 μg/g, 0.13 μg/g and 0.07 μg/ml, respectively.T max was 1 hour in all ocular tissues except in the lens, choroid, and vitreous body fluid, where T max was 0.5 hour.There was no significant difference among the concentrations of gatifloxacin in ocular tissues at 0.5 hour on days 4, 6 and 7 after multiple dosing ( P>0.05), and the AUC 0-t in the cornea, conjunctiva, and sclera was approximately 2.04, 2.12, and 2.32 times that of the single dosing.The concentration of gatifloxacin released into the systemic circulation after single and multiple dosing was less than 25.00 ng/ml.For both Staphylococcus aureus and Staphylococcus epidermidis, pharmacokinetic/pharmacodynamics in the conjunctiva, cornea, sclera, iris-ciliary body, aqueous humor, and choroid were satisfied with C max/MIC 90≥10 and AUC/MIC 90≥30 after continuous administration of gatifloxacin ophthalmic gel. Conclusions:A rapid and sensitive method for measuring gatifloxacin concentration in ocular tissues is successfully constructed.Gatifloxacin ophthalmic gel administered three times a day for three days can achieve stable concentrations in ocular tissues, and the concentration of gatifloxacin in ocular tissues is increased compared with a single dose.Effective treatment of common bacterial infections of the conjunctiva, cornea, sclera, and iris-ciliary body can be achieved with topical application of gatifloxacin ophthalmic gel.

Objective To investigate the clinicopathologic characteristics, differential diagnosis and prognosis of pulmonary epithelioid hemangioendotheliomas (PEHs).Methods The clinical symptoms and imaging findings of 6 cases of PEHs were investigated and pathologic analyses including histomorphologic and immunohistochemical studies were performed.Results Clinical symptoms of the patients were nonspecific and insidious.The typical radiological manifestation was characterized by multiple small pulmonary nodules. The pathological findings were well-demarcated hypocellular hyalinized nodules with more cellularity at the periphery of the nodule. The neoplastic cells showed mild nuclear atypia and prominent eosinophilic cytoplasm with vacuoles, attempting to form primitive vasculature.Immunohistochemically, tumor cells were positive to CD31, CD34 and ERG.Follow-up data from 8 months to 5 years showed no tumor progression, except for the development of bone metastases in one case at 6 months.Conclusions PEHs are uncommon vascular tumors with low-intermediate malignancy. Using H&E and immunohistochemistry, the final pathological diagnosis can be made and misdiagnosed as a benign fibrotic nodule or other malignant tumors can be avoided. The most effective treatment is surgical resection, if necessary, combined with chemotherapy or radiotherapy.

Objective:To investigate the effect and mechanism of local gastric hypothermia in rats with pancreatitis based on a GC?MS and LC?MS dual metabolomics strategy.Methods:Eighteen SD rats were randomly divided into the sham operation (SO), acute pancreatitis (AP) and acute pancreatitis hypothermia (APH) groups. The AP model was established by retrograde injection of 3.5% sodium taurocholate solution into the pancreaticobiliary duct in the AP and APH groups. In the APH group, gastrotomy was performed near the cardia, and a cooling balloon with 2 silicone catheters was placed in the stomach. After the successful establishment of the rat pancreatitis model in the APH group, the speed of ice water circulation was controlled and the output power of the heating pad was adjusted to achieve pancreatic surface temperature reduction while avoiding systemic hypothermia. Temperatures were not monitored and controlled in the SO and AP groups. Serum amylase was detected by ELISA. Pancreatic tissues were stained with HE and histopathologically scored. The expression of NF-κB, IL-6, TNF-α and IκBα in pancreatic tissue was detected by Western blotting. The AP and APH groups were compared by full-scan analysis, and the serum differential metabolites and metabolic pathways were detected by GC?MS- and LC?MS-based metabolomics strategies.Results:Compared with the SO group, the serum amylase level in the AP group and APH group were increased (all P<0.05). Compared with the AP group, the amylase levels at 3 h and 5 h after the operation were decreased in the APH group (both P<0.05). The pathological scores of the AP and APH groups were higher than those of the SO group (both P<0.05), and the pathological damage to pancreatic tissue in the APH group was less than that in the AP group ( P<0.05). IL-6, TNF-α and NF-κB were decreased and IκBα was increased in the APH group compared with the AP group by Western blotting (all P<0.05). A total of 53 differential metabolites were identified by GC?MS, and 236 differential metabolites were identified by LC?MS in the serum samples of the APH group compared with the AP group. The differential metabolites obtained from the blood samples of the APH group and AP group were imported into MetaboAnalyst 4.0 software for analysis, and the root data-log ( P value)>2, P<0.05, three major metabolic pathways were obtained, including ascorbate and aldarate metabolism, pentose and glucuronate interconversions and tryptophan metabolism. Conclusions:Local gastric hypothermia has a protective effect on the expression of inflammatory factors and alleviates pathological damage in rats with acute pancreatitis, which may be related to ascorbate and aldarate metabolism, pentose and glucuronate interconversions and tryptophan metabolism.

OBJECTIVE：To study the effects of different penetration enhancers on in vitro transdermal permeation of Flavaspidic acid BB cream. METHODS ：Flavaspidic acid BB cream was prepared ，containing 11 kinds of different penetration enhancers as 1％ azone，2％ azone，3％ azone，4％ azone，1％ menthol，1％ propylene glycol ，1％ oleic acid ，1％ azone+1％ menthol，1％ azone+1％ propanediol，1％ azone+1％ oleic acid or 1％ menthol+1％ propanediol. Modified Franz diffusion cell was adopted using abdominal skin of isolated male rat as transdermal barrier. The content of flavaspidic acid BB was determined by UPLC. The accumulative transdermal amount （Q24 h）and percutaneous permeability （Jss）within 24 h were calculated ；and compared with Flavaspidic acid BB cream without transdermal enhancer ，the enhancement ratio （ER）was calculated. RESULTS ： Q24 h of Flavaspidic acid BB cream with above 11 kinds of transdermal enhancers were （82.96±7.15），（80.17±0.66），（78.22± 1.87），（73.53±1.24），（35.65±2.23），（34.02±1.73），（42.68±2.66），（33.94±1.37），（34.16±1.54），（46.78±1.21），（43.66±1.69） μg/cm2，respectively. Jss value were （5.26±0.10），（4.69±0.12），（4.45±0.45），（4.00±0.06），（3.74±0.33），（3.23±0.18）， （3.73±0.53），（3.14±0.47），（3.54±0.11），（3.98±0.34），（4.34±0.14）μg（/ cm2·h），respectively. ER were 2.055，1.831，1.738， 1.564，1.462，1.263，1.456，1.227，1.385，1.557，1.698，respectively. CONCLUSIONS ：All of the above transdermal absorption enhancers can enhance the percutaneous absorption of Flavaspidic acid BB cream ，among which ，1％ azone is the best.

Objective:To evaluate the residual risk (RR) of transfusion transmitted HIV (TT-HIV) after the implementation of nucleic acid amplification test (NAT) in blood screening test among blood centers in China.Methods:The data of blood donors and HIV infection markers from 2017 to 2020 were collected from 28 blood centers via the Platform of Comparison of blood establishments Practice in Chinese Mainland. The new infection rate/window period mathematical model was used for two types of blood screening strategies, namely, two rounds ELISA plus individual NAT take turn with pooling NAT (2ELISA+ ID-NAT/MP-NAT) and two ELISA plus one round pooling NAT (2ELISA+ MP-NAT), and the RR of HIV infection was estimated also based on first donors (FDs) and repeated donors (RDs) in different blood donation years. T-test analyses were conducted for comparing TT HIV RR among FDs and RDs in different blood donation years with two blood screening strategies, and the variation trend of RR in HIV test was observed.Results:From 2017 to 2020, the RR of FDs in 2ELISA+ ID-NAT/MP-NAT blood screening strategy was 2.869/10 6 person-year, 3.795/10 6 persons-year, 3.879/10 6 person-year, and 2.890/10 6 person-year respectively. The RR of RDs was 1.797/10 6 person-year, 1.502/10 6 person-year, 1.857/10 6 person-year, and 1.483/10 6 person-year respectively. Significant difference exists between RR of FDs and RDs, with F=9.898 and p<0.05. In 2ELISA+ MP-NAT strategy, the RR of FDs was 3.508/10 6 person-year, 1.868/10 6 person-year, 2.204/10 6 person-year, and 1.765/10 6 person-year respectively. The RR of RDs was 0.948/10 6 person-year, 0.926/10 6 person-year, 0.748/10 6 person-year, and 0.682/10 6 person-year respectively. Statistical difference existed between RR of FDs and RDs, with F=17.126 and P<0.05. There was no significant difference between the RR of FDs in these two strategies with F=3.493 and P>0.05, while there was a difference between the RR of RDs in these two strategies with F=24.516 and P<0.05, and a difference between the RR of total donors (TDs) in these two strategies F=20.216 and P<0.05. Conclusions:The RR of TT HIV significantly decreased after the introduction of NAT into blood test among blood centers in China. There were some differences in the RR of HIV testing among different blood screening strategies. There could be significant differences in the RR of HIV testing among different groups of blood donors. Compared with FDs, RDs is the low risk group for HIV.